Neurology Reviews

LOS ANGELES — Artificial intelligence (AI) analysis of caregiver-recorded videos has the potential to diagnose infantile epileptic spasm syndrome, according to a new study.

Infants with the condition can have poor outcomes with even small delays in diagnosis and ensuing treatment, potentially leading to intellectual disability, autism, and worse epilepsy. “It’s super important to start the treatment early, but oftentimes, these symptoms are just misrecognized by primary care or ER physicians. It takes a long time to diagnose,” said Gadi Miron, MD, who presented the study at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

What Is This? What Should I Do?

Parents who observe unusual behavior often seek advice from friends and family members and receive false reassurance that such behavior isn’t unusual. Even physicians may contribute if they are unaware of infantile spasms, which is a rare disorder. “And then again, they get false reassurance, and because of that false reassurance, you get a diagnostic delay,” said Shaun Hussain, MD, who was asked to comment on the study.

The timing and frequency of infantile spasms create challenges for diagnosis. They only last about 1 second, and they tend to cluster in the morning. By the time a caregiver brings an infant to a healthcare provider, they may have trouble describing the behavior. “Parents are struggling to describe what they saw, and it often just does not resonate, or doesn’t make the healthcare provider think about infantile spasms,” said Hussain.

The idea to employ AI came from looking at videos of infants on YouTube and the realization that many patients upload them in an effort to seek advice. “So many parents upload these videos and ask in the comments, ‘What is this? What should I do? Can somebody help me?’ said Miron, who is a neurologist and researcher at Charité — Universitätsmedizin Berlin in Germany.

 

AI and Video Can Aid Diagnosis

The researchers built a model that they trained to recognize epileptic spasms using openly available YouTube videos, including 141 infants, 991 recorded seizures, and 597 non-seizure video segments, along with a non-seizure cohort of 127 infants with an accompanying 1385 video segments.

Each video segment was reviewed by two specialists, and they had to agree for it to be counted as an epileptic spasm.

The model detected epileptic seizures with an area under the curve (AUC) of 0.96. It had a sensitivity of 82%, specificity of 90%, and accuracy of 85% when applied to the training set.

The researchers then tested it against three validation sets. In the first, a smartphone-based set retrieved from TikTok of 26 infants with 70 epileptic spasms and 31 non-seizure 5-second video segments, the model had an AUC of 0.98, a sensitivity of 89%, a specificity of 100%, and an accuracy of 92%.

A second smartphone-based set of 67 infants, drawn from YouTube, showed a false detection rate of 0.75% (five detections out of 666 video segments). A third dataset collected from in-hospital EEG monitoring of 21 infants without seizures revealed a false-positive rate of 3.4% (365 of 10,860 video segments).

The group is now developing an app that will allow parents to upload videos that can be analyzed using the model. Physicians can then view the video and determine if there is suspicion of a seizure.

Miron also believes that this approach could find use in other types of seizures and populations, including older children and adults. “We have actually built some models for detection of seizures for videos in adults as well. Looking more towards the future, I’m sure AI will be used to analyze videos of other neurological disorders with motor symptoms [such as] movement disorders and gait,” he said.

 

Encouraging Early Research

Hussain, who is a professor of pediatrics at UCLA Health, lauded the work generally but emphasized that it is still in the early stage. “Their comparison was a relatively easy one. They’re just comparing normal versus infantile spasms, and they’re looking at the seizure versus normal behavior. Usually, the distinction is much harder in that there are kids who are having behaviors that are maybe other types of seizures, which is much harder to distinguish from infantile spasms, in contrast to just normal behaviors. The other mimic of infantile spasms is things like infant heartburn. Those kids will often have some posturing, and they often will be in pain. They might cry. That’s something that infantile spasms will often generate, so that’s why there’s a lot of confusion between those two,” said Hussain.

He noted that there have been efforts to raise awareness of infantile spasms among physicians and the general public, but that hasn’t reduced the increased detection.

 

Another Resource

In fact, parents with suspicions often go to social media sites like YouTube and a Facebook group dedicated to infantile spasms. “You can Google infantile spasms, and you’ll see examples of weird behaviors, and then you’ll look in the comments, and you’ll see this commenter said: ‘These could be infantile spasms. You should go to a children’s hospital. Don’t leave until you get an EEG to make sure that these are not seizures. There’s all kinds of great advice there, and it really shouldn’t be the situation where to get the best care, you need to go on YouTube,’ ” said Hussain.

Miron and Hussain had no relevant financial disclosures.

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

LOS ANGELES — Artificial intelligence (AI) analysis of caregiver-recorded videos has the potential to diagnose infantile epileptic spasm syndrome, according to a new study.

Infants with the condition can have poor outcomes with even small delays in diagnosis and ensuing treatment, potentially leading to intellectual disability, autism, and worse epilepsy. “It’s super important to start the treatment early, but oftentimes, these symptoms are just misrecognized by primary care or ER physicians. It takes a long time to diagnose,” said Gadi Miron, MD, who presented the study at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

What Is This? What Should I Do?

Parents who observe unusual behavior often seek advice from friends and family members and receive false reassurance that such behavior isn’t unusual. Even physicians may contribute if they are unaware of infantile spasms, which is a rare disorder. “And then again, they get false reassurance, and because of that false reassurance, you get a diagnostic delay,” said Shaun Hussain, MD, who was asked to comment on the study.

The timing and frequency of infantile spasms create challenges for diagnosis. They only last about 1 second, and they tend to cluster in the morning. By the time a caregiver brings an infant to a healthcare provider, they may have trouble describing the behavior. “Parents are struggling to describe what they saw, and it often just does not resonate, or doesn’t make the healthcare provider think about infantile spasms,” said Hussain.

The idea to employ AI came from looking at videos of infants on YouTube and the realization that many patients upload them in an effort to seek advice. “So many parents upload these videos and ask in the comments, ‘What is this? What should I do? Can somebody help me?’ said Miron, who is a neurologist and researcher at Charité — Universitätsmedizin Berlin in Germany.

 

AI and Video Can Aid Diagnosis

The researchers built a model that they trained to recognize epileptic spasms using openly available YouTube videos, including 141 infants, 991 recorded seizures, and 597 non-seizure video segments, along with a non-seizure cohort of 127 infants with an accompanying 1385 video segments.

Each video segment was reviewed by two specialists, and they had to agree for it to be counted as an epileptic spasm.

The model detected epileptic seizures with an area under the curve (AUC) of 0.96. It had a sensitivity of 82%, specificity of 90%, and accuracy of 85% when applied to the training set.

The researchers then tested it against three validation sets. In the first, a smartphone-based set retrieved from TikTok of 26 infants with 70 epileptic spasms and 31 non-seizure 5-second video segments, the model had an AUC of 0.98, a sensitivity of 89%, a specificity of 100%, and an accuracy of 92%.

A second smartphone-based set of 67 infants, drawn from YouTube, showed a false detection rate of 0.75% (five detections out of 666 video segments). A third dataset collected from in-hospital EEG monitoring of 21 infants without seizures revealed a false-positive rate of 3.4% (365 of 10,860 video segments).

The group is now developing an app that will allow parents to upload videos that can be analyzed using the model. Physicians can then view the video and determine if there is suspicion of a seizure.

Miron also believes that this approach could find use in other types of seizures and populations, including older children and adults. “We have actually built some models for detection of seizures for videos in adults as well. Looking more towards the future, I’m sure AI will be used to analyze videos of other neurological disorders with motor symptoms [such as] movement disorders and gait,” he said.

 

Encouraging Early Research

Hussain, who is a professor of pediatrics at UCLA Health, lauded the work generally but emphasized that it is still in the early stage. “Their comparison was a relatively easy one. They’re just comparing normal versus infantile spasms, and they’re looking at the seizure versus normal behavior. Usually, the distinction is much harder in that there are kids who are having behaviors that are maybe other types of seizures, which is much harder to distinguish from infantile spasms, in contrast to just normal behaviors. The other mimic of infantile spasms is things like infant heartburn. Those kids will often have some posturing, and they often will be in pain. They might cry. That’s something that infantile spasms will often generate, so that’s why there’s a lot of confusion between those two,” said Hussain.

He noted that there have been efforts to raise awareness of infantile spasms among physicians and the general public, but that hasn’t reduced the increased detection.

 

Another Resource

In fact, parents with suspicions often go to social media sites like YouTube and a Facebook group dedicated to infantile spasms. “You can Google infantile spasms, and you’ll see examples of weird behaviors, and then you’ll look in the comments, and you’ll see this commenter said: ‘These could be infantile spasms. You should go to a children’s hospital. Don’t leave until you get an EEG to make sure that these are not seizures. There’s all kinds of great advice there, and it really shouldn’t be the situation where to get the best care, you need to go on YouTube,’ ” said Hussain.

Miron and Hussain had no relevant financial disclosures.

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

LOS ANGELES — Artificial intelligence (AI) analysis of caregiver-recorded videos has the potential to diagnose infantile epileptic spasm syndrome, according to a new study.

Infants with the condition can have poor outcomes with even small delays in diagnosis and ensuing treatment, potentially leading to intellectual disability, autism, and worse epilepsy. “It’s super important to start the treatment early, but oftentimes, these symptoms are just misrecognized by primary care or ER physicians. It takes a long time to diagnose,” said Gadi Miron, MD, who presented the study at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

What Is This? What Should I Do?

Parents who observe unusual behavior often seek advice from friends and family members and receive false reassurance that such behavior isn’t unusual. Even physicians may contribute if they are unaware of infantile spasms, which is a rare disorder. “And then again, they get false reassurance, and because of that false reassurance, you get a diagnostic delay,” said Shaun Hussain, MD, who was asked to comment on the study.

The timing and frequency of infantile spasms create challenges for diagnosis. They only last about 1 second, and they tend to cluster in the morning. By the time a caregiver brings an infant to a healthcare provider, they may have trouble describing the behavior. “Parents are struggling to describe what they saw, and it often just does not resonate, or doesn’t make the healthcare provider think about infantile spasms,” said Hussain.

The idea to employ AI came from looking at videos of infants on YouTube and the realization that many patients upload them in an effort to seek advice. “So many parents upload these videos and ask in the comments, ‘What is this? What should I do? Can somebody help me?’ said Miron, who is a neurologist and researcher at Charité — Universitätsmedizin Berlin in Germany.

 

AI and Video Can Aid Diagnosis

The researchers built a model that they trained to recognize epileptic spasms using openly available YouTube videos, including 141 infants, 991 recorded seizures, and 597 non-seizure video segments, along with a non-seizure cohort of 127 infants with an accompanying 1385 video segments.

Each video segment was reviewed by two specialists, and they had to agree for it to be counted as an epileptic spasm.

The model detected epileptic seizures with an area under the curve (AUC) of 0.96. It had a sensitivity of 82%, specificity of 90%, and accuracy of 85% when applied to the training set.

The researchers then tested it against three validation sets. In the first, a smartphone-based set retrieved from TikTok of 26 infants with 70 epileptic spasms and 31 non-seizure 5-second video segments, the model had an AUC of 0.98, a sensitivity of 89%, a specificity of 100%, and an accuracy of 92%.

A second smartphone-based set of 67 infants, drawn from YouTube, showed a false detection rate of 0.75% (five detections out of 666 video segments). A third dataset collected from in-hospital EEG monitoring of 21 infants without seizures revealed a false-positive rate of 3.4% (365 of 10,860 video segments).

The group is now developing an app that will allow parents to upload videos that can be analyzed using the model. Physicians can then view the video and determine if there is suspicion of a seizure.

Miron also believes that this approach could find use in other types of seizures and populations, including older children and adults. “We have actually built some models for detection of seizures for videos in adults as well. Looking more towards the future, I’m sure AI will be used to analyze videos of other neurological disorders with motor symptoms [such as] movement disorders and gait,” he said.

 

Encouraging Early Research

Hussain, who is a professor of pediatrics at UCLA Health, lauded the work generally but emphasized that it is still in the early stage. “Their comparison was a relatively easy one. They’re just comparing normal versus infantile spasms, and they’re looking at the seizure versus normal behavior. Usually, the distinction is much harder in that there are kids who are having behaviors that are maybe other types of seizures, which is much harder to distinguish from infantile spasms, in contrast to just normal behaviors. The other mimic of infantile spasms is things like infant heartburn. Those kids will often have some posturing, and they often will be in pain. They might cry. That’s something that infantile spasms will often generate, so that’s why there’s a lot of confusion between those two,” said Hussain.

He noted that there have been efforts to raise awareness of infantile spasms among physicians and the general public, but that hasn’t reduced the increased detection.

 

Another Resource

In fact, parents with suspicions often go to social media sites like YouTube and a Facebook group dedicated to infantile spasms. “You can Google infantile spasms, and you’ll see examples of weird behaviors, and then you’ll look in the comments, and you’ll see this commenter said: ‘These could be infantile spasms. You should go to a children’s hospital. Don’t leave until you get an EEG to make sure that these are not seizures. There’s all kinds of great advice there, and it really shouldn’t be the situation where to get the best care, you need to go on YouTube,’ ” said Hussain.

Miron and Hussain had no relevant financial disclosures.

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

Recently, a 40-year-old woman took to Facebook to announce that she had died.

Rachel Davies, of Wales, wrote: “If you’re reading this, then it means I’m no longer here. What a life I’ve had, and surprisingly, since cancer entered my life. When I look through my photos, I’ve done and seen so much since cancer, and probably some of my best memories are from this period. In so many ways, I have to thank it for learning how to live fully. What I wish is that everyone can experience the same but without needing cancer. Get out there, experience life fully, and wear that dress!!! I’m so sad to leave my family and friends, I wish I never had to go. I’m so grateful to have had Charlie young so that I’ve watched him grow into the man he is today. I’m unbelievably proud of him. I am thankful I had the opportunity to have Kacey and Jacob in my life. Lastly, I was blessed to meet the love of my life, my husband, and my best friend. I have no regrets, I have had a wonderful life. So to all of you, don’t be sad I’ve gone. Live your life and live it well. Love, Rachel x.”

 

I didn’t know Ms. Davies, but am likely among many who wish I had. In a terrible situation she kept trying.

She had HER2 metastatic breast cancer, which can respond to the drug Enhertu (trastuzumab). Unfortunately, she never had the chance, because it wasn’t available to her in Wales. In the United Kingdom it’s available only in Scotland.

I’m not saying it was a cure. Statistically, it likely would have bought her another 6 months of family time. But that’s still another half year.

I’m not blaming the Welsh NHS, though they made the decision not to cover it because of cost. The jobs of such committees is a thankless one, trying to decide where the limited money goes — vaccines for many children that are proven to lessen morbidity and mortality over the course of a lifetime, or to add 6 months to the lives of comparatively fewer women with HER2 metastatic breast cancer.

I’m not blaming the company that makes Enhertu, though it was the cost that kept her from getting it. Bringing a drug to market, with all the labs and clinical research behind it, ain’t cheap. If the company can’t keep the lights on they’re not going to able to develop future pharmaceuticals to help others, though I do wonder if a better price could have been negotiated. (I’m not trying to justify the salaries of insurance CEOs — don’t even get me started on those.)

Money is always limited, and human suffering is infinite. Every health care organization, public or private, has to face that simple fact. There is no right place to draw the line, so we use the greatest good for the greatest many as our best guess.

In her last post, though, Ms. Davies didn’t dwell on any of this. She reflected on her joys and blessings, and encouraged others to live life fully. Things we should all focus on.

In a world that often seems to have gone mad, it’s good to keep in mind that there is more good than bad out there. 

Thank you, Ms. Davies, for the reminder.

Allan M. Block, MD, has a solo neurology practice in Scottsdale, Arizona.

Recently, a 40-year-old woman took to Facebook to announce that she had died.

Rachel Davies, of Wales, wrote: “If you’re reading this, then it means I’m no longer here. What a life I’ve had, and surprisingly, since cancer entered my life. When I look through my photos, I’ve done and seen so much since cancer, and probably some of my best memories are from this period. In so many ways, I have to thank it for learning how to live fully. What I wish is that everyone can experience the same but without needing cancer. Get out there, experience life fully, and wear that dress!!! I’m so sad to leave my family and friends, I wish I never had to go. I’m so grateful to have had Charlie young so that I’ve watched him grow into the man he is today. I’m unbelievably proud of him. I am thankful I had the opportunity to have Kacey and Jacob in my life. Lastly, I was blessed to meet the love of my life, my husband, and my best friend. I have no regrets, I have had a wonderful life. So to all of you, don’t be sad I’ve gone. Live your life and live it well. Love, Rachel x.”

 

I didn’t know Ms. Davies, but am likely among many who wish I had. In a terrible situation she kept trying.

She had HER2 metastatic breast cancer, which can respond to the drug Enhertu (trastuzumab). Unfortunately, she never had the chance, because it wasn’t available to her in Wales. In the United Kingdom it’s available only in Scotland.

I’m not saying it was a cure. Statistically, it likely would have bought her another 6 months of family time. But that’s still another half year.

I’m not blaming the Welsh NHS, though they made the decision not to cover it because of cost. The jobs of such committees is a thankless one, trying to decide where the limited money goes — vaccines for many children that are proven to lessen morbidity and mortality over the course of a lifetime, or to add 6 months to the lives of comparatively fewer women with HER2 metastatic breast cancer.

I’m not blaming the company that makes Enhertu, though it was the cost that kept her from getting it. Bringing a drug to market, with all the labs and clinical research behind it, ain’t cheap. If the company can’t keep the lights on they’re not going to able to develop future pharmaceuticals to help others, though I do wonder if a better price could have been negotiated. (I’m not trying to justify the salaries of insurance CEOs — don’t even get me started on those.)

Money is always limited, and human suffering is infinite. Every health care organization, public or private, has to face that simple fact. There is no right place to draw the line, so we use the greatest good for the greatest many as our best guess.

In her last post, though, Ms. Davies didn’t dwell on any of this. She reflected on her joys and blessings, and encouraged others to live life fully. Things we should all focus on.

In a world that often seems to have gone mad, it’s good to keep in mind that there is more good than bad out there. 

Thank you, Ms. Davies, for the reminder.

Allan M. Block, MD, has a solo neurology practice in Scottsdale, Arizona.

Recently, a 40-year-old woman took to Facebook to announce that she had died.

Rachel Davies, of Wales, wrote: “If you’re reading this, then it means I’m no longer here. What a life I’ve had, and surprisingly, since cancer entered my life. When I look through my photos, I’ve done and seen so much since cancer, and probably some of my best memories are from this period. In so many ways, I have to thank it for learning how to live fully. What I wish is that everyone can experience the same but without needing cancer. Get out there, experience life fully, and wear that dress!!! I’m so sad to leave my family and friends, I wish I never had to go. I’m so grateful to have had Charlie young so that I’ve watched him grow into the man he is today. I’m unbelievably proud of him. I am thankful I had the opportunity to have Kacey and Jacob in my life. Lastly, I was blessed to meet the love of my life, my husband, and my best friend. I have no regrets, I have had a wonderful life. So to all of you, don’t be sad I’ve gone. Live your life and live it well. Love, Rachel x.”

 

I didn’t know Ms. Davies, but am likely among many who wish I had. In a terrible situation she kept trying.

She had HER2 metastatic breast cancer, which can respond to the drug Enhertu (trastuzumab). Unfortunately, she never had the chance, because it wasn’t available to her in Wales. In the United Kingdom it’s available only in Scotland.

I’m not saying it was a cure. Statistically, it likely would have bought her another 6 months of family time. But that’s still another half year.

I’m not blaming the Welsh NHS, though they made the decision not to cover it because of cost. The jobs of such committees is a thankless one, trying to decide where the limited money goes — vaccines for many children that are proven to lessen morbidity and mortality over the course of a lifetime, or to add 6 months to the lives of comparatively fewer women with HER2 metastatic breast cancer.

I’m not blaming the company that makes Enhertu, though it was the cost that kept her from getting it. Bringing a drug to market, with all the labs and clinical research behind it, ain’t cheap. If the company can’t keep the lights on they’re not going to able to develop future pharmaceuticals to help others, though I do wonder if a better price could have been negotiated. (I’m not trying to justify the salaries of insurance CEOs — don’t even get me started on those.)

Money is always limited, and human suffering is infinite. Every health care organization, public or private, has to face that simple fact. There is no right place to draw the line, so we use the greatest good for the greatest many as our best guess.

In her last post, though, Ms. Davies didn’t dwell on any of this. She reflected on her joys and blessings, and encouraged others to live life fully. Things we should all focus on.

In a world that often seems to have gone mad, it’s good to keep in mind that there is more good than bad out there. 

Thank you, Ms. Davies, for the reminder.

Allan M. Block, MD, has a solo neurology practice in Scottsdale, Arizona.

TOPLINE:

Higher levels of environmental metals in urine are associated with poorer cognitive performance and an increased risk for dementia, new research suggests.

METHODOLOGY:

• This multicenter prospective cohort study included 6303 participants from six US study centers from 2000 to 2002, with follow-up through 2018.
• Participants were aged 45-84 years (median age at baseline, 60 years; 52% women) and were free of diagnosed cardiovascular disease.
• Researchers measured urinary levels of arsenic, cadmium, cobalt, copper, lead, manganese, tungsten, uranium, and zinc.
• Neuropsychological assessments included the Digit Symbol Coding, Cognitive Abilities Screening Instrument, and Digit Span tests.
• The median follow-up duration was 11.7 years for participants with dementia and 16.8 years for those without; 559 cases of dementia were identified during the study.

TAKEAWAY:

• Lower Digit Symbol Coding scores were associated with higher urinary concentrations of arsenic (mean difference [MD] in score per interquartile range [IQR] increase, –0.03), cobalt (MD per IQR increase, –0.05), copper (MD per IQR increase, –0.05), uranium (MD per IQR increase, –0.04), and zinc (MD per IQR increase, –0.03).
• Effects for cobalt, uranium, and zinc were stronger in apolipoprotein epsilon 4 allele (APOE4) carriers vs noncarriers.
• Higher urinary levels of copper were associated with lower Digit Span scores (MD, –0.043) and elevated levels of copper (MD, –0.028) and zinc (MD, –0.024) were associated with lower global cognitive scores.
• Individuals with urinary levels of the nine-metal mixture at the 95th percentile had a 71% higher risk for dementia compared to those with levels at the 25th percentile, with the risk more pronounced in APOE4 carriers than in noncarriers (MD, –0.30 vs –0.10, respectively).

IN PRACTICE:

“We found an inverse association of essential and nonessential metals in urine, both individually and as a mixture, with the speed of mental operations, as well as a positive association of urinary metal levels with dementia risk. As metal exposure and levels in the body are modifiable, these findings could inform early screening and precision interventions for dementia prevention based on individuals’ metal exposure and genetic profiles,” the investigators wrote.

 

SOURCE:

The study was led by Arce Domingo-Relloso, PhD, Columbia University Mailman School of Public Health, New York City. It was published online in JAMA Network Open.

 

LIMITATIONS:

Data may have been missed for patients with dementia who were never hospitalized, died, or were lost to follow-up. The dementia diagnosis included nonspecific International Classification of Diseases codes, potentially leading to false-positive reports. In addition, the sample size was not sufficient to evaluate the associations between metal exposure and cognitive test scores for carriers of two APOE4 alleles.

 

DISCLOSURES:

The study was supported by the National Heart, Lung, and Blood Institute. Several authors reported receiving grants from the National Institutes of Health and consulting fees, editorial stipends, teaching fees, or unrelated grant funding from various sources, which are fully listed in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Higher levels of environmental metals in urine are associated with poorer cognitive performance and an increased risk for dementia, new research suggests.

METHODOLOGY:

• This multicenter prospective cohort study included 6303 participants from six US study centers from 2000 to 2002, with follow-up through 2018.
• Participants were aged 45-84 years (median age at baseline, 60 years; 52% women) and were free of diagnosed cardiovascular disease.
• Researchers measured urinary levels of arsenic, cadmium, cobalt, copper, lead, manganese, tungsten, uranium, and zinc.
• Neuropsychological assessments included the Digit Symbol Coding, Cognitive Abilities Screening Instrument, and Digit Span tests.
• The median follow-up duration was 11.7 years for participants with dementia and 16.8 years for those without; 559 cases of dementia were identified during the study.

TAKEAWAY:

• Lower Digit Symbol Coding scores were associated with higher urinary concentrations of arsenic (mean difference [MD] in score per interquartile range [IQR] increase, –0.03), cobalt (MD per IQR increase, –0.05), copper (MD per IQR increase, –0.05), uranium (MD per IQR increase, –0.04), and zinc (MD per IQR increase, –0.03).
• Effects for cobalt, uranium, and zinc were stronger in apolipoprotein epsilon 4 allele (APOE4) carriers vs noncarriers.
• Higher urinary levels of copper were associated with lower Digit Span scores (MD, –0.043) and elevated levels of copper (MD, –0.028) and zinc (MD, –0.024) were associated with lower global cognitive scores.
• Individuals with urinary levels of the nine-metal mixture at the 95th percentile had a 71% higher risk for dementia compared to those with levels at the 25th percentile, with the risk more pronounced in APOE4 carriers than in noncarriers (MD, –0.30 vs –0.10, respectively).

IN PRACTICE:

“We found an inverse association of essential and nonessential metals in urine, both individually and as a mixture, with the speed of mental operations, as well as a positive association of urinary metal levels with dementia risk. As metal exposure and levels in the body are modifiable, these findings could inform early screening and precision interventions for dementia prevention based on individuals’ metal exposure and genetic profiles,” the investigators wrote.

 

SOURCE:

The study was led by Arce Domingo-Relloso, PhD, Columbia University Mailman School of Public Health, New York City. It was published online in JAMA Network Open.

 

LIMITATIONS:

Data may have been missed for patients with dementia who were never hospitalized, died, or were lost to follow-up. The dementia diagnosis included nonspecific International Classification of Diseases codes, potentially leading to false-positive reports. In addition, the sample size was not sufficient to evaluate the associations between metal exposure and cognitive test scores for carriers of two APOE4 alleles.

 

DISCLOSURES:

The study was supported by the National Heart, Lung, and Blood Institute. Several authors reported receiving grants from the National Institutes of Health and consulting fees, editorial stipends, teaching fees, or unrelated grant funding from various sources, which are fully listed in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Higher levels of environmental metals in urine are associated with poorer cognitive performance and an increased risk for dementia, new research suggests.

METHODOLOGY:

• This multicenter prospective cohort study included 6303 participants from six US study centers from 2000 to 2002, with follow-up through 2018.
• Participants were aged 45-84 years (median age at baseline, 60 years; 52% women) and were free of diagnosed cardiovascular disease.
• Researchers measured urinary levels of arsenic, cadmium, cobalt, copper, lead, manganese, tungsten, uranium, and zinc.
• Neuropsychological assessments included the Digit Symbol Coding, Cognitive Abilities Screening Instrument, and Digit Span tests.
• The median follow-up duration was 11.7 years for participants with dementia and 16.8 years for those without; 559 cases of dementia were identified during the study.

TAKEAWAY:

• Lower Digit Symbol Coding scores were associated with higher urinary concentrations of arsenic (mean difference [MD] in score per interquartile range [IQR] increase, –0.03), cobalt (MD per IQR increase, –0.05), copper (MD per IQR increase, –0.05), uranium (MD per IQR increase, –0.04), and zinc (MD per IQR increase, –0.03).
• Effects for cobalt, uranium, and zinc were stronger in apolipoprotein epsilon 4 allele (APOE4) carriers vs noncarriers.
• Higher urinary levels of copper were associated with lower Digit Span scores (MD, –0.043) and elevated levels of copper (MD, –0.028) and zinc (MD, –0.024) were associated with lower global cognitive scores.
• Individuals with urinary levels of the nine-metal mixture at the 95th percentile had a 71% higher risk for dementia compared to those with levels at the 25th percentile, with the risk more pronounced in APOE4 carriers than in noncarriers (MD, –0.30 vs –0.10, respectively).

IN PRACTICE:

“We found an inverse association of essential and nonessential metals in urine, both individually and as a mixture, with the speed of mental operations, as well as a positive association of urinary metal levels with dementia risk. As metal exposure and levels in the body are modifiable, these findings could inform early screening and precision interventions for dementia prevention based on individuals’ metal exposure and genetic profiles,” the investigators wrote.

 

SOURCE:

The study was led by Arce Domingo-Relloso, PhD, Columbia University Mailman School of Public Health, New York City. It was published online in JAMA Network Open.

 

LIMITATIONS:

Data may have been missed for patients with dementia who were never hospitalized, died, or were lost to follow-up. The dementia diagnosis included nonspecific International Classification of Diseases codes, potentially leading to false-positive reports. In addition, the sample size was not sufficient to evaluate the associations between metal exposure and cognitive test scores for carriers of two APOE4 alleles.

 

DISCLOSURES:

The study was supported by the National Heart, Lung, and Blood Institute. Several authors reported receiving grants from the National Institutes of Health and consulting fees, editorial stipends, teaching fees, or unrelated grant funding from various sources, which are fully listed in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

A rare coin-shaped headache long viewed as a primary headache disorder frequently has underlying causes, according to new research, and clinicians should refer people who present with it for imaging.

First described in 2003, nummular or coin-shaped headache comprises an intermittent or constant pain limited to a rounded region between 1 and 6 cm in diameter. Classed as a primary headache by the International Classification of Headache Disorders (ICHD-3), it usually occurs in the parietal, or top rear, region of the head.

Despite nummular headache’s classification as a primary disorder, studies have linked some cases of coin-shaped headache to cranial or intracranial lesions. Now, a group of Spanish researchers has revised 20 years’ worth of cases, representing the largest series to date, and found a wide variety of causes, some of which, they say, had not been reported before in connection to this headache type.

For their research, published online in Headache, Antonio Sánchez-Soblechero, MD, and colleagues at the University Hospital Gregorio Marañón in Madrid, Spain, looked at clinical and imaging findings from 131 patients (67% women, median age at onset 52) seen from 2002 to 2022 at their center, seeking to identify any differences among primary and secondary or symptomatic coin-shaped headache cases. All patients underwent cranial MRI, CT, or both.

Altogether, 26% of the nummular headaches (n = 34) were found associated with trauma, vascular malformations, cranial bone disorders, neoplasia, arachnoid cysts, hypertension, aneurysm, or skin disorders including, in one case, a psoriasis plaque. Hypertension, aneurysm, and psoriasis were not previously described as causes of this headache, the authors said.

The definition of a nummular headache includes that secondary causes need to be excluded, according to the ICHD-3. The study authors proposed that “definite” secondary cases should meet ICHD-3 diagnostic criteria for nummular headache as well as for secondary headache, while “probable” cases meet all criteria for the former and all but one of the criteria for the latter. In their study, eight patients met the proposed criteria for “definite,” while the rest were deemed “probable” secondary cases.

Headache symptoms remained similar regardless of etiology, Sánchez-Soblechero and colleagues found, but coin-shaped headaches deemed to have secondary etiologies were significantly more likely to be associated with previous headache, remote head trauma, and longer symptom duration. The authors described treatments, including surgical interventions, for cases with secondary causes.

Preventive treatment was more effective in patients with determined causes for their headaches, Sánchez-Soblechero and colleagues found, with 72% seeing their monthly headache days halved, compared with just 30% of patients in whom a cause was not identified.

“The presence of any previous headache or remote head trauma may suggest a diagnosis of symptomatic nummular headache; however, as certain nummular headache might be an early symptom of intracranial mass lesions, neuroimaging is necessary. Finding the cause of nummular headache is essential to offer the most effective targeted treatment,” the investigators wrote in their analysis.

 

Primary Headache or Secondary?

In an interview, neurologist and headache specialist Nina Riggins, MD, PhD, of VA Palo Alto Health Care in California, praised the new findings as underscoring the importance of a thorough clinical approach.

“What this study shows is applicable to many primary headache disorders, whether migraine or cluster or nummular,” Riggins said. “Secondary headache can look like all of these headache types.”

Understanding what should be done to rule out secondary causes of headache is key for the correct diagnosis, she said. “In cases of coin-shaped headache, one should do a detailed neurological exam, consider imaging, check blood pressure, do blood work, and consider exams to exclude autoimmune psoriasis and other disorders as appropriate.”

Despite the inherent limits of its retrospective, single-center design, the study by Sánchez-Soblechero and colleagues is “extremely helpful in emphasizing that we should not dismiss [nummular headache] because it’s a little area of 1-6 centimeters,” Riggins said. “We absolutely have to make sure that we have ruled out secondary causes.” And while it would be useful to have evidence from prospective studies of nummular headache, “with such a rare headache, it’s hard. That’s why it’s so precious to have a study like this one, with 131 patients.”

Riggins acknowledged that the study emphasized the challenges of classifying and diagnosing nummular headache. The ICHD, last revised in 2018, “is a living, breathing document,” she said. “The idea is that as we learn more about headache disorders over time, this may mean changing some primary headaches to secondary, but we are clearly not there with this research: Most participants did not have a secondary cause for their coin-shaped headache.”

For now, Riggins said, “I think it’s best to keep classification straightforward for primary and secondary headache. It’s helpful for my day-to-day clinic life to have this neat division in place. But we do have to exclude secondary headache whenever possible in order to say that this is primary headache.”

Sánchez-Soblechero and coauthors disclosed no financial conflicts of interest related to their findings. Riggins disclosed consulting work for Gerson Lehrman Group, receiving research support from electroCore, Theranica, and Eli Lilly, and serving on advisory boards for Theranica, Teva Pharmaceuticals, Lundbeck, and Amneal Pharmaceuticals.

A version of this article appeared on Medscape.com.

A rare coin-shaped headache long viewed as a primary headache disorder frequently has underlying causes, according to new research, and clinicians should refer people who present with it for imaging.

First described in 2003, nummular or coin-shaped headache comprises an intermittent or constant pain limited to a rounded region between 1 and 6 cm in diameter. Classed as a primary headache by the International Classification of Headache Disorders (ICHD-3), it usually occurs in the parietal, or top rear, region of the head.

Despite nummular headache’s classification as a primary disorder, studies have linked some cases of coin-shaped headache to cranial or intracranial lesions. Now, a group of Spanish researchers has revised 20 years’ worth of cases, representing the largest series to date, and found a wide variety of causes, some of which, they say, had not been reported before in connection to this headache type.

For their research, published online in Headache, Antonio Sánchez-Soblechero, MD, and colleagues at the University Hospital Gregorio Marañón in Madrid, Spain, looked at clinical and imaging findings from 131 patients (67% women, median age at onset 52) seen from 2002 to 2022 at their center, seeking to identify any differences among primary and secondary or symptomatic coin-shaped headache cases. All patients underwent cranial MRI, CT, or both.

Altogether, 26% of the nummular headaches (n = 34) were found associated with trauma, vascular malformations, cranial bone disorders, neoplasia, arachnoid cysts, hypertension, aneurysm, or skin disorders including, in one case, a psoriasis plaque. Hypertension, aneurysm, and psoriasis were not previously described as causes of this headache, the authors said.

The definition of a nummular headache includes that secondary causes need to be excluded, according to the ICHD-3. The study authors proposed that “definite” secondary cases should meet ICHD-3 diagnostic criteria for nummular headache as well as for secondary headache, while “probable” cases meet all criteria for the former and all but one of the criteria for the latter. In their study, eight patients met the proposed criteria for “definite,” while the rest were deemed “probable” secondary cases.

Headache symptoms remained similar regardless of etiology, Sánchez-Soblechero and colleagues found, but coin-shaped headaches deemed to have secondary etiologies were significantly more likely to be associated with previous headache, remote head trauma, and longer symptom duration. The authors described treatments, including surgical interventions, for cases with secondary causes.

Preventive treatment was more effective in patients with determined causes for their headaches, Sánchez-Soblechero and colleagues found, with 72% seeing their monthly headache days halved, compared with just 30% of patients in whom a cause was not identified.

“The presence of any previous headache or remote head trauma may suggest a diagnosis of symptomatic nummular headache; however, as certain nummular headache might be an early symptom of intracranial mass lesions, neuroimaging is necessary. Finding the cause of nummular headache is essential to offer the most effective targeted treatment,” the investigators wrote in their analysis.

 

Primary Headache or Secondary?

In an interview, neurologist and headache specialist Nina Riggins, MD, PhD, of VA Palo Alto Health Care in California, praised the new findings as underscoring the importance of a thorough clinical approach.

“What this study shows is applicable to many primary headache disorders, whether migraine or cluster or nummular,” Riggins said. “Secondary headache can look like all of these headache types.”

Understanding what should be done to rule out secondary causes of headache is key for the correct diagnosis, she said. “In cases of coin-shaped headache, one should do a detailed neurological exam, consider imaging, check blood pressure, do blood work, and consider exams to exclude autoimmune psoriasis and other disorders as appropriate.”

Despite the inherent limits of its retrospective, single-center design, the study by Sánchez-Soblechero and colleagues is “extremely helpful in emphasizing that we should not dismiss [nummular headache] because it’s a little area of 1-6 centimeters,” Riggins said. “We absolutely have to make sure that we have ruled out secondary causes.” And while it would be useful to have evidence from prospective studies of nummular headache, “with such a rare headache, it’s hard. That’s why it’s so precious to have a study like this one, with 131 patients.”

Riggins acknowledged that the study emphasized the challenges of classifying and diagnosing nummular headache. The ICHD, last revised in 2018, “is a living, breathing document,” she said. “The idea is that as we learn more about headache disorders over time, this may mean changing some primary headaches to secondary, but we are clearly not there with this research: Most participants did not have a secondary cause for their coin-shaped headache.”

For now, Riggins said, “I think it’s best to keep classification straightforward for primary and secondary headache. It’s helpful for my day-to-day clinic life to have this neat division in place. But we do have to exclude secondary headache whenever possible in order to say that this is primary headache.”

Sánchez-Soblechero and coauthors disclosed no financial conflicts of interest related to their findings. Riggins disclosed consulting work for Gerson Lehrman Group, receiving research support from electroCore, Theranica, and Eli Lilly, and serving on advisory boards for Theranica, Teva Pharmaceuticals, Lundbeck, and Amneal Pharmaceuticals.

A version of this article appeared on Medscape.com.

A rare coin-shaped headache long viewed as a primary headache disorder frequently has underlying causes, according to new research, and clinicians should refer people who present with it for imaging.

First described in 2003, nummular or coin-shaped headache comprises an intermittent or constant pain limited to a rounded region between 1 and 6 cm in diameter. Classed as a primary headache by the International Classification of Headache Disorders (ICHD-3), it usually occurs in the parietal, or top rear, region of the head.

Despite nummular headache’s classification as a primary disorder, studies have linked some cases of coin-shaped headache to cranial or intracranial lesions. Now, a group of Spanish researchers has revised 20 years’ worth of cases, representing the largest series to date, and found a wide variety of causes, some of which, they say, had not been reported before in connection to this headache type.

For their research, published online in Headache, Antonio Sánchez-Soblechero, MD, and colleagues at the University Hospital Gregorio Marañón in Madrid, Spain, looked at clinical and imaging findings from 131 patients (67% women, median age at onset 52) seen from 2002 to 2022 at their center, seeking to identify any differences among primary and secondary or symptomatic coin-shaped headache cases. All patients underwent cranial MRI, CT, or both.

Altogether, 26% of the nummular headaches (n = 34) were found associated with trauma, vascular malformations, cranial bone disorders, neoplasia, arachnoid cysts, hypertension, aneurysm, or skin disorders including, in one case, a psoriasis plaque. Hypertension, aneurysm, and psoriasis were not previously described as causes of this headache, the authors said.

The definition of a nummular headache includes that secondary causes need to be excluded, according to the ICHD-3. The study authors proposed that “definite” secondary cases should meet ICHD-3 diagnostic criteria for nummular headache as well as for secondary headache, while “probable” cases meet all criteria for the former and all but one of the criteria for the latter. In their study, eight patients met the proposed criteria for “definite,” while the rest were deemed “probable” secondary cases.

Headache symptoms remained similar regardless of etiology, Sánchez-Soblechero and colleagues found, but coin-shaped headaches deemed to have secondary etiologies were significantly more likely to be associated with previous headache, remote head trauma, and longer symptom duration. The authors described treatments, including surgical interventions, for cases with secondary causes.

Preventive treatment was more effective in patients with determined causes for their headaches, Sánchez-Soblechero and colleagues found, with 72% seeing their monthly headache days halved, compared with just 30% of patients in whom a cause was not identified.

“The presence of any previous headache or remote head trauma may suggest a diagnosis of symptomatic nummular headache; however, as certain nummular headache might be an early symptom of intracranial mass lesions, neuroimaging is necessary. Finding the cause of nummular headache is essential to offer the most effective targeted treatment,” the investigators wrote in their analysis.

 

Primary Headache or Secondary?

In an interview, neurologist and headache specialist Nina Riggins, MD, PhD, of VA Palo Alto Health Care in California, praised the new findings as underscoring the importance of a thorough clinical approach.

“What this study shows is applicable to many primary headache disorders, whether migraine or cluster or nummular,” Riggins said. “Secondary headache can look like all of these headache types.”

Understanding what should be done to rule out secondary causes of headache is key for the correct diagnosis, she said. “In cases of coin-shaped headache, one should do a detailed neurological exam, consider imaging, check blood pressure, do blood work, and consider exams to exclude autoimmune psoriasis and other disorders as appropriate.”

Despite the inherent limits of its retrospective, single-center design, the study by Sánchez-Soblechero and colleagues is “extremely helpful in emphasizing that we should not dismiss [nummular headache] because it’s a little area of 1-6 centimeters,” Riggins said. “We absolutely have to make sure that we have ruled out secondary causes.” And while it would be useful to have evidence from prospective studies of nummular headache, “with such a rare headache, it’s hard. That’s why it’s so precious to have a study like this one, with 131 patients.”

Riggins acknowledged that the study emphasized the challenges of classifying and diagnosing nummular headache. The ICHD, last revised in 2018, “is a living, breathing document,” she said. “The idea is that as we learn more about headache disorders over time, this may mean changing some primary headaches to secondary, but we are clearly not there with this research: Most participants did not have a secondary cause for their coin-shaped headache.”

For now, Riggins said, “I think it’s best to keep classification straightforward for primary and secondary headache. It’s helpful for my day-to-day clinic life to have this neat division in place. But we do have to exclude secondary headache whenever possible in order to say that this is primary headache.”

Sánchez-Soblechero and coauthors disclosed no financial conflicts of interest related to their findings. Riggins disclosed consulting work for Gerson Lehrman Group, receiving research support from electroCore, Theranica, and Eli Lilly, and serving on advisory boards for Theranica, Teva Pharmaceuticals, Lundbeck, and Amneal Pharmaceuticals.

A version of this article appeared on Medscape.com.

John Bolecek, 41, of Richmond, Virginia, was diagnosed with long COVID in May of 2022. While his acute infection was mild, once everyone else in his family had recovered, the heavy fatigue he experienced from the start has never lifted.

“When I wake up in the morning, I feel like I haven’t gone to sleep at all,” Bolecek said. “It’s this super fatigue that’s just never gone away.”

The urban planner who once rode his bike to work daily and spent weekends cycling had to quit working and now can barely get through a light walk before long COVID symptoms of post-exertional malaise, an intense fatigue after previously tolerated physical or mental activity, set in. His unrefreshing sleep, fatigue, and dysautonomia — a disruption of the autonomic nervous system that causes dizziness, heart rate changes, and nausea — have made it nearly impossible to share household duties with his wife. She has to do most of the cooking, cleaning, and tending to their two sons, ages 6 and 8 years.

It’s an increasingly familiar story for those hit with long COVID in their prime, a period of life when young and middle-aged adults are the most productive and the busiest, often in the thick of parenting while also taking care of their aging parents. And it’s a group that is among the hardest hit by long COVID both because of the sheer number of patients with the condition and the mental and financial strain that it’s putting on this age group. According to the Centers for Disease Control and Prevention (CDC), 6.9% of adults aged 18-34 years and 8.9% of adults aged 35-49 years have the disorder compared with 4.1% of older adults aged > 65 years who are the least likely to have long COVID.

In a study published recently in Scientific Reports, researchers found that in a population of California residents with long COVID, older individuals (who were sicker to start) had more severe symptoms associated with the condition. But researchers also found that younger people (aged 18-49 years) were more likely to experience symptoms that reduced their productivity and quality of life. They suggested this is both because they have more to do in a given day and because they have a longer life ahead of them living with a chronic condition.

“Much of California’s population falls within the 18-49 age group, [so] we would expect to see the highest overall burden coming from these individuals,” said lead study author Sophie Zhu, a researcher in the Division of Communicable Disease Control at the California Department of Public Health.

 

The Impact on Work and Life Productivity

Adults and especially those in middle age tend to have a lot of competing stressors during this period of life, said Nisha Viswanathan, MD, director of the UCLA Health Long COVID program. “Patients may need to decrease some of the pressures of life for their health and that can be impossible to do because they have so many other people who are depending on them.”

It’s a different set of circumstances compared with older individuals who may have more severe symptoms because they have underlying conditions. But older Americans are also more likely to be retired and don’t have children who are financially dependent on them. Previous research has shown the burden that long COVID is having on the workforce. A study published in the August 2023 edition of The Lancet Regional Health found that 5.8% of participating patients with long COVID reported occupational changes like moving to part time or remote work, including 1.6% who had completely dropped out of the workforce.

Middle age is also a time of life when patients may not have time to seek the care they need. The chronic nature of long COVID means that treatment can be time consuming and expensive, all of which drains resources from patients who are often supporting spouses, children, and sometimes older parents. A study published in Disability and Health Journal found that patients with long COVID have significantly higher rates of housing instability and financial concerns, such as worries about paying rent or a mortgage, than those without the condition.

 

The Financial Strain of Long COVID

For those who can’t work, the process of applying for long-term disability can also be complicated. That’s especially true for people whose illness keeps them from doing even basic tasks like filling out paperwork and dealing with disability insurance claims. It requires those applying as a result of their long COVID symptoms to show all records connected to long COVID as well as a medical history, the beginning of their symptoms, and their current treatments.

Even then, many patients complain of having their claims rejected, which can be financially disastrous to families already struggling to get by. Still, experts contend that it’s important to understand that as of July 2021, long COVID is considered a disability under the Americans with Disabilities Act (ADA).

“Long COVID is recognized as a disability under Section 504 of the ADA, and yet day after day, we see violations of the ADA for people with long COVID not getting the accommodations that they need in order to work,” said David Putrino, PhD, the Nash Family director of the Cohen Center for Recovery from Complex Chronic Illness at Mount Sinai in New York City and a renowned expert in long COVID.

He added that short- and long-term disability claims are sometimes denied because of a lack of diagnostic testing to prove a patient has the condition. “This is nonsensical and absurd because the CDC does not require a blood test for the diagnosis of long COVID. It’s at your physician’s discretion,” Putrino said.

Viswanathan agreed. She said that for many of her patients, getting long-term disability has been particularly challenging because there’s no blood test for long COVID to prove patients have the condition. “As a result, for many of our patients, especially when they’re young, they may have to return to work in one form or another,” Viswanathan said.

 

The Impact of Long COVID on Quality of Life

What’s worse, the full impact is yet unknown because this is likely an underestimated cohort as many of these patients had mild cases of acute COVID-19 and fewer underlying conditions. For others, their long COVID is undiagnosed.

“Much of the impact on productivity and quality of life for this group remains hidden,” said Ziyad Al-Aly, MD, a global expert on long COVID and chief of research and development at the Veterans Affairs St. Louis Health Care System in Missouri.

Unfortunately, the impact on Bolecek’s life isn’t so hidden. He can’t work, which has been a financial stressor on the family. He spends much of the day in bed so that he can help with a few things when his wife gets home from work. He can’t cycle anymore and, as a result, has lost many of the friends associated with his favorite hobby.

But he remains hopeful, and more than anything else, he’s thankful for his family. His wife and kids have given him the strength to push on even when the days are hard. “I just don’t know where I’d be without them,” Bolecek said.

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

John Bolecek, 41, of Richmond, Virginia, was diagnosed with long COVID in May of 2022. While his acute infection was mild, once everyone else in his family had recovered, the heavy fatigue he experienced from the start has never lifted.

“When I wake up in the morning, I feel like I haven’t gone to sleep at all,” Bolecek said. “It’s this super fatigue that’s just never gone away.”

The urban planner who once rode his bike to work daily and spent weekends cycling had to quit working and now can barely get through a light walk before long COVID symptoms of post-exertional malaise, an intense fatigue after previously tolerated physical or mental activity, set in. His unrefreshing sleep, fatigue, and dysautonomia — a disruption of the autonomic nervous system that causes dizziness, heart rate changes, and nausea — have made it nearly impossible to share household duties with his wife. She has to do most of the cooking, cleaning, and tending to their two sons, ages 6 and 8 years.

It’s an increasingly familiar story for those hit with long COVID in their prime, a period of life when young and middle-aged adults are the most productive and the busiest, often in the thick of parenting while also taking care of their aging parents. And it’s a group that is among the hardest hit by long COVID both because of the sheer number of patients with the condition and the mental and financial strain that it’s putting on this age group. According to the Centers for Disease Control and Prevention (CDC), 6.9% of adults aged 18-34 years and 8.9% of adults aged 35-49 years have the disorder compared with 4.1% of older adults aged > 65 years who are the least likely to have long COVID.

In a study published recently in Scientific Reports, researchers found that in a population of California residents with long COVID, older individuals (who were sicker to start) had more severe symptoms associated with the condition. But researchers also found that younger people (aged 18-49 years) were more likely to experience symptoms that reduced their productivity and quality of life. They suggested this is both because they have more to do in a given day and because they have a longer life ahead of them living with a chronic condition.

“Much of California’s population falls within the 18-49 age group, [so] we would expect to see the highest overall burden coming from these individuals,” said lead study author Sophie Zhu, a researcher in the Division of Communicable Disease Control at the California Department of Public Health.

 

The Impact on Work and Life Productivity

Adults and especially those in middle age tend to have a lot of competing stressors during this period of life, said Nisha Viswanathan, MD, director of the UCLA Health Long COVID program. “Patients may need to decrease some of the pressures of life for their health and that can be impossible to do because they have so many other people who are depending on them.”

It’s a different set of circumstances compared with older individuals who may have more severe symptoms because they have underlying conditions. But older Americans are also more likely to be retired and don’t have children who are financially dependent on them. Previous research has shown the burden that long COVID is having on the workforce. A study published in the August 2023 edition of The Lancet Regional Health found that 5.8% of participating patients with long COVID reported occupational changes like moving to part time or remote work, including 1.6% who had completely dropped out of the workforce.

Middle age is also a time of life when patients may not have time to seek the care they need. The chronic nature of long COVID means that treatment can be time consuming and expensive, all of which drains resources from patients who are often supporting spouses, children, and sometimes older parents. A study published in Disability and Health Journal found that patients with long COVID have significantly higher rates of housing instability and financial concerns, such as worries about paying rent or a mortgage, than those without the condition.

 

The Financial Strain of Long COVID

For those who can’t work, the process of applying for long-term disability can also be complicated. That’s especially true for people whose illness keeps them from doing even basic tasks like filling out paperwork and dealing with disability insurance claims. It requires those applying as a result of their long COVID symptoms to show all records connected to long COVID as well as a medical history, the beginning of their symptoms, and their current treatments.

Even then, many patients complain of having their claims rejected, which can be financially disastrous to families already struggling to get by. Still, experts contend that it’s important to understand that as of July 2021, long COVID is considered a disability under the Americans with Disabilities Act (ADA).

“Long COVID is recognized as a disability under Section 504 of the ADA, and yet day after day, we see violations of the ADA for people with long COVID not getting the accommodations that they need in order to work,” said David Putrino, PhD, the Nash Family director of the Cohen Center for Recovery from Complex Chronic Illness at Mount Sinai in New York City and a renowned expert in long COVID.

He added that short- and long-term disability claims are sometimes denied because of a lack of diagnostic testing to prove a patient has the condition. “This is nonsensical and absurd because the CDC does not require a blood test for the diagnosis of long COVID. It’s at your physician’s discretion,” Putrino said.

Viswanathan agreed. She said that for many of her patients, getting long-term disability has been particularly challenging because there’s no blood test for long COVID to prove patients have the condition. “As a result, for many of our patients, especially when they’re young, they may have to return to work in one form or another,” Viswanathan said.

 

The Impact of Long COVID on Quality of Life

What’s worse, the full impact is yet unknown because this is likely an underestimated cohort as many of these patients had mild cases of acute COVID-19 and fewer underlying conditions. For others, their long COVID is undiagnosed.

“Much of the impact on productivity and quality of life for this group remains hidden,” said Ziyad Al-Aly, MD, a global expert on long COVID and chief of research and development at the Veterans Affairs St. Louis Health Care System in Missouri.

Unfortunately, the impact on Bolecek’s life isn’t so hidden. He can’t work, which has been a financial stressor on the family. He spends much of the day in bed so that he can help with a few things when his wife gets home from work. He can’t cycle anymore and, as a result, has lost many of the friends associated with his favorite hobby.

But he remains hopeful, and more than anything else, he’s thankful for his family. His wife and kids have given him the strength to push on even when the days are hard. “I just don’t know where I’d be without them,” Bolecek said.

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

John Bolecek, 41, of Richmond, Virginia, was diagnosed with long COVID in May of 2022. While his acute infection was mild, once everyone else in his family had recovered, the heavy fatigue he experienced from the start has never lifted.

“When I wake up in the morning, I feel like I haven’t gone to sleep at all,” Bolecek said. “It’s this super fatigue that’s just never gone away.”

The urban planner who once rode his bike to work daily and spent weekends cycling had to quit working and now can barely get through a light walk before long COVID symptoms of post-exertional malaise, an intense fatigue after previously tolerated physical or mental activity, set in. His unrefreshing sleep, fatigue, and dysautonomia — a disruption of the autonomic nervous system that causes dizziness, heart rate changes, and nausea — have made it nearly impossible to share household duties with his wife. She has to do most of the cooking, cleaning, and tending to their two sons, ages 6 and 8 years.

It’s an increasingly familiar story for those hit with long COVID in their prime, a period of life when young and middle-aged adults are the most productive and the busiest, often in the thick of parenting while also taking care of their aging parents. And it’s a group that is among the hardest hit by long COVID both because of the sheer number of patients with the condition and the mental and financial strain that it’s putting on this age group. According to the Centers for Disease Control and Prevention (CDC), 6.9% of adults aged 18-34 years and 8.9% of adults aged 35-49 years have the disorder compared with 4.1% of older adults aged > 65 years who are the least likely to have long COVID.

In a study published recently in Scientific Reports, researchers found that in a population of California residents with long COVID, older individuals (who were sicker to start) had more severe symptoms associated with the condition. But researchers also found that younger people (aged 18-49 years) were more likely to experience symptoms that reduced their productivity and quality of life. They suggested this is both because they have more to do in a given day and because they have a longer life ahead of them living with a chronic condition.

“Much of California’s population falls within the 18-49 age group, [so] we would expect to see the highest overall burden coming from these individuals,” said lead study author Sophie Zhu, a researcher in the Division of Communicable Disease Control at the California Department of Public Health.

 

The Impact on Work and Life Productivity

Adults and especially those in middle age tend to have a lot of competing stressors during this period of life, said Nisha Viswanathan, MD, director of the UCLA Health Long COVID program. “Patients may need to decrease some of the pressures of life for their health and that can be impossible to do because they have so many other people who are depending on them.”

It’s a different set of circumstances compared with older individuals who may have more severe symptoms because they have underlying conditions. But older Americans are also more likely to be retired and don’t have children who are financially dependent on them. Previous research has shown the burden that long COVID is having on the workforce. A study published in the August 2023 edition of The Lancet Regional Health found that 5.8% of participating patients with long COVID reported occupational changes like moving to part time or remote work, including 1.6% who had completely dropped out of the workforce.

Middle age is also a time of life when patients may not have time to seek the care they need. The chronic nature of long COVID means that treatment can be time consuming and expensive, all of which drains resources from patients who are often supporting spouses, children, and sometimes older parents. A study published in Disability and Health Journal found that patients with long COVID have significantly higher rates of housing instability and financial concerns, such as worries about paying rent or a mortgage, than those without the condition.

 

The Financial Strain of Long COVID

For those who can’t work, the process of applying for long-term disability can also be complicated. That’s especially true for people whose illness keeps them from doing even basic tasks like filling out paperwork and dealing with disability insurance claims. It requires those applying as a result of their long COVID symptoms to show all records connected to long COVID as well as a medical history, the beginning of their symptoms, and their current treatments.

Even then, many patients complain of having their claims rejected, which can be financially disastrous to families already struggling to get by. Still, experts contend that it’s important to understand that as of July 2021, long COVID is considered a disability under the Americans with Disabilities Act (ADA).

“Long COVID is recognized as a disability under Section 504 of the ADA, and yet day after day, we see violations of the ADA for people with long COVID not getting the accommodations that they need in order to work,” said David Putrino, PhD, the Nash Family director of the Cohen Center for Recovery from Complex Chronic Illness at Mount Sinai in New York City and a renowned expert in long COVID.

He added that short- and long-term disability claims are sometimes denied because of a lack of diagnostic testing to prove a patient has the condition. “This is nonsensical and absurd because the CDC does not require a blood test for the diagnosis of long COVID. It’s at your physician’s discretion,” Putrino said.

Viswanathan agreed. She said that for many of her patients, getting long-term disability has been particularly challenging because there’s no blood test for long COVID to prove patients have the condition. “As a result, for many of our patients, especially when they’re young, they may have to return to work in one form or another,” Viswanathan said.

 

The Impact of Long COVID on Quality of Life

What’s worse, the full impact is yet unknown because this is likely an underestimated cohort as many of these patients had mild cases of acute COVID-19 and fewer underlying conditions. For others, their long COVID is undiagnosed.

“Much of the impact on productivity and quality of life for this group remains hidden,” said Ziyad Al-Aly, MD, a global expert on long COVID and chief of research and development at the Veterans Affairs St. Louis Health Care System in Missouri.

Unfortunately, the impact on Bolecek’s life isn’t so hidden. He can’t work, which has been a financial stressor on the family. He spends much of the day in bed so that he can help with a few things when his wife gets home from work. He can’t cycle anymore and, as a result, has lost many of the friends associated with his favorite hobby.

But he remains hopeful, and more than anything else, he’s thankful for his family. His wife and kids have given him the strength to push on even when the days are hard. “I just don’t know where I’d be without them,” Bolecek said.

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

For almost 2 decades, antidepressants have carried boxed warnings linking the medications to an increased risk for suicidal thoughts and behaviors in young people. Paradoxically, and for almost as long, evidence suggests these warnings may have led to fewer depression diagnoses, reduced prescriptions, and, ultimately, higher suicide rates.

With mounting evidence of these negative unintended consequences, some clinicians and researchers are urging the Food and Drug Administration (FDA) to consider revising — or even eliminating — boxed warnings on these medications.

The latest report challenging the utility of the 2005 warnings was particularly sobering. Published in October in Health Affairs, the systematic review of studies from 2003 to 2022 showed a 20%-40% decline in physician visits for depression, a 20%-50% decline in antidepressant use, and an abrupt increase in psychotropic drug poisonings and suicides — all after the warnings were added.

“FDA officials should review the totality of evidence and err on the side of caution in acknowledging possible harms of the antidepressant warnings,” lead author Stephen Soumerai, ScD, professor of population medicine at Harvard Medical School at Harvard Pilgrim Health Care Institute, Boston, Massachusetts and colleagues wrote. They called on the FDA to replace the boxed warnings with a routine warning in labeling.

While good prospective data on the risks and benefits of antidepressants in youth were limited when the boxed warnings were instituted, there is more information now, said Jeffrey Strawn, MD, professor of psychiatry and pediatrics at the University of Cincinnati College of Medicine in Ohio. Strawn, whose research on the topic has been cited frequently over the years, said the new evidence suggests it is time for the FDA to reevaluate the warnings.

“I don’t think that they’ve been useful. They’ve actually been harmful,” Strawn told this news organization. “These boxed warnings have decreased physicians’ and other clinicians’ comfort and tendency to prescribe.”

 

Decline in Diagnoses

The FDA issued its first warning about the potential for suicidal thoughts and behavior in children in 2003. After an advisory panel weighed the evidence, the agency added a boxed warning in 2005 to all antidepressants for children younger than 18 years. The warning was expanded in 2007 to include young adults through age 24.

Data suggesting that the warnings have had unintended effects can be found going back to just after they were issued. For instance, in 2009, after rising for years, the rate of new pediatric depression diagnoses fell precipitously after the warning was added, with primary care physicians diagnosing 44% fewer cases.

In 2014, citing evidence of fewer diagnoses and rising psychotropic drug poisonings, Weill Cornell Medicine Professor Richard A. Friedman, MD, called on the FDA in a perspective to remove the boxed warnings.

Strawn and colleagues reported in an often-cited 2014 systematic review and meta-analysis that, in nine trials involving 1673 patients and six medications, antidepressants were superior to placebo, with no increased risk for suicidal thoughts or behavior.

He has also studied adverse effects of the medications, reporting in Pharmacotherapy that suicidality risk might be more likely with some medications, such as paroxetine and venlafaxine, and that it could be influenced by baseline suicidality, among many other factors. A Swedish register study found that risk was highest the month before starting a medication, Strawn and colleagues wrote.

Dara Sakolsky, MD, PhD, associate professor of psychiatry and associate medical director, Services for Teens at Risk at the University of Pittsburgh School of Medicine, Pennsylvania, told this news organization that, because of “these negative unintended consequences,” the FDA should lower the temperature by putting the warnings in labeling.

“It makes sense based on the data that we have at hand now,” said Sakolsky.

 

The Dangers of Untreated Depression

Even with this new information, lingering concerns about earlier studies that pointed to increased suicidality risk may discourage prescribing by primary care physicians and pediatricians, and that worries researchers and psychiatrists.

“My concern is that the risk for suicide and suicidal behavior may be higher in untreated depression than the risk of suicidal thoughts or behaviors from antidepressants,” Jeffrey Bridge, PhD, director of the Center for Suicide Prevention and Research at Nationwide Children’s Hospital, Columbus, Ohio, told this news organization.

Bridge is the lead author of a much-cited 2007 meta-analysis in JAMA that showed that the benefits of antidepressants in children and adolescents appeared to be greater than the risks for suicidality. “The concern about antidepressants must be considered in the context of possible benefit,” wrote Bridge, who also is professor of pediatrics, psychiatry, and behavioral health at Ohio State University College of Medicine, Columbus.

Depression and suicide are a scourge for those younger than 25 years. A 2021 literature review noted that the prevalence of depression — which has been increasing for all Americans — has risen more among adolescents than adults. Depression is “strongly associated with suicide,” the authors wrote.

In 2021, the National Institute of Mental Health reported suicide was the second leading cause of death among 10- to 14-year-olds and the third leading cause of death among those aged 15-24 years.

Suicide kills more kids aged between 10 and 24 years than cancer and all other illnesses combined, John Campo, MD, director of child and adolescent psychiatry at Johns Hopkins University School of Medicine and vice president of psychiatric services at Kennedy Krieger Institute, told this news organization.

Meanwhile, he added, the medications work and clinicians balance risk and benefit in prescribing.

The landmark 2007 Treatment for Adolescents with Depression Study showed that fluoxetine, especially in combination with cognitive-behavioral therapy (CBT), was significantly better than placebo. Since that time, legions of trials have shown the drugs’ effectiveness.

The most effective treatment for teen depression is a combination of CBT and a selective serotonin reuptake inhibitor, said Sakolsky.

“We know that the evidence for that is pretty good,” she said. “On the flip side, we know the risk of having an adverse outcome is pretty low.”

Sakolsky tells patients and families that perhaps 1 in 146 will have a suicidal thought or behavior. “That’s pretty rare when we know how effective these medicines are.” 

Strawn said he always notes that no suicides took place in the trials that led to the warning and stresses that he closely monitors patients. “While the more recent prospective data are reassuring,” the suicidality risk “is something that we still talk about,” he said. He also discusses how some antidepressants seem to increase risk more than others.

For Campo, the discussion is based on his reading of the evidence, not the presence of the FDA warning.

“Based on what we know, I still think it’s fair to proceed with the idea that there is a small, but real risk,” he said. However, “at the same time, the medications might be exceptionally helpful for some kids.”

 

‘What Do We Do Now?’

When the FDA issued its warning in 2005, the agency said it identified the risk for suicidality in a combined analysis of short-term placebo-controlled trials of nine antidepressants. It ultimately included 24 trials involving more than 4400 patients. The risk was highest in the first few months. The average risk for those taking antidepressants was 4%, twice the placebo risk of 2%. There were no suicides in these trials, however.

The trials relied on spontaneous reports of adverse events, not predetermined measures, Campo said. Even so, that 2% difference is “nothing to sneeze at,” he noted.

Bridge’s meta-analysis showed a smaller difference — closer to 0.7%. “But it was still statistically significant,” Campo said. “I have trouble ignoring that.”

The unintended consequences of the warning can’t be studied in a randomized controlled trial. Studies have shown an association but not a direct cause-and-effect relationship between the warning and a decline in treatment and rise in suicides.

But the potential for suicidal thoughts and behavior with antidepressants has been studied prospectively. Some older studies found a significant risk, while more recent trials have not.

While the Health Affairs analysis “certainly makes a strong case,” it is observational data, Campo said.

“The question is, what do we do now in retrospect? Do you say, ‘Never mind. We don’t need the black box warning anymore?’ ” he said. “That would require a pretty careful look.”

The Health Affairs paper “makes me think that there are other areas of research that that need to be completed and done and updated, and then there should be an assessment, a reevaluation from the FDA,” said Bridge. A new meta-analysis “would be very informative,” he said.

 

What’s Next?

When asked about the Health Affairs paper and whether the agency would review the warnings, an FDA spokesperson told this news organization that the agency “does not comment on specific studies but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”

Sakolsky said the data clearly point to the damage that the warning has done over the past 2 decades, but that things might be improving. Studies conducted more recently might not have captured some changes in practice.

For instance, she noted, in 2022, the US Preventive Services Task Force recommended screening for major depressive disorder in adolescents aged 12-18 years. In turn, she has seen more patients in her office who were referred by pediatricians who had conducted the screening, said Sakolsky.

Strawn said the time for pontificating is long past due. “We’re withholding medications and other treatments that could potentially be effective for disorders that, in and of themselves, are associated with a significant increase in the risk of suicide.” 

After the FDA instituted the warning, “we were all very nervous,” about the potential fallout, said Campo, adding that a part of him wishes that the warnings had been “more mundane and less dramatic.”

Despite the unintended consequences, “it’s going to be hard to put the genie back in the bottle,” he said.

Campo and Sakolsky reported no relevant financial relationships. Strawn disclosed that his institution has received research funding from the National Institute of Child Health and Human Development, the Patient-Centered Outcomes Research Institute (PCORI), and AbbVie. Bridge reported that he received grant support from the National Institute of Mental Health, Centers for Disease Control and Prevention, and PCORI; is a scientific adviser to Clarigent Health; and is on the Scientific Council of the American Foundation for Suicide Prevention.

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

For almost 2 decades, antidepressants have carried boxed warnings linking the medications to an increased risk for suicidal thoughts and behaviors in young people. Paradoxically, and for almost as long, evidence suggests these warnings may have led to fewer depression diagnoses, reduced prescriptions, and, ultimately, higher suicide rates.

With mounting evidence of these negative unintended consequences, some clinicians and researchers are urging the Food and Drug Administration (FDA) to consider revising — or even eliminating — boxed warnings on these medications.

The latest report challenging the utility of the 2005 warnings was particularly sobering. Published in October in Health Affairs, the systematic review of studies from 2003 to 2022 showed a 20%-40% decline in physician visits for depression, a 20%-50% decline in antidepressant use, and an abrupt increase in psychotropic drug poisonings and suicides — all after the warnings were added.

“FDA officials should review the totality of evidence and err on the side of caution in acknowledging possible harms of the antidepressant warnings,” lead author Stephen Soumerai, ScD, professor of population medicine at Harvard Medical School at Harvard Pilgrim Health Care Institute, Boston, Massachusetts and colleagues wrote. They called on the FDA to replace the boxed warnings with a routine warning in labeling.

While good prospective data on the risks and benefits of antidepressants in youth were limited when the boxed warnings were instituted, there is more information now, said Jeffrey Strawn, MD, professor of psychiatry and pediatrics at the University of Cincinnati College of Medicine in Ohio. Strawn, whose research on the topic has been cited frequently over the years, said the new evidence suggests it is time for the FDA to reevaluate the warnings.

“I don’t think that they’ve been useful. They’ve actually been harmful,” Strawn told this news organization. “These boxed warnings have decreased physicians’ and other clinicians’ comfort and tendency to prescribe.”

 

Decline in Diagnoses

The FDA issued its first warning about the potential for suicidal thoughts and behavior in children in 2003. After an advisory panel weighed the evidence, the agency added a boxed warning in 2005 to all antidepressants for children younger than 18 years. The warning was expanded in 2007 to include young adults through age 24.

Data suggesting that the warnings have had unintended effects can be found going back to just after they were issued. For instance, in 2009, after rising for years, the rate of new pediatric depression diagnoses fell precipitously after the warning was added, with primary care physicians diagnosing 44% fewer cases.

In 2014, citing evidence of fewer diagnoses and rising psychotropic drug poisonings, Weill Cornell Medicine Professor Richard A. Friedman, MD, called on the FDA in a perspective to remove the boxed warnings.

Strawn and colleagues reported in an often-cited 2014 systematic review and meta-analysis that, in nine trials involving 1673 patients and six medications, antidepressants were superior to placebo, with no increased risk for suicidal thoughts or behavior.

He has also studied adverse effects of the medications, reporting in Pharmacotherapy that suicidality risk might be more likely with some medications, such as paroxetine and venlafaxine, and that it could be influenced by baseline suicidality, among many other factors. A Swedish register study found that risk was highest the month before starting a medication, Strawn and colleagues wrote.

Dara Sakolsky, MD, PhD, associate professor of psychiatry and associate medical director, Services for Teens at Risk at the University of Pittsburgh School of Medicine, Pennsylvania, told this news organization that, because of “these negative unintended consequences,” the FDA should lower the temperature by putting the warnings in labeling.

“It makes sense based on the data that we have at hand now,” said Sakolsky.

 

The Dangers of Untreated Depression

Even with this new information, lingering concerns about earlier studies that pointed to increased suicidality risk may discourage prescribing by primary care physicians and pediatricians, and that worries researchers and psychiatrists.

“My concern is that the risk for suicide and suicidal behavior may be higher in untreated depression than the risk of suicidal thoughts or behaviors from antidepressants,” Jeffrey Bridge, PhD, director of the Center for Suicide Prevention and Research at Nationwide Children’s Hospital, Columbus, Ohio, told this news organization.

Bridge is the lead author of a much-cited 2007 meta-analysis in JAMA that showed that the benefits of antidepressants in children and adolescents appeared to be greater than the risks for suicidality. “The concern about antidepressants must be considered in the context of possible benefit,” wrote Bridge, who also is professor of pediatrics, psychiatry, and behavioral health at Ohio State University College of Medicine, Columbus.

Depression and suicide are a scourge for those younger than 25 years. A 2021 literature review noted that the prevalence of depression — which has been increasing for all Americans — has risen more among adolescents than adults. Depression is “strongly associated with suicide,” the authors wrote.

In 2021, the National Institute of Mental Health reported suicide was the second leading cause of death among 10- to 14-year-olds and the third leading cause of death among those aged 15-24 years.

Suicide kills more kids aged between 10 and 24 years than cancer and all other illnesses combined, John Campo, MD, director of child and adolescent psychiatry at Johns Hopkins University School of Medicine and vice president of psychiatric services at Kennedy Krieger Institute, told this news organization.

Meanwhile, he added, the medications work and clinicians balance risk and benefit in prescribing.

The landmark 2007 Treatment for Adolescents with Depression Study showed that fluoxetine, especially in combination with cognitive-behavioral therapy (CBT), was significantly better than placebo. Since that time, legions of trials have shown the drugs’ effectiveness.

The most effective treatment for teen depression is a combination of CBT and a selective serotonin reuptake inhibitor, said Sakolsky.

“We know that the evidence for that is pretty good,” she said. “On the flip side, we know the risk of having an adverse outcome is pretty low.”

Sakolsky tells patients and families that perhaps 1 in 146 will have a suicidal thought or behavior. “That’s pretty rare when we know how effective these medicines are.” 

Strawn said he always notes that no suicides took place in the trials that led to the warning and stresses that he closely monitors patients. “While the more recent prospective data are reassuring,” the suicidality risk “is something that we still talk about,” he said. He also discusses how some antidepressants seem to increase risk more than others.

For Campo, the discussion is based on his reading of the evidence, not the presence of the FDA warning.

“Based on what we know, I still think it’s fair to proceed with the idea that there is a small, but real risk,” he said. However, “at the same time, the medications might be exceptionally helpful for some kids.”

 

‘What Do We Do Now?’

When the FDA issued its warning in 2005, the agency said it identified the risk for suicidality in a combined analysis of short-term placebo-controlled trials of nine antidepressants. It ultimately included 24 trials involving more than 4400 patients. The risk was highest in the first few months. The average risk for those taking antidepressants was 4%, twice the placebo risk of 2%. There were no suicides in these trials, however.

The trials relied on spontaneous reports of adverse events, not predetermined measures, Campo said. Even so, that 2% difference is “nothing to sneeze at,” he noted.

Bridge’s meta-analysis showed a smaller difference — closer to 0.7%. “But it was still statistically significant,” Campo said. “I have trouble ignoring that.”

The unintended consequences of the warning can’t be studied in a randomized controlled trial. Studies have shown an association but not a direct cause-and-effect relationship between the warning and a decline in treatment and rise in suicides.

But the potential for suicidal thoughts and behavior with antidepressants has been studied prospectively. Some older studies found a significant risk, while more recent trials have not.

While the Health Affairs analysis “certainly makes a strong case,” it is observational data, Campo said.

“The question is, what do we do now in retrospect? Do you say, ‘Never mind. We don’t need the black box warning anymore?’ ” he said. “That would require a pretty careful look.”

The Health Affairs paper “makes me think that there are other areas of research that that need to be completed and done and updated, and then there should be an assessment, a reevaluation from the FDA,” said Bridge. A new meta-analysis “would be very informative,” he said.

 

What’s Next?

When asked about the Health Affairs paper and whether the agency would review the warnings, an FDA spokesperson told this news organization that the agency “does not comment on specific studies but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”

Sakolsky said the data clearly point to the damage that the warning has done over the past 2 decades, but that things might be improving. Studies conducted more recently might not have captured some changes in practice.

For instance, she noted, in 2022, the US Preventive Services Task Force recommended screening for major depressive disorder in adolescents aged 12-18 years. In turn, she has seen more patients in her office who were referred by pediatricians who had conducted the screening, said Sakolsky.

Strawn said the time for pontificating is long past due. “We’re withholding medications and other treatments that could potentially be effective for disorders that, in and of themselves, are associated with a significant increase in the risk of suicide.” 

After the FDA instituted the warning, “we were all very nervous,” about the potential fallout, said Campo, adding that a part of him wishes that the warnings had been “more mundane and less dramatic.”

Despite the unintended consequences, “it’s going to be hard to put the genie back in the bottle,” he said.

Campo and Sakolsky reported no relevant financial relationships. Strawn disclosed that his institution has received research funding from the National Institute of Child Health and Human Development, the Patient-Centered Outcomes Research Institute (PCORI), and AbbVie. Bridge reported that he received grant support from the National Institute of Mental Health, Centers for Disease Control and Prevention, and PCORI; is a scientific adviser to Clarigent Health; and is on the Scientific Council of the American Foundation for Suicide Prevention.

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

For almost 2 decades, antidepressants have carried boxed warnings linking the medications to an increased risk for suicidal thoughts and behaviors in young people. Paradoxically, and for almost as long, evidence suggests these warnings may have led to fewer depression diagnoses, reduced prescriptions, and, ultimately, higher suicide rates.

With mounting evidence of these negative unintended consequences, some clinicians and researchers are urging the Food and Drug Administration (FDA) to consider revising — or even eliminating — boxed warnings on these medications.

The latest report challenging the utility of the 2005 warnings was particularly sobering. Published in October in Health Affairs, the systematic review of studies from 2003 to 2022 showed a 20%-40% decline in physician visits for depression, a 20%-50% decline in antidepressant use, and an abrupt increase in psychotropic drug poisonings and suicides — all after the warnings were added.

“FDA officials should review the totality of evidence and err on the side of caution in acknowledging possible harms of the antidepressant warnings,” lead author Stephen Soumerai, ScD, professor of population medicine at Harvard Medical School at Harvard Pilgrim Health Care Institute, Boston, Massachusetts and colleagues wrote. They called on the FDA to replace the boxed warnings with a routine warning in labeling.

While good prospective data on the risks and benefits of antidepressants in youth were limited when the boxed warnings were instituted, there is more information now, said Jeffrey Strawn, MD, professor of psychiatry and pediatrics at the University of Cincinnati College of Medicine in Ohio. Strawn, whose research on the topic has been cited frequently over the years, said the new evidence suggests it is time for the FDA to reevaluate the warnings.

“I don’t think that they’ve been useful. They’ve actually been harmful,” Strawn told this news organization. “These boxed warnings have decreased physicians’ and other clinicians’ comfort and tendency to prescribe.”

 

Decline in Diagnoses

The FDA issued its first warning about the potential for suicidal thoughts and behavior in children in 2003. After an advisory panel weighed the evidence, the agency added a boxed warning in 2005 to all antidepressants for children younger than 18 years. The warning was expanded in 2007 to include young adults through age 24.

Data suggesting that the warnings have had unintended effects can be found going back to just after they were issued. For instance, in 2009, after rising for years, the rate of new pediatric depression diagnoses fell precipitously after the warning was added, with primary care physicians diagnosing 44% fewer cases.

In 2014, citing evidence of fewer diagnoses and rising psychotropic drug poisonings, Weill Cornell Medicine Professor Richard A. Friedman, MD, called on the FDA in a perspective to remove the boxed warnings.

Strawn and colleagues reported in an often-cited 2014 systematic review and meta-analysis that, in nine trials involving 1673 patients and six medications, antidepressants were superior to placebo, with no increased risk for suicidal thoughts or behavior.

He has also studied adverse effects of the medications, reporting in Pharmacotherapy that suicidality risk might be more likely with some medications, such as paroxetine and venlafaxine, and that it could be influenced by baseline suicidality, among many other factors. A Swedish register study found that risk was highest the month before starting a medication, Strawn and colleagues wrote.

Dara Sakolsky, MD, PhD, associate professor of psychiatry and associate medical director, Services for Teens at Risk at the University of Pittsburgh School of Medicine, Pennsylvania, told this news organization that, because of “these negative unintended consequences,” the FDA should lower the temperature by putting the warnings in labeling.

“It makes sense based on the data that we have at hand now,” said Sakolsky.

 

The Dangers of Untreated Depression

Even with this new information, lingering concerns about earlier studies that pointed to increased suicidality risk may discourage prescribing by primary care physicians and pediatricians, and that worries researchers and psychiatrists.

“My concern is that the risk for suicide and suicidal behavior may be higher in untreated depression than the risk of suicidal thoughts or behaviors from antidepressants,” Jeffrey Bridge, PhD, director of the Center for Suicide Prevention and Research at Nationwide Children’s Hospital, Columbus, Ohio, told this news organization.

Bridge is the lead author of a much-cited 2007 meta-analysis in JAMA that showed that the benefits of antidepressants in children and adolescents appeared to be greater than the risks for suicidality. “The concern about antidepressants must be considered in the context of possible benefit,” wrote Bridge, who also is professor of pediatrics, psychiatry, and behavioral health at Ohio State University College of Medicine, Columbus.

Depression and suicide are a scourge for those younger than 25 years. A 2021 literature review noted that the prevalence of depression — which has been increasing for all Americans — has risen more among adolescents than adults. Depression is “strongly associated with suicide,” the authors wrote.

In 2021, the National Institute of Mental Health reported suicide was the second leading cause of death among 10- to 14-year-olds and the third leading cause of death among those aged 15-24 years.

Suicide kills more kids aged between 10 and 24 years than cancer and all other illnesses combined, John Campo, MD, director of child and adolescent psychiatry at Johns Hopkins University School of Medicine and vice president of psychiatric services at Kennedy Krieger Institute, told this news organization.

Meanwhile, he added, the medications work and clinicians balance risk and benefit in prescribing.

The landmark 2007 Treatment for Adolescents with Depression Study showed that fluoxetine, especially in combination with cognitive-behavioral therapy (CBT), was significantly better than placebo. Since that time, legions of trials have shown the drugs’ effectiveness.

The most effective treatment for teen depression is a combination of CBT and a selective serotonin reuptake inhibitor, said Sakolsky.

“We know that the evidence for that is pretty good,” she said. “On the flip side, we know the risk of having an adverse outcome is pretty low.”

Sakolsky tells patients and families that perhaps 1 in 146 will have a suicidal thought or behavior. “That’s pretty rare when we know how effective these medicines are.” 

Strawn said he always notes that no suicides took place in the trials that led to the warning and stresses that he closely monitors patients. “While the more recent prospective data are reassuring,” the suicidality risk “is something that we still talk about,” he said. He also discusses how some antidepressants seem to increase risk more than others.

For Campo, the discussion is based on his reading of the evidence, not the presence of the FDA warning.

“Based on what we know, I still think it’s fair to proceed with the idea that there is a small, but real risk,” he said. However, “at the same time, the medications might be exceptionally helpful for some kids.”

 

‘What Do We Do Now?’

When the FDA issued its warning in 2005, the agency said it identified the risk for suicidality in a combined analysis of short-term placebo-controlled trials of nine antidepressants. It ultimately included 24 trials involving more than 4400 patients. The risk was highest in the first few months. The average risk for those taking antidepressants was 4%, twice the placebo risk of 2%. There were no suicides in these trials, however.

The trials relied on spontaneous reports of adverse events, not predetermined measures, Campo said. Even so, that 2% difference is “nothing to sneeze at,” he noted.

Bridge’s meta-analysis showed a smaller difference — closer to 0.7%. “But it was still statistically significant,” Campo said. “I have trouble ignoring that.”

The unintended consequences of the warning can’t be studied in a randomized controlled trial. Studies have shown an association but not a direct cause-and-effect relationship between the warning and a decline in treatment and rise in suicides.

But the potential for suicidal thoughts and behavior with antidepressants has been studied prospectively. Some older studies found a significant risk, while more recent trials have not.

While the Health Affairs analysis “certainly makes a strong case,” it is observational data, Campo said.

“The question is, what do we do now in retrospect? Do you say, ‘Never mind. We don’t need the black box warning anymore?’ ” he said. “That would require a pretty careful look.”

The Health Affairs paper “makes me think that there are other areas of research that that need to be completed and done and updated, and then there should be an assessment, a reevaluation from the FDA,” said Bridge. A new meta-analysis “would be very informative,” he said.

 

What’s Next?

When asked about the Health Affairs paper and whether the agency would review the warnings, an FDA spokesperson told this news organization that the agency “does not comment on specific studies but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”

Sakolsky said the data clearly point to the damage that the warning has done over the past 2 decades, but that things might be improving. Studies conducted more recently might not have captured some changes in practice.

For instance, she noted, in 2022, the US Preventive Services Task Force recommended screening for major depressive disorder in adolescents aged 12-18 years. In turn, she has seen more patients in her office who were referred by pediatricians who had conducted the screening, said Sakolsky.

Strawn said the time for pontificating is long past due. “We’re withholding medications and other treatments that could potentially be effective for disorders that, in and of themselves, are associated with a significant increase in the risk of suicide.” 

After the FDA instituted the warning, “we were all very nervous,” about the potential fallout, said Campo, adding that a part of him wishes that the warnings had been “more mundane and less dramatic.”

Despite the unintended consequences, “it’s going to be hard to put the genie back in the bottle,” he said.

Campo and Sakolsky reported no relevant financial relationships. Strawn disclosed that his institution has received research funding from the National Institute of Child Health and Human Development, the Patient-Centered Outcomes Research Institute (PCORI), and AbbVie. Bridge reported that he received grant support from the National Institute of Mental Health, Centers for Disease Control and Prevention, and PCORI; is a scientific adviser to Clarigent Health; and is on the Scientific Council of the American Foundation for Suicide Prevention.

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

Researchers are gaining new insight into the relationship between the human cytomegalovirus (HCMV), a common herpes virus found in the gut, and the immune response associated with CD83 antibody in some individuals with Alzheimer’s disease (AD).

Using tissue samples from deceased donors with AD, the study showed CD83-positive (CD83+) microglia in the superior frontal gyrus (SFG) are significantly associated with elevated immunoglobulin gamma 4 (IgG4) and HCMV in the transverse colon (TC), increased anti-HCMV IgG4 in the cerebrospinal fluid (CSF), and both HCMV and IgG4 in the SFG and vagus nerve.

“Our results indicate a complex, cross-tissue interaction between HCMV and the host adaptive immune response associated with CD83+ microglia in persons with AD,” noted the investigators, including Benjamin P. Readhead, MBBS, research associate professor, ASU-Banner Neurodegenerative Disease Research Center, Arizona State University, Tempe.

The results suggest antiviral therapy in patients with biomarker evidence of HCMV, IgG4, or CD83+ microglia might ward off dementia.

“We’re preparing to conduct a clinical trial to evaluate whether careful use of existing antivirals might be clinically helpful in preventing or slowing progression of CD83+ associated Alzheimer’s disease,” Readhead said in an interview.

The study was published on December 19, 2024, in Alzheimer’s & Dementia.

 

Vagus Nerve a Potential Pathway?

CMV is a common virus. In the United States, nearly one in three children are already infected with CMV by age 5 years. Over half the adults have been infected with CMV by age 40 years, the Centers for Disease Control and Prevention reported.

It is typically passed through bodily fluids and spread only when the virus is active. It’s not considered a sexually transmitted disease.

Compared with other IgG subclasses, IgG4 is believed to be a less inflammatory, and therefore less damaging, immune response. But this response may be less effective at clearing infections and allow invasion of HCMV into the brain.

Experts speculate HCMV may travel via the vagus nerve from the colon to the brain where it triggers the onset of AD. 

The researchers previously found a CD83+ microglial subtype in the SFG of 47% of brain donors with AD vs 25% of unaffected control individuals. They reported this subtype is associated with increased IgG4 in the TC.

The current analysis extends investigations of the potential etiology and clinicopathologic relevance of CD83+ microglia in the context of AD.

Researchers conducted experiments using donated tissue samples from deceased patients with AD and control individuals. Sources for these samples included the Banner cohort, for whom classifications for the presence of CD83+ microglia were available, as were tissue samples from the SFG, TC, and vagus nerve, and the Religious Orders Study and Rush Memory and Aging Project (ROSMAP), in which participants without known dementia are evaluated annually.

From the Banner cohort, researchers completed immunohistochemistry (IHC) studies on 34 SFG samples (21 AD and 13 control individuals) and included 25 TC samples (13 AD and 12 control individuals) and 8 vagal nerve samples (6 AD and 2 control individuals) in the study. From the ROSMAP cohort, they completed IHC studies on 27 prefrontal cortex samples from individuals with AD.

They carefully selected these samples to ensure matching for critical factors such as postmortem interval, age, and sex, as well as other relevant covariates, said the authors.

The study verified that CD83+ microglia are associated with IgG4 and HCMV in the TC and showed a significant association between CD83+ microglia and IgG4 immunoreactivity in the TC.

Investigators confirmed HCMV positivity in all nine CD83+ TC samples evaluated and in one CD83– TC sample, indicating a strong positive association between HCMV within the TC and CD83+ microglia within the SFG.

HCMV IgG seroprevalence is common, varies by age and comorbidity, and is present in 79% of 85-year-olds, the investigators noted. “Despite this, we note that HCMV presence in the TC was not ubiquitous and was significantly associated with CD83+ microglia and HCMV in the SFG,” they wrote.

This observation, they added, “may help reconcile how a common pathogen might contribute to a disease that most individuals do not develop.”

The experiments also uncovered increased anti-HCMV IgG4 in the CSF and evidence of HCMV and IgG4 in the vagus nerve.

“Overall, the histochemical staining patterns observed in TC, SFG, and vagus nerve of CD83+ subjects are consistent with active HCMV infection,” the investigators wrote. “Taken together, these results indicate a multiorgan presence of IgG4 and HCMV in subjects with CD83+ microglia within the SFG,” they added.

 

Accelerated AD Pathology

The team showed HCMV infection accelerates production of two pathologic features of AD — amyloid beta (Abeta) and tau — and causes neuronal death. “We observed high, positive correlations between the abundance of HCMV, and both Abeta42 and pTau-212,” they wrote.

As HCMV histochemistry is consistent with an active HCMV infection, the findings “may indicate an opportunity for the administration of antiviral therapy in subjects with AD and biomarker evidence of HCMV, IgG4, or CD83+ microglia,” they added.

In addition to planning a clinical trial of existing antivirals, the research team is developing a blood test that can help identify patients with an active HCMV infection who might benefit from such an intervention, said Readhead.

But he emphasized that the research is still in its infancy. “Our study is best understood as a series of interesting scientific findings that warrant further exploration, replication, and validation in additional study populations.”

Although it’s too early for the study to impact practice, “we’re motivated to understand whether these findings have implications for clinical care,” he added.

 

Tipping the Balance

A number of experts have weighed in on the research via the Science Media Center, an independent forum featuring the voices and views on science news from experts in the field.

Andrew Doig, PhD, professor, Division of Neuroscience, University of Manchester in England, said the new work supports the hypothesis that HCMV might be a trigger that tips the balance from a healthy brain to one with dementia. “If so, antiviral drugs against HCMV might be beneficial in reducing the risk of AD.”

Doig noted newly approved drugs for AD are expensive, provide only a small benefit, and have significant risks, such as causing brain hemorrhages. “Antiviral drugs are an attractive alternative that are well worth exploring.”

Richard Oakley, PhD, associate director of research and innovation, Alzheimer’s Society, cautioned the study only established a connection and didn’t directly show the virus leads to AD. “Also, the virus is not found in the brain of everyone with Alzheimer’s disease, the most common form of dementia.”

The significance of the new findings is “far from clear,” commented William McEwan, PhD, group leader at the UK Dementia Research Institute at Cambridge, England. “The study does not address how common this infection is in people without Alzheimer’s and therefore cannot by itself suggest that HCMV infection, or the associated immune response, is a driver of disease.”

The experts agreed follow-up research is needed to confirm these new findings and understand what they mean.

The study received support from the National Institute on Aging, National Institutes of Health, Global Lyme Alliance, National Institute of Neurological Disorders and Stroke, Arizona Alzheimer’s Consortium, The Benter Foundation, and NOMIS Stiftung. Readhead is a coinventor on a patent application for an IgG4-based peripheral biomarker for the detection of CD83+ microglia. Doig is a founder, director, and consultant for PharmaKure, which works on AD drugs and diagnostics, although not on viruses. He has cowritten a review on Viral Involvement in Alzheimer’s Disease. McEwan reported receiving research funding from Takeda Pharmaceuticals and is a founder and consultant to Trimtech Therapeutics.

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

Researchers are gaining new insight into the relationship between the human cytomegalovirus (HCMV), a common herpes virus found in the gut, and the immune response associated with CD83 antibody in some individuals with Alzheimer’s disease (AD).

Using tissue samples from deceased donors with AD, the study showed CD83-positive (CD83+) microglia in the superior frontal gyrus (SFG) are significantly associated with elevated immunoglobulin gamma 4 (IgG4) and HCMV in the transverse colon (TC), increased anti-HCMV IgG4 in the cerebrospinal fluid (CSF), and both HCMV and IgG4 in the SFG and vagus nerve.

“Our results indicate a complex, cross-tissue interaction between HCMV and the host adaptive immune response associated with CD83+ microglia in persons with AD,” noted the investigators, including Benjamin P. Readhead, MBBS, research associate professor, ASU-Banner Neurodegenerative Disease Research Center, Arizona State University, Tempe.

The results suggest antiviral therapy in patients with biomarker evidence of HCMV, IgG4, or CD83+ microglia might ward off dementia.

“We’re preparing to conduct a clinical trial to evaluate whether careful use of existing antivirals might be clinically helpful in preventing or slowing progression of CD83+ associated Alzheimer’s disease,” Readhead said in an interview.

The study was published on December 19, 2024, in Alzheimer’s & Dementia.

 

Vagus Nerve a Potential Pathway?

CMV is a common virus. In the United States, nearly one in three children are already infected with CMV by age 5 years. Over half the adults have been infected with CMV by age 40 years, the Centers for Disease Control and Prevention reported.

It is typically passed through bodily fluids and spread only when the virus is active. It’s not considered a sexually transmitted disease.

Compared with other IgG subclasses, IgG4 is believed to be a less inflammatory, and therefore less damaging, immune response. But this response may be less effective at clearing infections and allow invasion of HCMV into the brain.

Experts speculate HCMV may travel via the vagus nerve from the colon to the brain where it triggers the onset of AD. 

The researchers previously found a CD83+ microglial subtype in the SFG of 47% of brain donors with AD vs 25% of unaffected control individuals. They reported this subtype is associated with increased IgG4 in the TC.

The current analysis extends investigations of the potential etiology and clinicopathologic relevance of CD83+ microglia in the context of AD.

Researchers conducted experiments using donated tissue samples from deceased patients with AD and control individuals. Sources for these samples included the Banner cohort, for whom classifications for the presence of CD83+ microglia were available, as were tissue samples from the SFG, TC, and vagus nerve, and the Religious Orders Study and Rush Memory and Aging Project (ROSMAP), in which participants without known dementia are evaluated annually.

From the Banner cohort, researchers completed immunohistochemistry (IHC) studies on 34 SFG samples (21 AD and 13 control individuals) and included 25 TC samples (13 AD and 12 control individuals) and 8 vagal nerve samples (6 AD and 2 control individuals) in the study. From the ROSMAP cohort, they completed IHC studies on 27 prefrontal cortex samples from individuals with AD.

They carefully selected these samples to ensure matching for critical factors such as postmortem interval, age, and sex, as well as other relevant covariates, said the authors.

The study verified that CD83+ microglia are associated with IgG4 and HCMV in the TC and showed a significant association between CD83+ microglia and IgG4 immunoreactivity in the TC.

Investigators confirmed HCMV positivity in all nine CD83+ TC samples evaluated and in one CD83– TC sample, indicating a strong positive association between HCMV within the TC and CD83+ microglia within the SFG.

HCMV IgG seroprevalence is common, varies by age and comorbidity, and is present in 79% of 85-year-olds, the investigators noted. “Despite this, we note that HCMV presence in the TC was not ubiquitous and was significantly associated with CD83+ microglia and HCMV in the SFG,” they wrote.

This observation, they added, “may help reconcile how a common pathogen might contribute to a disease that most individuals do not develop.”

The experiments also uncovered increased anti-HCMV IgG4 in the CSF and evidence of HCMV and IgG4 in the vagus nerve.

“Overall, the histochemical staining patterns observed in TC, SFG, and vagus nerve of CD83+ subjects are consistent with active HCMV infection,” the investigators wrote. “Taken together, these results indicate a multiorgan presence of IgG4 and HCMV in subjects with CD83+ microglia within the SFG,” they added.

 

Accelerated AD Pathology

The team showed HCMV infection accelerates production of two pathologic features of AD — amyloid beta (Abeta) and tau — and causes neuronal death. “We observed high, positive correlations between the abundance of HCMV, and both Abeta42 and pTau-212,” they wrote.

As HCMV histochemistry is consistent with an active HCMV infection, the findings “may indicate an opportunity for the administration of antiviral therapy in subjects with AD and biomarker evidence of HCMV, IgG4, or CD83+ microglia,” they added.

In addition to planning a clinical trial of existing antivirals, the research team is developing a blood test that can help identify patients with an active HCMV infection who might benefit from such an intervention, said Readhead.

But he emphasized that the research is still in its infancy. “Our study is best understood as a series of interesting scientific findings that warrant further exploration, replication, and validation in additional study populations.”

Although it’s too early for the study to impact practice, “we’re motivated to understand whether these findings have implications for clinical care,” he added.

 

Tipping the Balance

A number of experts have weighed in on the research via the Science Media Center, an independent forum featuring the voices and views on science news from experts in the field.

Andrew Doig, PhD, professor, Division of Neuroscience, University of Manchester in England, said the new work supports the hypothesis that HCMV might be a trigger that tips the balance from a healthy brain to one with dementia. “If so, antiviral drugs against HCMV might be beneficial in reducing the risk of AD.”

Doig noted newly approved drugs for AD are expensive, provide only a small benefit, and have significant risks, such as causing brain hemorrhages. “Antiviral drugs are an attractive alternative that are well worth exploring.”

Richard Oakley, PhD, associate director of research and innovation, Alzheimer’s Society, cautioned the study only established a connection and didn’t directly show the virus leads to AD. “Also, the virus is not found in the brain of everyone with Alzheimer’s disease, the most common form of dementia.”

The significance of the new findings is “far from clear,” commented William McEwan, PhD, group leader at the UK Dementia Research Institute at Cambridge, England. “The study does not address how common this infection is in people without Alzheimer’s and therefore cannot by itself suggest that HCMV infection, or the associated immune response, is a driver of disease.”

The experts agreed follow-up research is needed to confirm these new findings and understand what they mean.

The study received support from the National Institute on Aging, National Institutes of Health, Global Lyme Alliance, National Institute of Neurological Disorders and Stroke, Arizona Alzheimer’s Consortium, The Benter Foundation, and NOMIS Stiftung. Readhead is a coinventor on a patent application for an IgG4-based peripheral biomarker for the detection of CD83+ microglia. Doig is a founder, director, and consultant for PharmaKure, which works on AD drugs and diagnostics, although not on viruses. He has cowritten a review on Viral Involvement in Alzheimer’s Disease. McEwan reported receiving research funding from Takeda Pharmaceuticals and is a founder and consultant to Trimtech Therapeutics.

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

Researchers are gaining new insight into the relationship between the human cytomegalovirus (HCMV), a common herpes virus found in the gut, and the immune response associated with CD83 antibody in some individuals with Alzheimer’s disease (AD).

Using tissue samples from deceased donors with AD, the study showed CD83-positive (CD83+) microglia in the superior frontal gyrus (SFG) are significantly associated with elevated immunoglobulin gamma 4 (IgG4) and HCMV in the transverse colon (TC), increased anti-HCMV IgG4 in the cerebrospinal fluid (CSF), and both HCMV and IgG4 in the SFG and vagus nerve.

“Our results indicate a complex, cross-tissue interaction between HCMV and the host adaptive immune response associated with CD83+ microglia in persons with AD,” noted the investigators, including Benjamin P. Readhead, MBBS, research associate professor, ASU-Banner Neurodegenerative Disease Research Center, Arizona State University, Tempe.

The results suggest antiviral therapy in patients with biomarker evidence of HCMV, IgG4, or CD83+ microglia might ward off dementia.

“We’re preparing to conduct a clinical trial to evaluate whether careful use of existing antivirals might be clinically helpful in preventing or slowing progression of CD83+ associated Alzheimer’s disease,” Readhead said in an interview.

The study was published on December 19, 2024, in Alzheimer’s & Dementia.

 

Vagus Nerve a Potential Pathway?

CMV is a common virus. In the United States, nearly one in three children are already infected with CMV by age 5 years. Over half the adults have been infected with CMV by age 40 years, the Centers for Disease Control and Prevention reported.

It is typically passed through bodily fluids and spread only when the virus is active. It’s not considered a sexually transmitted disease.

Compared with other IgG subclasses, IgG4 is believed to be a less inflammatory, and therefore less damaging, immune response. But this response may be less effective at clearing infections and allow invasion of HCMV into the brain.

Experts speculate HCMV may travel via the vagus nerve from the colon to the brain where it triggers the onset of AD. 

The researchers previously found a CD83+ microglial subtype in the SFG of 47% of brain donors with AD vs 25% of unaffected control individuals. They reported this subtype is associated with increased IgG4 in the TC.

The current analysis extends investigations of the potential etiology and clinicopathologic relevance of CD83+ microglia in the context of AD.

Researchers conducted experiments using donated tissue samples from deceased patients with AD and control individuals. Sources for these samples included the Banner cohort, for whom classifications for the presence of CD83+ microglia were available, as were tissue samples from the SFG, TC, and vagus nerve, and the Religious Orders Study and Rush Memory and Aging Project (ROSMAP), in which participants without known dementia are evaluated annually.

From the Banner cohort, researchers completed immunohistochemistry (IHC) studies on 34 SFG samples (21 AD and 13 control individuals) and included 25 TC samples (13 AD and 12 control individuals) and 8 vagal nerve samples (6 AD and 2 control individuals) in the study. From the ROSMAP cohort, they completed IHC studies on 27 prefrontal cortex samples from individuals with AD.

They carefully selected these samples to ensure matching for critical factors such as postmortem interval, age, and sex, as well as other relevant covariates, said the authors.

The study verified that CD83+ microglia are associated with IgG4 and HCMV in the TC and showed a significant association between CD83+ microglia and IgG4 immunoreactivity in the TC.

Investigators confirmed HCMV positivity in all nine CD83+ TC samples evaluated and in one CD83– TC sample, indicating a strong positive association between HCMV within the TC and CD83+ microglia within the SFG.

HCMV IgG seroprevalence is common, varies by age and comorbidity, and is present in 79% of 85-year-olds, the investigators noted. “Despite this, we note that HCMV presence in the TC was not ubiquitous and was significantly associated with CD83+ microglia and HCMV in the SFG,” they wrote.

This observation, they added, “may help reconcile how a common pathogen might contribute to a disease that most individuals do not develop.”

The experiments also uncovered increased anti-HCMV IgG4 in the CSF and evidence of HCMV and IgG4 in the vagus nerve.

“Overall, the histochemical staining patterns observed in TC, SFG, and vagus nerve of CD83+ subjects are consistent with active HCMV infection,” the investigators wrote. “Taken together, these results indicate a multiorgan presence of IgG4 and HCMV in subjects with CD83+ microglia within the SFG,” they added.

 

Accelerated AD Pathology

The team showed HCMV infection accelerates production of two pathologic features of AD — amyloid beta (Abeta) and tau — and causes neuronal death. “We observed high, positive correlations between the abundance of HCMV, and both Abeta42 and pTau-212,” they wrote.

As HCMV histochemistry is consistent with an active HCMV infection, the findings “may indicate an opportunity for the administration of antiviral therapy in subjects with AD and biomarker evidence of HCMV, IgG4, or CD83+ microglia,” they added.

In addition to planning a clinical trial of existing antivirals, the research team is developing a blood test that can help identify patients with an active HCMV infection who might benefit from such an intervention, said Readhead.

But he emphasized that the research is still in its infancy. “Our study is best understood as a series of interesting scientific findings that warrant further exploration, replication, and validation in additional study populations.”

Although it’s too early for the study to impact practice, “we’re motivated to understand whether these findings have implications for clinical care,” he added.

 

Tipping the Balance

A number of experts have weighed in on the research via the Science Media Center, an independent forum featuring the voices and views on science news from experts in the field.

Andrew Doig, PhD, professor, Division of Neuroscience, University of Manchester in England, said the new work supports the hypothesis that HCMV might be a trigger that tips the balance from a healthy brain to one with dementia. “If so, antiviral drugs against HCMV might be beneficial in reducing the risk of AD.”

Doig noted newly approved drugs for AD are expensive, provide only a small benefit, and have significant risks, such as causing brain hemorrhages. “Antiviral drugs are an attractive alternative that are well worth exploring.”

Richard Oakley, PhD, associate director of research and innovation, Alzheimer’s Society, cautioned the study only established a connection and didn’t directly show the virus leads to AD. “Also, the virus is not found in the brain of everyone with Alzheimer’s disease, the most common form of dementia.”

The significance of the new findings is “far from clear,” commented William McEwan, PhD, group leader at the UK Dementia Research Institute at Cambridge, England. “The study does not address how common this infection is in people without Alzheimer’s and therefore cannot by itself suggest that HCMV infection, or the associated immune response, is a driver of disease.”

The experts agreed follow-up research is needed to confirm these new findings and understand what they mean.

The study received support from the National Institute on Aging, National Institutes of Health, Global Lyme Alliance, National Institute of Neurological Disorders and Stroke, Arizona Alzheimer’s Consortium, The Benter Foundation, and NOMIS Stiftung. Readhead is a coinventor on a patent application for an IgG4-based peripheral biomarker for the detection of CD83+ microglia. Doig is a founder, director, and consultant for PharmaKure, which works on AD drugs and diagnostics, although not on viruses. He has cowritten a review on Viral Involvement in Alzheimer’s Disease. McEwan reported receiving research funding from Takeda Pharmaceuticals and is a founder and consultant to Trimtech Therapeutics.

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

Laura Vater remembers sneaking into her home after 12-hour night shifts during medical training while her husband distracted their toddler. The stealthy tag-teaming effort helped her get enough undisturbed sleep before returning to an Indiana University hospital the following night to repeat the pattern.

“He would pretend to take out the trash when I pulled in,” said Vater, MD, now a gastrointestinal oncologist and assistant professor of medicine at IU Health Simon Cancer Center in Indianapolis. “I would sneak in so she [their daughter] wouldn’t see me, and then he would go back in.”

For Vater, prioritizing sleep during the day to combat sleep deprivation common among doctors-in-training on night shifts required enlisting a supportive spouse. It’s just one of the tips she and a few chief residents shared with this news organization for staying sharp and healthy during overnight rotations.

While the pace of patient rounds may slow from the frenetic daytime rush, training as a doctor after the sun goes down can be quite challenging for residents, they told this news organization. From sleep deprivation working while the rest of us slumbers to the after-effects of late-night caffeine, learning to manage night rotations requires a balance of preparation and attention to personal health while caring for others, the residents and adviser said.

Compromised sleep is one of the biggest hurdles residents have to overcome. Sleep loss comes with risks to cardiovascular disease and type 2 diabetes, among other heath conditions, according to Medscape Medical News reports. And night shift workers  who sleep 6 or fewer hours a night have at least one sleep disorder.

Sleep deprivation associated with overnight call schedules also can worsen a resident’s mood and motivation while impairing their judgment, leading to medical errors, according to a new study published in JAMA Open Network. The study proposed shorter consecutive night shifts and naps as ways to offset the results of sleep loss, especially for interns or first-year residents. 

Residency programs recently have been experimenting with shorter call schedules.

 

Catching Zzs

Working the night shift demands a disciplined sleep schedule, said Nat deQuillfeldt, MD, a Denver Health chief resident in the University of Colorado’s internal medicine residency program.

“When I was on night admissions, I was very strict about going to sleep at 8 AM and waking at 3 PM every single day. It can be very tempting to try to stay up and spend time with loved ones, but my husband and I both prioritized my physical well-being for those weeks,” said deQuillfeldt, a PGY-4 resident. “It was especially challenging for me because I had to commute about 50 minutes each way and without such a rigid schedule I would have struggled to be on time.”

deQuillfeldt doesn’t have young children at home, a noisy community, or other distractions to interrupt sleep during the day. But it was still difficult for her to sleep while the sun was out. “I used an eye mask and ear plugs but definitely woke up more often than I would at night.”

Blackout curtains may have helped, she added.

“Without adequate sleep, your clinical thinking is not as sharp. When emergencies happen overnight, you’re often the first person to arrive and need to be able to make rapid, accurate assessments and decisions.”

As a chief resident, she chooses never to sleep during night shifts.

“I personally didn’t want to leave my interns alone or make them feel like they were waking me up or bothering me if they needed help, and I also didn’t want to be groggy in case of a rapid response or code blue.”

But napping on night shift is definitely possible, deQuillfeldt said. Between following up on overnight lab results, answering nurses’ questions, and responding to emergencies, she found downtime on night shift to eat and hydrate. She believes others can catch an hour or 2 of shut eye, even if they work in the intensive care unit, or 3-4 hours on rare quiet nights.

Vater suggests residents transitioning from daytime work to night shift prepare by trying to catch an afternoon nap, staying up later the night before the change, and banking sleep hours in advance.

When he knows he’s starting night shifts, Apurva Popat, MD, said he tries to go to sleep an hour or so later nights before to avoid becoming sleep deprived. The chief resident of internal medicine at Marshfield Clinic Health System in Marshfield, Wisconsin, doesn’t recommend sleeping during the night shift.

“I typically try not to sleep, even if I have time, so I can go home and sleep later in the morning,” said Popat, a PGY-3 resident.

To help him snooze, he uses blackout curtains and a fan to block out noise. His wife, a first-year internal medicine intern, often works a different shift, so she helps set up his sleeping environment and he reciprocates when it’s her turn for night shifts.

Some interns may need to catch a 20- to 30-minute nap on the first night shift, he said.

Popat also seeks out brighter areas of the hospital, such as the emergency department, where there are more people and colleagues to keep him alert.

 

Bypass Vending Machines

Lack of sleep makes it even more difficult to eat healthy on night shift, said Vater, who advises residents about wellness issues at IU and on social media.

“When you are sleep deprived, when you do not get enough sleep, you eat but you don’t feel full,” she said. “It’s hard to eat well on night shift. It’s harder if you go to the break room and there’s candy and junk food.”

Vater said that, as a resident, she brought a lunch bag to the hospital during night shifts. “I never had time to prep food, so I’d bring a whole apple, a whole orange, a whole avocado or nuts. It allowed me to eat more fruits and vegetables than I normally would.”

She advises caution when considering coffee to stay awake, especially after about 9 PM, which could interfere with sleep residents need later when they finish their shifts. Caffeine may help in the moment, but it prevents deep sleep, Vater said. So when residents finally get sleep after their shifts, they may wake up feeling tired, she said.

To avoid sleepiness, Popat brings protein shakes with him to night shifts. They stave off sugar spikes and keep his energy level high, he said. He might have a protein shake and fruit before he leaves home and carry his vegetarian dinner with him to eat in the early morning hours when the hospital is calm.

Eating small and frequent meals also helps ward off sleepiness, deQuillfeldt said.

 

Take the Stairs

Trying to stay healthy on night shifts, Vater also checked on patients by taking the stairs. “I’d set the timer on my phone for 30 minutes and if I got paged at 15, I’d pause the timer and reset it if I had a moment later. I’d get at least 30 minutes in, although not always continuous. I think some activity is better than none.”

Vater said her hospital had a gym, but it wasn’t practical for her because it was further away from where she worked. “Sometimes my coresidents would be more creative, and we would do squats.”

Popat tries to lift weights 2 hours before his night shift, but he also takes short walks between patients’ rooms in the early morning hours when it’s quietest. He also promotes deep breathing to stay alert.

 

Ask for a Ride

Vater urges those coming off night shifts, especially those transitioning for the first time from daytime rotations, not to drive if they’re exhausted. “Get an Uber. ... Make sure you get a ride home.”

The CU residency program covers the cost of a ridesharing service when doctors-in-training are too tired to drive home, deQuillfeldt said. “We really try to encourage people to use this to reduce the risk of car accidents.”

 

Promoting Mental Health

The residency program also links residents with primary care and mental health services. People who really struggle with shift work sleep disorder may qualify for medications to help them stay awake overnight, in addition to sleep hygiene apps and sleep aides.

“Night shifts can put a strain on mental health, especially when you’re only working, eating, and sleeping and not spending any time with family and friends,” deQuillfeldt said. “My husband works late afternoons, so we often would go weeks seeing each other for 15-20 minutes a day.”

“Sleeping when the sun is out often leads to a lack of light exposure which can compound the problem. Seeking mental health support early is really important to avoiding burnout,” she said.

She also recommended planning a fun weekend activity, trip, or celebration with friends or family after night shifts end “so you have something to look forward to…It’s so important to have a light at the end of the tunnel, which will allow you to enjoy the sense of accomplishment even more.”

For more advice on the subject, consider the American Medical Association guide to managing sleep deprivation in residency or Laura Vater’s tips for night shifts.

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

Laura Vater remembers sneaking into her home after 12-hour night shifts during medical training while her husband distracted their toddler. The stealthy tag-teaming effort helped her get enough undisturbed sleep before returning to an Indiana University hospital the following night to repeat the pattern.

“He would pretend to take out the trash when I pulled in,” said Vater, MD, now a gastrointestinal oncologist and assistant professor of medicine at IU Health Simon Cancer Center in Indianapolis. “I would sneak in so she [their daughter] wouldn’t see me, and then he would go back in.”

For Vater, prioritizing sleep during the day to combat sleep deprivation common among doctors-in-training on night shifts required enlisting a supportive spouse. It’s just one of the tips she and a few chief residents shared with this news organization for staying sharp and healthy during overnight rotations.

While the pace of patient rounds may slow from the frenetic daytime rush, training as a doctor after the sun goes down can be quite challenging for residents, they told this news organization. From sleep deprivation working while the rest of us slumbers to the after-effects of late-night caffeine, learning to manage night rotations requires a balance of preparation and attention to personal health while caring for others, the residents and adviser said.

Compromised sleep is one of the biggest hurdles residents have to overcome. Sleep loss comes with risks to cardiovascular disease and type 2 diabetes, among other heath conditions, according to Medscape Medical News reports. And night shift workers  who sleep 6 or fewer hours a night have at least one sleep disorder.

Sleep deprivation associated with overnight call schedules also can worsen a resident’s mood and motivation while impairing their judgment, leading to medical errors, according to a new study published in JAMA Open Network. The study proposed shorter consecutive night shifts and naps as ways to offset the results of sleep loss, especially for interns or first-year residents. 

Residency programs recently have been experimenting with shorter call schedules.

 

Catching Zzs

Working the night shift demands a disciplined sleep schedule, said Nat deQuillfeldt, MD, a Denver Health chief resident in the University of Colorado’s internal medicine residency program.

“When I was on night admissions, I was very strict about going to sleep at 8 AM and waking at 3 PM every single day. It can be very tempting to try to stay up and spend time with loved ones, but my husband and I both prioritized my physical well-being for those weeks,” said deQuillfeldt, a PGY-4 resident. “It was especially challenging for me because I had to commute about 50 minutes each way and without such a rigid schedule I would have struggled to be on time.”

deQuillfeldt doesn’t have young children at home, a noisy community, or other distractions to interrupt sleep during the day. But it was still difficult for her to sleep while the sun was out. “I used an eye mask and ear plugs but definitely woke up more often than I would at night.”

Blackout curtains may have helped, she added.

“Without adequate sleep, your clinical thinking is not as sharp. When emergencies happen overnight, you’re often the first person to arrive and need to be able to make rapid, accurate assessments and decisions.”

As a chief resident, she chooses never to sleep during night shifts.

“I personally didn’t want to leave my interns alone or make them feel like they were waking me up or bothering me if they needed help, and I also didn’t want to be groggy in case of a rapid response or code blue.”

But napping on night shift is definitely possible, deQuillfeldt said. Between following up on overnight lab results, answering nurses’ questions, and responding to emergencies, she found downtime on night shift to eat and hydrate. She believes others can catch an hour or 2 of shut eye, even if they work in the intensive care unit, or 3-4 hours on rare quiet nights.

Vater suggests residents transitioning from daytime work to night shift prepare by trying to catch an afternoon nap, staying up later the night before the change, and banking sleep hours in advance.

When he knows he’s starting night shifts, Apurva Popat, MD, said he tries to go to sleep an hour or so later nights before to avoid becoming sleep deprived. The chief resident of internal medicine at Marshfield Clinic Health System in Marshfield, Wisconsin, doesn’t recommend sleeping during the night shift.

“I typically try not to sleep, even if I have time, so I can go home and sleep later in the morning,” said Popat, a PGY-3 resident.

To help him snooze, he uses blackout curtains and a fan to block out noise. His wife, a first-year internal medicine intern, often works a different shift, so she helps set up his sleeping environment and he reciprocates when it’s her turn for night shifts.

Some interns may need to catch a 20- to 30-minute nap on the first night shift, he said.

Popat also seeks out brighter areas of the hospital, such as the emergency department, where there are more people and colleagues to keep him alert.

 

Bypass Vending Machines

Lack of sleep makes it even more difficult to eat healthy on night shift, said Vater, who advises residents about wellness issues at IU and on social media.

“When you are sleep deprived, when you do not get enough sleep, you eat but you don’t feel full,” she said. “It’s hard to eat well on night shift. It’s harder if you go to the break room and there’s candy and junk food.”

Vater said that, as a resident, she brought a lunch bag to the hospital during night shifts. “I never had time to prep food, so I’d bring a whole apple, a whole orange, a whole avocado or nuts. It allowed me to eat more fruits and vegetables than I normally would.”

She advises caution when considering coffee to stay awake, especially after about 9 PM, which could interfere with sleep residents need later when they finish their shifts. Caffeine may help in the moment, but it prevents deep sleep, Vater said. So when residents finally get sleep after their shifts, they may wake up feeling tired, she said.

To avoid sleepiness, Popat brings protein shakes with him to night shifts. They stave off sugar spikes and keep his energy level high, he said. He might have a protein shake and fruit before he leaves home and carry his vegetarian dinner with him to eat in the early morning hours when the hospital is calm.

Eating small and frequent meals also helps ward off sleepiness, deQuillfeldt said.

 

Take the Stairs

Trying to stay healthy on night shifts, Vater also checked on patients by taking the stairs. “I’d set the timer on my phone for 30 minutes and if I got paged at 15, I’d pause the timer and reset it if I had a moment later. I’d get at least 30 minutes in, although not always continuous. I think some activity is better than none.”

Vater said her hospital had a gym, but it wasn’t practical for her because it was further away from where she worked. “Sometimes my coresidents would be more creative, and we would do squats.”

Popat tries to lift weights 2 hours before his night shift, but he also takes short walks between patients’ rooms in the early morning hours when it’s quietest. He also promotes deep breathing to stay alert.

 

Ask for a Ride

Vater urges those coming off night shifts, especially those transitioning for the first time from daytime rotations, not to drive if they’re exhausted. “Get an Uber. ... Make sure you get a ride home.”

The CU residency program covers the cost of a ridesharing service when doctors-in-training are too tired to drive home, deQuillfeldt said. “We really try to encourage people to use this to reduce the risk of car accidents.”

 

Promoting Mental Health

The residency program also links residents with primary care and mental health services. People who really struggle with shift work sleep disorder may qualify for medications to help them stay awake overnight, in addition to sleep hygiene apps and sleep aides.

“Night shifts can put a strain on mental health, especially when you’re only working, eating, and sleeping and not spending any time with family and friends,” deQuillfeldt said. “My husband works late afternoons, so we often would go weeks seeing each other for 15-20 minutes a day.”

“Sleeping when the sun is out often leads to a lack of light exposure which can compound the problem. Seeking mental health support early is really important to avoiding burnout,” she said.

She also recommended planning a fun weekend activity, trip, or celebration with friends or family after night shifts end “so you have something to look forward to…It’s so important to have a light at the end of the tunnel, which will allow you to enjoy the sense of accomplishment even more.”

For more advice on the subject, consider the American Medical Association guide to managing sleep deprivation in residency or Laura Vater’s tips for night shifts.

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

Laura Vater remembers sneaking into her home after 12-hour night shifts during medical training while her husband distracted their toddler. The stealthy tag-teaming effort helped her get enough undisturbed sleep before returning to an Indiana University hospital the following night to repeat the pattern.

“He would pretend to take out the trash when I pulled in,” said Vater, MD, now a gastrointestinal oncologist and assistant professor of medicine at IU Health Simon Cancer Center in Indianapolis. “I would sneak in so she [their daughter] wouldn’t see me, and then he would go back in.”

For Vater, prioritizing sleep during the day to combat sleep deprivation common among doctors-in-training on night shifts required enlisting a supportive spouse. It’s just one of the tips she and a few chief residents shared with this news organization for staying sharp and healthy during overnight rotations.

While the pace of patient rounds may slow from the frenetic daytime rush, training as a doctor after the sun goes down can be quite challenging for residents, they told this news organization. From sleep deprivation working while the rest of us slumbers to the after-effects of late-night caffeine, learning to manage night rotations requires a balance of preparation and attention to personal health while caring for others, the residents and adviser said.

Compromised sleep is one of the biggest hurdles residents have to overcome. Sleep loss comes with risks to cardiovascular disease and type 2 diabetes, among other heath conditions, according to Medscape Medical News reports. And night shift workers  who sleep 6 or fewer hours a night have at least one sleep disorder.

Sleep deprivation associated with overnight call schedules also can worsen a resident’s mood and motivation while impairing their judgment, leading to medical errors, according to a new study published in JAMA Open Network. The study proposed shorter consecutive night shifts and naps as ways to offset the results of sleep loss, especially for interns or first-year residents. 

Residency programs recently have been experimenting with shorter call schedules.

 

Catching Zzs

Working the night shift demands a disciplined sleep schedule, said Nat deQuillfeldt, MD, a Denver Health chief resident in the University of Colorado’s internal medicine residency program.

“When I was on night admissions, I was very strict about going to sleep at 8 AM and waking at 3 PM every single day. It can be very tempting to try to stay up and spend time with loved ones, but my husband and I both prioritized my physical well-being for those weeks,” said deQuillfeldt, a PGY-4 resident. “It was especially challenging for me because I had to commute about 50 minutes each way and without such a rigid schedule I would have struggled to be on time.”

deQuillfeldt doesn’t have young children at home, a noisy community, or other distractions to interrupt sleep during the day. But it was still difficult for her to sleep while the sun was out. “I used an eye mask and ear plugs but definitely woke up more often than I would at night.”

Blackout curtains may have helped, she added.

“Without adequate sleep, your clinical thinking is not as sharp. When emergencies happen overnight, you’re often the first person to arrive and need to be able to make rapid, accurate assessments and decisions.”

As a chief resident, she chooses never to sleep during night shifts.

“I personally didn’t want to leave my interns alone or make them feel like they were waking me up or bothering me if they needed help, and I also didn’t want to be groggy in case of a rapid response or code blue.”

But napping on night shift is definitely possible, deQuillfeldt said. Between following up on overnight lab results, answering nurses’ questions, and responding to emergencies, she found downtime on night shift to eat and hydrate. She believes others can catch an hour or 2 of shut eye, even if they work in the intensive care unit, or 3-4 hours on rare quiet nights.

Vater suggests residents transitioning from daytime work to night shift prepare by trying to catch an afternoon nap, staying up later the night before the change, and banking sleep hours in advance.

When he knows he’s starting night shifts, Apurva Popat, MD, said he tries to go to sleep an hour or so later nights before to avoid becoming sleep deprived. The chief resident of internal medicine at Marshfield Clinic Health System in Marshfield, Wisconsin, doesn’t recommend sleeping during the night shift.

“I typically try not to sleep, even if I have time, so I can go home and sleep later in the morning,” said Popat, a PGY-3 resident.

To help him snooze, he uses blackout curtains and a fan to block out noise. His wife, a first-year internal medicine intern, often works a different shift, so she helps set up his sleeping environment and he reciprocates when it’s her turn for night shifts.

Some interns may need to catch a 20- to 30-minute nap on the first night shift, he said.

Popat also seeks out brighter areas of the hospital, such as the emergency department, where there are more people and colleagues to keep him alert.

 

Bypass Vending Machines

Lack of sleep makes it even more difficult to eat healthy on night shift, said Vater, who advises residents about wellness issues at IU and on social media.

“When you are sleep deprived, when you do not get enough sleep, you eat but you don’t feel full,” she said. “It’s hard to eat well on night shift. It’s harder if you go to the break room and there’s candy and junk food.”

Vater said that, as a resident, she brought a lunch bag to the hospital during night shifts. “I never had time to prep food, so I’d bring a whole apple, a whole orange, a whole avocado or nuts. It allowed me to eat more fruits and vegetables than I normally would.”

She advises caution when considering coffee to stay awake, especially after about 9 PM, which could interfere with sleep residents need later when they finish their shifts. Caffeine may help in the moment, but it prevents deep sleep, Vater said. So when residents finally get sleep after their shifts, they may wake up feeling tired, she said.

To avoid sleepiness, Popat brings protein shakes with him to night shifts. They stave off sugar spikes and keep his energy level high, he said. He might have a protein shake and fruit before he leaves home and carry his vegetarian dinner with him to eat in the early morning hours when the hospital is calm.

Eating small and frequent meals also helps ward off sleepiness, deQuillfeldt said.

 

Take the Stairs

Trying to stay healthy on night shifts, Vater also checked on patients by taking the stairs. “I’d set the timer on my phone for 30 minutes and if I got paged at 15, I’d pause the timer and reset it if I had a moment later. I’d get at least 30 minutes in, although not always continuous. I think some activity is better than none.”

Vater said her hospital had a gym, but it wasn’t practical for her because it was further away from where she worked. “Sometimes my coresidents would be more creative, and we would do squats.”

Popat tries to lift weights 2 hours before his night shift, but he also takes short walks between patients’ rooms in the early morning hours when it’s quietest. He also promotes deep breathing to stay alert.

 

Ask for a Ride

Vater urges those coming off night shifts, especially those transitioning for the first time from daytime rotations, not to drive if they’re exhausted. “Get an Uber. ... Make sure you get a ride home.”

The CU residency program covers the cost of a ridesharing service when doctors-in-training are too tired to drive home, deQuillfeldt said. “We really try to encourage people to use this to reduce the risk of car accidents.”

 

Promoting Mental Health

The residency program also links residents with primary care and mental health services. People who really struggle with shift work sleep disorder may qualify for medications to help them stay awake overnight, in addition to sleep hygiene apps and sleep aides.

“Night shifts can put a strain on mental health, especially when you’re only working, eating, and sleeping and not spending any time with family and friends,” deQuillfeldt said. “My husband works late afternoons, so we often would go weeks seeing each other for 15-20 minutes a day.”

“Sleeping when the sun is out often leads to a lack of light exposure which can compound the problem. Seeking mental health support early is really important to avoiding burnout,” she said.

She also recommended planning a fun weekend activity, trip, or celebration with friends or family after night shifts end “so you have something to look forward to…It’s so important to have a light at the end of the tunnel, which will allow you to enjoy the sense of accomplishment even more.”

For more advice on the subject, consider the American Medical Association guide to managing sleep deprivation in residency or Laura Vater’s tips for night shifts.

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

Children aged 5-12 years with concussion have similar recovery trajectories, regardless of whether the injury is linked to sports or to other causes, such as falls, new data indicated. 

“With that result, it means we don’t need to change management protocols” depending on the cause of the concussion, study author Andrée-Anne Ledoux, PhD, a scientist at Children’s Hospital of Eastern Ontario Research Institute in Ottawa, Ontario, Canada, said in an interview. “That’s kind of good news. We’re applying the right management protocols with them.”

The data were published on December 4 in JAMA Network Open.

 

Secondary Analysis

The results stem from a planned secondary analysis of the prospective Predicting and Preventing Postconcussive Problems in Pediatrics study. Conducted from August 2013 to June 2015 at nine pediatric emergency departments in Canada, it included children of different ages (5 to < 18 years), genders, demographic characteristics, and comorbidities. All participants had a concussion.

The secondary analysis focused on study participants who were aged 5-12 years and had presented within 48 hours of injury. The primary outcome was symptom change, which was defined as current ratings minus preinjury ratings, across time (1, 2, 4, 8, and 12 weeks), measured using the Post-Concussion Symptom Inventory.

No significant differences in postinjury recovery curves were found between participants with sport-related concussions (SRC) and those with non-SRC. The latter injuries resulted from causes such as falls and objects dropped on heads. SRC and non-SRC showed a nonlinear association with time, with symptoms decreasing over time.

Perhaps surprisingly, the researchers also reported a higher rate of persisting symptoms after concussion (PSAC) following limited contact sports than following contact sports such as hockey, soccer, rugby, lacrosse, and football. Limited contact sports include activities such as bicycling, horseback riding, tobogganing, gymnastics, and cheerleading.

This finding suggests that the management of SRC may not require distinct strategies based on sports classification, the researchers wrote. “Instead, it may be more appropriate for clinicians to consider the specific dynamics of the activity, such as velocity and risk of falls from heights. This nuanced perspective can aid in assessing the likelihood of persisting symptoms.” The researchers urged more investigation of this question. “A larger sample with more information on injury height and velocity would be required to confirm whether an association exists.”

In addition, the researchers cited guidelines that include a recommendation for a gradual return to low to moderate physical and cognitive activity starting 24-48 hours after a concussion at a level that does not result in recurrence or exacerbation of symptoms.

“Children do need to return to their lives. They need to return to school,” said Ledoux. “They can have accommodations while they return to school, but just returning to school has huge benefits because you’re reintegrating the child into their typical lifestyle and socialization as well.”

A potential limitation of the study was its reliance on participants who had been seen in emergency departments and thus may have been experiencing more intense symptoms than those seen elsewhere.

The researchers also excluded cases of concussion resulting from assaults and motor vehicle crashes. This decision may explain why they didn’t reproduce the previous observation that patients with SRC tended to recover faster than those with concussions from other causes.

Injuries resulting from assaults and motor vehicle crashes can involve damage beyond concussions, Ledoux said. Including these cases would not allow for an apples-to-apples comparison of SRC and non-SRC.

 

‘Don’t Cocoon Kids’

The authors of an accompanying editorial wrote that the researchers had done “a beautiful job highlighting this important nuance.” Noncontact sports with seemingly little risk “actually carry substantial risks when one imagines the high-impact forces that can occur with a fall from height, albeit rare,” Scott Zuckerman, MD, MPH, assistant professor of neurological surgery at Vanderbilt University Medical Center, Nashville, Tennessee, and colleagues wrote.

The new analysis suggests a need to rethink a “somewhat archaic way of classifying sport risk, which may oversimplify how we categorize risk of brain and spine injuries.”

The commentary also noted how the researchers used the term PSAC to describe lingering symptoms instead of more widely used terms like “persistent postconcussive symptoms” or “postconcussive syndrome.”

“These traditional terms often connote a permanent syndrome or assumption that the concussion itself is solely responsible for 100% of symptoms, which can be harmful to a patient’s recovery,” the editorialists wrote. “Conversely, PSAC offers room for the clinician to discuss how other causes may be maintaining, magnifying, or mimicking concussion symptoms.”

Commenting on the findings, Richard Figler, MD, an orthopedic surgeon at the Cleveland Clinic, Cleveland, praised the researchers for addressing concussion in younger children, a field in which little research has been conducted. The research supports the current approaches to treatment. The approach has shifted toward easing children quickly and safely back into normal routines. “We don’t cocoon kids. We don’t send them to dark rooms,” Figler added.

He also commended the researchers’ decision to examine data about concussions linked to limited contact sports. In contact sports, participants may be more likely to anticipate and prepare for a hit. That’s not the case with injuries sustained in limited contact sports.

“Dodgeball is basically a sucker punch. That’s why these kids have so many concussions,” said Figler. “They typically don’t see the ball coming, or they can’t get out of the way, and they can’t tense themselves to take that blow.”

The Predicting and Preventing Postconcussive Problems in Pediatrics study was funded by the Canadian Institutes of Health Research and the Canadian Institutes of Health Research-Ontario Neurotrauma Foundation Mild Traumatic Brain Injury Team. Ledoux reported receiving grants from the Children’s Hospital of Eastern Ontario Foundation, Ontario Brain Institute, and University of Ottawa Brain and Mind Research Institute. She received nonfinancial support from Mobio Interactive outside the submitted work. Zuckerman reported receiving personal fees from the National Football League and Medtronic outside the submitted work. Figler had no relevant financial disclosures.

A version of this article appeared on Medscape.com.

Children aged 5-12 years with concussion have similar recovery trajectories, regardless of whether the injury is linked to sports or to other causes, such as falls, new data indicated. 

“With that result, it means we don’t need to change management protocols” depending on the cause of the concussion, study author Andrée-Anne Ledoux, PhD, a scientist at Children’s Hospital of Eastern Ontario Research Institute in Ottawa, Ontario, Canada, said in an interview. “That’s kind of good news. We’re applying the right management protocols with them.”

The data were published on December 4 in JAMA Network Open.

 

Secondary Analysis

The results stem from a planned secondary analysis of the prospective Predicting and Preventing Postconcussive Problems in Pediatrics study. Conducted from August 2013 to June 2015 at nine pediatric emergency departments in Canada, it included children of different ages (5 to < 18 years), genders, demographic characteristics, and comorbidities. All participants had a concussion.

The secondary analysis focused on study participants who were aged 5-12 years and had presented within 48 hours of injury. The primary outcome was symptom change, which was defined as current ratings minus preinjury ratings, across time (1, 2, 4, 8, and 12 weeks), measured using the Post-Concussion Symptom Inventory.

No significant differences in postinjury recovery curves were found between participants with sport-related concussions (SRC) and those with non-SRC. The latter injuries resulted from causes such as falls and objects dropped on heads. SRC and non-SRC showed a nonlinear association with time, with symptoms decreasing over time.

Perhaps surprisingly, the researchers also reported a higher rate of persisting symptoms after concussion (PSAC) following limited contact sports than following contact sports such as hockey, soccer, rugby, lacrosse, and football. Limited contact sports include activities such as bicycling, horseback riding, tobogganing, gymnastics, and cheerleading.

This finding suggests that the management of SRC may not require distinct strategies based on sports classification, the researchers wrote. “Instead, it may be more appropriate for clinicians to consider the specific dynamics of the activity, such as velocity and risk of falls from heights. This nuanced perspective can aid in assessing the likelihood of persisting symptoms.” The researchers urged more investigation of this question. “A larger sample with more information on injury height and velocity would be required to confirm whether an association exists.”

In addition, the researchers cited guidelines that include a recommendation for a gradual return to low to moderate physical and cognitive activity starting 24-48 hours after a concussion at a level that does not result in recurrence or exacerbation of symptoms.

“Children do need to return to their lives. They need to return to school,” said Ledoux. “They can have accommodations while they return to school, but just returning to school has huge benefits because you’re reintegrating the child into their typical lifestyle and socialization as well.”

A potential limitation of the study was its reliance on participants who had been seen in emergency departments and thus may have been experiencing more intense symptoms than those seen elsewhere.

The researchers also excluded cases of concussion resulting from assaults and motor vehicle crashes. This decision may explain why they didn’t reproduce the previous observation that patients with SRC tended to recover faster than those with concussions from other causes.

Injuries resulting from assaults and motor vehicle crashes can involve damage beyond concussions, Ledoux said. Including these cases would not allow for an apples-to-apples comparison of SRC and non-SRC.

 

‘Don’t Cocoon Kids’

The authors of an accompanying editorial wrote that the researchers had done “a beautiful job highlighting this important nuance.” Noncontact sports with seemingly little risk “actually carry substantial risks when one imagines the high-impact forces that can occur with a fall from height, albeit rare,” Scott Zuckerman, MD, MPH, assistant professor of neurological surgery at Vanderbilt University Medical Center, Nashville, Tennessee, and colleagues wrote.

The new analysis suggests a need to rethink a “somewhat archaic way of classifying sport risk, which may oversimplify how we categorize risk of brain and spine injuries.”

The commentary also noted how the researchers used the term PSAC to describe lingering symptoms instead of more widely used terms like “persistent postconcussive symptoms” or “postconcussive syndrome.”

“These traditional terms often connote a permanent syndrome or assumption that the concussion itself is solely responsible for 100% of symptoms, which can be harmful to a patient’s recovery,” the editorialists wrote. “Conversely, PSAC offers room for the clinician to discuss how other causes may be maintaining, magnifying, or mimicking concussion symptoms.”

Commenting on the findings, Richard Figler, MD, an orthopedic surgeon at the Cleveland Clinic, Cleveland, praised the researchers for addressing concussion in younger children, a field in which little research has been conducted. The research supports the current approaches to treatment. The approach has shifted toward easing children quickly and safely back into normal routines. “We don’t cocoon kids. We don’t send them to dark rooms,” Figler added.

He also commended the researchers’ decision to examine data about concussions linked to limited contact sports. In contact sports, participants may be more likely to anticipate and prepare for a hit. That’s not the case with injuries sustained in limited contact sports.

“Dodgeball is basically a sucker punch. That’s why these kids have so many concussions,” said Figler. “They typically don’t see the ball coming, or they can’t get out of the way, and they can’t tense themselves to take that blow.”

The Predicting and Preventing Postconcussive Problems in Pediatrics study was funded by the Canadian Institutes of Health Research and the Canadian Institutes of Health Research-Ontario Neurotrauma Foundation Mild Traumatic Brain Injury Team. Ledoux reported receiving grants from the Children’s Hospital of Eastern Ontario Foundation, Ontario Brain Institute, and University of Ottawa Brain and Mind Research Institute. She received nonfinancial support from Mobio Interactive outside the submitted work. Zuckerman reported receiving personal fees from the National Football League and Medtronic outside the submitted work. Figler had no relevant financial disclosures.

A version of this article appeared on Medscape.com.

Children aged 5-12 years with concussion have similar recovery trajectories, regardless of whether the injury is linked to sports or to other causes, such as falls, new data indicated. 

“With that result, it means we don’t need to change management protocols” depending on the cause of the concussion, study author Andrée-Anne Ledoux, PhD, a scientist at Children’s Hospital of Eastern Ontario Research Institute in Ottawa, Ontario, Canada, said in an interview. “That’s kind of good news. We’re applying the right management protocols with them.”

The data were published on December 4 in JAMA Network Open.

 

Secondary Analysis

The results stem from a planned secondary analysis of the prospective Predicting and Preventing Postconcussive Problems in Pediatrics study. Conducted from August 2013 to June 2015 at nine pediatric emergency departments in Canada, it included children of different ages (5 to < 18 years), genders, demographic characteristics, and comorbidities. All participants had a concussion.

The secondary analysis focused on study participants who were aged 5-12 years and had presented within 48 hours of injury. The primary outcome was symptom change, which was defined as current ratings minus preinjury ratings, across time (1, 2, 4, 8, and 12 weeks), measured using the Post-Concussion Symptom Inventory.

No significant differences in postinjury recovery curves were found between participants with sport-related concussions (SRC) and those with non-SRC. The latter injuries resulted from causes such as falls and objects dropped on heads. SRC and non-SRC showed a nonlinear association with time, with symptoms decreasing over time.

Perhaps surprisingly, the researchers also reported a higher rate of persisting symptoms after concussion (PSAC) following limited contact sports than following contact sports such as hockey, soccer, rugby, lacrosse, and football. Limited contact sports include activities such as bicycling, horseback riding, tobogganing, gymnastics, and cheerleading.

This finding suggests that the management of SRC may not require distinct strategies based on sports classification, the researchers wrote. “Instead, it may be more appropriate for clinicians to consider the specific dynamics of the activity, such as velocity and risk of falls from heights. This nuanced perspective can aid in assessing the likelihood of persisting symptoms.” The researchers urged more investigation of this question. “A larger sample with more information on injury height and velocity would be required to confirm whether an association exists.”

In addition, the researchers cited guidelines that include a recommendation for a gradual return to low to moderate physical and cognitive activity starting 24-48 hours after a concussion at a level that does not result in recurrence or exacerbation of symptoms.

“Children do need to return to their lives. They need to return to school,” said Ledoux. “They can have accommodations while they return to school, but just returning to school has huge benefits because you’re reintegrating the child into their typical lifestyle and socialization as well.”

A potential limitation of the study was its reliance on participants who had been seen in emergency departments and thus may have been experiencing more intense symptoms than those seen elsewhere.

The researchers also excluded cases of concussion resulting from assaults and motor vehicle crashes. This decision may explain why they didn’t reproduce the previous observation that patients with SRC tended to recover faster than those with concussions from other causes.

Injuries resulting from assaults and motor vehicle crashes can involve damage beyond concussions, Ledoux said. Including these cases would not allow for an apples-to-apples comparison of SRC and non-SRC.

 

‘Don’t Cocoon Kids’

The authors of an accompanying editorial wrote that the researchers had done “a beautiful job highlighting this important nuance.” Noncontact sports with seemingly little risk “actually carry substantial risks when one imagines the high-impact forces that can occur with a fall from height, albeit rare,” Scott Zuckerman, MD, MPH, assistant professor of neurological surgery at Vanderbilt University Medical Center, Nashville, Tennessee, and colleagues wrote.

The new analysis suggests a need to rethink a “somewhat archaic way of classifying sport risk, which may oversimplify how we categorize risk of brain and spine injuries.”

The commentary also noted how the researchers used the term PSAC to describe lingering symptoms instead of more widely used terms like “persistent postconcussive symptoms” or “postconcussive syndrome.”

“These traditional terms often connote a permanent syndrome or assumption that the concussion itself is solely responsible for 100% of symptoms, which can be harmful to a patient’s recovery,” the editorialists wrote. “Conversely, PSAC offers room for the clinician to discuss how other causes may be maintaining, magnifying, or mimicking concussion symptoms.”

Commenting on the findings, Richard Figler, MD, an orthopedic surgeon at the Cleveland Clinic, Cleveland, praised the researchers for addressing concussion in younger children, a field in which little research has been conducted. The research supports the current approaches to treatment. The approach has shifted toward easing children quickly and safely back into normal routines. “We don’t cocoon kids. We don’t send them to dark rooms,” Figler added.

He also commended the researchers’ decision to examine data about concussions linked to limited contact sports. In contact sports, participants may be more likely to anticipate and prepare for a hit. That’s not the case with injuries sustained in limited contact sports.

“Dodgeball is basically a sucker punch. That’s why these kids have so many concussions,” said Figler. “They typically don’t see the ball coming, or they can’t get out of the way, and they can’t tense themselves to take that blow.”

The Predicting and Preventing Postconcussive Problems in Pediatrics study was funded by the Canadian Institutes of Health Research and the Canadian Institutes of Health Research-Ontario Neurotrauma Foundation Mild Traumatic Brain Injury Team. Ledoux reported receiving grants from the Children’s Hospital of Eastern Ontario Foundation, Ontario Brain Institute, and University of Ottawa Brain and Mind Research Institute. She received nonfinancial support from Mobio Interactive outside the submitted work. Zuckerman reported receiving personal fees from the National Football League and Medtronic outside the submitted work. Figler had no relevant financial disclosures.

A version of this article appeared on Medscape.com.

While fewer than 10% of US physicians are unionized, the number of official union drives among private-sector doctors have skyrocketed in the last 2 years, compared with 2 decades prior, according to a new study. 

Researchers counted 21 union drives in 2023 and 12 in the first 5 months of 2024, compared with 0-6 drives each year between 2000 and 2022. 

If the 2023 and 2024 drives succeed, unions will represent 3523 new physicians — nearly equal to the 3541 doctors who sought unionization between 2000 and 2022.

“We were able to document a significant uptick in union petitions and success in certification drives,” said corresponding author Hayden Rooke-Ley, JD, of the Center for Advancing Health Policy Through Research, Brown University School of Public Health, Providence, Rhode Island. “We were surprised to see such a marked shift in 2023.”

About 72,000 physicians, an estimated 8% of all US doctors, are covered by unions, including some in the public sector. Physicians who are self-employed, now comprising less than a fifth of all doctors, are not eligible to join labor unions.

The study authors launched their research to better understand trends in physician unionization in light of high-profile union drives, especially among residents. Rooke-Ley said: “We suspected that declining morale and increased corporate employment for physicians were leading them to consider unionization.”

The researchers gathered data from the National Labor Relations Board about union drives by potential bargaining units that included physicians. From 2000 to 2022, 44 union petitions were filed. The number jumped to 33 from 2023-2024. 

 

“Tip of the Iceberg”

“This is the tip of the iceberg,” said ethicist Joseph F. Kras, MD, DDS, MA, an associate professor of anesthesiology at Washington University in St. Louis, Missouri, and corresponding author of a recent Anesthesia & Analgesia report about physician unionization.

“We are independent by nature,” Kras said. “But when you put us in an employed environment and start treating us as widgets, then we will act like employees of Amazon, Starbucks, and other companies and join together to push back against the increasing emphasis on profit over all at the expense of our independent judgment on what’s best for the patient.”

Of the 66 unionization efforts between 2000 and 2024 that were decided, 62% were certified, according to the JAMA study. The drives targeted hospitals (49%), community health centers (38%), and nonhospital corporate owners (13%).

The researchers only analyzed private-sector unionization and did not include physicians who are unionized at public institutions. 

 

What’s Behind Union Drives?

Alyssa Burgart, MD, MA, an ethicist and clinical associate professor of anesthesiology and pediatrics at Stanford University in California, told this news organization that physician unionization “is a big topic with a lot of really strong opinions.” 

Many doctors wrongly assume they can’t unionize because they’re physicians, said Burgart, a coauthor of the Anesthesia & Analgesia report.

Supporters of unionization believe it’s a strategy to be “recognized not as simply as a single physician with a concern,” she said. “When you’re among clinicians who can speak as a more unified group, organizations are more likely to take that seriously.”

A union may also be able to hold employers to account in areas such as the gender wage gap, sexual harassment, and bias in hiring and firing, Burgart said. And union supporters believe they’ll make more money if they collectively bargain. 

Other factors driving interest in unions include “increasing physician burnout, increasing physician exhaustion, and immense frustration with the ways that private equity is influencing how physicians need to work in order to practice,” she said. 

Earlier in 2024, physicians in Delaware’s ChristianaCare health system voted 288-130 to be represented by Doctors Council/Service Employees International, according to the union. 

“We have still not been able to staff up enough to where us physicians can get back to just focusing on taking care of patients,” a unionization leader told WHYY. 

The JAMA study examined news reports regarding most of the 2023-2024 union drives and found that supporters claimed they were motivated by working conditions (85%), lack of voice in management (81%), patient care concerns (54%), and pay (4%).

 

Critics Worry They’ll Lose Pay Because of Unions

Skeptics of unionization worry about whether “I’m going to be required to stand by some union stance that is actually out of alignment with my values as a physician,” Burgart said. And, she said, critics such as highly paid surgeons fear that adjustments to salaries because of union contracts could cause them to lose income.

In regard to compensation, a 2024 study surveyed unionized residents — along with faculty and staff — at general surgery programs and found evidence that unionization didn’t improve resident well-being or benefits, although it “provided a mechanism for resident voice and agency.”

“It is critical to study the outcomes of those who unionized to ensure that the reasons for unionizing were realized over time,” said that study’s coauthor Karl Bilimoria, MD, MS, chair of surgery at Indiana University School of Medicine, Indianapolis. “The unintended consequences of unionization must be examined along with the potential improvements.”

Rooke-Ley discloses consulting fees from the American Economic Liberties Project, National Academy of State Health Policy, and 32BJ Funds. Kras and Burgart disclose previous union membership. Bilimoria has no disclosures.

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

While fewer than 10% of US physicians are unionized, the number of official union drives among private-sector doctors have skyrocketed in the last 2 years, compared with 2 decades prior, according to a new study. 

Researchers counted 21 union drives in 2023 and 12 in the first 5 months of 2024, compared with 0-6 drives each year between 2000 and 2022. 

If the 2023 and 2024 drives succeed, unions will represent 3523 new physicians — nearly equal to the 3541 doctors who sought unionization between 2000 and 2022.

“We were able to document a significant uptick in union petitions and success in certification drives,” said corresponding author Hayden Rooke-Ley, JD, of the Center for Advancing Health Policy Through Research, Brown University School of Public Health, Providence, Rhode Island. “We were surprised to see such a marked shift in 2023.”

About 72,000 physicians, an estimated 8% of all US doctors, are covered by unions, including some in the public sector. Physicians who are self-employed, now comprising less than a fifth of all doctors, are not eligible to join labor unions.

The study authors launched their research to better understand trends in physician unionization in light of high-profile union drives, especially among residents. Rooke-Ley said: “We suspected that declining morale and increased corporate employment for physicians were leading them to consider unionization.”

The researchers gathered data from the National Labor Relations Board about union drives by potential bargaining units that included physicians. From 2000 to 2022, 44 union petitions were filed. The number jumped to 33 from 2023-2024. 

 

“Tip of the Iceberg”

“This is the tip of the iceberg,” said ethicist Joseph F. Kras, MD, DDS, MA, an associate professor of anesthesiology at Washington University in St. Louis, Missouri, and corresponding author of a recent Anesthesia & Analgesia report about physician unionization.

“We are independent by nature,” Kras said. “But when you put us in an employed environment and start treating us as widgets, then we will act like employees of Amazon, Starbucks, and other companies and join together to push back against the increasing emphasis on profit over all at the expense of our independent judgment on what’s best for the patient.”

Of the 66 unionization efforts between 2000 and 2024 that were decided, 62% were certified, according to the JAMA study. The drives targeted hospitals (49%), community health centers (38%), and nonhospital corporate owners (13%).

The researchers only analyzed private-sector unionization and did not include physicians who are unionized at public institutions. 

 

What’s Behind Union Drives?

Alyssa Burgart, MD, MA, an ethicist and clinical associate professor of anesthesiology and pediatrics at Stanford University in California, told this news organization that physician unionization “is a big topic with a lot of really strong opinions.” 

Many doctors wrongly assume they can’t unionize because they’re physicians, said Burgart, a coauthor of the Anesthesia & Analgesia report.

Supporters of unionization believe it’s a strategy to be “recognized not as simply as a single physician with a concern,” she said. “When you’re among clinicians who can speak as a more unified group, organizations are more likely to take that seriously.”

A union may also be able to hold employers to account in areas such as the gender wage gap, sexual harassment, and bias in hiring and firing, Burgart said. And union supporters believe they’ll make more money if they collectively bargain. 

Other factors driving interest in unions include “increasing physician burnout, increasing physician exhaustion, and immense frustration with the ways that private equity is influencing how physicians need to work in order to practice,” she said. 

Earlier in 2024, physicians in Delaware’s ChristianaCare health system voted 288-130 to be represented by Doctors Council/Service Employees International, according to the union. 

“We have still not been able to staff up enough to where us physicians can get back to just focusing on taking care of patients,” a unionization leader told WHYY. 

The JAMA study examined news reports regarding most of the 2023-2024 union drives and found that supporters claimed they were motivated by working conditions (85%), lack of voice in management (81%), patient care concerns (54%), and pay (4%).

 

Critics Worry They’ll Lose Pay Because of Unions

Skeptics of unionization worry about whether “I’m going to be required to stand by some union stance that is actually out of alignment with my values as a physician,” Burgart said. And, she said, critics such as highly paid surgeons fear that adjustments to salaries because of union contracts could cause them to lose income.

In regard to compensation, a 2024 study surveyed unionized residents — along with faculty and staff — at general surgery programs and found evidence that unionization didn’t improve resident well-being or benefits, although it “provided a mechanism for resident voice and agency.”

“It is critical to study the outcomes of those who unionized to ensure that the reasons for unionizing were realized over time,” said that study’s coauthor Karl Bilimoria, MD, MS, chair of surgery at Indiana University School of Medicine, Indianapolis. “The unintended consequences of unionization must be examined along with the potential improvements.”

Rooke-Ley discloses consulting fees from the American Economic Liberties Project, National Academy of State Health Policy, and 32BJ Funds. Kras and Burgart disclose previous union membership. Bilimoria has no disclosures.

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

While fewer than 10% of US physicians are unionized, the number of official union drives among private-sector doctors have skyrocketed in the last 2 years, compared with 2 decades prior, according to a new study. 

Researchers counted 21 union drives in 2023 and 12 in the first 5 months of 2024, compared with 0-6 drives each year between 2000 and 2022. 

If the 2023 and 2024 drives succeed, unions will represent 3523 new physicians — nearly equal to the 3541 doctors who sought unionization between 2000 and 2022.

“We were able to document a significant uptick in union petitions and success in certification drives,” said corresponding author Hayden Rooke-Ley, JD, of the Center for Advancing Health Policy Through Research, Brown University School of Public Health, Providence, Rhode Island. “We were surprised to see such a marked shift in 2023.”

About 72,000 physicians, an estimated 8% of all US doctors, are covered by unions, including some in the public sector. Physicians who are self-employed, now comprising less than a fifth of all doctors, are not eligible to join labor unions.

The study authors launched their research to better understand trends in physician unionization in light of high-profile union drives, especially among residents. Rooke-Ley said: “We suspected that declining morale and increased corporate employment for physicians were leading them to consider unionization.”

The researchers gathered data from the National Labor Relations Board about union drives by potential bargaining units that included physicians. From 2000 to 2022, 44 union petitions were filed. The number jumped to 33 from 2023-2024. 

 

“Tip of the Iceberg”

“This is the tip of the iceberg,” said ethicist Joseph F. Kras, MD, DDS, MA, an associate professor of anesthesiology at Washington University in St. Louis, Missouri, and corresponding author of a recent Anesthesia & Analgesia report about physician unionization.

“We are independent by nature,” Kras said. “But when you put us in an employed environment and start treating us as widgets, then we will act like employees of Amazon, Starbucks, and other companies and join together to push back against the increasing emphasis on profit over all at the expense of our independent judgment on what’s best for the patient.”

Of the 66 unionization efforts between 2000 and 2024 that were decided, 62% were certified, according to the JAMA study. The drives targeted hospitals (49%), community health centers (38%), and nonhospital corporate owners (13%).

The researchers only analyzed private-sector unionization and did not include physicians who are unionized at public institutions. 

 

What’s Behind Union Drives?

Alyssa Burgart, MD, MA, an ethicist and clinical associate professor of anesthesiology and pediatrics at Stanford University in California, told this news organization that physician unionization “is a big topic with a lot of really strong opinions.” 

Many doctors wrongly assume they can’t unionize because they’re physicians, said Burgart, a coauthor of the Anesthesia & Analgesia report.

Supporters of unionization believe it’s a strategy to be “recognized not as simply as a single physician with a concern,” she said. “When you’re among clinicians who can speak as a more unified group, organizations are more likely to take that seriously.”

A union may also be able to hold employers to account in areas such as the gender wage gap, sexual harassment, and bias in hiring and firing, Burgart said. And union supporters believe they’ll make more money if they collectively bargain. 

Other factors driving interest in unions include “increasing physician burnout, increasing physician exhaustion, and immense frustration with the ways that private equity is influencing how physicians need to work in order to practice,” she said. 

Earlier in 2024, physicians in Delaware’s ChristianaCare health system voted 288-130 to be represented by Doctors Council/Service Employees International, according to the union. 

“We have still not been able to staff up enough to where us physicians can get back to just focusing on taking care of patients,” a unionization leader told WHYY. 

The JAMA study examined news reports regarding most of the 2023-2024 union drives and found that supporters claimed they were motivated by working conditions (85%), lack of voice in management (81%), patient care concerns (54%), and pay (4%).

 

Critics Worry They’ll Lose Pay Because of Unions

Skeptics of unionization worry about whether “I’m going to be required to stand by some union stance that is actually out of alignment with my values as a physician,” Burgart said. And, she said, critics such as highly paid surgeons fear that adjustments to salaries because of union contracts could cause them to lose income.

In regard to compensation, a 2024 study surveyed unionized residents — along with faculty and staff — at general surgery programs and found evidence that unionization didn’t improve resident well-being or benefits, although it “provided a mechanism for resident voice and agency.”

“It is critical to study the outcomes of those who unionized to ensure that the reasons for unionizing were realized over time,” said that study’s coauthor Karl Bilimoria, MD, MS, chair of surgery at Indiana University School of Medicine, Indianapolis. “The unintended consequences of unionization must be examined along with the potential improvements.”

Rooke-Ley discloses consulting fees from the American Economic Liberties Project, National Academy of State Health Policy, and 32BJ Funds. Kras and Burgart disclose previous union membership. Bilimoria has no disclosures.

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