Federal Practitioner

Rashelle Bernal vaped and ended up in an induced coma for a week. She was one of almost 3,000 people who were hospitalized during 2019 and early 2020 with severe lung damage from vaping and became part of what is now known as the epidemic of e-cigarette, or vaping, product use–associated lung injury (EVALI).

For many, the EVALI epidemic is a distant, pre-COVID memory.

But the vaping-related injuries are still happening. And for Ms. Bernal, the aftermath is her reality. Her pulmonologist from that time described the harm from the vape ingredients as an oil spill in her lungs. Eventually, the toxins would probably clear. But she will likely wrestle with the injuries for a very long time.

More than 3 years later, she frequently finds herself in the emergency department.

“If I get sick, if there’s anything that irritates my lungs – it could be something as simple as pollen in the air – it will cause me to get like a bacterial infection or other issues, and I can’t breathe,” Ms. Ms. Bernal, now 30, said in a recent interview. “I get really winded, to the point where I’ll walk up the stairs and I feel like I just ran a mile.”

In 2019 and 2020, a media firestorm erupted as hospitals notified the public of outbreaks of vaping-related lung injuries. News headlines reported e-cigarettes were killing teens from Texas to the Bronx. Investigators at the U.S. Centers for Disease Control and Prevention tracked most of the cases to vitamin E acetate, an additive in illicit cannabis vaping products intended to promote the metabolism of tetrahydrocannabinol (THC). The agency stopped tracking EVALI in February 2020.

But 2 months later, in April 2020, the agency’s National Center for Health Statistics implemented a diagnostic code, U07.0, for health care professionals in the United States to diagnose EVALI for the first time. The code is also used for lung damage related to use of electronic cigarettes and “dabbing” – a method of inhaling cannabis. Damage could include inflammation of the lungs, pulmonary hemorrhage, and eosinophilic pneumonia.

The incidence of these diagnoses appears to have risen sharply since 2020. In the last three months of 2020, a total of 11,300 medical claims included the U07.0 code. That figure rose to 22,000 in 2021 and hit 31,600 in 2022, according to data compiled for and provided to Medscape by Komodo Health, a health care technology company that holds a database of more than 330 million U.S. patients from Medicare, Medicaid, and commercial insurers’ medical, pharmacy, and laboratory claims.

Harm from vaping, including EVALI, has continued.

“We’re still seeing a number of patients diagnosed with vaping disorders, but it’s not top of mind,” said Usha Periyanayagam, MD, MPH, head of clinic product and real-world evidence for Komodo and a former emergency medicine physician.
 

Where it started

Devika Rao, MD, a pediatric pulmonology specialist at UT Southwestern Medical Center, Dallas, has cared for most of her EVALI patients in the hospital, with the most recent case in early 2023. But in January, for the first time, she saw an EVALI patient in an outpatient clinic. The person had not been admitted to the hospital – like most were pre-pandemic. And like most who were seen during the pandemic, this patient had milder symptoms, not requiring intubation or take-home oxygen.

In 2019 and the beginning of 2020, many EVALI patients who were eventually hospitalized first sought help at urgent care centers or with primary care doctors and were presumed to have pneumonia or gastroenteritis and sent home.

“But they got worse, and they would present to our emergency room; their chest X-rays and CT scans showed extensive lung disease,” Dr. Rao said, adding that the damage was striking among patients all under age 18. “They were short of breath. Their oxygen levels were low. They had diminished lung function. And they had a lot of GI issues like abdominal pain and weight loss from nausea and vomiting.”

“These overwhelming inflammatory reactions that we see with EVALI,” said Karen M. Wilson, MD, MPH, a pediatric hospitalist at the University of Rochester (N.Y.) Medical Center and a tobacco use researcher. “You might find some microvascular changes with normal inhaling of smoke or aerosol, but you’re not going to find macro changes like we see with the EVALI.”

In late 2019, images of the CT scans of patients with EVALI were published, grabbing the attention of Arun Kannappan, MD, an assistant professor of pulmonary sciences and critical care at the University of Colorado Anschutz School of Medicine, Aurora. Dr. Kannappan knew a patient with such severe lung damage could develop acute respiratory distress syndrome, which means a patient would be put on a ventilator because their inflamed lungs could not oxygenate blood.

“That confers within somewhere between 30% to 50% chance of dying; it made all of the pulmonary specialists really turn their heads to make sure that we keep a lookout for it,” said Dr. Kannappan.

CT scans of lungs proved to be a critical diagnostic tool for doctors. Most of the images from patients showed acute inflammation and diffuse lung damage. Ehab Ali, MD, a critical care and pulmonary disease medicine specialist in Louisville, Ky., said the damage was often spread across both lungs in many areas and appeared opaque and hazy, known as “ground glass.” COVID-19, meanwhile, appeared differently in lung scans, often with damage that was more isolated.

But many diseases carry a “ground glass” appearance, with many potential causes, like infections, cigarette smoke, or an autoimmune condition.

“Before you even talk to the patient, you can immediately put it in your mind that ‘I’m going to ask this patient if they vape,’ when I see the distribution of ground glass appearance,” Dr. Ali said.

Dr. Ali said other factors, like the age of the patient – about three-quarters of EVALI patients are under age 34, according to the CDC – would spur him to ask about vaping. But because so many patients were young, discerning vape usage wasn’t always easy.  

“When you’re talking to teenagers, if you ask them upon admission, with the parents in the room, they’re going say ‘no,’ ” said Rachel Boykan, MD, a pediatric hospitalist at Stony Brook (N.Y.) Children’s. She added that her hospital is still seeing cases.

Dr. Rao said it often takes two to three people asking a patient about any vape usage before they confess.

Ms. Bernal, who was 27 at the time of her hospital admission for EVALI, said she bought vapes with THC at a retail shop in California. She’d been a traditional marijuana smoker, using the leaf product, but switched when someone told her it was healthier to vape THC than inhale smoke from burned marijuana leaves into her lungs. “I thought this was safe.”

Dr. Rao and her colleagues recently published a study of 41 teenage patients with EVALI who were seen at Children’s Medical Center Dallas between December 2018 and July 2021. All but one reported using e-cigarettes containing THC, and the CDC in its most recent report from February 2020 said about 80% of patients had used vapes containing THC.

The CDC also found that vitamin E acetate, an oily substance that allows THC to travel from the lungs to the brain quickly and an ingredient used in the food and cosmetics industries, was found in many of the lungs of EVALI patients, though not all.
 

The aftermath

The outcomes of the thousands of patients who had EVALI – and those who may still be developing it – are largely untracked.

Bonnie Halpern-Felsher, PhD, director at the Stanford (Calif.) Reach Lab that bears her name and a researcher on tobacco in youth, said she and many of her colleagues are frustrated that the CDC is not continuing to collect data on EVALI.

“I know a lot of colleagues who’ve said that they’re still seeing EVALI, but because of COVID-19 they stopped collecting the data. And that’s been very frustrating because it’s hard to say whether the kinds of lung issues you’re having are related to e-cigarettes, generally, or EVALI,” Dr. Halpern-Felsher said.

Researchers and doctors affiliated with the American Thoracic Society published a report with solutions on how to better track EVALI. They recommended that a national case registry and biorepository be created.

Doctors also worry that many cases were missed. Dr. Boykan said that while protocol dictated nurses and other clinicians ask about a history of vaping – a key part of EVALI diagnosis – many did not. Dr. Ali, the Louisville critical care physician, said EVALI symptoms of nausea, cough, and fever are associated with viral infections.

“I’m sure that some of these cases might be discharged from the emergency room as a virus,” Dr. Ali said. “Most of the time patients would get prescribed steroids for viral infections, which may help EVALI patients even though it’s never been studied.”

Dr. Rao also said the treatment regimen at Children’s MC Dallas, which included high doses of intravenous steroids, seemed to help. But the best management approach for treatment, or long-term follow up care, has not been studied.

The report in the Annals of the American Thoracic Society said prospective studies are showing that a significant portion of patients with EVALI experience prolonged respiratory issues and cognitive and mood impairment. Dr. Rao said a common thread for many of her EVALI patients has been significant stress in their lives with school or family, which led them to vape in an attempt to reduce stress.

That was certainly the case for Ms. Bernal before her hospital admission. She had recently moved across the country for her husband’s job, was trying to buy a house, and had spent months in a hotel with three children. She vaped to cope.

But she said her mental and cognitive health has worsened. Back in Louisville, she saw a neurologist, who told her that her brain had shrunk, she said. She hasn’t found a new neurologist in Portland, Ore., where her family moved a year after the EVALI episode.

But she often finds herself overwhelmed and overstimulated with tasks that she said she never had problems with before. She tears up while talking about the newfound limitations. She struggled to find a primary care physician who could medically manage her mental health and a counselor who can understand what she’s been through with EVALI.

But, “a lot of doctors aren’t educated in it, and they don’t know how to respond or they don’t know what to do,” Ms. Bernal said. “And that makes me feel like, I guess, what I had wasn’t important.”

Ms. Bernal does have a new pulmonologist and is going in for a round of pulmonary tests soon because she often finds herself unable to breathe while completing simple tasks. She is tired of rushing to the ER. She wants answers, or some kind of treatment to help her feel normal again.

“I feel like this is my fault,” Ms. Bernal said. “Had I not smoked, I would be fine, and that’s hard to live with. Every day. Telling yourself, ‘It’s your fault.’ It’s been how many years now? And I still haven’t found peace yet. I don’t know if ever will.”

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

Rashelle Bernal vaped and ended up in an induced coma for a week. She was one of almost 3,000 people who were hospitalized during 2019 and early 2020 with severe lung damage from vaping and became part of what is now known as the epidemic of e-cigarette, or vaping, product use–associated lung injury (EVALI).

For many, the EVALI epidemic is a distant, pre-COVID memory.

But the vaping-related injuries are still happening. And for Ms. Bernal, the aftermath is her reality. Her pulmonologist from that time described the harm from the vape ingredients as an oil spill in her lungs. Eventually, the toxins would probably clear. But she will likely wrestle with the injuries for a very long time.

More than 3 years later, she frequently finds herself in the emergency department.

“If I get sick, if there’s anything that irritates my lungs – it could be something as simple as pollen in the air – it will cause me to get like a bacterial infection or other issues, and I can’t breathe,” Ms. Ms. Bernal, now 30, said in a recent interview. “I get really winded, to the point where I’ll walk up the stairs and I feel like I just ran a mile.”

In 2019 and 2020, a media firestorm erupted as hospitals notified the public of outbreaks of vaping-related lung injuries. News headlines reported e-cigarettes were killing teens from Texas to the Bronx. Investigators at the U.S. Centers for Disease Control and Prevention tracked most of the cases to vitamin E acetate, an additive in illicit cannabis vaping products intended to promote the metabolism of tetrahydrocannabinol (THC). The agency stopped tracking EVALI in February 2020.

But 2 months later, in April 2020, the agency’s National Center for Health Statistics implemented a diagnostic code, U07.0, for health care professionals in the United States to diagnose EVALI for the first time. The code is also used for lung damage related to use of electronic cigarettes and “dabbing” – a method of inhaling cannabis. Damage could include inflammation of the lungs, pulmonary hemorrhage, and eosinophilic pneumonia.

The incidence of these diagnoses appears to have risen sharply since 2020. In the last three months of 2020, a total of 11,300 medical claims included the U07.0 code. That figure rose to 22,000 in 2021 and hit 31,600 in 2022, according to data compiled for and provided to Medscape by Komodo Health, a health care technology company that holds a database of more than 330 million U.S. patients from Medicare, Medicaid, and commercial insurers’ medical, pharmacy, and laboratory claims.

Harm from vaping, including EVALI, has continued.

“We’re still seeing a number of patients diagnosed with vaping disorders, but it’s not top of mind,” said Usha Periyanayagam, MD, MPH, head of clinic product and real-world evidence for Komodo and a former emergency medicine physician.
 

Where it started

Devika Rao, MD, a pediatric pulmonology specialist at UT Southwestern Medical Center, Dallas, has cared for most of her EVALI patients in the hospital, with the most recent case in early 2023. But in January, for the first time, she saw an EVALI patient in an outpatient clinic. The person had not been admitted to the hospital – like most were pre-pandemic. And like most who were seen during the pandemic, this patient had milder symptoms, not requiring intubation or take-home oxygen.

In 2019 and the beginning of 2020, many EVALI patients who were eventually hospitalized first sought help at urgent care centers or with primary care doctors and were presumed to have pneumonia or gastroenteritis and sent home.

“But they got worse, and they would present to our emergency room; their chest X-rays and CT scans showed extensive lung disease,” Dr. Rao said, adding that the damage was striking among patients all under age 18. “They were short of breath. Their oxygen levels were low. They had diminished lung function. And they had a lot of GI issues like abdominal pain and weight loss from nausea and vomiting.”

“These overwhelming inflammatory reactions that we see with EVALI,” said Karen M. Wilson, MD, MPH, a pediatric hospitalist at the University of Rochester (N.Y.) Medical Center and a tobacco use researcher. “You might find some microvascular changes with normal inhaling of smoke or aerosol, but you’re not going to find macro changes like we see with the EVALI.”

In late 2019, images of the CT scans of patients with EVALI were published, grabbing the attention of Arun Kannappan, MD, an assistant professor of pulmonary sciences and critical care at the University of Colorado Anschutz School of Medicine, Aurora. Dr. Kannappan knew a patient with such severe lung damage could develop acute respiratory distress syndrome, which means a patient would be put on a ventilator because their inflamed lungs could not oxygenate blood.

“That confers within somewhere between 30% to 50% chance of dying; it made all of the pulmonary specialists really turn their heads to make sure that we keep a lookout for it,” said Dr. Kannappan.

CT scans of lungs proved to be a critical diagnostic tool for doctors. Most of the images from patients showed acute inflammation and diffuse lung damage. Ehab Ali, MD, a critical care and pulmonary disease medicine specialist in Louisville, Ky., said the damage was often spread across both lungs in many areas and appeared opaque and hazy, known as “ground glass.” COVID-19, meanwhile, appeared differently in lung scans, often with damage that was more isolated.

But many diseases carry a “ground glass” appearance, with many potential causes, like infections, cigarette smoke, or an autoimmune condition.

“Before you even talk to the patient, you can immediately put it in your mind that ‘I’m going to ask this patient if they vape,’ when I see the distribution of ground glass appearance,” Dr. Ali said.

Dr. Ali said other factors, like the age of the patient – about three-quarters of EVALI patients are under age 34, according to the CDC – would spur him to ask about vaping. But because so many patients were young, discerning vape usage wasn’t always easy.  

“When you’re talking to teenagers, if you ask them upon admission, with the parents in the room, they’re going say ‘no,’ ” said Rachel Boykan, MD, a pediatric hospitalist at Stony Brook (N.Y.) Children’s. She added that her hospital is still seeing cases.

Dr. Rao said it often takes two to three people asking a patient about any vape usage before they confess.

Ms. Bernal, who was 27 at the time of her hospital admission for EVALI, said she bought vapes with THC at a retail shop in California. She’d been a traditional marijuana smoker, using the leaf product, but switched when someone told her it was healthier to vape THC than inhale smoke from burned marijuana leaves into her lungs. “I thought this was safe.”

Dr. Rao and her colleagues recently published a study of 41 teenage patients with EVALI who were seen at Children’s Medical Center Dallas between December 2018 and July 2021. All but one reported using e-cigarettes containing THC, and the CDC in its most recent report from February 2020 said about 80% of patients had used vapes containing THC.

The CDC also found that vitamin E acetate, an oily substance that allows THC to travel from the lungs to the brain quickly and an ingredient used in the food and cosmetics industries, was found in many of the lungs of EVALI patients, though not all.
 

The aftermath

The outcomes of the thousands of patients who had EVALI – and those who may still be developing it – are largely untracked.

Bonnie Halpern-Felsher, PhD, director at the Stanford (Calif.) Reach Lab that bears her name and a researcher on tobacco in youth, said she and many of her colleagues are frustrated that the CDC is not continuing to collect data on EVALI.

“I know a lot of colleagues who’ve said that they’re still seeing EVALI, but because of COVID-19 they stopped collecting the data. And that’s been very frustrating because it’s hard to say whether the kinds of lung issues you’re having are related to e-cigarettes, generally, or EVALI,” Dr. Halpern-Felsher said.

Researchers and doctors affiliated with the American Thoracic Society published a report with solutions on how to better track EVALI. They recommended that a national case registry and biorepository be created.

Doctors also worry that many cases were missed. Dr. Boykan said that while protocol dictated nurses and other clinicians ask about a history of vaping – a key part of EVALI diagnosis – many did not. Dr. Ali, the Louisville critical care physician, said EVALI symptoms of nausea, cough, and fever are associated with viral infections.

“I’m sure that some of these cases might be discharged from the emergency room as a virus,” Dr. Ali said. “Most of the time patients would get prescribed steroids for viral infections, which may help EVALI patients even though it’s never been studied.”

Dr. Rao also said the treatment regimen at Children’s MC Dallas, which included high doses of intravenous steroids, seemed to help. But the best management approach for treatment, or long-term follow up care, has not been studied.

The report in the Annals of the American Thoracic Society said prospective studies are showing that a significant portion of patients with EVALI experience prolonged respiratory issues and cognitive and mood impairment. Dr. Rao said a common thread for many of her EVALI patients has been significant stress in their lives with school or family, which led them to vape in an attempt to reduce stress.

That was certainly the case for Ms. Bernal before her hospital admission. She had recently moved across the country for her husband’s job, was trying to buy a house, and had spent months in a hotel with three children. She vaped to cope.

But she said her mental and cognitive health has worsened. Back in Louisville, she saw a neurologist, who told her that her brain had shrunk, she said. She hasn’t found a new neurologist in Portland, Ore., where her family moved a year after the EVALI episode.

But she often finds herself overwhelmed and overstimulated with tasks that she said she never had problems with before. She tears up while talking about the newfound limitations. She struggled to find a primary care physician who could medically manage her mental health and a counselor who can understand what she’s been through with EVALI.

But, “a lot of doctors aren’t educated in it, and they don’t know how to respond or they don’t know what to do,” Ms. Bernal said. “And that makes me feel like, I guess, what I had wasn’t important.”

Ms. Bernal does have a new pulmonologist and is going in for a round of pulmonary tests soon because she often finds herself unable to breathe while completing simple tasks. She is tired of rushing to the ER. She wants answers, or some kind of treatment to help her feel normal again.

“I feel like this is my fault,” Ms. Bernal said. “Had I not smoked, I would be fine, and that’s hard to live with. Every day. Telling yourself, ‘It’s your fault.’ It’s been how many years now? And I still haven’t found peace yet. I don’t know if ever will.”

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

Rashelle Bernal vaped and ended up in an induced coma for a week. She was one of almost 3,000 people who were hospitalized during 2019 and early 2020 with severe lung damage from vaping and became part of what is now known as the epidemic of e-cigarette, or vaping, product use–associated lung injury (EVALI).

For many, the EVALI epidemic is a distant, pre-COVID memory.

But the vaping-related injuries are still happening. And for Ms. Bernal, the aftermath is her reality. Her pulmonologist from that time described the harm from the vape ingredients as an oil spill in her lungs. Eventually, the toxins would probably clear. But she will likely wrestle with the injuries for a very long time.

More than 3 years later, she frequently finds herself in the emergency department.

“If I get sick, if there’s anything that irritates my lungs – it could be something as simple as pollen in the air – it will cause me to get like a bacterial infection or other issues, and I can’t breathe,” Ms. Ms. Bernal, now 30, said in a recent interview. “I get really winded, to the point where I’ll walk up the stairs and I feel like I just ran a mile.”

In 2019 and 2020, a media firestorm erupted as hospitals notified the public of outbreaks of vaping-related lung injuries. News headlines reported e-cigarettes were killing teens from Texas to the Bronx. Investigators at the U.S. Centers for Disease Control and Prevention tracked most of the cases to vitamin E acetate, an additive in illicit cannabis vaping products intended to promote the metabolism of tetrahydrocannabinol (THC). The agency stopped tracking EVALI in February 2020.

But 2 months later, in April 2020, the agency’s National Center for Health Statistics implemented a diagnostic code, U07.0, for health care professionals in the United States to diagnose EVALI for the first time. The code is also used for lung damage related to use of electronic cigarettes and “dabbing” – a method of inhaling cannabis. Damage could include inflammation of the lungs, pulmonary hemorrhage, and eosinophilic pneumonia.

The incidence of these diagnoses appears to have risen sharply since 2020. In the last three months of 2020, a total of 11,300 medical claims included the U07.0 code. That figure rose to 22,000 in 2021 and hit 31,600 in 2022, according to data compiled for and provided to Medscape by Komodo Health, a health care technology company that holds a database of more than 330 million U.S. patients from Medicare, Medicaid, and commercial insurers’ medical, pharmacy, and laboratory claims.

Harm from vaping, including EVALI, has continued.

“We’re still seeing a number of patients diagnosed with vaping disorders, but it’s not top of mind,” said Usha Periyanayagam, MD, MPH, head of clinic product and real-world evidence for Komodo and a former emergency medicine physician.
 

Where it started

Devika Rao, MD, a pediatric pulmonology specialist at UT Southwestern Medical Center, Dallas, has cared for most of her EVALI patients in the hospital, with the most recent case in early 2023. But in January, for the first time, she saw an EVALI patient in an outpatient clinic. The person had not been admitted to the hospital – like most were pre-pandemic. And like most who were seen during the pandemic, this patient had milder symptoms, not requiring intubation or take-home oxygen.

In 2019 and the beginning of 2020, many EVALI patients who were eventually hospitalized first sought help at urgent care centers or with primary care doctors and were presumed to have pneumonia or gastroenteritis and sent home.

“But they got worse, and they would present to our emergency room; their chest X-rays and CT scans showed extensive lung disease,” Dr. Rao said, adding that the damage was striking among patients all under age 18. “They were short of breath. Their oxygen levels were low. They had diminished lung function. And they had a lot of GI issues like abdominal pain and weight loss from nausea and vomiting.”

“These overwhelming inflammatory reactions that we see with EVALI,” said Karen M. Wilson, MD, MPH, a pediatric hospitalist at the University of Rochester (N.Y.) Medical Center and a tobacco use researcher. “You might find some microvascular changes with normal inhaling of smoke or aerosol, but you’re not going to find macro changes like we see with the EVALI.”

In late 2019, images of the CT scans of patients with EVALI were published, grabbing the attention of Arun Kannappan, MD, an assistant professor of pulmonary sciences and critical care at the University of Colorado Anschutz School of Medicine, Aurora. Dr. Kannappan knew a patient with such severe lung damage could develop acute respiratory distress syndrome, which means a patient would be put on a ventilator because their inflamed lungs could not oxygenate blood.

“That confers within somewhere between 30% to 50% chance of dying; it made all of the pulmonary specialists really turn their heads to make sure that we keep a lookout for it,” said Dr. Kannappan.

CT scans of lungs proved to be a critical diagnostic tool for doctors. Most of the images from patients showed acute inflammation and diffuse lung damage. Ehab Ali, MD, a critical care and pulmonary disease medicine specialist in Louisville, Ky., said the damage was often spread across both lungs in many areas and appeared opaque and hazy, known as “ground glass.” COVID-19, meanwhile, appeared differently in lung scans, often with damage that was more isolated.

But many diseases carry a “ground glass” appearance, with many potential causes, like infections, cigarette smoke, or an autoimmune condition.

“Before you even talk to the patient, you can immediately put it in your mind that ‘I’m going to ask this patient if they vape,’ when I see the distribution of ground glass appearance,” Dr. Ali said.

Dr. Ali said other factors, like the age of the patient – about three-quarters of EVALI patients are under age 34, according to the CDC – would spur him to ask about vaping. But because so many patients were young, discerning vape usage wasn’t always easy.  

“When you’re talking to teenagers, if you ask them upon admission, with the parents in the room, they’re going say ‘no,’ ” said Rachel Boykan, MD, a pediatric hospitalist at Stony Brook (N.Y.) Children’s. She added that her hospital is still seeing cases.

Dr. Rao said it often takes two to three people asking a patient about any vape usage before they confess.

Ms. Bernal, who was 27 at the time of her hospital admission for EVALI, said she bought vapes with THC at a retail shop in California. She’d been a traditional marijuana smoker, using the leaf product, but switched when someone told her it was healthier to vape THC than inhale smoke from burned marijuana leaves into her lungs. “I thought this was safe.”

Dr. Rao and her colleagues recently published a study of 41 teenage patients with EVALI who were seen at Children’s Medical Center Dallas between December 2018 and July 2021. All but one reported using e-cigarettes containing THC, and the CDC in its most recent report from February 2020 said about 80% of patients had used vapes containing THC.

The CDC also found that vitamin E acetate, an oily substance that allows THC to travel from the lungs to the brain quickly and an ingredient used in the food and cosmetics industries, was found in many of the lungs of EVALI patients, though not all.
 

The aftermath

The outcomes of the thousands of patients who had EVALI – and those who may still be developing it – are largely untracked.

Bonnie Halpern-Felsher, PhD, director at the Stanford (Calif.) Reach Lab that bears her name and a researcher on tobacco in youth, said she and many of her colleagues are frustrated that the CDC is not continuing to collect data on EVALI.

“I know a lot of colleagues who’ve said that they’re still seeing EVALI, but because of COVID-19 they stopped collecting the data. And that’s been very frustrating because it’s hard to say whether the kinds of lung issues you’re having are related to e-cigarettes, generally, or EVALI,” Dr. Halpern-Felsher said.

Researchers and doctors affiliated with the American Thoracic Society published a report with solutions on how to better track EVALI. They recommended that a national case registry and biorepository be created.

Doctors also worry that many cases were missed. Dr. Boykan said that while protocol dictated nurses and other clinicians ask about a history of vaping – a key part of EVALI diagnosis – many did not. Dr. Ali, the Louisville critical care physician, said EVALI symptoms of nausea, cough, and fever are associated with viral infections.

“I’m sure that some of these cases might be discharged from the emergency room as a virus,” Dr. Ali said. “Most of the time patients would get prescribed steroids for viral infections, which may help EVALI patients even though it’s never been studied.”

Dr. Rao also said the treatment regimen at Children’s MC Dallas, which included high doses of intravenous steroids, seemed to help. But the best management approach for treatment, or long-term follow up care, has not been studied.

The report in the Annals of the American Thoracic Society said prospective studies are showing that a significant portion of patients with EVALI experience prolonged respiratory issues and cognitive and mood impairment. Dr. Rao said a common thread for many of her EVALI patients has been significant stress in their lives with school or family, which led them to vape in an attempt to reduce stress.

That was certainly the case for Ms. Bernal before her hospital admission. She had recently moved across the country for her husband’s job, was trying to buy a house, and had spent months in a hotel with three children. She vaped to cope.

But she said her mental and cognitive health has worsened. Back in Louisville, she saw a neurologist, who told her that her brain had shrunk, she said. She hasn’t found a new neurologist in Portland, Ore., where her family moved a year after the EVALI episode.

But she often finds herself overwhelmed and overstimulated with tasks that she said she never had problems with before. She tears up while talking about the newfound limitations. She struggled to find a primary care physician who could medically manage her mental health and a counselor who can understand what she’s been through with EVALI.

But, “a lot of doctors aren’t educated in it, and they don’t know how to respond or they don’t know what to do,” Ms. Bernal said. “And that makes me feel like, I guess, what I had wasn’t important.”

Ms. Bernal does have a new pulmonologist and is going in for a round of pulmonary tests soon because she often finds herself unable to breathe while completing simple tasks. She is tired of rushing to the ER. She wants answers, or some kind of treatment to help her feel normal again.

“I feel like this is my fault,” Ms. Bernal said. “Had I not smoked, I would be fine, and that’s hard to live with. Every day. Telling yourself, ‘It’s your fault.’ It’s been how many years now? And I still haven’t found peace yet. I don’t know if ever will.”

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

Poor-quality sleep and irregular sleep could be important drivers of breathlessness in patients who were previously hospitalized for COVID-19, according to data from the U.K.’s CircCOVID study.

The researchers, led by John Blaikley, MRCP, PhD, respiratory physician and clinical scientist from the University of Manchester (England), found that sleep disturbance is a common problem after hospital admission for COVID-19 and may last for at least 1 year.

The study also showed that sleep disturbance after COVID hospitalization was associated with dyspnea and lower lung function. Further in-depth analysis revealed that the effects of sleep disturbance on dyspnea were partially mediated through both anxiety and muscle weakness; however, “this does not fully explain the association, suggesting other pathways are involved,” said Dr. Blaikley.

The study was jointly conducted by researchers from the University of Leicester (England), as well as 20 other U.K. institutes and the University of Helsinki. It was presented at the European Congress of Clinical Microbiology & Infectious Diseases and was simultaneously published in The Lancet Respiratory Medicine.

“Sleep disturbance is a common problem after hospitalization for COVID-19 and is associated with several symptoms in the post-COVID syndrome,” said Dr. Blaikley. “Clinicians should be aware of this association in their post-COVID syndrome clinics.”

He added that further work needs to be done to define the mechanism and to see whether the links are causal. “However, if they are, then treating sleep disturbance could have beneficial effects beyond improving sleep quality,” he said in an interview.

A large study recently showed that 4 in 10 people with post-COVID syndrome had moderate to severe sleep problems. Black people were at least three times more likely than White people to experience sleep problems. A total of 59% of all participants with long COVID reported having normal sleep or mild sleep disturbances, and 41% reported having moderate to severe sleep disturbances.

Unlike prior studies that evaluated sleep quality after COVID-19, which used either objective or subjective measures of sleep disturbance, the current study used both. “Using both measures revealed previously poorly described associations between sleep disturbance, breathlessness, reduced lung function, anxiety, and muscle weakness,” Dr. Blaikley pointed out.

Subjective and objective measures of sleep

The multicenter CircCOVID cohort study aimed to shed light on the prevalence and nature of sleep disturbance after patients are discharged from hospital for COVID-19 and to assess whether this was associated with dyspnea.

The study recruited a total of 2,320 participants who were part of a larger parent PHOSP-COVID study. After attending an early follow-up visit (at a median of 5 months after discharge from 83 U.K. hospitals for COVID-19), 638 participants provided data for analysis as measured by the Pittsburgh Sleep Quality Index (a subjective measure of sleep quality); 729 participants provided data for analysis as measured by actigraphy (an objective, wrist-worn, device-based measure of sleep quality) at a median of 7 months.

Breathlessness, the primary outcome, was assessed using the Dyspnea-12 validated questionnaire.

Actigraphy measurements were compared with an age-matched, sex-matched, body mass index (BMI)–matched, and time from discharge–matched cohort from the UK Biobank (a prepandemic comparator longitudinal cohort of 502,540 individuals, one-fifth of whom wore actigraphy devices). Sleep regularity was found to be 19% less in previously hospitalized patients with post-COVID syndrome, compared with matched controls who had been hospitalized for other reasons.

This “revealed that the actigraphy changes may be, in part, due to COVID-19 rather than hospitalization alone,” said Dr. Blaikley.

Data were collected at two time points after hospital discharge: 2-7 months (early), and 10-14 months (late). At the early time point, participants were clinically assessed with respect to anxiety, muscle function, and dyspnea, and lung function.

After discharge from hospital, the majority (62%) of post–COVID-19 participants reported poor sleep quality on the Pittsburgh Sleep Quality Index questionnaire. A “comparable” proportion (53%) felt that their quality of sleep had deteriorated following hospital discharge according to the numerical rating scale (subjective measure).

Also, sleep disturbance was found likely to persist for at least 12 months, since subjective sleep quality hardly changed between the early and late time points after hospital discharge.

Both subjective metrics (sleep quality and sleep quality deterioration after hospital discharge) and objective, device-based metrics (sleep regularity) were found to be associated with dyspnea and reduced lung function in patients with post-COVID syndrome.

“One of the striking findings in our study is the consistency with breathlessness and reduced lung function across different methods used to evaluate sleep,” highlighted Dr. Blaikley.

“The other striking finding was that participants following COVID-19 hospitalization actually slept longer [65 min; 95% confidence interval, 59-71 min] than participants hospitalized for non-COVID; however, their bedtimes were irregular, and it was this irregularity that was associated with breathlessness,” he added.

In comparison with nonhospitalized controls, also from the UK Biobank, study participants with lower sleep regularity had higher Dyspnea-12 scores (unadjusted effect estimate, 4.38; 95%: CI, 2.10-6.65). Those with poor sleep quality overall also had higher Dyspnea-12 scores (unadjusted effect estimate, 3.94; 95% CI, 2.78-5.10), and those who reported sleep quality deterioration had higher Dyspnea-12 scores (unadjusted effect estimate, 3,00; 95% CI, 1.82-4.28).

In comparison with hospitalized controls, CircCOVID participants had lower sleep regularity index (–19%; 95% CI, –20 to –16) and lower sleep efficiency (3.83 percentage points; 95% CI, 3.40-4.26).

Sleep disturbance after COVID hospitalization was also associated with lower lung function, from a 7% to a 14% reduction in predicted forced vital capacity, depending on which sleep measure used.

In an analysis of mediating factors active in the relationship between sleep disturbance and dyspnea/decreased lung function, the researchers found that reduced muscle function and anxiety, which are both recognized causes of dyspnea, could partially contribute to the association.

Regarding anxiety, and depending on the sleep metric, anxiety mediated 18%-39% of the effect of sleep disturbance on dyspnea, while muscle weakness mediated 27%-41% of this effect, reported Dr. Blaikley. Those with poor sleep quality were more likely to have mild, moderate, or severe anxiety, compared with participants who reported good-quality sleep.

A similar association was observed between anxiety and sleep quality deterioration.

“Two key questions are raised by our study: Do sleep interventions have a beneficial effect in post–COVID-19 syndrome, and are the associations causal?” asked Dr. Blaikley. “We hope to do a sleep intervention trial to answer these questions to explore if this is an effective treatment for post–COVID-19 syndrome.”

‘Underlying mechanisms remain unclear’

Amitava Banerjee, MD, professor of clinical data science and honorary consultant cardiologist, Institute of Health Informatics, UCL, London, welcomed the study but noted that it did not include nonhospitalized post-COVID patients.

“The majority of people with long COVID were not hospitalized for COVID, so the results may not be generalizable to this larger group,” she said in an interview. “Good-quality sleep is important for health and reduces risk of chronic diseases; quality of sleep is therefore likely to be important for those with long COVID in reducing their risk of chronic disease, but the role of sleep in the mechanism of long COVID needs further research.”

In a commentary also published in The Lancet Respiratory Medicine, W. Cameron McGuire, MD, pulmonary and critical care specialist from San Diego, California, and colleagues wrote: “These findings suggest that sleep disturbance, dyspnea, and anxiety are common after COVID-19 and are associated with one another, although the underlying mechanisms remain unclear.”

The commentators “applauded” the work overall but noted that the findings represent correlation rather than causation. “It is unclear whether sleep disturbance is causing anxiety or whether anxiety is contributing to poor sleep. ... For the sleep disturbances, increased BMI in the cohort reporting poor sleep, compared with those reporting good sleep might suggest underlying obstructive sleep apnea,” they wrote.

Dr. McGuire and colleagues added that many questions remain for researchers and clinicians, including “whether anxiety and dyspnoea are contributing to a low arousal threshold [disrupting sleep] ... whether the observed abnormalities (e.g., in dyspnea score) are clinically significant,” and “whether therapies such as glucocorticoids, anticoagulants, or previous vaccinations mitigate the observed abnormalities during COVID-19 recovery.”

Dr. Blaikley has received support to his institute from an MRC Transition Fellowship, Asthma + Lung UK, NIHR Manchester BRC, and UKRI; grants to his institution from the Small Business Research Initiative Home Spirometer and the National Institute of Academic Anaesthesia; and support from TEVA and Therakos for attending meetings. He is a committee member of the Royal Society of Medicine. A coauthor received funding from the National Institutes of Health and income for medical education from Zoll, Livanova, Jazz, and Eli Lilly. Dr. Banerjee is the chief investigator of STIMULATE-ICP (an NIHR-funded study) and has received research funding from AstraZeneca.

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

Poor-quality sleep and irregular sleep could be important drivers of breathlessness in patients who were previously hospitalized for COVID-19, according to data from the U.K.’s CircCOVID study.

The researchers, led by John Blaikley, MRCP, PhD, respiratory physician and clinical scientist from the University of Manchester (England), found that sleep disturbance is a common problem after hospital admission for COVID-19 and may last for at least 1 year.

The study also showed that sleep disturbance after COVID hospitalization was associated with dyspnea and lower lung function. Further in-depth analysis revealed that the effects of sleep disturbance on dyspnea were partially mediated through both anxiety and muscle weakness; however, “this does not fully explain the association, suggesting other pathways are involved,” said Dr. Blaikley.

The study was jointly conducted by researchers from the University of Leicester (England), as well as 20 other U.K. institutes and the University of Helsinki. It was presented at the European Congress of Clinical Microbiology & Infectious Diseases and was simultaneously published in The Lancet Respiratory Medicine.

“Sleep disturbance is a common problem after hospitalization for COVID-19 and is associated with several symptoms in the post-COVID syndrome,” said Dr. Blaikley. “Clinicians should be aware of this association in their post-COVID syndrome clinics.”

He added that further work needs to be done to define the mechanism and to see whether the links are causal. “However, if they are, then treating sleep disturbance could have beneficial effects beyond improving sleep quality,” he said in an interview.

A large study recently showed that 4 in 10 people with post-COVID syndrome had moderate to severe sleep problems. Black people were at least three times more likely than White people to experience sleep problems. A total of 59% of all participants with long COVID reported having normal sleep or mild sleep disturbances, and 41% reported having moderate to severe sleep disturbances.

Unlike prior studies that evaluated sleep quality after COVID-19, which used either objective or subjective measures of sleep disturbance, the current study used both. “Using both measures revealed previously poorly described associations between sleep disturbance, breathlessness, reduced lung function, anxiety, and muscle weakness,” Dr. Blaikley pointed out.

Subjective and objective measures of sleep

The multicenter CircCOVID cohort study aimed to shed light on the prevalence and nature of sleep disturbance after patients are discharged from hospital for COVID-19 and to assess whether this was associated with dyspnea.

The study recruited a total of 2,320 participants who were part of a larger parent PHOSP-COVID study. After attending an early follow-up visit (at a median of 5 months after discharge from 83 U.K. hospitals for COVID-19), 638 participants provided data for analysis as measured by the Pittsburgh Sleep Quality Index (a subjective measure of sleep quality); 729 participants provided data for analysis as measured by actigraphy (an objective, wrist-worn, device-based measure of sleep quality) at a median of 7 months.

Breathlessness, the primary outcome, was assessed using the Dyspnea-12 validated questionnaire.

Actigraphy measurements were compared with an age-matched, sex-matched, body mass index (BMI)–matched, and time from discharge–matched cohort from the UK Biobank (a prepandemic comparator longitudinal cohort of 502,540 individuals, one-fifth of whom wore actigraphy devices). Sleep regularity was found to be 19% less in previously hospitalized patients with post-COVID syndrome, compared with matched controls who had been hospitalized for other reasons.

This “revealed that the actigraphy changes may be, in part, due to COVID-19 rather than hospitalization alone,” said Dr. Blaikley.

Data were collected at two time points after hospital discharge: 2-7 months (early), and 10-14 months (late). At the early time point, participants were clinically assessed with respect to anxiety, muscle function, and dyspnea, and lung function.

After discharge from hospital, the majority (62%) of post–COVID-19 participants reported poor sleep quality on the Pittsburgh Sleep Quality Index questionnaire. A “comparable” proportion (53%) felt that their quality of sleep had deteriorated following hospital discharge according to the numerical rating scale (subjective measure).

Also, sleep disturbance was found likely to persist for at least 12 months, since subjective sleep quality hardly changed between the early and late time points after hospital discharge.

Both subjective metrics (sleep quality and sleep quality deterioration after hospital discharge) and objective, device-based metrics (sleep regularity) were found to be associated with dyspnea and reduced lung function in patients with post-COVID syndrome.

“One of the striking findings in our study is the consistency with breathlessness and reduced lung function across different methods used to evaluate sleep,” highlighted Dr. Blaikley.

“The other striking finding was that participants following COVID-19 hospitalization actually slept longer [65 min; 95% confidence interval, 59-71 min] than participants hospitalized for non-COVID; however, their bedtimes were irregular, and it was this irregularity that was associated with breathlessness,” he added.

In comparison with nonhospitalized controls, also from the UK Biobank, study participants with lower sleep regularity had higher Dyspnea-12 scores (unadjusted effect estimate, 4.38; 95%: CI, 2.10-6.65). Those with poor sleep quality overall also had higher Dyspnea-12 scores (unadjusted effect estimate, 3.94; 95% CI, 2.78-5.10), and those who reported sleep quality deterioration had higher Dyspnea-12 scores (unadjusted effect estimate, 3,00; 95% CI, 1.82-4.28).

In comparison with hospitalized controls, CircCOVID participants had lower sleep regularity index (–19%; 95% CI, –20 to –16) and lower sleep efficiency (3.83 percentage points; 95% CI, 3.40-4.26).

Sleep disturbance after COVID hospitalization was also associated with lower lung function, from a 7% to a 14% reduction in predicted forced vital capacity, depending on which sleep measure used.

In an analysis of mediating factors active in the relationship between sleep disturbance and dyspnea/decreased lung function, the researchers found that reduced muscle function and anxiety, which are both recognized causes of dyspnea, could partially contribute to the association.

Regarding anxiety, and depending on the sleep metric, anxiety mediated 18%-39% of the effect of sleep disturbance on dyspnea, while muscle weakness mediated 27%-41% of this effect, reported Dr. Blaikley. Those with poor sleep quality were more likely to have mild, moderate, or severe anxiety, compared with participants who reported good-quality sleep.

A similar association was observed between anxiety and sleep quality deterioration.

“Two key questions are raised by our study: Do sleep interventions have a beneficial effect in post–COVID-19 syndrome, and are the associations causal?” asked Dr. Blaikley. “We hope to do a sleep intervention trial to answer these questions to explore if this is an effective treatment for post–COVID-19 syndrome.”

‘Underlying mechanisms remain unclear’

Amitava Banerjee, MD, professor of clinical data science and honorary consultant cardiologist, Institute of Health Informatics, UCL, London, welcomed the study but noted that it did not include nonhospitalized post-COVID patients.

“The majority of people with long COVID were not hospitalized for COVID, so the results may not be generalizable to this larger group,” she said in an interview. “Good-quality sleep is important for health and reduces risk of chronic diseases; quality of sleep is therefore likely to be important for those with long COVID in reducing their risk of chronic disease, but the role of sleep in the mechanism of long COVID needs further research.”

In a commentary also published in The Lancet Respiratory Medicine, W. Cameron McGuire, MD, pulmonary and critical care specialist from San Diego, California, and colleagues wrote: “These findings suggest that sleep disturbance, dyspnea, and anxiety are common after COVID-19 and are associated with one another, although the underlying mechanisms remain unclear.”

The commentators “applauded” the work overall but noted that the findings represent correlation rather than causation. “It is unclear whether sleep disturbance is causing anxiety or whether anxiety is contributing to poor sleep. ... For the sleep disturbances, increased BMI in the cohort reporting poor sleep, compared with those reporting good sleep might suggest underlying obstructive sleep apnea,” they wrote.

Dr. McGuire and colleagues added that many questions remain for researchers and clinicians, including “whether anxiety and dyspnoea are contributing to a low arousal threshold [disrupting sleep] ... whether the observed abnormalities (e.g., in dyspnea score) are clinically significant,” and “whether therapies such as glucocorticoids, anticoagulants, or previous vaccinations mitigate the observed abnormalities during COVID-19 recovery.”

Dr. Blaikley has received support to his institute from an MRC Transition Fellowship, Asthma + Lung UK, NIHR Manchester BRC, and UKRI; grants to his institution from the Small Business Research Initiative Home Spirometer and the National Institute of Academic Anaesthesia; and support from TEVA and Therakos for attending meetings. He is a committee member of the Royal Society of Medicine. A coauthor received funding from the National Institutes of Health and income for medical education from Zoll, Livanova, Jazz, and Eli Lilly. Dr. Banerjee is the chief investigator of STIMULATE-ICP (an NIHR-funded study) and has received research funding from AstraZeneca.

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

Poor-quality sleep and irregular sleep could be important drivers of breathlessness in patients who were previously hospitalized for COVID-19, according to data from the U.K.’s CircCOVID study.

The researchers, led by John Blaikley, MRCP, PhD, respiratory physician and clinical scientist from the University of Manchester (England), found that sleep disturbance is a common problem after hospital admission for COVID-19 and may last for at least 1 year.

The study also showed that sleep disturbance after COVID hospitalization was associated with dyspnea and lower lung function. Further in-depth analysis revealed that the effects of sleep disturbance on dyspnea were partially mediated through both anxiety and muscle weakness; however, “this does not fully explain the association, suggesting other pathways are involved,” said Dr. Blaikley.

The study was jointly conducted by researchers from the University of Leicester (England), as well as 20 other U.K. institutes and the University of Helsinki. It was presented at the European Congress of Clinical Microbiology & Infectious Diseases and was simultaneously published in The Lancet Respiratory Medicine.

“Sleep disturbance is a common problem after hospitalization for COVID-19 and is associated with several symptoms in the post-COVID syndrome,” said Dr. Blaikley. “Clinicians should be aware of this association in their post-COVID syndrome clinics.”

He added that further work needs to be done to define the mechanism and to see whether the links are causal. “However, if they are, then treating sleep disturbance could have beneficial effects beyond improving sleep quality,” he said in an interview.

A large study recently showed that 4 in 10 people with post-COVID syndrome had moderate to severe sleep problems. Black people were at least three times more likely than White people to experience sleep problems. A total of 59% of all participants with long COVID reported having normal sleep or mild sleep disturbances, and 41% reported having moderate to severe sleep disturbances.

Unlike prior studies that evaluated sleep quality after COVID-19, which used either objective or subjective measures of sleep disturbance, the current study used both. “Using both measures revealed previously poorly described associations between sleep disturbance, breathlessness, reduced lung function, anxiety, and muscle weakness,” Dr. Blaikley pointed out.

Subjective and objective measures of sleep

The multicenter CircCOVID cohort study aimed to shed light on the prevalence and nature of sleep disturbance after patients are discharged from hospital for COVID-19 and to assess whether this was associated with dyspnea.

The study recruited a total of 2,320 participants who were part of a larger parent PHOSP-COVID study. After attending an early follow-up visit (at a median of 5 months after discharge from 83 U.K. hospitals for COVID-19), 638 participants provided data for analysis as measured by the Pittsburgh Sleep Quality Index (a subjective measure of sleep quality); 729 participants provided data for analysis as measured by actigraphy (an objective, wrist-worn, device-based measure of sleep quality) at a median of 7 months.

Breathlessness, the primary outcome, was assessed using the Dyspnea-12 validated questionnaire.

Actigraphy measurements were compared with an age-matched, sex-matched, body mass index (BMI)–matched, and time from discharge–matched cohort from the UK Biobank (a prepandemic comparator longitudinal cohort of 502,540 individuals, one-fifth of whom wore actigraphy devices). Sleep regularity was found to be 19% less in previously hospitalized patients with post-COVID syndrome, compared with matched controls who had been hospitalized for other reasons.

This “revealed that the actigraphy changes may be, in part, due to COVID-19 rather than hospitalization alone,” said Dr. Blaikley.

Data were collected at two time points after hospital discharge: 2-7 months (early), and 10-14 months (late). At the early time point, participants were clinically assessed with respect to anxiety, muscle function, and dyspnea, and lung function.

After discharge from hospital, the majority (62%) of post–COVID-19 participants reported poor sleep quality on the Pittsburgh Sleep Quality Index questionnaire. A “comparable” proportion (53%) felt that their quality of sleep had deteriorated following hospital discharge according to the numerical rating scale (subjective measure).

Also, sleep disturbance was found likely to persist for at least 12 months, since subjective sleep quality hardly changed between the early and late time points after hospital discharge.

Both subjective metrics (sleep quality and sleep quality deterioration after hospital discharge) and objective, device-based metrics (sleep regularity) were found to be associated with dyspnea and reduced lung function in patients with post-COVID syndrome.

“One of the striking findings in our study is the consistency with breathlessness and reduced lung function across different methods used to evaluate sleep,” highlighted Dr. Blaikley.

“The other striking finding was that participants following COVID-19 hospitalization actually slept longer [65 min; 95% confidence interval, 59-71 min] than participants hospitalized for non-COVID; however, their bedtimes were irregular, and it was this irregularity that was associated with breathlessness,” he added.

In comparison with nonhospitalized controls, also from the UK Biobank, study participants with lower sleep regularity had higher Dyspnea-12 scores (unadjusted effect estimate, 4.38; 95%: CI, 2.10-6.65). Those with poor sleep quality overall also had higher Dyspnea-12 scores (unadjusted effect estimate, 3.94; 95% CI, 2.78-5.10), and those who reported sleep quality deterioration had higher Dyspnea-12 scores (unadjusted effect estimate, 3,00; 95% CI, 1.82-4.28).

In comparison with hospitalized controls, CircCOVID participants had lower sleep regularity index (–19%; 95% CI, –20 to –16) and lower sleep efficiency (3.83 percentage points; 95% CI, 3.40-4.26).

Sleep disturbance after COVID hospitalization was also associated with lower lung function, from a 7% to a 14% reduction in predicted forced vital capacity, depending on which sleep measure used.

In an analysis of mediating factors active in the relationship between sleep disturbance and dyspnea/decreased lung function, the researchers found that reduced muscle function and anxiety, which are both recognized causes of dyspnea, could partially contribute to the association.

Regarding anxiety, and depending on the sleep metric, anxiety mediated 18%-39% of the effect of sleep disturbance on dyspnea, while muscle weakness mediated 27%-41% of this effect, reported Dr. Blaikley. Those with poor sleep quality were more likely to have mild, moderate, or severe anxiety, compared with participants who reported good-quality sleep.

A similar association was observed between anxiety and sleep quality deterioration.

“Two key questions are raised by our study: Do sleep interventions have a beneficial effect in post–COVID-19 syndrome, and are the associations causal?” asked Dr. Blaikley. “We hope to do a sleep intervention trial to answer these questions to explore if this is an effective treatment for post–COVID-19 syndrome.”

‘Underlying mechanisms remain unclear’

Amitava Banerjee, MD, professor of clinical data science and honorary consultant cardiologist, Institute of Health Informatics, UCL, London, welcomed the study but noted that it did not include nonhospitalized post-COVID patients.

“The majority of people with long COVID were not hospitalized for COVID, so the results may not be generalizable to this larger group,” she said in an interview. “Good-quality sleep is important for health and reduces risk of chronic diseases; quality of sleep is therefore likely to be important for those with long COVID in reducing their risk of chronic disease, but the role of sleep in the mechanism of long COVID needs further research.”

In a commentary also published in The Lancet Respiratory Medicine, W. Cameron McGuire, MD, pulmonary and critical care specialist from San Diego, California, and colleagues wrote: “These findings suggest that sleep disturbance, dyspnea, and anxiety are common after COVID-19 and are associated with one another, although the underlying mechanisms remain unclear.”

The commentators “applauded” the work overall but noted that the findings represent correlation rather than causation. “It is unclear whether sleep disturbance is causing anxiety or whether anxiety is contributing to poor sleep. ... For the sleep disturbances, increased BMI in the cohort reporting poor sleep, compared with those reporting good sleep might suggest underlying obstructive sleep apnea,” they wrote.

Dr. McGuire and colleagues added that many questions remain for researchers and clinicians, including “whether anxiety and dyspnoea are contributing to a low arousal threshold [disrupting sleep] ... whether the observed abnormalities (e.g., in dyspnea score) are clinically significant,” and “whether therapies such as glucocorticoids, anticoagulants, or previous vaccinations mitigate the observed abnormalities during COVID-19 recovery.”

Dr. Blaikley has received support to his institute from an MRC Transition Fellowship, Asthma + Lung UK, NIHR Manchester BRC, and UKRI; grants to his institution from the Small Business Research Initiative Home Spirometer and the National Institute of Academic Anaesthesia; and support from TEVA and Therakos for attending meetings. He is a committee member of the Royal Society of Medicine. A coauthor received funding from the National Institutes of Health and income for medical education from Zoll, Livanova, Jazz, and Eli Lilly. Dr. Banerjee is the chief investigator of STIMULATE-ICP (an NIHR-funded study) and has received research funding from AstraZeneca.

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

Patients taking metformin for type 2 diabetes had a lower risk of developing osteoarthritis than did patients taking a sulfonylurea, according to a cohort study published in JAMA Network Open. The findings jibe with those seen in a 2022 systematic review of preclinical and observational human studies finding potentially protective effects of metformin on osteoarthritis.

“Our study provides further, robust epidemiological evidence that metformin may be associated with protection in the development and progression of osteoarthritis in individuals with type 2 diabetes,” wrote Matthew C. Baker, MD, MS, an assistant professor of medicine in immunology and rheumatology at Stanford (Calif.) University, and his colleagues.

Thinglass/iStock Editorial/Getty Images

The findings also fit with the results of a poster presented at the Osteoarthritis Research Society International 2023 World Congress, although that abstract’s findings did not reach statistical significance.

In the published study, the researchers analyzed deidentified claims data from Optum’s Clinformatics Data Mart Database between December 2003 and December 2019. The database includes more than 15 million people with private insurance or Medicare Advantage Part D but does not include people with Medicaid, thereby excluding people from lower socioeconomic groups.

The researchers included all patients who were at least 40 years old, had type 2 diabetes, were taking metformin, and had been enrolled in the database for at least 1 uninterrupted year. They excluded anyone with type 1 diabetes or a prior diagnosis of osteoarthritis, inflammatory arthritis, or joint replacement. The authors then compared the incidence of osteoarthritis and joint replacement in these 20,937 participants to 20,937 control participants who were taking a sulfonylurea, matched to those taking metformin on the basis of age, sex, race, a comorbidity score, and duration of treatment. More than half the overall population (58%) was male with an average age of 62.

Patients needed to be on either drug for at least 3 months, but those who were initially treated with metformin before later taking a sulfonylurea could also be included and contribute to both groups. Those who first took a sulfonylurea and later switched to metformin were included only for the sulfonylurea group and censored after their switch to ensure the sulfonylurea group had enough participants. The comparison was further adjusted for age, sex, race, ethnicity, geographic region, education, comorbidities, and outpatient visit frequency.

The results revealed that those who were taking metformin were 24% less likely to develop osteoarthritis at least 3 months after starting the medication than were those taking a sulfonylurea (P < .001). The rate of joint replacements was not significantly different between those taking metformin and those taking a sulfonylurea. These two results did not change in a sensitivity analysis that compared patients who only ever took metformin or a sulfonylurea (as opposed to those who took one drug before switching to the other).

“When stratified by prior exposure to metformin within the sulfonylurea group, the observed benefit associated with metformin ... was attenuated in the people treated with a sulfonylurea with prior exposure to metformin, compared with those treated with a sulfonylurea with no prior exposure to metformin,” the authors further reported. A possible reason for this finding is that those taking a sulfonylurea after having previously taken metformin gained some protection from the earlier metformin exposure, the authors hypothesized.

This observational study could not show a causative effect from the metformin, but the researchers speculated on potential mechanisms if a causative effect were present, based on past research.

”Several preclinical studies have suggested a protective association of metformin in osteoarthritis through activating AMP-activated protein kinase signaling, decreasing the level of matrix metalloproteinase, increasing autophagy and reducing chondrocyte apoptosis, and augmenting chondroprotective and anti-inflammatory properties of mesenchymal stem cells,” the authors wrote.

Among this study’s limitations, however, was the lack of data on body mass index, which is associated with osteoarthritis in the literature and may differ between patients taking metformin versus a sulfonylurea. The researchers also did not have data on physical activity or a history of trauma to the joints, though there’s no reason to think these rates might differ between those taking one or the other medication.

Another substantial limitation is that all patients had type 2 diabetes, making it impossible to determine whether a similar protective effect from metformin might exist in people without diabetes.

Nonsignificant lower risk for posttraumatic knee osteoarthritis

Similar to the published study, the OARSI poster compared 5-year odds of incident osteoarthritis or total knee replacement surgery between patients taking metformin and those taking sulfonylureas, but it focused on younger patients, aged 18-40 years, who underwent anterior cruciate ligament or meniscus surgery.

Using data from MarketScan commercial insurance claims databases between 2006 and 2020, the authors identified 2,376 participants who were taking metformin or a sulfonylurea when they underwent their surgery or began taking it in the 6 months after their surgery. More than half the participants were female (57%) with an average age of 35.

Within 5 years, 10.8% of those taking metformin developed osteoarthritis, compared with 17.9% of those taking a sulfonylurea. In addition, 3% of those taking metformin underwent a total knee replacement, compared with 5.3% of those taking a sulfonylurea. After adjustment for age, sex, obesity, and a history of chronic kidney disease, liver disease, and depression, however, both risk difference and odds ratios were not statistically significant.

Risk of osteoarthritis was 17% lower in patients taking metformin (95% confidence interval, –0.18 to 0.09), whose odds of osteoarthritis were approximately half the odds of those taking a sulfonylurea (OR, 0.5; 95% CI, 0.21-1.67). Risk of a total knee replacement was 10% lower in metformin users (95% CI, –0.28 to 0.08) with a similar reduction in odds, compared with those taking a sulfonylurea (OR, 0.53; 95% CI, 0.2-1.44).

In this study, the researchers did not specifically determine whether the participants were diagnosed with diabetes, but they assumed all, or at least most, were, according to S. Reza Jafarzadeh, PhD, DVM, an assistant professor of medicine at Boston University.

“The goal was not to only focus on the diabetes population, but on people who received that exposure [of metformin or sulfonylureas],” Dr. Jafarzadeh said in an interview. Dr. Jafarzadeh noted that a larger randomized controlled trial is underway to look at whether metformin reduces the risk of osteoarthritis independent of whether a patient has diabetes.

The published study was funded by grants from the National Institutes of Health, the Department of Veterans Affairs, and Stanford University, and the authors reported no disclosures. The poster at OARSI was funded by NIH and the Arthritis Foundation, and the authors reported no disclosures.

Patients taking metformin for type 2 diabetes had a lower risk of developing osteoarthritis than did patients taking a sulfonylurea, according to a cohort study published in JAMA Network Open. The findings jibe with those seen in a 2022 systematic review of preclinical and observational human studies finding potentially protective effects of metformin on osteoarthritis.

“Our study provides further, robust epidemiological evidence that metformin may be associated with protection in the development and progression of osteoarthritis in individuals with type 2 diabetes,” wrote Matthew C. Baker, MD, MS, an assistant professor of medicine in immunology and rheumatology at Stanford (Calif.) University, and his colleagues.

Thinglass/iStock Editorial/Getty Images

The findings also fit with the results of a poster presented at the Osteoarthritis Research Society International 2023 World Congress, although that abstract’s findings did not reach statistical significance.

In the published study, the researchers analyzed deidentified claims data from Optum’s Clinformatics Data Mart Database between December 2003 and December 2019. The database includes more than 15 million people with private insurance or Medicare Advantage Part D but does not include people with Medicaid, thereby excluding people from lower socioeconomic groups.

The researchers included all patients who were at least 40 years old, had type 2 diabetes, were taking metformin, and had been enrolled in the database for at least 1 uninterrupted year. They excluded anyone with type 1 diabetes or a prior diagnosis of osteoarthritis, inflammatory arthritis, or joint replacement. The authors then compared the incidence of osteoarthritis and joint replacement in these 20,937 participants to 20,937 control participants who were taking a sulfonylurea, matched to those taking metformin on the basis of age, sex, race, a comorbidity score, and duration of treatment. More than half the overall population (58%) was male with an average age of 62.

Patients needed to be on either drug for at least 3 months, but those who were initially treated with metformin before later taking a sulfonylurea could also be included and contribute to both groups. Those who first took a sulfonylurea and later switched to metformin were included only for the sulfonylurea group and censored after their switch to ensure the sulfonylurea group had enough participants. The comparison was further adjusted for age, sex, race, ethnicity, geographic region, education, comorbidities, and outpatient visit frequency.

The results revealed that those who were taking metformin were 24% less likely to develop osteoarthritis at least 3 months after starting the medication than were those taking a sulfonylurea (P < .001). The rate of joint replacements was not significantly different between those taking metformin and those taking a sulfonylurea. These two results did not change in a sensitivity analysis that compared patients who only ever took metformin or a sulfonylurea (as opposed to those who took one drug before switching to the other).

“When stratified by prior exposure to metformin within the sulfonylurea group, the observed benefit associated with metformin ... was attenuated in the people treated with a sulfonylurea with prior exposure to metformin, compared with those treated with a sulfonylurea with no prior exposure to metformin,” the authors further reported. A possible reason for this finding is that those taking a sulfonylurea after having previously taken metformin gained some protection from the earlier metformin exposure, the authors hypothesized.

This observational study could not show a causative effect from the metformin, but the researchers speculated on potential mechanisms if a causative effect were present, based on past research.

”Several preclinical studies have suggested a protective association of metformin in osteoarthritis through activating AMP-activated protein kinase signaling, decreasing the level of matrix metalloproteinase, increasing autophagy and reducing chondrocyte apoptosis, and augmenting chondroprotective and anti-inflammatory properties of mesenchymal stem cells,” the authors wrote.

Among this study’s limitations, however, was the lack of data on body mass index, which is associated with osteoarthritis in the literature and may differ between patients taking metformin versus a sulfonylurea. The researchers also did not have data on physical activity or a history of trauma to the joints, though there’s no reason to think these rates might differ between those taking one or the other medication.

Another substantial limitation is that all patients had type 2 diabetes, making it impossible to determine whether a similar protective effect from metformin might exist in people without diabetes.

Nonsignificant lower risk for posttraumatic knee osteoarthritis

Similar to the published study, the OARSI poster compared 5-year odds of incident osteoarthritis or total knee replacement surgery between patients taking metformin and those taking sulfonylureas, but it focused on younger patients, aged 18-40 years, who underwent anterior cruciate ligament or meniscus surgery.

Using data from MarketScan commercial insurance claims databases between 2006 and 2020, the authors identified 2,376 participants who were taking metformin or a sulfonylurea when they underwent their surgery or began taking it in the 6 months after their surgery. More than half the participants were female (57%) with an average age of 35.

Within 5 years, 10.8% of those taking metformin developed osteoarthritis, compared with 17.9% of those taking a sulfonylurea. In addition, 3% of those taking metformin underwent a total knee replacement, compared with 5.3% of those taking a sulfonylurea. After adjustment for age, sex, obesity, and a history of chronic kidney disease, liver disease, and depression, however, both risk difference and odds ratios were not statistically significant.

Risk of osteoarthritis was 17% lower in patients taking metformin (95% confidence interval, –0.18 to 0.09), whose odds of osteoarthritis were approximately half the odds of those taking a sulfonylurea (OR, 0.5; 95% CI, 0.21-1.67). Risk of a total knee replacement was 10% lower in metformin users (95% CI, –0.28 to 0.08) with a similar reduction in odds, compared with those taking a sulfonylurea (OR, 0.53; 95% CI, 0.2-1.44).

In this study, the researchers did not specifically determine whether the participants were diagnosed with diabetes, but they assumed all, or at least most, were, according to S. Reza Jafarzadeh, PhD, DVM, an assistant professor of medicine at Boston University.

“The goal was not to only focus on the diabetes population, but on people who received that exposure [of metformin or sulfonylureas],” Dr. Jafarzadeh said in an interview. Dr. Jafarzadeh noted that a larger randomized controlled trial is underway to look at whether metformin reduces the risk of osteoarthritis independent of whether a patient has diabetes.

The published study was funded by grants from the National Institutes of Health, the Department of Veterans Affairs, and Stanford University, and the authors reported no disclosures. The poster at OARSI was funded by NIH and the Arthritis Foundation, and the authors reported no disclosures.

Patients taking metformin for type 2 diabetes had a lower risk of developing osteoarthritis than did patients taking a sulfonylurea, according to a cohort study published in JAMA Network Open. The findings jibe with those seen in a 2022 systematic review of preclinical and observational human studies finding potentially protective effects of metformin on osteoarthritis.

“Our study provides further, robust epidemiological evidence that metformin may be associated with protection in the development and progression of osteoarthritis in individuals with type 2 diabetes,” wrote Matthew C. Baker, MD, MS, an assistant professor of medicine in immunology and rheumatology at Stanford (Calif.) University, and his colleagues.

Thinglass/iStock Editorial/Getty Images

The findings also fit with the results of a poster presented at the Osteoarthritis Research Society International 2023 World Congress, although that abstract’s findings did not reach statistical significance.

In the published study, the researchers analyzed deidentified claims data from Optum’s Clinformatics Data Mart Database between December 2003 and December 2019. The database includes more than 15 million people with private insurance or Medicare Advantage Part D but does not include people with Medicaid, thereby excluding people from lower socioeconomic groups.

The researchers included all patients who were at least 40 years old, had type 2 diabetes, were taking metformin, and had been enrolled in the database for at least 1 uninterrupted year. They excluded anyone with type 1 diabetes or a prior diagnosis of osteoarthritis, inflammatory arthritis, or joint replacement. The authors then compared the incidence of osteoarthritis and joint replacement in these 20,937 participants to 20,937 control participants who were taking a sulfonylurea, matched to those taking metformin on the basis of age, sex, race, a comorbidity score, and duration of treatment. More than half the overall population (58%) was male with an average age of 62.

Patients needed to be on either drug for at least 3 months, but those who were initially treated with metformin before later taking a sulfonylurea could also be included and contribute to both groups. Those who first took a sulfonylurea and later switched to metformin were included only for the sulfonylurea group and censored after their switch to ensure the sulfonylurea group had enough participants. The comparison was further adjusted for age, sex, race, ethnicity, geographic region, education, comorbidities, and outpatient visit frequency.

The results revealed that those who were taking metformin were 24% less likely to develop osteoarthritis at least 3 months after starting the medication than were those taking a sulfonylurea (P < .001). The rate of joint replacements was not significantly different between those taking metformin and those taking a sulfonylurea. These two results did not change in a sensitivity analysis that compared patients who only ever took metformin or a sulfonylurea (as opposed to those who took one drug before switching to the other).

“When stratified by prior exposure to metformin within the sulfonylurea group, the observed benefit associated with metformin ... was attenuated in the people treated with a sulfonylurea with prior exposure to metformin, compared with those treated with a sulfonylurea with no prior exposure to metformin,” the authors further reported. A possible reason for this finding is that those taking a sulfonylurea after having previously taken metformin gained some protection from the earlier metformin exposure, the authors hypothesized.

This observational study could not show a causative effect from the metformin, but the researchers speculated on potential mechanisms if a causative effect were present, based on past research.

”Several preclinical studies have suggested a protective association of metformin in osteoarthritis through activating AMP-activated protein kinase signaling, decreasing the level of matrix metalloproteinase, increasing autophagy and reducing chondrocyte apoptosis, and augmenting chondroprotective and anti-inflammatory properties of mesenchymal stem cells,” the authors wrote.

Among this study’s limitations, however, was the lack of data on body mass index, which is associated with osteoarthritis in the literature and may differ between patients taking metformin versus a sulfonylurea. The researchers also did not have data on physical activity or a history of trauma to the joints, though there’s no reason to think these rates might differ between those taking one or the other medication.

Another substantial limitation is that all patients had type 2 diabetes, making it impossible to determine whether a similar protective effect from metformin might exist in people without diabetes.

Nonsignificant lower risk for posttraumatic knee osteoarthritis

Similar to the published study, the OARSI poster compared 5-year odds of incident osteoarthritis or total knee replacement surgery between patients taking metformin and those taking sulfonylureas, but it focused on younger patients, aged 18-40 years, who underwent anterior cruciate ligament or meniscus surgery.

Using data from MarketScan commercial insurance claims databases between 2006 and 2020, the authors identified 2,376 participants who were taking metformin or a sulfonylurea when they underwent their surgery or began taking it in the 6 months after their surgery. More than half the participants were female (57%) with an average age of 35.

Within 5 years, 10.8% of those taking metformin developed osteoarthritis, compared with 17.9% of those taking a sulfonylurea. In addition, 3% of those taking metformin underwent a total knee replacement, compared with 5.3% of those taking a sulfonylurea. After adjustment for age, sex, obesity, and a history of chronic kidney disease, liver disease, and depression, however, both risk difference and odds ratios were not statistically significant.

Risk of osteoarthritis was 17% lower in patients taking metformin (95% confidence interval, –0.18 to 0.09), whose odds of osteoarthritis were approximately half the odds of those taking a sulfonylurea (OR, 0.5; 95% CI, 0.21-1.67). Risk of a total knee replacement was 10% lower in metformin users (95% CI, –0.28 to 0.08) with a similar reduction in odds, compared with those taking a sulfonylurea (OR, 0.53; 95% CI, 0.2-1.44).

In this study, the researchers did not specifically determine whether the participants were diagnosed with diabetes, but they assumed all, or at least most, were, according to S. Reza Jafarzadeh, PhD, DVM, an assistant professor of medicine at Boston University.

“The goal was not to only focus on the diabetes population, but on people who received that exposure [of metformin or sulfonylureas],” Dr. Jafarzadeh said in an interview. Dr. Jafarzadeh noted that a larger randomized controlled trial is underway to look at whether metformin reduces the risk of osteoarthritis independent of whether a patient has diabetes.

The published study was funded by grants from the National Institutes of Health, the Department of Veterans Affairs, and Stanford University, and the authors reported no disclosures. The poster at OARSI was funded by NIH and the Arthritis Foundation, and the authors reported no disclosures.

In an update to its 2016 recommendations for skin cancer screening, the U.S. Preventive Services Task Force (USPSTF) has once again determined that there is not enough evidence to recommend for or against screening with a visual skin exam in adolescents and adults without symptoms.

This final recommendation applies to the general public and is not meant for those at higher risk, such as people with a family history of skin cancer or who have any signs or symptoms, such as irregular moles.

“The new recommendations are consistent with those from 2016, and we are unable to balance benefits and harms,” said Task Force member Katrina Donahue, MD, MPH, professor and vice chair of research in the department of family medicine at the University of North Carolina, Chapel Hill. “Unfortunately, there is not enough evidence to recommend for or against screening, and health care professionals should use their judgment when deciding whether or not to screen.”

Dr. Donahue told this news organization that this is a call for more research: “Our recommendations are for patients who present to primary care without symptoms, and after a careful assessment of benefit and harms, we didn’t have evidence to push us towards screening as a benefit. We did look at data from two large screening programs, but they were from Europe and not representative of the U.S. population. They also did not show a benefit for reducing melanoma-related mortality.”

The USPSTF final recommendation statement and corresponding evidence summary have been published online in JAMA, as well as on the USPSTF website.

Skin cancer is the most commonly diagnosed cancer in the United States, but there are different types that vary in their incidence and severity. Basal and squamous cell carcinomas are the most common types of skin cancer, but they infrequently lead to death or substantial morbidity, notes the USPTSF. Melanomas represent about 1% of skin cancer and cause the most skin cancer deaths. An estimated 8,000 individuals in the United States will die of melanoma in 2023.

There are racial differences in melanoma incidence; it is about 30 times more common in White versus Black persons, but disease in persons with darker skin color tends to be diagnosed at a later stage. These disparities may be due to differences in risk factors, access to care, and clinical presentation.

In an accompanying editorial, Maryam M. Asgari, MD, MPH, of the department of dermatology, Massachusetts General Hospital, Boston, and Lori A. Crane, PhD, MPH, of the Colorado School of Public Health, University of Colorado, Aurora, point out that people with darker skin phenotypes also tend to be affected by skin cancers that are not associated with UV radiation, such as acral melanoma, which arises on the palms and soles, and skin cancers that arise in areas of chronic inflammation, such as wounds.

Review of evidence

The USPSTF commissioned a systematic review to evaluate the benefits and harms of screening for skin cancer in asymptomatic adolescents and adults, including evidence for both keratinocyte carcinoma (basal cell carcinoma and squamous cell carcinoma) and cutaneous melanoma.

Foundational evidence showed that the sensitivity of visual skin examination by a clinician to detect melanoma ranged from 40% to 70% and specificity ranged from 86% to 98%. Evidence that evaluated the diagnostic accuracy of visual skin examination to detect keratinocyte carcinoma was limited and inconsistent. There were no new studies reporting on diagnostic accuracy for an asymptomatic screening population.

The USPSTF also reviewed 20 studies in 29 articles (n = 6,053,411). This included three nonrandomized studies evaluating two skin cancer screening programs in Germany, but results were inconsistent. In addition, the ecological and nonrandomized design of the studies limited the conclusions that could be drawn and the applicability to a U.S. population was difficult to assess because of differences in population diversity and health care delivery in the United States.

Other nonrandomized studies that looked at various outcomes, such as harms and stage at diagnosis and melanoma or all-cause mortality, also did not provide sufficient evidence to support screening.
 

Research is needed

In a second accompanying editorial published in JAMA Dermatology, Adewole S. Adamson, MD, MPP, of the division of dermatology and dermatologic surgery at the University of Texas, Austin, pointed out that unlike other cancer screening programs, such as those for breast, colon, and prostate cancer, skin cancer screening programs are somewhat less organized.

The other programs focus on defined groups of the population, generally with easily identifiable characteristics such as age, sex, and family history, and importantly, there are always defined ages for initiation and halting of screening and intervals for screening frequency. None of these basic screening parameters have been widely adopted among dermatologists in the United States, he wrote. “One important reason why skin cancer screening has remained inconsistent is that it is not covered by Medicare or by many commercial insurance companies,” Dr. Adamson told this news organization. “The test, in this case the skin exam, is often performed as part of a routine dermatology visit.”

Dermatologists should take the lead on this, he said. “Dermatologists should push for a high quality prospective clinical trial of skin cancer screening, preferably in a high-risk population.”

Dr. Donahue agrees that research is needed, as noted in the recommendation. For example, studies are needed demonstrating consistent data of the effects of screening on morbidity and mortality or early detection of skin cancer, and clearer descriptions of skin color and inclusion of a full spectrum of skin colors in study participants. Clinical research is also needed on outcomes in participants that reflect the diversity of the U.S. population.

“I hope funding agencies will be interested in this area of study,” she said. “We put out the whole systematic review and point out the gaps. We need consistent evidence in detecting cancer early and reducing complications from skin cancer.”

The U.S. Congress mandates that the Agency for Healthcare Research and Quality support the operations of the USPSTF.

None of the USPSTF authors report any disclosures. Dr. Asgari reported receiving royalties from UpToDate. Dr. Crane did not make any disclosures. Dr. Adamson reported serving as an expert reviewer for the U.S. Preventive Services Task Force skin cancer screening report, as well as support from the Robert Wood Johnson Foundation, the Dermatology Foundation Public Health Career Development Award, the National Institutes of Health, the American Cancer Society, and Meredith’s Mission for Melanoma.

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

In an update to its 2016 recommendations for skin cancer screening, the U.S. Preventive Services Task Force (USPSTF) has once again determined that there is not enough evidence to recommend for or against screening with a visual skin exam in adolescents and adults without symptoms.

This final recommendation applies to the general public and is not meant for those at higher risk, such as people with a family history of skin cancer or who have any signs or symptoms, such as irregular moles.

“The new recommendations are consistent with those from 2016, and we are unable to balance benefits and harms,” said Task Force member Katrina Donahue, MD, MPH, professor and vice chair of research in the department of family medicine at the University of North Carolina, Chapel Hill. “Unfortunately, there is not enough evidence to recommend for or against screening, and health care professionals should use their judgment when deciding whether or not to screen.”

Dr. Donahue told this news organization that this is a call for more research: “Our recommendations are for patients who present to primary care without symptoms, and after a careful assessment of benefit and harms, we didn’t have evidence to push us towards screening as a benefit. We did look at data from two large screening programs, but they were from Europe and not representative of the U.S. population. They also did not show a benefit for reducing melanoma-related mortality.”

The USPSTF final recommendation statement and corresponding evidence summary have been published online in JAMA, as well as on the USPSTF website.

Skin cancer is the most commonly diagnosed cancer in the United States, but there are different types that vary in their incidence and severity. Basal and squamous cell carcinomas are the most common types of skin cancer, but they infrequently lead to death or substantial morbidity, notes the USPTSF. Melanomas represent about 1% of skin cancer and cause the most skin cancer deaths. An estimated 8,000 individuals in the United States will die of melanoma in 2023.

There are racial differences in melanoma incidence; it is about 30 times more common in White versus Black persons, but disease in persons with darker skin color tends to be diagnosed at a later stage. These disparities may be due to differences in risk factors, access to care, and clinical presentation.

In an accompanying editorial, Maryam M. Asgari, MD, MPH, of the department of dermatology, Massachusetts General Hospital, Boston, and Lori A. Crane, PhD, MPH, of the Colorado School of Public Health, University of Colorado, Aurora, point out that people with darker skin phenotypes also tend to be affected by skin cancers that are not associated with UV radiation, such as acral melanoma, which arises on the palms and soles, and skin cancers that arise in areas of chronic inflammation, such as wounds.

Review of evidence

The USPSTF commissioned a systematic review to evaluate the benefits and harms of screening for skin cancer in asymptomatic adolescents and adults, including evidence for both keratinocyte carcinoma (basal cell carcinoma and squamous cell carcinoma) and cutaneous melanoma.

Foundational evidence showed that the sensitivity of visual skin examination by a clinician to detect melanoma ranged from 40% to 70% and specificity ranged from 86% to 98%. Evidence that evaluated the diagnostic accuracy of visual skin examination to detect keratinocyte carcinoma was limited and inconsistent. There were no new studies reporting on diagnostic accuracy for an asymptomatic screening population.

The USPSTF also reviewed 20 studies in 29 articles (n = 6,053,411). This included three nonrandomized studies evaluating two skin cancer screening programs in Germany, but results were inconsistent. In addition, the ecological and nonrandomized design of the studies limited the conclusions that could be drawn and the applicability to a U.S. population was difficult to assess because of differences in population diversity and health care delivery in the United States.

Other nonrandomized studies that looked at various outcomes, such as harms and stage at diagnosis and melanoma or all-cause mortality, also did not provide sufficient evidence to support screening.
 

Research is needed

In a second accompanying editorial published in JAMA Dermatology, Adewole S. Adamson, MD, MPP, of the division of dermatology and dermatologic surgery at the University of Texas, Austin, pointed out that unlike other cancer screening programs, such as those for breast, colon, and prostate cancer, skin cancer screening programs are somewhat less organized.

The other programs focus on defined groups of the population, generally with easily identifiable characteristics such as age, sex, and family history, and importantly, there are always defined ages for initiation and halting of screening and intervals for screening frequency. None of these basic screening parameters have been widely adopted among dermatologists in the United States, he wrote. “One important reason why skin cancer screening has remained inconsistent is that it is not covered by Medicare or by many commercial insurance companies,” Dr. Adamson told this news organization. “The test, in this case the skin exam, is often performed as part of a routine dermatology visit.”

Dermatologists should take the lead on this, he said. “Dermatologists should push for a high quality prospective clinical trial of skin cancer screening, preferably in a high-risk population.”

Dr. Donahue agrees that research is needed, as noted in the recommendation. For example, studies are needed demonstrating consistent data of the effects of screening on morbidity and mortality or early detection of skin cancer, and clearer descriptions of skin color and inclusion of a full spectrum of skin colors in study participants. Clinical research is also needed on outcomes in participants that reflect the diversity of the U.S. population.

“I hope funding agencies will be interested in this area of study,” she said. “We put out the whole systematic review and point out the gaps. We need consistent evidence in detecting cancer early and reducing complications from skin cancer.”

The U.S. Congress mandates that the Agency for Healthcare Research and Quality support the operations of the USPSTF.

None of the USPSTF authors report any disclosures. Dr. Asgari reported receiving royalties from UpToDate. Dr. Crane did not make any disclosures. Dr. Adamson reported serving as an expert reviewer for the U.S. Preventive Services Task Force skin cancer screening report, as well as support from the Robert Wood Johnson Foundation, the Dermatology Foundation Public Health Career Development Award, the National Institutes of Health, the American Cancer Society, and Meredith’s Mission for Melanoma.

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

In an update to its 2016 recommendations for skin cancer screening, the U.S. Preventive Services Task Force (USPSTF) has once again determined that there is not enough evidence to recommend for or against screening with a visual skin exam in adolescents and adults without symptoms.

This final recommendation applies to the general public and is not meant for those at higher risk, such as people with a family history of skin cancer or who have any signs or symptoms, such as irregular moles.

“The new recommendations are consistent with those from 2016, and we are unable to balance benefits and harms,” said Task Force member Katrina Donahue, MD, MPH, professor and vice chair of research in the department of family medicine at the University of North Carolina, Chapel Hill. “Unfortunately, there is not enough evidence to recommend for or against screening, and health care professionals should use their judgment when deciding whether or not to screen.”

Dr. Donahue told this news organization that this is a call for more research: “Our recommendations are for patients who present to primary care without symptoms, and after a careful assessment of benefit and harms, we didn’t have evidence to push us towards screening as a benefit. We did look at data from two large screening programs, but they were from Europe and not representative of the U.S. population. They also did not show a benefit for reducing melanoma-related mortality.”

The USPSTF final recommendation statement and corresponding evidence summary have been published online in JAMA, as well as on the USPSTF website.

Skin cancer is the most commonly diagnosed cancer in the United States, but there are different types that vary in their incidence and severity. Basal and squamous cell carcinomas are the most common types of skin cancer, but they infrequently lead to death or substantial morbidity, notes the USPTSF. Melanomas represent about 1% of skin cancer and cause the most skin cancer deaths. An estimated 8,000 individuals in the United States will die of melanoma in 2023.

There are racial differences in melanoma incidence; it is about 30 times more common in White versus Black persons, but disease in persons with darker skin color tends to be diagnosed at a later stage. These disparities may be due to differences in risk factors, access to care, and clinical presentation.

In an accompanying editorial, Maryam M. Asgari, MD, MPH, of the department of dermatology, Massachusetts General Hospital, Boston, and Lori A. Crane, PhD, MPH, of the Colorado School of Public Health, University of Colorado, Aurora, point out that people with darker skin phenotypes also tend to be affected by skin cancers that are not associated with UV radiation, such as acral melanoma, which arises on the palms and soles, and skin cancers that arise in areas of chronic inflammation, such as wounds.

Review of evidence

The USPSTF commissioned a systematic review to evaluate the benefits and harms of screening for skin cancer in asymptomatic adolescents and adults, including evidence for both keratinocyte carcinoma (basal cell carcinoma and squamous cell carcinoma) and cutaneous melanoma.

Foundational evidence showed that the sensitivity of visual skin examination by a clinician to detect melanoma ranged from 40% to 70% and specificity ranged from 86% to 98%. Evidence that evaluated the diagnostic accuracy of visual skin examination to detect keratinocyte carcinoma was limited and inconsistent. There were no new studies reporting on diagnostic accuracy for an asymptomatic screening population.

The USPSTF also reviewed 20 studies in 29 articles (n = 6,053,411). This included three nonrandomized studies evaluating two skin cancer screening programs in Germany, but results were inconsistent. In addition, the ecological and nonrandomized design of the studies limited the conclusions that could be drawn and the applicability to a U.S. population was difficult to assess because of differences in population diversity and health care delivery in the United States.

Other nonrandomized studies that looked at various outcomes, such as harms and stage at diagnosis and melanoma or all-cause mortality, also did not provide sufficient evidence to support screening.
 

Research is needed

In a second accompanying editorial published in JAMA Dermatology, Adewole S. Adamson, MD, MPP, of the division of dermatology and dermatologic surgery at the University of Texas, Austin, pointed out that unlike other cancer screening programs, such as those for breast, colon, and prostate cancer, skin cancer screening programs are somewhat less organized.

The other programs focus on defined groups of the population, generally with easily identifiable characteristics such as age, sex, and family history, and importantly, there are always defined ages for initiation and halting of screening and intervals for screening frequency. None of these basic screening parameters have been widely adopted among dermatologists in the United States, he wrote. “One important reason why skin cancer screening has remained inconsistent is that it is not covered by Medicare or by many commercial insurance companies,” Dr. Adamson told this news organization. “The test, in this case the skin exam, is often performed as part of a routine dermatology visit.”

Dermatologists should take the lead on this, he said. “Dermatologists should push for a high quality prospective clinical trial of skin cancer screening, preferably in a high-risk population.”

Dr. Donahue agrees that research is needed, as noted in the recommendation. For example, studies are needed demonstrating consistent data of the effects of screening on morbidity and mortality or early detection of skin cancer, and clearer descriptions of skin color and inclusion of a full spectrum of skin colors in study participants. Clinical research is also needed on outcomes in participants that reflect the diversity of the U.S. population.

“I hope funding agencies will be interested in this area of study,” she said. “We put out the whole systematic review and point out the gaps. We need consistent evidence in detecting cancer early and reducing complications from skin cancer.”

The U.S. Congress mandates that the Agency for Healthcare Research and Quality support the operations of the USPSTF.

None of the USPSTF authors report any disclosures. Dr. Asgari reported receiving royalties from UpToDate. Dr. Crane did not make any disclosures. Dr. Adamson reported serving as an expert reviewer for the U.S. Preventive Services Task Force skin cancer screening report, as well as support from the Robert Wood Johnson Foundation, the Dermatology Foundation Public Health Career Development Award, the National Institutes of Health, the American Cancer Society, and Meredith’s Mission for Melanoma.

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

Rates of perinatal HIV have dropped so much that the disease is effectively eliminated in the United States, with less than 1 baby for every 100,000 live births having the virus, a new study released by researchers at the Centers for Disease Control and Prevention finds.

The report marks significant progress on the U.S. government’s goal to eradicate perinatal HIV, an immune-weakening and potentially deadly virus that is passed from mother to baby during pregnancy. Just 32 children in the country were diagnosed in 2019, compared with twice as many in 2010, according to the CDC.

Mothers who are HIV positive can prevent transmission of the infection by receiving antiretroviral therapy, according to Monica Gandhi, MD, MPH, a professor of medicine at University of California, San Francisco’s division of HIV, infectious disease and global medicine.

Dr. Gandhi said she could recall only one case of perinatal HIV in the San Francisco area over the last decade.

“This country has been really aggressive about counseling women who are pregnant and getting mothers in care,” Dr. Gandhi said.

The treatment method was discovered more than 30 years ago. Prior to the therapy and ensuing awareness campaigns to prevent transmission, mothers with HIV would typically pass the virus to their child in utero, during delivery, or while breastfeeding.

“There should be zero children born with HIV, given that we’ve had these drugs for so long,” Dr. Ghandi said. 
 

Disparities persist

But challenges remain in some communities, where babies born to Black mothers are disproportionately affected by the disease, the new study found. “Racial and ethnic differences in perinatal HIV diagnoses persisted through the 10-year period,” the report’s authors concluded. “The highest rates of perinatal HIV diagnoses were seen among infants born to Black women.”

Although rates of perinatal HIV declined for babies born to Black mothers over the decade-long study, the diagnosis rate was above the goal of elimination at 3.1 for every 100,000 live births, according to the data.

Meanwhile, transmission rates hovered around 1%-2% for Latinx and Hispanic women and mothers who identified as “other races,” including Native American.

Despite the availability of medication, expectant mothers may face several hurdles to getting the daily treatment they need to prevent transmission to their fetus, according to Jennifer Jao, MD, MPH, a physician of infectious diseases at Lurie Children’s Hospital of Chicago.

They might have trouble securing health insurance or finding transportation to doctor’s appointments, or face other problems like lacking secure housing or food – all factors that prevent them from prioritizing the care.

“All of those things play into the mix,” Dr. Jao said. “We see over and over again that closing the gap means you’ve got to reach the women who are pregnant and who don’t have resources.”
 

Progress in ‘danger’

Experts said they’re not sure what the impact of the COVID-19 pandemic, accompanied by a recent uptick in sexually transmitted diseases, will be on rates of perinatal HIV. Some women were unable to access prenatal health care during the pandemic because they couldn’t access public transportation or childcare, the U.S. Government Accountability Office said in 2022.

Globally, a decline in rates of HIV and AIDS rates has slowed, prompting the World Health Organization to warn last year that progress on the disease is in danger. Researchers only included HIV rates in the United States through 2019, so the data are outdated, Dr. Gandhi noted.

“All of this put together means we don’t know where we are with perinatal transmission over the last 3 years,” she said.

In an accompanying editorial, coauthors Nahida Chakhtoura, MD, MsGH, and Bill Kapogiannis, MD, both with the National Institutes of Health, urge health care professionals to take an active role in eliminating these racial and ethnic disparities in an effort to – as the title of their editorial proclaims – achieve a “road to zero perinatal HIV transmission” in the United States.

“The more proactive we are in identifying and promptly addressing systematic deficiencies that exacerbate health inequities in cutting-edge research innovations and optimal clinical service provision,” they write, “the less reactive we will need to be when new transmissible infections appear at our doorstep.”

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

Rates of perinatal HIV have dropped so much that the disease is effectively eliminated in the United States, with less than 1 baby for every 100,000 live births having the virus, a new study released by researchers at the Centers for Disease Control and Prevention finds.

The report marks significant progress on the U.S. government’s goal to eradicate perinatal HIV, an immune-weakening and potentially deadly virus that is passed from mother to baby during pregnancy. Just 32 children in the country were diagnosed in 2019, compared with twice as many in 2010, according to the CDC.

Mothers who are HIV positive can prevent transmission of the infection by receiving antiretroviral therapy, according to Monica Gandhi, MD, MPH, a professor of medicine at University of California, San Francisco’s division of HIV, infectious disease and global medicine.

Dr. Gandhi said she could recall only one case of perinatal HIV in the San Francisco area over the last decade.

“This country has been really aggressive about counseling women who are pregnant and getting mothers in care,” Dr. Gandhi said.

The treatment method was discovered more than 30 years ago. Prior to the therapy and ensuing awareness campaigns to prevent transmission, mothers with HIV would typically pass the virus to their child in utero, during delivery, or while breastfeeding.

“There should be zero children born with HIV, given that we’ve had these drugs for so long,” Dr. Ghandi said. 
 

Disparities persist

But challenges remain in some communities, where babies born to Black mothers are disproportionately affected by the disease, the new study found. “Racial and ethnic differences in perinatal HIV diagnoses persisted through the 10-year period,” the report’s authors concluded. “The highest rates of perinatal HIV diagnoses were seen among infants born to Black women.”

Although rates of perinatal HIV declined for babies born to Black mothers over the decade-long study, the diagnosis rate was above the goal of elimination at 3.1 for every 100,000 live births, according to the data.

Meanwhile, transmission rates hovered around 1%-2% for Latinx and Hispanic women and mothers who identified as “other races,” including Native American.

Despite the availability of medication, expectant mothers may face several hurdles to getting the daily treatment they need to prevent transmission to their fetus, according to Jennifer Jao, MD, MPH, a physician of infectious diseases at Lurie Children’s Hospital of Chicago.

They might have trouble securing health insurance or finding transportation to doctor’s appointments, or face other problems like lacking secure housing or food – all factors that prevent them from prioritizing the care.

“All of those things play into the mix,” Dr. Jao said. “We see over and over again that closing the gap means you’ve got to reach the women who are pregnant and who don’t have resources.”
 

Progress in ‘danger’

Experts said they’re not sure what the impact of the COVID-19 pandemic, accompanied by a recent uptick in sexually transmitted diseases, will be on rates of perinatal HIV. Some women were unable to access prenatal health care during the pandemic because they couldn’t access public transportation or childcare, the U.S. Government Accountability Office said in 2022.

Globally, a decline in rates of HIV and AIDS rates has slowed, prompting the World Health Organization to warn last year that progress on the disease is in danger. Researchers only included HIV rates in the United States through 2019, so the data are outdated, Dr. Gandhi noted.

“All of this put together means we don’t know where we are with perinatal transmission over the last 3 years,” she said.

In an accompanying editorial, coauthors Nahida Chakhtoura, MD, MsGH, and Bill Kapogiannis, MD, both with the National Institutes of Health, urge health care professionals to take an active role in eliminating these racial and ethnic disparities in an effort to – as the title of their editorial proclaims – achieve a “road to zero perinatal HIV transmission” in the United States.

“The more proactive we are in identifying and promptly addressing systematic deficiencies that exacerbate health inequities in cutting-edge research innovations and optimal clinical service provision,” they write, “the less reactive we will need to be when new transmissible infections appear at our doorstep.”

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

Rates of perinatal HIV have dropped so much that the disease is effectively eliminated in the United States, with less than 1 baby for every 100,000 live births having the virus, a new study released by researchers at the Centers for Disease Control and Prevention finds.

The report marks significant progress on the U.S. government’s goal to eradicate perinatal HIV, an immune-weakening and potentially deadly virus that is passed from mother to baby during pregnancy. Just 32 children in the country were diagnosed in 2019, compared with twice as many in 2010, according to the CDC.

Mothers who are HIV positive can prevent transmission of the infection by receiving antiretroviral therapy, according to Monica Gandhi, MD, MPH, a professor of medicine at University of California, San Francisco’s division of HIV, infectious disease and global medicine.

Dr. Gandhi said she could recall only one case of perinatal HIV in the San Francisco area over the last decade.

“This country has been really aggressive about counseling women who are pregnant and getting mothers in care,” Dr. Gandhi said.

The treatment method was discovered more than 30 years ago. Prior to the therapy and ensuing awareness campaigns to prevent transmission, mothers with HIV would typically pass the virus to their child in utero, during delivery, or while breastfeeding.

“There should be zero children born with HIV, given that we’ve had these drugs for so long,” Dr. Ghandi said. 
 

Disparities persist

But challenges remain in some communities, where babies born to Black mothers are disproportionately affected by the disease, the new study found. “Racial and ethnic differences in perinatal HIV diagnoses persisted through the 10-year period,” the report’s authors concluded. “The highest rates of perinatal HIV diagnoses were seen among infants born to Black women.”

Although rates of perinatal HIV declined for babies born to Black mothers over the decade-long study, the diagnosis rate was above the goal of elimination at 3.1 for every 100,000 live births, according to the data.

Meanwhile, transmission rates hovered around 1%-2% for Latinx and Hispanic women and mothers who identified as “other races,” including Native American.

Despite the availability of medication, expectant mothers may face several hurdles to getting the daily treatment they need to prevent transmission to their fetus, according to Jennifer Jao, MD, MPH, a physician of infectious diseases at Lurie Children’s Hospital of Chicago.

They might have trouble securing health insurance or finding transportation to doctor’s appointments, or face other problems like lacking secure housing or food – all factors that prevent them from prioritizing the care.

“All of those things play into the mix,” Dr. Jao said. “We see over and over again that closing the gap means you’ve got to reach the women who are pregnant and who don’t have resources.”
 

Progress in ‘danger’

Experts said they’re not sure what the impact of the COVID-19 pandemic, accompanied by a recent uptick in sexually transmitted diseases, will be on rates of perinatal HIV. Some women were unable to access prenatal health care during the pandemic because they couldn’t access public transportation or childcare, the U.S. Government Accountability Office said in 2022.

Globally, a decline in rates of HIV and AIDS rates has slowed, prompting the World Health Organization to warn last year that progress on the disease is in danger. Researchers only included HIV rates in the United States through 2019, so the data are outdated, Dr. Gandhi noted.

“All of this put together means we don’t know where we are with perinatal transmission over the last 3 years,” she said.

In an accompanying editorial, coauthors Nahida Chakhtoura, MD, MsGH, and Bill Kapogiannis, MD, both with the National Institutes of Health, urge health care professionals to take an active role in eliminating these racial and ethnic disparities in an effort to – as the title of their editorial proclaims – achieve a “road to zero perinatal HIV transmission” in the United States.

“The more proactive we are in identifying and promptly addressing systematic deficiencies that exacerbate health inequities in cutting-edge research innovations and optimal clinical service provision,” they write, “the less reactive we will need to be when new transmissible infections appear at our doorstep.”

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

The Food and Drug Administration approved omidubicel-onlv (Omisirge) for reducing infections and hastening neutrophil recovery for blood cancer patients aged 12 years and older who are undergoing allogeneic umbilical cord blood stem cell transplants.

Omidubicel is made from umbilical cord donor stem cells that are processed with nicotinamide, a form of vitamin B₃, to enhance and expand the number of progenitor cells, the product’s maker, Jerusalem-based Gamida Cell, explained in a press announcement.

The FDA approval was based on phase 3 testing that pitted the use of omidubicel in 62 patients against standard unmanipulated cord blood transplants in 63 patients following myeloablative conditioning.

The median time to neutrophil recovery was 12 days in the omidubicel group, compared with 22 days with standard care. Overall, 87% of patients who received omidubicel achieved neutrophil recovery versus 83% of patients with standard transplants.

The incidence of grade 2/3 bacterial or grade 3 fungal infections 100 days following transplant was 39% with omidubicel versus 60% with standard transplants.

The FDA’s “approval is an important advance in cell therapy treatment in patients with blood cancers. Hastening the return of the body’s white blood cells can reduce the possibility of serious or overwhelming infection associated with stem cell transplantation,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in an agency press release.

Abbey Jenkins, president and CEO of Gamida, called the approval “a major advancement in the treatment of patients with hematologic malignancies that we believe may increase access to stem cell transplant and help improve patient outcomes.”

The most common grade 3–5 adverse reactions in the approval study were pain (33%), mucosal inflammation (31%), hypertension (25%), and gastrointestinal toxicity (19%).

Adverse events are consistent with allogeneic hematopoietic stem cell transplantation. Among 117 patients who received omidubicel for any indication, infusion reactions occurred in 47% of patients, acute graft-versus-host disease occurred in 58%, chronic GVHD occurred in 35%, and graft failure occurred in 3%. Labeling includes a boxed warning of the possibilities. There is also a small risk of infections and malignancies from donor blood.

Omidubicel is manufactured in Gamida’s facility in Kiryat Gat, Israel. It is available for order now and is expected to be delivered to transplant centers within 30 days after the start of manufacturing, the company said.

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

The Food and Drug Administration approved omidubicel-onlv (Omisirge) for reducing infections and hastening neutrophil recovery for blood cancer patients aged 12 years and older who are undergoing allogeneic umbilical cord blood stem cell transplants.

Omidubicel is made from umbilical cord donor stem cells that are processed with nicotinamide, a form of vitamin B₃, to enhance and expand the number of progenitor cells, the product’s maker, Jerusalem-based Gamida Cell, explained in a press announcement.

The FDA approval was based on phase 3 testing that pitted the use of omidubicel in 62 patients against standard unmanipulated cord blood transplants in 63 patients following myeloablative conditioning.

The median time to neutrophil recovery was 12 days in the omidubicel group, compared with 22 days with standard care. Overall, 87% of patients who received omidubicel achieved neutrophil recovery versus 83% of patients with standard transplants.

The incidence of grade 2/3 bacterial or grade 3 fungal infections 100 days following transplant was 39% with omidubicel versus 60% with standard transplants.

The FDA’s “approval is an important advance in cell therapy treatment in patients with blood cancers. Hastening the return of the body’s white blood cells can reduce the possibility of serious or overwhelming infection associated with stem cell transplantation,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in an agency press release.

Abbey Jenkins, president and CEO of Gamida, called the approval “a major advancement in the treatment of patients with hematologic malignancies that we believe may increase access to stem cell transplant and help improve patient outcomes.”

The most common grade 3–5 adverse reactions in the approval study were pain (33%), mucosal inflammation (31%), hypertension (25%), and gastrointestinal toxicity (19%).

Adverse events are consistent with allogeneic hematopoietic stem cell transplantation. Among 117 patients who received omidubicel for any indication, infusion reactions occurred in 47% of patients, acute graft-versus-host disease occurred in 58%, chronic GVHD occurred in 35%, and graft failure occurred in 3%. Labeling includes a boxed warning of the possibilities. There is also a small risk of infections and malignancies from donor blood.

Omidubicel is manufactured in Gamida’s facility in Kiryat Gat, Israel. It is available for order now and is expected to be delivered to transplant centers within 30 days after the start of manufacturing, the company said.

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

The Food and Drug Administration approved omidubicel-onlv (Omisirge) for reducing infections and hastening neutrophil recovery for blood cancer patients aged 12 years and older who are undergoing allogeneic umbilical cord blood stem cell transplants.

Omidubicel is made from umbilical cord donor stem cells that are processed with nicotinamide, a form of vitamin B₃, to enhance and expand the number of progenitor cells, the product’s maker, Jerusalem-based Gamida Cell, explained in a press announcement.

The FDA approval was based on phase 3 testing that pitted the use of omidubicel in 62 patients against standard unmanipulated cord blood transplants in 63 patients following myeloablative conditioning.

The median time to neutrophil recovery was 12 days in the omidubicel group, compared with 22 days with standard care. Overall, 87% of patients who received omidubicel achieved neutrophil recovery versus 83% of patients with standard transplants.

The incidence of grade 2/3 bacterial or grade 3 fungal infections 100 days following transplant was 39% with omidubicel versus 60% with standard transplants.

The FDA’s “approval is an important advance in cell therapy treatment in patients with blood cancers. Hastening the return of the body’s white blood cells can reduce the possibility of serious or overwhelming infection associated with stem cell transplantation,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in an agency press release.

Abbey Jenkins, president and CEO of Gamida, called the approval “a major advancement in the treatment of patients with hematologic malignancies that we believe may increase access to stem cell transplant and help improve patient outcomes.”

The most common grade 3–5 adverse reactions in the approval study were pain (33%), mucosal inflammation (31%), hypertension (25%), and gastrointestinal toxicity (19%).

Adverse events are consistent with allogeneic hematopoietic stem cell transplantation. Among 117 patients who received omidubicel for any indication, infusion reactions occurred in 47% of patients, acute graft-versus-host disease occurred in 58%, chronic GVHD occurred in 35%, and graft failure occurred in 3%. Labeling includes a boxed warning of the possibilities. There is also a small risk of infections and malignancies from donor blood.

Omidubicel is manufactured in Gamida’s facility in Kiryat Gat, Israel. It is available for order now and is expected to be delivered to transplant centers within 30 days after the start of manufacturing, the company said.

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

Individuals at increased risk of type 2 diabetes may be able to reduce their risk via a novel intervention combining intermittent fasting (IF) with early time-restricted eating, indicate the results of a randomized controlled trial.

The study involved more than 200 individuals randomized to one of three groups: eat only in the morning (from 8:00 a.m. to noon) followed by 20 hours of fasting 3 days per week and eat as desired on the other days; daily calorie restriction to 70% of requirements; or standard weight loss advice.

The IF plus early time-restricted eating intervention was associated with a significant improvement in a key measure of glucose control versus calorie restriction at 6 months, while both interventions were linked to benefits in terms of cardiovascular risk markers and body composition, compared with the standard weight loss advice.

However, the research, published in Nature Medicine, showed that the additional benefit of IF plus early time-restricted eating did not persist, and less than half of participants were still following the plan at 18 months, compared with almost 80% of those in the calorie-restriction group.

“Following a time-restricted, IF diet could help lower the chances of developing type 2 diabetes,” senior author Leonie K. Heilbronn, PhD, University of Adelaide, South Australia, said in a press release.

This is “the largest study in the world to date, and the first powered to assess how the body processes and uses glucose after eating a meal,” with the latter being a better indicator of diabetes risk than a fasting glucose test, added first author Xiao Tong Teong, a PhD student, also at the University of Adelaide.

“The results of this study add to the growing body of evidence to indicate that meal timing and fasting advice extends the health benefits of a restricted-calorie diet, independently from weight loss, and this may be influential in clinical practice,” Ms. Teong added.
 

Adherence difficult to IF plus early time-restricted eating

Asked to comment, Krista Varady, PhD, said that the study design “would have been stronger if the time-restricted eating and IF interventions were separated” and compared.

“Time-restricted eating has been shown to naturally reduce calorie intake by 300-500 kcal/day,” she said in an interview, “so I’m not sure why the investigators chose to combine [it] with IF. It ... defeats the point of time-restricted eating.”

Dr. Varady, who recently coauthored a review of the clinical application of IF for weight loss, also doubted whether individuals would adhere to combined early time-restricted eating and IF. “In all honesty, I don’t think anyone would follow this diet for very long,” she said.

She added that the feasibility of this particular approach is “very questionable. In general, people don’t like diets that require them to skip dinner with family/friends on multiple days of the week,” explained Dr. Varady, professor of nutrition at the University of Illinois, Chicago.  “These regimens make social eating very difficult, which results in high attrition.

“Indeed, evidence from a recent large-scale observational study of nearly 800,000 adults shows that Americans who engage in time-restricted eating placed their eating window in the afternoon or evening,” she noted.

Dr. Varady therefore suggested that future trials should test “more feasible time-restricted eating approaches,” such as those with later eating windows and without “vigilant calorie monitoring.”

“These types of diets are much easier to follow and are more likely to produce lasting weight and glycemic control in people with obesity and prediabetes,” she observed.
 

A novel way to cut calories?

The Australian authors say there is growing interest in extending the established health benefits of calorie restriction through new approaches such as timing of meals and prolonged fasting, with IF – defined as fasting interspersed with days of ad libitum eating – gaining in popularity as an alternative to simple calorie restriction.

Time-restricted eating, which emphasizes shorter daily eating windows in alignment with circadian rhythms, has also become popular in recent years, although the authors acknowledge that current evidence suggests any benefits over calorie restriction alone in terms of body composition, blood lipids, or glucose parameters are small.

To examine the combination of IF plus early time-restricted eating, in the DIRECT trial, the team recruited individuals aged 35-75 years who had a score of at least 12 on the Australian Type 2 Diabetes Risk Assessment Tool but did not have a diagnosis of diabetes and had stable weight for more than 6 months prior to study entry.

The participants were randomized to one of three groups:

• IF plus early time-restricted eating, which allowed consumption of 30% of calculated baseline energy requirements between 8:00 a.m. and midday, followed by a 20-hour fast from midday on 3 nonconsecutive days per week. They consumed their regular diet on nonfasting days.
• Calorie restriction, where they consumed 70% of daily calculated baseline energy requirements each day and were given rotating menu plans, but no specific mealtimes.
• Standard care, where they were given a booklet on current guidelines, with no counseling or meal replacement.

There were clinic visits every 2 weeks for the first 6 months of follow-up, and then monthly visits for 12 months. The two intervention groups had one-on-one diet counseling for the first 6 months. All groups were instructed to maintain their usual physical activity levels.

A total of 209 individuals were enrolled between Sept. 26, 2018, and May 4, 2020. Their mean age was 58 years, and 57% were women. Mean body mass index was 34.8 kg/m².

In all, 40.7% of participants were allocated to IF plus early time-restricted eating, 39.7% to calorie restriction, and the remaining 19.6% to standard care.

The results showed that IF plus early time-restricted eating was associated with a significantly greater improvement in the primary outcome of postprandial glucose area under the curve (AUC) at month 6 compared with calorie restriction, at –10.1 mg/dL/min versus –3.6 mg/dL/min (P = .03).

“To our knowledge, no [prior] studies have been powered for postprandial assessments of glycemia, which are better indicators of diabetes risk than fasting assessment,” the authors underlined.

IF plus early time-restricted eating was also associated with greater reductions in postprandial insulin AUC versus calorie restriction at 6 months (P = .04). However, the differences between the IF plus early time-restricted eating and calorie restriction groups for postmeal insulin did not remain significant at 18 months of follow-up.

Both IF plus early time-restricted eating and calorie restriction were associated with greater reductions in A1c levels at 6 months versus standard care, but there was no significant difference between the two active interventions (P = .46).

Both interventions were also associated with improvements in markers of cardiovascular risk versus standard care, such as systolic blood pressure at 2 months, diastolic blood pressure at 6 months, and fasting triglycerides at both time points, with no significant differences between the two intervention groups.

IF plus early time-restricted eating and calorie restriction were also both associated with greater reductions in BMI and fat mass in the first 6 months, as well as in waist circumference.
 

Calorie restriction easier to stick to, less likely to cause fatigue

When offered the chance to modify their diet plan at 6 months, 46% of participants in the IF plus early time-restricted eating group said they would maintain 3 days of restrictions per week, while 51% chose to reduce the restrictions to 2 days per week.

In contrast, 97% of those who completed the calorie-restriction plan indicated they would continue with their current diet plan.

At 18 months, 42% of participants in the IF plus early time-restricted eating group said they still undertook 2-3 days of restrictions per week, while 78% of those assigned to calorie restriction reported that they followed a calorie-restricted diet.

Fatigue was more common with IF plus early time-restricted eating, reported by 56% of participants versus 37% of those following calorie restriction, and 35% of those in the standard care group at 6 months. Headaches and constipation were more common in the intervention groups than with standard care.

The study was supported by a National Health and Medical Research Council Project Grant, an Australian Government Research Training Program Scholarship from the University of Adelaide, and a Diabetes Australia Research Program Grant.

No relevant financial relationships were declared.
 

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

Individuals at increased risk of type 2 diabetes may be able to reduce their risk via a novel intervention combining intermittent fasting (IF) with early time-restricted eating, indicate the results of a randomized controlled trial.

The study involved more than 200 individuals randomized to one of three groups: eat only in the morning (from 8:00 a.m. to noon) followed by 20 hours of fasting 3 days per week and eat as desired on the other days; daily calorie restriction to 70% of requirements; or standard weight loss advice.

The IF plus early time-restricted eating intervention was associated with a significant improvement in a key measure of glucose control versus calorie restriction at 6 months, while both interventions were linked to benefits in terms of cardiovascular risk markers and body composition, compared with the standard weight loss advice.

However, the research, published in Nature Medicine, showed that the additional benefit of IF plus early time-restricted eating did not persist, and less than half of participants were still following the plan at 18 months, compared with almost 80% of those in the calorie-restriction group.

“Following a time-restricted, IF diet could help lower the chances of developing type 2 diabetes,” senior author Leonie K. Heilbronn, PhD, University of Adelaide, South Australia, said in a press release.

This is “the largest study in the world to date, and the first powered to assess how the body processes and uses glucose after eating a meal,” with the latter being a better indicator of diabetes risk than a fasting glucose test, added first author Xiao Tong Teong, a PhD student, also at the University of Adelaide.

“The results of this study add to the growing body of evidence to indicate that meal timing and fasting advice extends the health benefits of a restricted-calorie diet, independently from weight loss, and this may be influential in clinical practice,” Ms. Teong added.
 

Adherence difficult to IF plus early time-restricted eating

Asked to comment, Krista Varady, PhD, said that the study design “would have been stronger if the time-restricted eating and IF interventions were separated” and compared.

“Time-restricted eating has been shown to naturally reduce calorie intake by 300-500 kcal/day,” she said in an interview, “so I’m not sure why the investigators chose to combine [it] with IF. It ... defeats the point of time-restricted eating.”

Dr. Varady, who recently coauthored a review of the clinical application of IF for weight loss, also doubted whether individuals would adhere to combined early time-restricted eating and IF. “In all honesty, I don’t think anyone would follow this diet for very long,” she said.

She added that the feasibility of this particular approach is “very questionable. In general, people don’t like diets that require them to skip dinner with family/friends on multiple days of the week,” explained Dr. Varady, professor of nutrition at the University of Illinois, Chicago.  “These regimens make social eating very difficult, which results in high attrition.

“Indeed, evidence from a recent large-scale observational study of nearly 800,000 adults shows that Americans who engage in time-restricted eating placed their eating window in the afternoon or evening,” she noted.

Dr. Varady therefore suggested that future trials should test “more feasible time-restricted eating approaches,” such as those with later eating windows and without “vigilant calorie monitoring.”

“These types of diets are much easier to follow and are more likely to produce lasting weight and glycemic control in people with obesity and prediabetes,” she observed.
 

A novel way to cut calories?

The Australian authors say there is growing interest in extending the established health benefits of calorie restriction through new approaches such as timing of meals and prolonged fasting, with IF – defined as fasting interspersed with days of ad libitum eating – gaining in popularity as an alternative to simple calorie restriction.

Time-restricted eating, which emphasizes shorter daily eating windows in alignment with circadian rhythms, has also become popular in recent years, although the authors acknowledge that current evidence suggests any benefits over calorie restriction alone in terms of body composition, blood lipids, or glucose parameters are small.

To examine the combination of IF plus early time-restricted eating, in the DIRECT trial, the team recruited individuals aged 35-75 years who had a score of at least 12 on the Australian Type 2 Diabetes Risk Assessment Tool but did not have a diagnosis of diabetes and had stable weight for more than 6 months prior to study entry.

The participants were randomized to one of three groups:

• IF plus early time-restricted eating, which allowed consumption of 30% of calculated baseline energy requirements between 8:00 a.m. and midday, followed by a 20-hour fast from midday on 3 nonconsecutive days per week. They consumed their regular diet on nonfasting days.
• Calorie restriction, where they consumed 70% of daily calculated baseline energy requirements each day and were given rotating menu plans, but no specific mealtimes.
• Standard care, where they were given a booklet on current guidelines, with no counseling or meal replacement.

There were clinic visits every 2 weeks for the first 6 months of follow-up, and then monthly visits for 12 months. The two intervention groups had one-on-one diet counseling for the first 6 months. All groups were instructed to maintain their usual physical activity levels.

A total of 209 individuals were enrolled between Sept. 26, 2018, and May 4, 2020. Their mean age was 58 years, and 57% were women. Mean body mass index was 34.8 kg/m².

In all, 40.7% of participants were allocated to IF plus early time-restricted eating, 39.7% to calorie restriction, and the remaining 19.6% to standard care.

The results showed that IF plus early time-restricted eating was associated with a significantly greater improvement in the primary outcome of postprandial glucose area under the curve (AUC) at month 6 compared with calorie restriction, at –10.1 mg/dL/min versus –3.6 mg/dL/min (P = .03).

“To our knowledge, no [prior] studies have been powered for postprandial assessments of glycemia, which are better indicators of diabetes risk than fasting assessment,” the authors underlined.

IF plus early time-restricted eating was also associated with greater reductions in postprandial insulin AUC versus calorie restriction at 6 months (P = .04). However, the differences between the IF plus early time-restricted eating and calorie restriction groups for postmeal insulin did not remain significant at 18 months of follow-up.

Both IF plus early time-restricted eating and calorie restriction were associated with greater reductions in A1c levels at 6 months versus standard care, but there was no significant difference between the two active interventions (P = .46).

Both interventions were also associated with improvements in markers of cardiovascular risk versus standard care, such as systolic blood pressure at 2 months, diastolic blood pressure at 6 months, and fasting triglycerides at both time points, with no significant differences between the two intervention groups.

IF plus early time-restricted eating and calorie restriction were also both associated with greater reductions in BMI and fat mass in the first 6 months, as well as in waist circumference.
 

Calorie restriction easier to stick to, less likely to cause fatigue

When offered the chance to modify their diet plan at 6 months, 46% of participants in the IF plus early time-restricted eating group said they would maintain 3 days of restrictions per week, while 51% chose to reduce the restrictions to 2 days per week.

In contrast, 97% of those who completed the calorie-restriction plan indicated they would continue with their current diet plan.

At 18 months, 42% of participants in the IF plus early time-restricted eating group said they still undertook 2-3 days of restrictions per week, while 78% of those assigned to calorie restriction reported that they followed a calorie-restricted diet.

Fatigue was more common with IF plus early time-restricted eating, reported by 56% of participants versus 37% of those following calorie restriction, and 35% of those in the standard care group at 6 months. Headaches and constipation were more common in the intervention groups than with standard care.

The study was supported by a National Health and Medical Research Council Project Grant, an Australian Government Research Training Program Scholarship from the University of Adelaide, and a Diabetes Australia Research Program Grant.

No relevant financial relationships were declared.
 

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

Individuals at increased risk of type 2 diabetes may be able to reduce their risk via a novel intervention combining intermittent fasting (IF) with early time-restricted eating, indicate the results of a randomized controlled trial.

The study involved more than 200 individuals randomized to one of three groups: eat only in the morning (from 8:00 a.m. to noon) followed by 20 hours of fasting 3 days per week and eat as desired on the other days; daily calorie restriction to 70% of requirements; or standard weight loss advice.

The IF plus early time-restricted eating intervention was associated with a significant improvement in a key measure of glucose control versus calorie restriction at 6 months, while both interventions were linked to benefits in terms of cardiovascular risk markers and body composition, compared with the standard weight loss advice.

However, the research, published in Nature Medicine, showed that the additional benefit of IF plus early time-restricted eating did not persist, and less than half of participants were still following the plan at 18 months, compared with almost 80% of those in the calorie-restriction group.

“Following a time-restricted, IF diet could help lower the chances of developing type 2 diabetes,” senior author Leonie K. Heilbronn, PhD, University of Adelaide, South Australia, said in a press release.

This is “the largest study in the world to date, and the first powered to assess how the body processes and uses glucose after eating a meal,” with the latter being a better indicator of diabetes risk than a fasting glucose test, added first author Xiao Tong Teong, a PhD student, also at the University of Adelaide.

“The results of this study add to the growing body of evidence to indicate that meal timing and fasting advice extends the health benefits of a restricted-calorie diet, independently from weight loss, and this may be influential in clinical practice,” Ms. Teong added.
 

Adherence difficult to IF plus early time-restricted eating

Asked to comment, Krista Varady, PhD, said that the study design “would have been stronger if the time-restricted eating and IF interventions were separated” and compared.

“Time-restricted eating has been shown to naturally reduce calorie intake by 300-500 kcal/day,” she said in an interview, “so I’m not sure why the investigators chose to combine [it] with IF. It ... defeats the point of time-restricted eating.”

Dr. Varady, who recently coauthored a review of the clinical application of IF for weight loss, also doubted whether individuals would adhere to combined early time-restricted eating and IF. “In all honesty, I don’t think anyone would follow this diet for very long,” she said.

She added that the feasibility of this particular approach is “very questionable. In general, people don’t like diets that require them to skip dinner with family/friends on multiple days of the week,” explained Dr. Varady, professor of nutrition at the University of Illinois, Chicago.  “These regimens make social eating very difficult, which results in high attrition.

“Indeed, evidence from a recent large-scale observational study of nearly 800,000 adults shows that Americans who engage in time-restricted eating placed their eating window in the afternoon or evening,” she noted.

Dr. Varady therefore suggested that future trials should test “more feasible time-restricted eating approaches,” such as those with later eating windows and without “vigilant calorie monitoring.”

“These types of diets are much easier to follow and are more likely to produce lasting weight and glycemic control in people with obesity and prediabetes,” she observed.
 

A novel way to cut calories?

The Australian authors say there is growing interest in extending the established health benefits of calorie restriction through new approaches such as timing of meals and prolonged fasting, with IF – defined as fasting interspersed with days of ad libitum eating – gaining in popularity as an alternative to simple calorie restriction.

Time-restricted eating, which emphasizes shorter daily eating windows in alignment with circadian rhythms, has also become popular in recent years, although the authors acknowledge that current evidence suggests any benefits over calorie restriction alone in terms of body composition, blood lipids, or glucose parameters are small.

To examine the combination of IF plus early time-restricted eating, in the DIRECT trial, the team recruited individuals aged 35-75 years who had a score of at least 12 on the Australian Type 2 Diabetes Risk Assessment Tool but did not have a diagnosis of diabetes and had stable weight for more than 6 months prior to study entry.

The participants were randomized to one of three groups:

• IF plus early time-restricted eating, which allowed consumption of 30% of calculated baseline energy requirements between 8:00 a.m. and midday, followed by a 20-hour fast from midday on 3 nonconsecutive days per week. They consumed their regular diet on nonfasting days.
• Calorie restriction, where they consumed 70% of daily calculated baseline energy requirements each day and were given rotating menu plans, but no specific mealtimes.
• Standard care, where they were given a booklet on current guidelines, with no counseling or meal replacement.

There were clinic visits every 2 weeks for the first 6 months of follow-up, and then monthly visits for 12 months. The two intervention groups had one-on-one diet counseling for the first 6 months. All groups were instructed to maintain their usual physical activity levels.

A total of 209 individuals were enrolled between Sept. 26, 2018, and May 4, 2020. Their mean age was 58 years, and 57% were women. Mean body mass index was 34.8 kg/m².

In all, 40.7% of participants were allocated to IF plus early time-restricted eating, 39.7% to calorie restriction, and the remaining 19.6% to standard care.

The results showed that IF plus early time-restricted eating was associated with a significantly greater improvement in the primary outcome of postprandial glucose area under the curve (AUC) at month 6 compared with calorie restriction, at –10.1 mg/dL/min versus –3.6 mg/dL/min (P = .03).

“To our knowledge, no [prior] studies have been powered for postprandial assessments of glycemia, which are better indicators of diabetes risk than fasting assessment,” the authors underlined.

IF plus early time-restricted eating was also associated with greater reductions in postprandial insulin AUC versus calorie restriction at 6 months (P = .04). However, the differences between the IF plus early time-restricted eating and calorie restriction groups for postmeal insulin did not remain significant at 18 months of follow-up.

Both IF plus early time-restricted eating and calorie restriction were associated with greater reductions in A1c levels at 6 months versus standard care, but there was no significant difference between the two active interventions (P = .46).

Both interventions were also associated with improvements in markers of cardiovascular risk versus standard care, such as systolic blood pressure at 2 months, diastolic blood pressure at 6 months, and fasting triglycerides at both time points, with no significant differences between the two intervention groups.

IF plus early time-restricted eating and calorie restriction were also both associated with greater reductions in BMI and fat mass in the first 6 months, as well as in waist circumference.
 

Calorie restriction easier to stick to, less likely to cause fatigue

When offered the chance to modify their diet plan at 6 months, 46% of participants in the IF plus early time-restricted eating group said they would maintain 3 days of restrictions per week, while 51% chose to reduce the restrictions to 2 days per week.

In contrast, 97% of those who completed the calorie-restriction plan indicated they would continue with their current diet plan.

At 18 months, 42% of participants in the IF plus early time-restricted eating group said they still undertook 2-3 days of restrictions per week, while 78% of those assigned to calorie restriction reported that they followed a calorie-restricted diet.

Fatigue was more common with IF plus early time-restricted eating, reported by 56% of participants versus 37% of those following calorie restriction, and 35% of those in the standard care group at 6 months. Headaches and constipation were more common in the intervention groups than with standard care.

The study was supported by a National Health and Medical Research Council Project Grant, an Australian Government Research Training Program Scholarship from the University of Adelaide, and a Diabetes Australia Research Program Grant.

No relevant financial relationships were declared.
 

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

The U.S. Food and Drug Administration has granted breakthrough device designation to the Avantis spinal cord stimulation system (Reach Neuro), which has been shown in early testing to restore arm and hand movement in patients with post-stroke upper limb paresis.

“We are excited about the FDA’s recognition of our technology’s potential to change the lives of millions of people living with disability,” Marc Powell, PhD, CEO, and co-founder of Reach Neuro, said in a company news release.

“The breakthrough device designation is an incredible opportunity to work closely with FDA experts to expedite the clinical translation of the Avantis system,” Dr. Powell added.

Results of the first-in-human study of the system were published in Nature Medicine.

Investigators percutaneously implanted two linear leads in the dorsolateral epidural space targeting neural circuits that control arm and hand muscles in two chronic post-stroke patients.

In both patients, continuous stimulation of the targeted neural circuits led to significant and immediate improvement in arm and hand strength and dexterity. This enabled the patients to perform movements that they couldn’t perform without spinal cord stimulation.

The process also enabled fine motor skills, such as opening a lock and using utensils to eat independently – tasks that one patient had not been able to do for 9 years.

“Having the stimulation working and being able to move my arm/hand again after 9 years was one of the most surreal experiences of my life – it was as if my brain was in control of my arm again. This technology gave me such immense hope that one day I will regain a sense of independence again,” study participant Heather Rendulic said in the news release.

Surprisingly, some improvements were retained up to 1 month after the study, even without stimulation. No serious adverse events were reported.

Nearly three-quarters of patients with stroke experience lasting deficits in motor control of their arm and hand as a result of permanent damage to the brain’s ability to send signals to muscles.

The early results with the Avantis system provide “promising, albeit preliminary, evidence that spinal cord stimulation could be an assistive as well as a restorative approach for upper-limb recovery after stroke,” the study team said in Nature Medicine.

Reach Neuro was founded in 2021 as a spinout company of the University of Pittsburgh and Carnegie Mellon University, also in Pittsburgh, where the technology is currently being tested in a clinical trial funded by the National Institutes of Health.

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

The U.S. Food and Drug Administration has granted breakthrough device designation to the Avantis spinal cord stimulation system (Reach Neuro), which has been shown in early testing to restore arm and hand movement in patients with post-stroke upper limb paresis.

“We are excited about the FDA’s recognition of our technology’s potential to change the lives of millions of people living with disability,” Marc Powell, PhD, CEO, and co-founder of Reach Neuro, said in a company news release.

“The breakthrough device designation is an incredible opportunity to work closely with FDA experts to expedite the clinical translation of the Avantis system,” Dr. Powell added.

Results of the first-in-human study of the system were published in Nature Medicine.

Investigators percutaneously implanted two linear leads in the dorsolateral epidural space targeting neural circuits that control arm and hand muscles in two chronic post-stroke patients.

In both patients, continuous stimulation of the targeted neural circuits led to significant and immediate improvement in arm and hand strength and dexterity. This enabled the patients to perform movements that they couldn’t perform without spinal cord stimulation.

The process also enabled fine motor skills, such as opening a lock and using utensils to eat independently – tasks that one patient had not been able to do for 9 years.

“Having the stimulation working and being able to move my arm/hand again after 9 years was one of the most surreal experiences of my life – it was as if my brain was in control of my arm again. This technology gave me such immense hope that one day I will regain a sense of independence again,” study participant Heather Rendulic said in the news release.

Surprisingly, some improvements were retained up to 1 month after the study, even without stimulation. No serious adverse events were reported.

Nearly three-quarters of patients with stroke experience lasting deficits in motor control of their arm and hand as a result of permanent damage to the brain’s ability to send signals to muscles.

The early results with the Avantis system provide “promising, albeit preliminary, evidence that spinal cord stimulation could be an assistive as well as a restorative approach for upper-limb recovery after stroke,” the study team said in Nature Medicine.

Reach Neuro was founded in 2021 as a spinout company of the University of Pittsburgh and Carnegie Mellon University, also in Pittsburgh, where the technology is currently being tested in a clinical trial funded by the National Institutes of Health.

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

The U.S. Food and Drug Administration has granted breakthrough device designation to the Avantis spinal cord stimulation system (Reach Neuro), which has been shown in early testing to restore arm and hand movement in patients with post-stroke upper limb paresis.

“We are excited about the FDA’s recognition of our technology’s potential to change the lives of millions of people living with disability,” Marc Powell, PhD, CEO, and co-founder of Reach Neuro, said in a company news release.

“The breakthrough device designation is an incredible opportunity to work closely with FDA experts to expedite the clinical translation of the Avantis system,” Dr. Powell added.

Results of the first-in-human study of the system were published in Nature Medicine.

Investigators percutaneously implanted two linear leads in the dorsolateral epidural space targeting neural circuits that control arm and hand muscles in two chronic post-stroke patients.

In both patients, continuous stimulation of the targeted neural circuits led to significant and immediate improvement in arm and hand strength and dexterity. This enabled the patients to perform movements that they couldn’t perform without spinal cord stimulation.

The process also enabled fine motor skills, such as opening a lock and using utensils to eat independently – tasks that one patient had not been able to do for 9 years.

“Having the stimulation working and being able to move my arm/hand again after 9 years was one of the most surreal experiences of my life – it was as if my brain was in control of my arm again. This technology gave me such immense hope that one day I will regain a sense of independence again,” study participant Heather Rendulic said in the news release.

Surprisingly, some improvements were retained up to 1 month after the study, even without stimulation. No serious adverse events were reported.

Nearly three-quarters of patients with stroke experience lasting deficits in motor control of their arm and hand as a result of permanent damage to the brain’s ability to send signals to muscles.

The early results with the Avantis system provide “promising, albeit preliminary, evidence that spinal cord stimulation could be an assistive as well as a restorative approach for upper-limb recovery after stroke,” the study team said in Nature Medicine.

Reach Neuro was founded in 2021 as a spinout company of the University of Pittsburgh and Carnegie Mellon University, also in Pittsburgh, where the technology is currently being tested in a clinical trial funded by the National Institutes of Health.

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

Pediatricians increasingly are stepping in to prescribe drugs for anxiety and depression independently, easing the burden on subspecialists amid the child and adolescent mental health crisis, but a review of electronic health records highlights areas for improvement in delivering the care.

The findings were published online in Pediatrics.

The researchers, led by Talia R. Lester, MD, with the division of developmental behavioral pediatrics in the quantitative science unit at Stanford (Calif.) University, identified 1,685 patients aged 6-18 years who had at least one visit with a diagnosis of anxiety and/or depression in a large primary care network in northern California and who were prescribed an SSRI by a network primary care pediatrician (PCP). The team randomly chose 110 patients and reviewed charts from the visit when the SSRI was first prescribed (medication visit); the immediately previous visit; and immediately subsequent visit.
 

Encouraging signs

The chart reviews showed some encouraging signs. For example, when pediatricians prescribe an SSRI, 82% are appropriately documenting rationales for starting the medication at the medication visit. However, they are not monitoring medication side effects systematically, according to the report. Of 69 patients with a visit after the medication visit, fewer than half (48%) had documentation of monitoring for side effects.

Three areas for improvement

The researchers identified three main shortfall areas and suggested improvements.

PCPs often referred patients for unspecified therapy at the medication visit; however, they rarely prescribed evidence-based therapies such as cognitive-behavioral therapy (CBT) (4% of patients). The authors suggested embedding a summary of evidence-based treatment into order sets.

Secondly, PCPs are not often using screening tools. The data show only 26% of patients had a documented depression- or anxiety-specific screening tool result at the medication visit. The authors recommend making the screening tools accessible through the EHR to increase use.

The researchers also found many patients didn’t have a follow-up visit after SSRI medication was prescribed. Even when they did, the range was so wide between the medication visit and the follow-up (7-365 days) that it’s clear pediatricians are taking inconsistent approaches to scheduling follow-up.
 

Half are seeing only their primary care pediatrician

About half of children and adolescents prescribed an SSRI by a pediatrician for mental health reasons were seeing only their primary care pediatrician, the data showed.

Eric M. Butter, PhD, chief of psychology at Nationwide Children’s Hospital and Ohio State University, Columbus, pointed out in an accompanying editorial that some of the news in pediatricians’ expanded role is particularly encouraging.

Pediatricians, he noted, are making medication decisions consistent with decisions a subspecialist would make.

Of cases in which a subspecialist became involved after a pediatrician initiated medication, subspecialists changed the medication for only two patients, which “is encouraging because it validates pediatricians’ decisions,” Dr. Butter said.

It’s important for pediatricians to understand key evidence-based programs that can work in combination with medications to achieve better results, Dr. Butter said. For example, CBT can help with depression “and break the cycle of avoidance that worsens symptoms of anxiety.”

He highlighted Interpersonal Therapy for Adolescents, a 12-session treatment that “can also address depression by improving patients’ personal relationships.”

“No primary care pediatrician will have the training or time to implement the many treatments that are available,” Dr. Butter wrote. “However, pediatricians can work to understand the key features of the evidence-based treatments referenced by Lester et al.”
 

Most concerning statistics

Dr. Butter said the most concerning shortcoming in the pediatricians’ health care delivery was lack of referral for evidence-based psychological treatments and low rates for referral to access supports from schools through programs such as the education 504 plan and Individualized Education Plans.

Dr. Lester’s team found that pediatricians recommended that patients receive support from such programs in only 8% of cases.

“The children’s mental health crisis requires all child-serving health care providers to do more. Improved care for anxiety and depression in pediatric primary care is needed and does not have to be overly burdensome to pediatricians,” Dr. Butter wrote.

The authors and Dr. Butter declared no relevant financial relationships.

Pediatricians increasingly are stepping in to prescribe drugs for anxiety and depression independently, easing the burden on subspecialists amid the child and adolescent mental health crisis, but a review of electronic health records highlights areas for improvement in delivering the care.

The findings were published online in Pediatrics.

The researchers, led by Talia R. Lester, MD, with the division of developmental behavioral pediatrics in the quantitative science unit at Stanford (Calif.) University, identified 1,685 patients aged 6-18 years who had at least one visit with a diagnosis of anxiety and/or depression in a large primary care network in northern California and who were prescribed an SSRI by a network primary care pediatrician (PCP). The team randomly chose 110 patients and reviewed charts from the visit when the SSRI was first prescribed (medication visit); the immediately previous visit; and immediately subsequent visit.
 

Encouraging signs

The chart reviews showed some encouraging signs. For example, when pediatricians prescribe an SSRI, 82% are appropriately documenting rationales for starting the medication at the medication visit. However, they are not monitoring medication side effects systematically, according to the report. Of 69 patients with a visit after the medication visit, fewer than half (48%) had documentation of monitoring for side effects.

Three areas for improvement

The researchers identified three main shortfall areas and suggested improvements.

PCPs often referred patients for unspecified therapy at the medication visit; however, they rarely prescribed evidence-based therapies such as cognitive-behavioral therapy (CBT) (4% of patients). The authors suggested embedding a summary of evidence-based treatment into order sets.

Secondly, PCPs are not often using screening tools. The data show only 26% of patients had a documented depression- or anxiety-specific screening tool result at the medication visit. The authors recommend making the screening tools accessible through the EHR to increase use.

The researchers also found many patients didn’t have a follow-up visit after SSRI medication was prescribed. Even when they did, the range was so wide between the medication visit and the follow-up (7-365 days) that it’s clear pediatricians are taking inconsistent approaches to scheduling follow-up.
 

Half are seeing only their primary care pediatrician

About half of children and adolescents prescribed an SSRI by a pediatrician for mental health reasons were seeing only their primary care pediatrician, the data showed.

Eric M. Butter, PhD, chief of psychology at Nationwide Children’s Hospital and Ohio State University, Columbus, pointed out in an accompanying editorial that some of the news in pediatricians’ expanded role is particularly encouraging.

Pediatricians, he noted, are making medication decisions consistent with decisions a subspecialist would make.

Of cases in which a subspecialist became involved after a pediatrician initiated medication, subspecialists changed the medication for only two patients, which “is encouraging because it validates pediatricians’ decisions,” Dr. Butter said.

It’s important for pediatricians to understand key evidence-based programs that can work in combination with medications to achieve better results, Dr. Butter said. For example, CBT can help with depression “and break the cycle of avoidance that worsens symptoms of anxiety.”

He highlighted Interpersonal Therapy for Adolescents, a 12-session treatment that “can also address depression by improving patients’ personal relationships.”

“No primary care pediatrician will have the training or time to implement the many treatments that are available,” Dr. Butter wrote. “However, pediatricians can work to understand the key features of the evidence-based treatments referenced by Lester et al.”
 

Most concerning statistics

Dr. Butter said the most concerning shortcoming in the pediatricians’ health care delivery was lack of referral for evidence-based psychological treatments and low rates for referral to access supports from schools through programs such as the education 504 plan and Individualized Education Plans.

Dr. Lester’s team found that pediatricians recommended that patients receive support from such programs in only 8% of cases.

“The children’s mental health crisis requires all child-serving health care providers to do more. Improved care for anxiety and depression in pediatric primary care is needed and does not have to be overly burdensome to pediatricians,” Dr. Butter wrote.

The authors and Dr. Butter declared no relevant financial relationships.

Pediatricians increasingly are stepping in to prescribe drugs for anxiety and depression independently, easing the burden on subspecialists amid the child and adolescent mental health crisis, but a review of electronic health records highlights areas for improvement in delivering the care.

The findings were published online in Pediatrics.

The researchers, led by Talia R. Lester, MD, with the division of developmental behavioral pediatrics in the quantitative science unit at Stanford (Calif.) University, identified 1,685 patients aged 6-18 years who had at least one visit with a diagnosis of anxiety and/or depression in a large primary care network in northern California and who were prescribed an SSRI by a network primary care pediatrician (PCP). The team randomly chose 110 patients and reviewed charts from the visit when the SSRI was first prescribed (medication visit); the immediately previous visit; and immediately subsequent visit.
 

Encouraging signs

The chart reviews showed some encouraging signs. For example, when pediatricians prescribe an SSRI, 82% are appropriately documenting rationales for starting the medication at the medication visit. However, they are not monitoring medication side effects systematically, according to the report. Of 69 patients with a visit after the medication visit, fewer than half (48%) had documentation of monitoring for side effects.

Three areas for improvement

The researchers identified three main shortfall areas and suggested improvements.

PCPs often referred patients for unspecified therapy at the medication visit; however, they rarely prescribed evidence-based therapies such as cognitive-behavioral therapy (CBT) (4% of patients). The authors suggested embedding a summary of evidence-based treatment into order sets.

Secondly, PCPs are not often using screening tools. The data show only 26% of patients had a documented depression- or anxiety-specific screening tool result at the medication visit. The authors recommend making the screening tools accessible through the EHR to increase use.

The researchers also found many patients didn’t have a follow-up visit after SSRI medication was prescribed. Even when they did, the range was so wide between the medication visit and the follow-up (7-365 days) that it’s clear pediatricians are taking inconsistent approaches to scheduling follow-up.
 

Half are seeing only their primary care pediatrician

About half of children and adolescents prescribed an SSRI by a pediatrician for mental health reasons were seeing only their primary care pediatrician, the data showed.

Eric M. Butter, PhD, chief of psychology at Nationwide Children’s Hospital and Ohio State University, Columbus, pointed out in an accompanying editorial that some of the news in pediatricians’ expanded role is particularly encouraging.

Pediatricians, he noted, are making medication decisions consistent with decisions a subspecialist would make.

Of cases in which a subspecialist became involved after a pediatrician initiated medication, subspecialists changed the medication for only two patients, which “is encouraging because it validates pediatricians’ decisions,” Dr. Butter said.

It’s important for pediatricians to understand key evidence-based programs that can work in combination with medications to achieve better results, Dr. Butter said. For example, CBT can help with depression “and break the cycle of avoidance that worsens symptoms of anxiety.”

He highlighted Interpersonal Therapy for Adolescents, a 12-session treatment that “can also address depression by improving patients’ personal relationships.”

“No primary care pediatrician will have the training or time to implement the many treatments that are available,” Dr. Butter wrote. “However, pediatricians can work to understand the key features of the evidence-based treatments referenced by Lester et al.”
 

Most concerning statistics

Dr. Butter said the most concerning shortcoming in the pediatricians’ health care delivery was lack of referral for evidence-based psychological treatments and low rates for referral to access supports from schools through programs such as the education 504 plan and Individualized Education Plans.

Dr. Lester’s team found that pediatricians recommended that patients receive support from such programs in only 8% of cases.

“The children’s mental health crisis requires all child-serving health care providers to do more. Improved care for anxiety and depression in pediatric primary care is needed and does not have to be overly burdensome to pediatricians,” Dr. Butter wrote.

The authors and Dr. Butter declared no relevant financial relationships.