MDedge Rheumatology

Exercising to lose weight is not for every ‘body’

This first item comes from the “You’ve got to be kidding” section of LOTME’s supersecret topics-of-interest file.

Maya23K/Thinkstock

Investigators at the Shenzhen Institute of Advanced Technology of the Chinese Academy of Sciences and the University of Roehampton noticed that some people who enrolled in exercise programs to lose weight did just the opposite: they gained weight.

Being scientists, they decided to look at the effects of energy expenditure and how those effects varied among individuals. The likely culprit in this case, they determined, is something called compensatory mechanisms. One such mechanism involves eating more food because exercise stimulates appetite, and another might reduce energy expenditure on other components like resting metabolism so that the exercise is, in effect, less costly.

A look at the numbers shows how compensatory mechanisms worked in the study population of 1,750 adults. Among individuals with the highest BMI, 51% of the calories burned during activity translated into calories burned at the end of the day. For those with normal BMI, however, 72% of calories burned during activity were reflected in total expenditure.

“People living with obesity cut back their resting metabolism when they are more active. The result is that for every calorie they spend on exercise they save about half a calorie on resting,” the investigators explained.

In other words, some bodies will, unconsciously, work against the conscious effort of exercising to lose weight. Thank you very much, compensatory mechanisms, for the boundarylessness exhibited in exceeding your job description.
 

When it comes to the mix, walnuts go nuts

When it comes to mixed nuts, walnuts get no love. But we may be able to give you a reason to not pick them out: Your arteries.

PxHere

Participants in a recent study who ate about a half-cup of walnuts every day for 2 years saw a drop in their low-density lipoprotein (LDL) cholesterol. The number and quality of LDL particles in healthy older adults also improved. How? Good ol’ omega-3 fatty acids.

Omega-3 is found in many foods linked to lower risks of heart disease, lower cholesterol levels, and lower blood sugar levels, but the one thing that makes the walnut a front runner for Miss Super Food 2021 is their ability to improve the quality of LDL particles.

“LDL particles come in various sizes [and] research has shown that small, dense LDL particles are more often associated with atherosclerosis, the plaque or fatty deposits that build up in the arteries,” Emilio Ros, MD, PhD, of the Hospital Clínic of Barcelona and the study’s senior investigator, said in a written statement.

The 708 participants, aged 63-79 years and mostly women, were divided into two groups: One received the walnut diet and the other did not. After 2 years, the walnut group had lower LDL levels by an average of 4.3 mg/dL. Total cholesterol was reduced by an average of 8.5 mg/dL. Also, their total LDL particle count was 4.3% lower and small LDL particles were down by 6.1%.

So instead of picking the walnuts out of the mix, try to find it in your heart to appreciate them. Your body already does.
 

Begun, the clone war has

Well, not quite yet, Master Yoda, but perhaps one day soon, if a study from Japan into the uncanny valley of the usage of cloned humanlike faces in robotics and artificial intelligence, published in PLOS One, is to be believed.

Patrick Bursa/Pixabay

The study consisted of a number of six smaller experiments in which participants judged a series of images based on subjective eeriness, emotional valence, and realism. The images included people with the same cloned face; people with different faces; dogs; identical twins, triplets, quadruplets, etc.; and cloned animated characters. In the sixth experiment, the photos were the same as in the second (six cloned faces, six different faces, and a single face) but participants also answered the Disgust Scale–Revised to accurately analyze disgust sensitivity.

The results of all these experiments were quite clear: People found the cloned faces far creepier than the varied or single face, an effect the researchers called clone devaluation. Notably, this effect only applied to realistic human faces; most people didn’t find the cloned dogs or cloned animated characters creepy. However, those who did were more likely to find the human clones eerie on the Disgust Scale.

The authors noted that future robotics technology needs to be carefully considered to avoid the uncanny valley and this clone devaluation effect, which is a very good point. The last thing we need is a few million robots with identical faces getting angry at us and pulling a Terminator/Order 66 combo. We’re already in a viral apocalypse; we don’t need a robot one on top of that.
 

Congratulations to our new favorite reader

The winner of last week’s inaugural Pandemic Pandemonium comes to us from Tiffanie Roe. By getting her entry in first, just ahead of the flood of responses we received – and by flood we mean a very slow and very quickly repaired drip – Ms. Roe puts the gold medal for COVID-related insanity around the necks of Australian magpies, who may start attacking people wearing face masks during “swooping season” because the birds don’t recognize them.

Exercising to lose weight is not for every ‘body’

This first item comes from the “You’ve got to be kidding” section of LOTME’s supersecret topics-of-interest file.

Maya23K/Thinkstock

Investigators at the Shenzhen Institute of Advanced Technology of the Chinese Academy of Sciences and the University of Roehampton noticed that some people who enrolled in exercise programs to lose weight did just the opposite: they gained weight.

Being scientists, they decided to look at the effects of energy expenditure and how those effects varied among individuals. The likely culprit in this case, they determined, is something called compensatory mechanisms. One such mechanism involves eating more food because exercise stimulates appetite, and another might reduce energy expenditure on other components like resting metabolism so that the exercise is, in effect, less costly.

A look at the numbers shows how compensatory mechanisms worked in the study population of 1,750 adults. Among individuals with the highest BMI, 51% of the calories burned during activity translated into calories burned at the end of the day. For those with normal BMI, however, 72% of calories burned during activity were reflected in total expenditure.

“People living with obesity cut back their resting metabolism when they are more active. The result is that for every calorie they spend on exercise they save about half a calorie on resting,” the investigators explained.

In other words, some bodies will, unconsciously, work against the conscious effort of exercising to lose weight. Thank you very much, compensatory mechanisms, for the boundarylessness exhibited in exceeding your job description.
 

When it comes to the mix, walnuts go nuts

When it comes to mixed nuts, walnuts get no love. But we may be able to give you a reason to not pick them out: Your arteries.

PxHere

Participants in a recent study who ate about a half-cup of walnuts every day for 2 years saw a drop in their low-density lipoprotein (LDL) cholesterol. The number and quality of LDL particles in healthy older adults also improved. How? Good ol’ omega-3 fatty acids.

Omega-3 is found in many foods linked to lower risks of heart disease, lower cholesterol levels, and lower blood sugar levels, but the one thing that makes the walnut a front runner for Miss Super Food 2021 is their ability to improve the quality of LDL particles.

“LDL particles come in various sizes [and] research has shown that small, dense LDL particles are more often associated with atherosclerosis, the plaque or fatty deposits that build up in the arteries,” Emilio Ros, MD, PhD, of the Hospital Clínic of Barcelona and the study’s senior investigator, said in a written statement.

The 708 participants, aged 63-79 years and mostly women, were divided into two groups: One received the walnut diet and the other did not. After 2 years, the walnut group had lower LDL levels by an average of 4.3 mg/dL. Total cholesterol was reduced by an average of 8.5 mg/dL. Also, their total LDL particle count was 4.3% lower and small LDL particles were down by 6.1%.

So instead of picking the walnuts out of the mix, try to find it in your heart to appreciate them. Your body already does.
 

Begun, the clone war has

Well, not quite yet, Master Yoda, but perhaps one day soon, if a study from Japan into the uncanny valley of the usage of cloned humanlike faces in robotics and artificial intelligence, published in PLOS One, is to be believed.

Patrick Bursa/Pixabay

The study consisted of a number of six smaller experiments in which participants judged a series of images based on subjective eeriness, emotional valence, and realism. The images included people with the same cloned face; people with different faces; dogs; identical twins, triplets, quadruplets, etc.; and cloned animated characters. In the sixth experiment, the photos were the same as in the second (six cloned faces, six different faces, and a single face) but participants also answered the Disgust Scale–Revised to accurately analyze disgust sensitivity.

The results of all these experiments were quite clear: People found the cloned faces far creepier than the varied or single face, an effect the researchers called clone devaluation. Notably, this effect only applied to realistic human faces; most people didn’t find the cloned dogs or cloned animated characters creepy. However, those who did were more likely to find the human clones eerie on the Disgust Scale.

The authors noted that future robotics technology needs to be carefully considered to avoid the uncanny valley and this clone devaluation effect, which is a very good point. The last thing we need is a few million robots with identical faces getting angry at us and pulling a Terminator/Order 66 combo. We’re already in a viral apocalypse; we don’t need a robot one on top of that.
 

Congratulations to our new favorite reader

The winner of last week’s inaugural Pandemic Pandemonium comes to us from Tiffanie Roe. By getting her entry in first, just ahead of the flood of responses we received – and by flood we mean a very slow and very quickly repaired drip – Ms. Roe puts the gold medal for COVID-related insanity around the necks of Australian magpies, who may start attacking people wearing face masks during “swooping season” because the birds don’t recognize them.

Exercising to lose weight is not for every ‘body’

This first item comes from the “You’ve got to be kidding” section of LOTME’s supersecret topics-of-interest file.

Maya23K/Thinkstock

Investigators at the Shenzhen Institute of Advanced Technology of the Chinese Academy of Sciences and the University of Roehampton noticed that some people who enrolled in exercise programs to lose weight did just the opposite: they gained weight.

Being scientists, they decided to look at the effects of energy expenditure and how those effects varied among individuals. The likely culprit in this case, they determined, is something called compensatory mechanisms. One such mechanism involves eating more food because exercise stimulates appetite, and another might reduce energy expenditure on other components like resting metabolism so that the exercise is, in effect, less costly.

A look at the numbers shows how compensatory mechanisms worked in the study population of 1,750 adults. Among individuals with the highest BMI, 51% of the calories burned during activity translated into calories burned at the end of the day. For those with normal BMI, however, 72% of calories burned during activity were reflected in total expenditure.

“People living with obesity cut back their resting metabolism when they are more active. The result is that for every calorie they spend on exercise they save about half a calorie on resting,” the investigators explained.

In other words, some bodies will, unconsciously, work against the conscious effort of exercising to lose weight. Thank you very much, compensatory mechanisms, for the boundarylessness exhibited in exceeding your job description.
 

When it comes to the mix, walnuts go nuts

When it comes to mixed nuts, walnuts get no love. But we may be able to give you a reason to not pick them out: Your arteries.

PxHere

Participants in a recent study who ate about a half-cup of walnuts every day for 2 years saw a drop in their low-density lipoprotein (LDL) cholesterol. The number and quality of LDL particles in healthy older adults also improved. How? Good ol’ omega-3 fatty acids.

Omega-3 is found in many foods linked to lower risks of heart disease, lower cholesterol levels, and lower blood sugar levels, but the one thing that makes the walnut a front runner for Miss Super Food 2021 is their ability to improve the quality of LDL particles.

“LDL particles come in various sizes [and] research has shown that small, dense LDL particles are more often associated with atherosclerosis, the plaque or fatty deposits that build up in the arteries,” Emilio Ros, MD, PhD, of the Hospital Clínic of Barcelona and the study’s senior investigator, said in a written statement.

The 708 participants, aged 63-79 years and mostly women, were divided into two groups: One received the walnut diet and the other did not. After 2 years, the walnut group had lower LDL levels by an average of 4.3 mg/dL. Total cholesterol was reduced by an average of 8.5 mg/dL. Also, their total LDL particle count was 4.3% lower and small LDL particles were down by 6.1%.

So instead of picking the walnuts out of the mix, try to find it in your heart to appreciate them. Your body already does.
 

Begun, the clone war has

Well, not quite yet, Master Yoda, but perhaps one day soon, if a study from Japan into the uncanny valley of the usage of cloned humanlike faces in robotics and artificial intelligence, published in PLOS One, is to be believed.

Patrick Bursa/Pixabay

The study consisted of a number of six smaller experiments in which participants judged a series of images based on subjective eeriness, emotional valence, and realism. The images included people with the same cloned face; people with different faces; dogs; identical twins, triplets, quadruplets, etc.; and cloned animated characters. In the sixth experiment, the photos were the same as in the second (six cloned faces, six different faces, and a single face) but participants also answered the Disgust Scale–Revised to accurately analyze disgust sensitivity.

The results of all these experiments were quite clear: People found the cloned faces far creepier than the varied or single face, an effect the researchers called clone devaluation. Notably, this effect only applied to realistic human faces; most people didn’t find the cloned dogs or cloned animated characters creepy. However, those who did were more likely to find the human clones eerie on the Disgust Scale.

The authors noted that future robotics technology needs to be carefully considered to avoid the uncanny valley and this clone devaluation effect, which is a very good point. The last thing we need is a few million robots with identical faces getting angry at us and pulling a Terminator/Order 66 combo. We’re already in a viral apocalypse; we don’t need a robot one on top of that.
 

Congratulations to our new favorite reader

The winner of last week’s inaugural Pandemic Pandemonium comes to us from Tiffanie Roe. By getting her entry in first, just ahead of the flood of responses we received – and by flood we mean a very slow and very quickly repaired drip – Ms. Roe puts the gold medal for COVID-related insanity around the necks of Australian magpies, who may start attacking people wearing face masks during “swooping season” because the birds don’t recognize them.

Jessica Gosnell, MD, 41, from Portland, Oregon, lives daily with the knowledge that her rare disease — a form of hereditary angioedema — could cause a sudden, severe swelling in her throat that could require quick intubation and land her in an intensive care unit (ICU) for days.

“I’ve been hospitalized for throat swells three times in the last year,” she said in an interview.

Dr. Gosnell no longer practices medicine because of a combination of illnesses, but lives with her husband, Andrew, and two young children, and said they are all “terrified” she will have to go to the hospital amid a COVID-19 surge that had shrunk the number of available ICU beds to 152 from 780 in Oregon as of Aug. 30. Thirty percent of the beds are in use for patients with COVID-19.

She said her life depends on being near hospitals that have ICUs and having access to highly specialized medications, one of which can cost up to $50,000 for the rescue dose.

Her fear has her “literally living bedbound.” In addition to hereditary angioedema, she has Ehlers-Danlos syndrome, which weakens connective tissue. She wears a cervical collar 24/7 to keep from tearing tissues, as any tissue injury can trigger a swell.
 

Patients worry there won’t be room

As ICU beds in most states are filling with COVID-19 patients as the Delta variant spreads, fears are rising among people like Dr. Gosnell, who have chronic conditions and diseases with unpredictable emergency visits, who worry that if they need emergency care there won’t be room.

As of Aug. 30, in the United States, 79% of ICU beds nationally were in use, 30% of them for COVID-19 patients, according to the U.S. Department of Health and Human Services.

In individual states, the picture is dire. Alabama has fewer than 10% of its ICU beds open across the entire state. In Florida, 93% of ICU beds are filled, 53% of them with COVID patients. In Louisiana, 87% of beds were already in use, 45% of them with COVID patients, just as category 4 hurricane Ida smashed into the coastline on Aug. 29.

News reports have told of people transported and airlifted as hospitals reach capacity.

In Bellville, Tex., U.S. Army veteran Daniel Wilkinson needed advanced care for gallstone pancreatitis that normally would take 30 minutes to treat, his Bellville doctor, Hasan Kakli, MD, told CBS News.

Mr. Wilkinson’s house was three doors from Bellville Hospital, but the hospital was not equipped to treat the condition. Calls to other hospitals found the same answer: no empty ICU beds. After a 7-hour wait on a stretcher, he was airlifted to a Veterans Affairs hospital in Houston, but it was too late. He died on August 22 at age 46.

Dr. Kakli said, “I’ve never lost a patient with this diagnosis. Ever. I’m scared that the next patient I see is someone that I can’t get to where they need to get to. We are playing musical chairs with 100 people and 10 chairs. When the music stops, what happens?”

Also in Texas in August, Joe Valdez, who was shot six times as an unlucky bystander in a domestic dispute, waited for more than a week for surgery at Ben Taub Hospital in Houston, which was over capacity with COVID patients, the Washington Post reported.

Others with chronic diseases fear needing emergency services or even entering a hospital for regular care with the COVID surge.

Nicole Seefeldt, 44, from Easton, Penn., who had a double-lung transplant in 2016, said that she hasn’t been able to see her lung transplant specialists in Philadelphia — an hour-and-a-half drive — for almost 2 years because of fear of contracting COVID. Before the pandemic, she made the trip almost weekly.

“I protect my lungs like they’re children,” she said. 

She relies on her local hospital for care, but has put off some needed care, such as a colonoscopy, and has relied on telemedicine because she wants to limit her hospital exposure.

Ms. Seefeldt now faces an eventual kidney transplant, as her kidney function has been reduced to 20%. In the meantime, she worries she will need emergency care for either her lungs or kidneys.

“For those of us who are chronically ill or disabled, what if we have an emergency that is not COVID-related? Are we going to be able to get a bed? Are we going to be able to get treatment? It’s not just COVID patients who come to the [emergency room],” she said.
 

A pandemic problem

Paul E. Casey, MD, MBA, chief medical officer at Rush University Medical Center in Chicago, said that high vaccination rates in Chicago have helped Rush continue to accommodate both non-COVID and COVID patients in the emergency department.

Though the hospital treated a large volume of COVID patients, “The vast majority of people we see and did see through the pandemic were non-COVID patents,” he said.

Dr. Casey said that in the first wave the hospital noticed a concerning drop in patients coming in for strokes and heart attacks — “things we knew hadn’t gone away.”

And the data backs it up. Over the course of the pandemic, the Centers for Disease Control and Prevention’s National Health Interview Survey found that the percentage of Americans who reported seeing a doctor or health professional fell from 85% at the end of 2019 to about 80% in the first three months of 2021. The survey did not differentiate between in-person visits and telehealth appointments.

Medical practices and patients themselves postponed elective procedures and delayed routine visits during the early months of the crisis.

Patients also reported staying away from hospitals’ emergency departments throughout the pandemic. At the end of 2019, 22% of respondents reported visiting an emergency department in the past year. That dropped to 17% by the end of 2020, and was at 17.7% in the first 3 months of 2021.

Dr. Casey said that, in his hospital’s case, clear messaging became very important to assure patients it was safe to come back. And the message is still critical.

“We want to be loud and clear that patients should continue to seek care for those conditions,” Dr. Casey said. “Deferring healthcare only comes with the long-term sequelae of disease left untreated so we want people to be as proactive in seeking care as they always would be.”

In some cases, fears of entering emergency rooms because of excess patients and risk for infection are keeping some patients from seeking necessary care for minor injuries.

Jim Rickert, MD, an orthopedic surgeon with Indiana University Health in Bloomington, said that some of his patients have expressed fears of coming into the hospital for fractures.

Some patients, particularly elderly patients, he said, are having falls and fractures and wearing slings or braces at home rather than going into the hospital for injuries that need immediate attention.

Bones start healing incorrectly, Dr. Rickert said, and the correction becomes much more difficult.
 

Plea for vaccinations

Dr. Gosnell made a plea posted on her neighborhood news forum for people to get COVID vaccinations.

“It seems to me it’s easy for other people who are not in bodies like mine to take health for granted,” she said. “But there are a lot of us who live in very fragile bodies and our entire life is at the intersection of us and getting healthcare treatment. Small complications to getting treatment can be life altering.”

Dr. Gosnell, Ms. Seefeldt, Dr. Casey, and Dr. Rickert reported no relevant financial relationships.

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

Jessica Gosnell, MD, 41, from Portland, Oregon, lives daily with the knowledge that her rare disease — a form of hereditary angioedema — could cause a sudden, severe swelling in her throat that could require quick intubation and land her in an intensive care unit (ICU) for days.

“I’ve been hospitalized for throat swells three times in the last year,” she said in an interview.

Dr. Gosnell no longer practices medicine because of a combination of illnesses, but lives with her husband, Andrew, and two young children, and said they are all “terrified” she will have to go to the hospital amid a COVID-19 surge that had shrunk the number of available ICU beds to 152 from 780 in Oregon as of Aug. 30. Thirty percent of the beds are in use for patients with COVID-19.

She said her life depends on being near hospitals that have ICUs and having access to highly specialized medications, one of which can cost up to $50,000 for the rescue dose.

Her fear has her “literally living bedbound.” In addition to hereditary angioedema, she has Ehlers-Danlos syndrome, which weakens connective tissue. She wears a cervical collar 24/7 to keep from tearing tissues, as any tissue injury can trigger a swell.
 

Patients worry there won’t be room

As ICU beds in most states are filling with COVID-19 patients as the Delta variant spreads, fears are rising among people like Dr. Gosnell, who have chronic conditions and diseases with unpredictable emergency visits, who worry that if they need emergency care there won’t be room.

As of Aug. 30, in the United States, 79% of ICU beds nationally were in use, 30% of them for COVID-19 patients, according to the U.S. Department of Health and Human Services.

In individual states, the picture is dire. Alabama has fewer than 10% of its ICU beds open across the entire state. In Florida, 93% of ICU beds are filled, 53% of them with COVID patients. In Louisiana, 87% of beds were already in use, 45% of them with COVID patients, just as category 4 hurricane Ida smashed into the coastline on Aug. 29.

News reports have told of people transported and airlifted as hospitals reach capacity.

In Bellville, Tex., U.S. Army veteran Daniel Wilkinson needed advanced care for gallstone pancreatitis that normally would take 30 minutes to treat, his Bellville doctor, Hasan Kakli, MD, told CBS News.

Mr. Wilkinson’s house was three doors from Bellville Hospital, but the hospital was not equipped to treat the condition. Calls to other hospitals found the same answer: no empty ICU beds. After a 7-hour wait on a stretcher, he was airlifted to a Veterans Affairs hospital in Houston, but it was too late. He died on August 22 at age 46.

Dr. Kakli said, “I’ve never lost a patient with this diagnosis. Ever. I’m scared that the next patient I see is someone that I can’t get to where they need to get to. We are playing musical chairs with 100 people and 10 chairs. When the music stops, what happens?”

Also in Texas in August, Joe Valdez, who was shot six times as an unlucky bystander in a domestic dispute, waited for more than a week for surgery at Ben Taub Hospital in Houston, which was over capacity with COVID patients, the Washington Post reported.

Others with chronic diseases fear needing emergency services or even entering a hospital for regular care with the COVID surge.

Nicole Seefeldt, 44, from Easton, Penn., who had a double-lung transplant in 2016, said that she hasn’t been able to see her lung transplant specialists in Philadelphia — an hour-and-a-half drive — for almost 2 years because of fear of contracting COVID. Before the pandemic, she made the trip almost weekly.

“I protect my lungs like they’re children,” she said. 

She relies on her local hospital for care, but has put off some needed care, such as a colonoscopy, and has relied on telemedicine because she wants to limit her hospital exposure.

Ms. Seefeldt now faces an eventual kidney transplant, as her kidney function has been reduced to 20%. In the meantime, she worries she will need emergency care for either her lungs or kidneys.

“For those of us who are chronically ill or disabled, what if we have an emergency that is not COVID-related? Are we going to be able to get a bed? Are we going to be able to get treatment? It’s not just COVID patients who come to the [emergency room],” she said.
 

A pandemic problem

Paul E. Casey, MD, MBA, chief medical officer at Rush University Medical Center in Chicago, said that high vaccination rates in Chicago have helped Rush continue to accommodate both non-COVID and COVID patients in the emergency department.

Though the hospital treated a large volume of COVID patients, “The vast majority of people we see and did see through the pandemic were non-COVID patents,” he said.

Dr. Casey said that in the first wave the hospital noticed a concerning drop in patients coming in for strokes and heart attacks — “things we knew hadn’t gone away.”

And the data backs it up. Over the course of the pandemic, the Centers for Disease Control and Prevention’s National Health Interview Survey found that the percentage of Americans who reported seeing a doctor or health professional fell from 85% at the end of 2019 to about 80% in the first three months of 2021. The survey did not differentiate between in-person visits and telehealth appointments.

Medical practices and patients themselves postponed elective procedures and delayed routine visits during the early months of the crisis.

Patients also reported staying away from hospitals’ emergency departments throughout the pandemic. At the end of 2019, 22% of respondents reported visiting an emergency department in the past year. That dropped to 17% by the end of 2020, and was at 17.7% in the first 3 months of 2021.

Dr. Casey said that, in his hospital’s case, clear messaging became very important to assure patients it was safe to come back. And the message is still critical.

“We want to be loud and clear that patients should continue to seek care for those conditions,” Dr. Casey said. “Deferring healthcare only comes with the long-term sequelae of disease left untreated so we want people to be as proactive in seeking care as they always would be.”

In some cases, fears of entering emergency rooms because of excess patients and risk for infection are keeping some patients from seeking necessary care for minor injuries.

Jim Rickert, MD, an orthopedic surgeon with Indiana University Health in Bloomington, said that some of his patients have expressed fears of coming into the hospital for fractures.

Some patients, particularly elderly patients, he said, are having falls and fractures and wearing slings or braces at home rather than going into the hospital for injuries that need immediate attention.

Bones start healing incorrectly, Dr. Rickert said, and the correction becomes much more difficult.
 

Plea for vaccinations

Dr. Gosnell made a plea posted on her neighborhood news forum for people to get COVID vaccinations.

“It seems to me it’s easy for other people who are not in bodies like mine to take health for granted,” she said. “But there are a lot of us who live in very fragile bodies and our entire life is at the intersection of us and getting healthcare treatment. Small complications to getting treatment can be life altering.”

Dr. Gosnell, Ms. Seefeldt, Dr. Casey, and Dr. Rickert reported no relevant financial relationships.

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

Jessica Gosnell, MD, 41, from Portland, Oregon, lives daily with the knowledge that her rare disease — a form of hereditary angioedema — could cause a sudden, severe swelling in her throat that could require quick intubation and land her in an intensive care unit (ICU) for days.

“I’ve been hospitalized for throat swells three times in the last year,” she said in an interview.

Dr. Gosnell no longer practices medicine because of a combination of illnesses, but lives with her husband, Andrew, and two young children, and said they are all “terrified” she will have to go to the hospital amid a COVID-19 surge that had shrunk the number of available ICU beds to 152 from 780 in Oregon as of Aug. 30. Thirty percent of the beds are in use for patients with COVID-19.

She said her life depends on being near hospitals that have ICUs and having access to highly specialized medications, one of which can cost up to $50,000 for the rescue dose.

Her fear has her “literally living bedbound.” In addition to hereditary angioedema, she has Ehlers-Danlos syndrome, which weakens connective tissue. She wears a cervical collar 24/7 to keep from tearing tissues, as any tissue injury can trigger a swell.
 

Patients worry there won’t be room

As ICU beds in most states are filling with COVID-19 patients as the Delta variant spreads, fears are rising among people like Dr. Gosnell, who have chronic conditions and diseases with unpredictable emergency visits, who worry that if they need emergency care there won’t be room.

As of Aug. 30, in the United States, 79% of ICU beds nationally were in use, 30% of them for COVID-19 patients, according to the U.S. Department of Health and Human Services.

In individual states, the picture is dire. Alabama has fewer than 10% of its ICU beds open across the entire state. In Florida, 93% of ICU beds are filled, 53% of them with COVID patients. In Louisiana, 87% of beds were already in use, 45% of them with COVID patients, just as category 4 hurricane Ida smashed into the coastline on Aug. 29.

News reports have told of people transported and airlifted as hospitals reach capacity.

In Bellville, Tex., U.S. Army veteran Daniel Wilkinson needed advanced care for gallstone pancreatitis that normally would take 30 minutes to treat, his Bellville doctor, Hasan Kakli, MD, told CBS News.

Mr. Wilkinson’s house was three doors from Bellville Hospital, but the hospital was not equipped to treat the condition. Calls to other hospitals found the same answer: no empty ICU beds. After a 7-hour wait on a stretcher, he was airlifted to a Veterans Affairs hospital in Houston, but it was too late. He died on August 22 at age 46.

Dr. Kakli said, “I’ve never lost a patient with this diagnosis. Ever. I’m scared that the next patient I see is someone that I can’t get to where they need to get to. We are playing musical chairs with 100 people and 10 chairs. When the music stops, what happens?”

Also in Texas in August, Joe Valdez, who was shot six times as an unlucky bystander in a domestic dispute, waited for more than a week for surgery at Ben Taub Hospital in Houston, which was over capacity with COVID patients, the Washington Post reported.

Others with chronic diseases fear needing emergency services or even entering a hospital for regular care with the COVID surge.

Nicole Seefeldt, 44, from Easton, Penn., who had a double-lung transplant in 2016, said that she hasn’t been able to see her lung transplant specialists in Philadelphia — an hour-and-a-half drive — for almost 2 years because of fear of contracting COVID. Before the pandemic, she made the trip almost weekly.

“I protect my lungs like they’re children,” she said. 

She relies on her local hospital for care, but has put off some needed care, such as a colonoscopy, and has relied on telemedicine because she wants to limit her hospital exposure.

Ms. Seefeldt now faces an eventual kidney transplant, as her kidney function has been reduced to 20%. In the meantime, she worries she will need emergency care for either her lungs or kidneys.

“For those of us who are chronically ill or disabled, what if we have an emergency that is not COVID-related? Are we going to be able to get a bed? Are we going to be able to get treatment? It’s not just COVID patients who come to the [emergency room],” she said.
 

A pandemic problem

Paul E. Casey, MD, MBA, chief medical officer at Rush University Medical Center in Chicago, said that high vaccination rates in Chicago have helped Rush continue to accommodate both non-COVID and COVID patients in the emergency department.

Though the hospital treated a large volume of COVID patients, “The vast majority of people we see and did see through the pandemic were non-COVID patents,” he said.

Dr. Casey said that in the first wave the hospital noticed a concerning drop in patients coming in for strokes and heart attacks — “things we knew hadn’t gone away.”

And the data backs it up. Over the course of the pandemic, the Centers for Disease Control and Prevention’s National Health Interview Survey found that the percentage of Americans who reported seeing a doctor or health professional fell from 85% at the end of 2019 to about 80% in the first three months of 2021. The survey did not differentiate between in-person visits and telehealth appointments.

Medical practices and patients themselves postponed elective procedures and delayed routine visits during the early months of the crisis.

Patients also reported staying away from hospitals’ emergency departments throughout the pandemic. At the end of 2019, 22% of respondents reported visiting an emergency department in the past year. That dropped to 17% by the end of 2020, and was at 17.7% in the first 3 months of 2021.

Dr. Casey said that, in his hospital’s case, clear messaging became very important to assure patients it was safe to come back. And the message is still critical.

“We want to be loud and clear that patients should continue to seek care for those conditions,” Dr. Casey said. “Deferring healthcare only comes with the long-term sequelae of disease left untreated so we want people to be as proactive in seeking care as they always would be.”

In some cases, fears of entering emergency rooms because of excess patients and risk for infection are keeping some patients from seeking necessary care for minor injuries.

Jim Rickert, MD, an orthopedic surgeon with Indiana University Health in Bloomington, said that some of his patients have expressed fears of coming into the hospital for fractures.

Some patients, particularly elderly patients, he said, are having falls and fractures and wearing slings or braces at home rather than going into the hospital for injuries that need immediate attention.

Bones start healing incorrectly, Dr. Rickert said, and the correction becomes much more difficult.
 

Plea for vaccinations

Dr. Gosnell made a plea posted on her neighborhood news forum for people to get COVID vaccinations.

“It seems to me it’s easy for other people who are not in bodies like mine to take health for granted,” she said. “But there are a lot of us who live in very fragile bodies and our entire life is at the intersection of us and getting healthcare treatment. Small complications to getting treatment can be life altering.”

Dr. Gosnell, Ms. Seefeldt, Dr. Casey, and Dr. Rickert reported no relevant financial relationships.

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

The anti-inflammatory agents colchicine and icosapent ethyl (Vascepa; Amarin) failed to provide substantial benefits in separate randomized COVID-19 trials.

Both were reported at the European Society of Cardiology (ESC) Congress 2021.

The open-label ECLA PHRI COLCOVID trial randomized 1,277 hospitalized adults (mean age 62 years) to usual care alone or with colchicine at a loading dose of 1.5 mg for 2 hours followed by 0.5 mg on day 1 and then 0.5 mg twice daily for 14 days or until discharge.

The investigators hypothesized that colchicine, which is widely used to treat gout and other inflammatory conditions, might modulate the hyperinflammatory syndrome, or cytokine storm, associated with COVID-19.

Results showed that the need for mechanical ventilation or death occurred in 25.0% of patients receiving colchicine and 28.8% with usual care (P = .08).

The coprimary endpoint of death at 28 days was also not significantly different between groups (20.5% vs. 22.2%), principal investigator Rafael Diaz, MD, said in a late-breaking COVID-19 trials session at the congress.

Among the secondary outcomes at 28 days, colchicine significantly reduced the incidence of new intubation or death from respiratory failure from 27.0% to 22.3% (hazard ratio, 0.79; 95% confidence interval, 0.63-0.99) but not mortality from respiratory failure (19.5% vs. 16.8%).

The only important adverse effect was severe diarrhea, which was reported in 11.3% of the colchicine group vs. 4.5% in the control group, said Dr. Diaz, director of Estudios Clínicos Latinoamérica (ECLA), Rosario, Argentina.

The results are consistent with those from the massive RECOVERY trial, which earlier this year stopped enrollment in the colchicine arm for lack of efficacy in patients hospitalized with COVID-19, and COLCORONA, which missed its primary endpoint using colchicine among nonhospitalized adults with COVID-19.

Session chair and COLCORONA principal investigator Jean-Claude Tardif, MD, pointed out that, as clinicians, it’s fairly uncommon to combine systemic steroids with colchicine, which was the case in 92% of patients in ECLA PHRI COLCOVID.

“I think it is an inherent limitation of testing colchicine on top of steroids,” said Dr. Tardif, of the Montreal Heart Institute.
 

Icosapent ethyl in PREPARE-IT

Dr. Diaz returned in the ESC session to present the results of the PREPARE-IT trial, which tested whether icosapent ethyl – at a loading dose of 8 grams (4 capsules) for the first 3 days and 4 g/d on days 4-60 – could reduce the risk for SARS-CoV-2 infection in 2,041 health care and other public workers in Argentina at high risk for infection (mean age 40.5 years).

Vascepa was approved by the Food and Drug Administration in 2012 for the reduction of elevated triglyceride levels, with an added indication in 2019 to reduce cardiovascular (CV) events in people with elevated triglycerides and established CV disease or diabetes with other CV risk factors.

The rationale for using the high-dose prescription eicosapentaenoic acid (EPA) preparation includes its anti-inflammatory and antithrombotic effects, and that unsaturated fatty acids, especially EPA, might inactivate the enveloped virus, he explained.

Among 1,712 participants followed for up to 60 days, however, the SARS-CoV-2 infection rate was 7.9% with icosapent ethyl vs. 7.1% with a mineral oil placebo (P = .58).

There were also no significant changes from baseline in the icosapent ethyl and placebo groups for the secondary outcomes of high-sensitivity C-reactive protein (0 vs. 0), triglycerides (median –2 mg/dL vs. 7 mg/dL), or Influenza Patient-Reported Outcome (FLU-PRO) questionnaire scores (median 0.01 vs. 0.03).

The use of a mineral oil placebo has been the subject of controversy in previous fish oil trials, but, Dr. Diaz noted, it did not have a significant proinflammatory effect or cause any excess adverse events.

Overall, adverse events were similar between the active and placebo groups, including atrial fibrillation (none), major bleeding (none), minor bleeding (7 events vs. 10 events), gastrointestinal symptoms (6.8% vs. 7.0%), and diarrhea (8.6% vs. 7.7%).

Although it missed the primary endpoint, Dr. Diaz said, “this is the first large, randomized blinded trial to demonstrate excellent safety and tolerability of an 8-gram-per-day loading dose of icosapent ethyl, opening up the potential for acute use in randomized trials of myocardial infarction, acute coronary syndromes, strokes, and revascularization.”

During a discussion of the results, Dr. Diaz said the Delta variant was not present at the time of the analysis and that the second half of the trial will report on whether icosapent ethyl can reduce the risk for hospitalization or death in participants diagnosed with COVID-19.

ECLA PHRI COLCOVID was supported by the Estudios Clínicos Latinoamérica Population Health Research Institute. PREPARE-IT was supported by Estudios Clínicos Latinoamérica with collaboration from Amarin. Dr. Diaz reports no relevant financial relationships.

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

The anti-inflammatory agents colchicine and icosapent ethyl (Vascepa; Amarin) failed to provide substantial benefits in separate randomized COVID-19 trials.

Both were reported at the European Society of Cardiology (ESC) Congress 2021.

The open-label ECLA PHRI COLCOVID trial randomized 1,277 hospitalized adults (mean age 62 years) to usual care alone or with colchicine at a loading dose of 1.5 mg for 2 hours followed by 0.5 mg on day 1 and then 0.5 mg twice daily for 14 days or until discharge.

The investigators hypothesized that colchicine, which is widely used to treat gout and other inflammatory conditions, might modulate the hyperinflammatory syndrome, or cytokine storm, associated with COVID-19.

Results showed that the need for mechanical ventilation or death occurred in 25.0% of patients receiving colchicine and 28.8% with usual care (P = .08).

The coprimary endpoint of death at 28 days was also not significantly different between groups (20.5% vs. 22.2%), principal investigator Rafael Diaz, MD, said in a late-breaking COVID-19 trials session at the congress.

Among the secondary outcomes at 28 days, colchicine significantly reduced the incidence of new intubation or death from respiratory failure from 27.0% to 22.3% (hazard ratio, 0.79; 95% confidence interval, 0.63-0.99) but not mortality from respiratory failure (19.5% vs. 16.8%).

The only important adverse effect was severe diarrhea, which was reported in 11.3% of the colchicine group vs. 4.5% in the control group, said Dr. Diaz, director of Estudios Clínicos Latinoamérica (ECLA), Rosario, Argentina.

The results are consistent with those from the massive RECOVERY trial, which earlier this year stopped enrollment in the colchicine arm for lack of efficacy in patients hospitalized with COVID-19, and COLCORONA, which missed its primary endpoint using colchicine among nonhospitalized adults with COVID-19.

Session chair and COLCORONA principal investigator Jean-Claude Tardif, MD, pointed out that, as clinicians, it’s fairly uncommon to combine systemic steroids with colchicine, which was the case in 92% of patients in ECLA PHRI COLCOVID.

“I think it is an inherent limitation of testing colchicine on top of steroids,” said Dr. Tardif, of the Montreal Heart Institute.
 

Icosapent ethyl in PREPARE-IT

Dr. Diaz returned in the ESC session to present the results of the PREPARE-IT trial, which tested whether icosapent ethyl – at a loading dose of 8 grams (4 capsules) for the first 3 days and 4 g/d on days 4-60 – could reduce the risk for SARS-CoV-2 infection in 2,041 health care and other public workers in Argentina at high risk for infection (mean age 40.5 years).

Vascepa was approved by the Food and Drug Administration in 2012 for the reduction of elevated triglyceride levels, with an added indication in 2019 to reduce cardiovascular (CV) events in people with elevated triglycerides and established CV disease or diabetes with other CV risk factors.

The rationale for using the high-dose prescription eicosapentaenoic acid (EPA) preparation includes its anti-inflammatory and antithrombotic effects, and that unsaturated fatty acids, especially EPA, might inactivate the enveloped virus, he explained.

Among 1,712 participants followed for up to 60 days, however, the SARS-CoV-2 infection rate was 7.9% with icosapent ethyl vs. 7.1% with a mineral oil placebo (P = .58).

There were also no significant changes from baseline in the icosapent ethyl and placebo groups for the secondary outcomes of high-sensitivity C-reactive protein (0 vs. 0), triglycerides (median –2 mg/dL vs. 7 mg/dL), or Influenza Patient-Reported Outcome (FLU-PRO) questionnaire scores (median 0.01 vs. 0.03).

The use of a mineral oil placebo has been the subject of controversy in previous fish oil trials, but, Dr. Diaz noted, it did not have a significant proinflammatory effect or cause any excess adverse events.

Overall, adverse events were similar between the active and placebo groups, including atrial fibrillation (none), major bleeding (none), minor bleeding (7 events vs. 10 events), gastrointestinal symptoms (6.8% vs. 7.0%), and diarrhea (8.6% vs. 7.7%).

Although it missed the primary endpoint, Dr. Diaz said, “this is the first large, randomized blinded trial to demonstrate excellent safety and tolerability of an 8-gram-per-day loading dose of icosapent ethyl, opening up the potential for acute use in randomized trials of myocardial infarction, acute coronary syndromes, strokes, and revascularization.”

During a discussion of the results, Dr. Diaz said the Delta variant was not present at the time of the analysis and that the second half of the trial will report on whether icosapent ethyl can reduce the risk for hospitalization or death in participants diagnosed with COVID-19.

ECLA PHRI COLCOVID was supported by the Estudios Clínicos Latinoamérica Population Health Research Institute. PREPARE-IT was supported by Estudios Clínicos Latinoamérica with collaboration from Amarin. Dr. Diaz reports no relevant financial relationships.

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

The anti-inflammatory agents colchicine and icosapent ethyl (Vascepa; Amarin) failed to provide substantial benefits in separate randomized COVID-19 trials.

Both were reported at the European Society of Cardiology (ESC) Congress 2021.

The open-label ECLA PHRI COLCOVID trial randomized 1,277 hospitalized adults (mean age 62 years) to usual care alone or with colchicine at a loading dose of 1.5 mg for 2 hours followed by 0.5 mg on day 1 and then 0.5 mg twice daily for 14 days or until discharge.

The investigators hypothesized that colchicine, which is widely used to treat gout and other inflammatory conditions, might modulate the hyperinflammatory syndrome, or cytokine storm, associated with COVID-19.

Results showed that the need for mechanical ventilation or death occurred in 25.0% of patients receiving colchicine and 28.8% with usual care (P = .08).

The coprimary endpoint of death at 28 days was also not significantly different between groups (20.5% vs. 22.2%), principal investigator Rafael Diaz, MD, said in a late-breaking COVID-19 trials session at the congress.

Among the secondary outcomes at 28 days, colchicine significantly reduced the incidence of new intubation or death from respiratory failure from 27.0% to 22.3% (hazard ratio, 0.79; 95% confidence interval, 0.63-0.99) but not mortality from respiratory failure (19.5% vs. 16.8%).

The only important adverse effect was severe diarrhea, which was reported in 11.3% of the colchicine group vs. 4.5% in the control group, said Dr. Diaz, director of Estudios Clínicos Latinoamérica (ECLA), Rosario, Argentina.

The results are consistent with those from the massive RECOVERY trial, which earlier this year stopped enrollment in the colchicine arm for lack of efficacy in patients hospitalized with COVID-19, and COLCORONA, which missed its primary endpoint using colchicine among nonhospitalized adults with COVID-19.

Session chair and COLCORONA principal investigator Jean-Claude Tardif, MD, pointed out that, as clinicians, it’s fairly uncommon to combine systemic steroids with colchicine, which was the case in 92% of patients in ECLA PHRI COLCOVID.

“I think it is an inherent limitation of testing colchicine on top of steroids,” said Dr. Tardif, of the Montreal Heart Institute.
 

Icosapent ethyl in PREPARE-IT

Dr. Diaz returned in the ESC session to present the results of the PREPARE-IT trial, which tested whether icosapent ethyl – at a loading dose of 8 grams (4 capsules) for the first 3 days and 4 g/d on days 4-60 – could reduce the risk for SARS-CoV-2 infection in 2,041 health care and other public workers in Argentina at high risk for infection (mean age 40.5 years).

Vascepa was approved by the Food and Drug Administration in 2012 for the reduction of elevated triglyceride levels, with an added indication in 2019 to reduce cardiovascular (CV) events in people with elevated triglycerides and established CV disease or diabetes with other CV risk factors.

The rationale for using the high-dose prescription eicosapentaenoic acid (EPA) preparation includes its anti-inflammatory and antithrombotic effects, and that unsaturated fatty acids, especially EPA, might inactivate the enveloped virus, he explained.

Among 1,712 participants followed for up to 60 days, however, the SARS-CoV-2 infection rate was 7.9% with icosapent ethyl vs. 7.1% with a mineral oil placebo (P = .58).

There were also no significant changes from baseline in the icosapent ethyl and placebo groups for the secondary outcomes of high-sensitivity C-reactive protein (0 vs. 0), triglycerides (median –2 mg/dL vs. 7 mg/dL), or Influenza Patient-Reported Outcome (FLU-PRO) questionnaire scores (median 0.01 vs. 0.03).

The use of a mineral oil placebo has been the subject of controversy in previous fish oil trials, but, Dr. Diaz noted, it did not have a significant proinflammatory effect or cause any excess adverse events.

Overall, adverse events were similar between the active and placebo groups, including atrial fibrillation (none), major bleeding (none), minor bleeding (7 events vs. 10 events), gastrointestinal symptoms (6.8% vs. 7.0%), and diarrhea (8.6% vs. 7.7%).

Although it missed the primary endpoint, Dr. Diaz said, “this is the first large, randomized blinded trial to demonstrate excellent safety and tolerability of an 8-gram-per-day loading dose of icosapent ethyl, opening up the potential for acute use in randomized trials of myocardial infarction, acute coronary syndromes, strokes, and revascularization.”

During a discussion of the results, Dr. Diaz said the Delta variant was not present at the time of the analysis and that the second half of the trial will report on whether icosapent ethyl can reduce the risk for hospitalization or death in participants diagnosed with COVID-19.

ECLA PHRI COLCOVID was supported by the Estudios Clínicos Latinoamérica Population Health Research Institute. PREPARE-IT was supported by Estudios Clínicos Latinoamérica with collaboration from Amarin. Dr. Diaz reports no relevant financial relationships.

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

Opioid overdose deaths were significantly higher during 2020, but occurrences were not homogeneous across nine states. Male deaths were higher than in the 2 previous years in two states, according to a new, granular examination of data collected by researchers at the Massachusetts General Hospital (Mass General), Boston.

The analysis also showed that synthetic opioids such as fentanyl played an outsized role in most of the states that were reviewed. Additional drugs of abuse found in decedents, such as cocaine and psychostimulants, were more prevalent in some states than in others.

The Centers for Disease Control and Prevention used provisional death data in its recent report. It found that opioid-related deaths substantially rose in 2020 and that synthetic opioids were a primary driver.

The current Mass General analysis provides a more timely and detailed dive, senior author Mohammad Jalali, PhD, who is a senior scientist at Mass General’s Institute for Technology Assessment, told this news organization.

The findings, which have not yet been peer reviewed, were published in MedRxiv.
 

Shifting sands of opioid use disorder

Dr. Jalali and colleagues used a decision analysis approach to study opioid data in the hopes of providing better tools for policymakers to analyze and project trends and also to be better prepared to address the shifting sands of opioid use disorder in the United States.

They attempted to collect data on confirmed opioid overdose deaths from all 50 states and Washington, D.C. to assess what might have changed during the COVID-19 pandemic. Only nine states provided enough data for the analysis, which has been submitted to a peer reviewed publication.

These states were Alaska, Connecticut, Indiana, Massachusetts, North Carolina, Rhode Island, Colorado, Utah, and Wyoming.

“Drug overdose data are collected and reported more slowly than COVID-19 data,” Dr. Jalali said in a press release. The data reflected a lag time of about 4 to 8 months in Massachusetts and North Carolina to more than a year in Maryland and Ohio, he noted.

The reporting lag “has clouded the understanding of the effects of the COVID-19 pandemic on opioid-related overdose deaths,” said Dr. Jalali.

Commenting on the findings, Brandon Marshall, PhD, associate professor of epidemiology at Brown University, Providence, R.I, said that “the overall pattern of what’s being reported here is not surprising,” given the national trends seen in the CDC data.

“This paper adds a deeper dive into some of the sociodemographic trends that we’re starting to observe in specific states,” Dr. Marshall said.

Also commenting for this news organization, Brian Fuehrlein, MD, PhD, director of the psychiatric emergency department at the VA Connecticut Healthcare System in West Haven, Connecticut, noted that the current study “highlights things that we are currently seeing at VA Connecticut.”
 

Decrease in heroin, rise in fentanyl

The investigators found a significant reduction in overdose deaths that involved heroin in Alaska, Connecticut, Indiana, Massachusetts, North Carolina, and Rhode Island. That was a new trend for Alaska, Indiana, and Rhode Island, although with only 3 years of data, it’s hard to say whether it will continue, Dr. Jalali noted.

The decrease in heroin involvement seemed to continue a trend previously observed in Colorado, Connecticut, Massachusetts, and North Carolina.

In Connecticut, heroin was involved in 36% of deaths in 2018, 30% in 2019, and 16% in 2020, according to the study.

“We have begun seeing more and more heroin-negative, fentanyl-positive drug screens,” said Dr. Fuehrlein, who is also associate professor of psychiatry at Yale University, New Haven, Conn.

“There is a shift from fentanyl being an adulterant to fentanyl being what is sold and used exclusively,” he added.

In 2020, 92% (n = 887) of deaths in Connecticut involved synthetic opioids, continuing a trend. In Alaska, however, synthetic opioids were involved in 60% (44) of deaths, which is a big jump from 23% (9) in 2018.

Synthetic opioids were involved in the largest percentage of overdoses in all of the states studied. The fewest deaths, 17 (49%), occurred in Wyoming.

Cocaine is also increasingly found in addition to other substances in decedents. In Alaska, about 14% of individuals who overdosed in 2020 also had cocaine in their system, which was a jump from 2% in the prior year.

In Colorado, 19% (94) of those who died also had taken cocaine, up from 13% in 2019. Cocaine was also frequently found in those who died in the northeast: 39% (467) of those who died in Massachusetts, 29% (280) in Connecticut, and 47% (109) in Rhode Island.

There was also an increase in psychostimulants found in those who had died in Massachusetts in 2020.
 

More male overdoses in 2020

Results also showed that, compared to 2019, significantly more men died from overdoses in 2020 in Colorado (61% vs. 70%, P = .017) and Indiana (62% vs. 70%, P = .026).

This finding was unexpected, said Dr. Marshall, who has observed the same phenomenon in Rhode Island. He is the scientific director of PreventOverdoseRI, Rhode Island’s drug overdose surveillance and information dashboard.

Dr. Marshall and his colleagues conducted a study that also found disproportionate increases in overdoses among men. The findings of that study will be published in September.

“We’re still trying to wrap our head around why that is,” he said. He added that a deeper dive into the Rhode Island data showed that the deaths were increased especially among middle-aged men who had been diagnosed with depression and anxiety.

The same patterns were not seen among women in either Dr. Jalali’s study or his own analysis of the Rhode Island data, said Dr. Marshall.

“That suggests the COVID-19 pandemic impacted men who are at risk for overdose in some particularly severe way,” he noted.

Dr. Fuehrlein said he believes a variety of factors have led to an increase in overdose deaths during the pandemic, including the fact that many patients who would normally seek help avoided care or dropped out of treatment because of COVID fears. In addition, other support systems, such as group therapy and Narcotics Anonymous, were unavailable.

The pandemic increased stress, which can lead to worsening substance use, said Dr. Fuehrlein. He also noted that regular opioid suppliers were often not available, which led some to buy from different dealers, “which can lead to overdose if the fentanyl content is different.”
 

Identifying at-risk individuals

Dr. Jalali and colleagues note that clinicians and policymakers could use the new study to help identify and treat at-risk individuals.

“Practitioners and policy makers can use our findings to help them anticipate which groups of people might be most affected by opioid overdose and which types of policy interventions might be most effective given each state’s unique situation,” said lead study author Gian-Gabriel P. Garcia, PhD, in a press release. At the time of the study, Dr. Garcia was a postdoctoral fellow at Mass General and Harvard Medical School. He is currently an assistant professor at Georgia Tech, Atlanta.

Dr. Marshall pointed out that Dr. Jalali’s study is also relevant for emergency departments.

ED clinicians “are and will be seeing patients coming in who have no idea they were exposed to an opioid, nevermind fentanyl,” he said. ED clinicians can discuss with patients various harm reduction techniques, including the use of naloxone as well as test strips that can detect fentanyl in the drug supply, he added.

“Given the increasing use of fentanyl, which is very dangerous in overdose, clinicians need to be well versed in a harm reduction/overdose prevention approach to patient care,” Dr. Fuehrlein agreed.

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

Opioid overdose deaths were significantly higher during 2020, but occurrences were not homogeneous across nine states. Male deaths were higher than in the 2 previous years in two states, according to a new, granular examination of data collected by researchers at the Massachusetts General Hospital (Mass General), Boston.

The analysis also showed that synthetic opioids such as fentanyl played an outsized role in most of the states that were reviewed. Additional drugs of abuse found in decedents, such as cocaine and psychostimulants, were more prevalent in some states than in others.

The Centers for Disease Control and Prevention used provisional death data in its recent report. It found that opioid-related deaths substantially rose in 2020 and that synthetic opioids were a primary driver.

The current Mass General analysis provides a more timely and detailed dive, senior author Mohammad Jalali, PhD, who is a senior scientist at Mass General’s Institute for Technology Assessment, told this news organization.

The findings, which have not yet been peer reviewed, were published in MedRxiv.
 

Shifting sands of opioid use disorder

Dr. Jalali and colleagues used a decision analysis approach to study opioid data in the hopes of providing better tools for policymakers to analyze and project trends and also to be better prepared to address the shifting sands of opioid use disorder in the United States.

They attempted to collect data on confirmed opioid overdose deaths from all 50 states and Washington, D.C. to assess what might have changed during the COVID-19 pandemic. Only nine states provided enough data for the analysis, which has been submitted to a peer reviewed publication.

These states were Alaska, Connecticut, Indiana, Massachusetts, North Carolina, Rhode Island, Colorado, Utah, and Wyoming.

“Drug overdose data are collected and reported more slowly than COVID-19 data,” Dr. Jalali said in a press release. The data reflected a lag time of about 4 to 8 months in Massachusetts and North Carolina to more than a year in Maryland and Ohio, he noted.

The reporting lag “has clouded the understanding of the effects of the COVID-19 pandemic on opioid-related overdose deaths,” said Dr. Jalali.

Commenting on the findings, Brandon Marshall, PhD, associate professor of epidemiology at Brown University, Providence, R.I, said that “the overall pattern of what’s being reported here is not surprising,” given the national trends seen in the CDC data.

“This paper adds a deeper dive into some of the sociodemographic trends that we’re starting to observe in specific states,” Dr. Marshall said.

Also commenting for this news organization, Brian Fuehrlein, MD, PhD, director of the psychiatric emergency department at the VA Connecticut Healthcare System in West Haven, Connecticut, noted that the current study “highlights things that we are currently seeing at VA Connecticut.”
 

Decrease in heroin, rise in fentanyl

The investigators found a significant reduction in overdose deaths that involved heroin in Alaska, Connecticut, Indiana, Massachusetts, North Carolina, and Rhode Island. That was a new trend for Alaska, Indiana, and Rhode Island, although with only 3 years of data, it’s hard to say whether it will continue, Dr. Jalali noted.

The decrease in heroin involvement seemed to continue a trend previously observed in Colorado, Connecticut, Massachusetts, and North Carolina.

In Connecticut, heroin was involved in 36% of deaths in 2018, 30% in 2019, and 16% in 2020, according to the study.

“We have begun seeing more and more heroin-negative, fentanyl-positive drug screens,” said Dr. Fuehrlein, who is also associate professor of psychiatry at Yale University, New Haven, Conn.

“There is a shift from fentanyl being an adulterant to fentanyl being what is sold and used exclusively,” he added.

In 2020, 92% (n = 887) of deaths in Connecticut involved synthetic opioids, continuing a trend. In Alaska, however, synthetic opioids were involved in 60% (44) of deaths, which is a big jump from 23% (9) in 2018.

Synthetic opioids were involved in the largest percentage of overdoses in all of the states studied. The fewest deaths, 17 (49%), occurred in Wyoming.

Cocaine is also increasingly found in addition to other substances in decedents. In Alaska, about 14% of individuals who overdosed in 2020 also had cocaine in their system, which was a jump from 2% in the prior year.

In Colorado, 19% (94) of those who died also had taken cocaine, up from 13% in 2019. Cocaine was also frequently found in those who died in the northeast: 39% (467) of those who died in Massachusetts, 29% (280) in Connecticut, and 47% (109) in Rhode Island.

There was also an increase in psychostimulants found in those who had died in Massachusetts in 2020.
 

More male overdoses in 2020

Results also showed that, compared to 2019, significantly more men died from overdoses in 2020 in Colorado (61% vs. 70%, P = .017) and Indiana (62% vs. 70%, P = .026).

This finding was unexpected, said Dr. Marshall, who has observed the same phenomenon in Rhode Island. He is the scientific director of PreventOverdoseRI, Rhode Island’s drug overdose surveillance and information dashboard.

Dr. Marshall and his colleagues conducted a study that also found disproportionate increases in overdoses among men. The findings of that study will be published in September.

“We’re still trying to wrap our head around why that is,” he said. He added that a deeper dive into the Rhode Island data showed that the deaths were increased especially among middle-aged men who had been diagnosed with depression and anxiety.

The same patterns were not seen among women in either Dr. Jalali’s study or his own analysis of the Rhode Island data, said Dr. Marshall.

“That suggests the COVID-19 pandemic impacted men who are at risk for overdose in some particularly severe way,” he noted.

Dr. Fuehrlein said he believes a variety of factors have led to an increase in overdose deaths during the pandemic, including the fact that many patients who would normally seek help avoided care or dropped out of treatment because of COVID fears. In addition, other support systems, such as group therapy and Narcotics Anonymous, were unavailable.

The pandemic increased stress, which can lead to worsening substance use, said Dr. Fuehrlein. He also noted that regular opioid suppliers were often not available, which led some to buy from different dealers, “which can lead to overdose if the fentanyl content is different.”
 

Identifying at-risk individuals

Dr. Jalali and colleagues note that clinicians and policymakers could use the new study to help identify and treat at-risk individuals.

“Practitioners and policy makers can use our findings to help them anticipate which groups of people might be most affected by opioid overdose and which types of policy interventions might be most effective given each state’s unique situation,” said lead study author Gian-Gabriel P. Garcia, PhD, in a press release. At the time of the study, Dr. Garcia was a postdoctoral fellow at Mass General and Harvard Medical School. He is currently an assistant professor at Georgia Tech, Atlanta.

Dr. Marshall pointed out that Dr. Jalali’s study is also relevant for emergency departments.

ED clinicians “are and will be seeing patients coming in who have no idea they were exposed to an opioid, nevermind fentanyl,” he said. ED clinicians can discuss with patients various harm reduction techniques, including the use of naloxone as well as test strips that can detect fentanyl in the drug supply, he added.

“Given the increasing use of fentanyl, which is very dangerous in overdose, clinicians need to be well versed in a harm reduction/overdose prevention approach to patient care,” Dr. Fuehrlein agreed.

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

Opioid overdose deaths were significantly higher during 2020, but occurrences were not homogeneous across nine states. Male deaths were higher than in the 2 previous years in two states, according to a new, granular examination of data collected by researchers at the Massachusetts General Hospital (Mass General), Boston.

The analysis also showed that synthetic opioids such as fentanyl played an outsized role in most of the states that were reviewed. Additional drugs of abuse found in decedents, such as cocaine and psychostimulants, were more prevalent in some states than in others.

The Centers for Disease Control and Prevention used provisional death data in its recent report. It found that opioid-related deaths substantially rose in 2020 and that synthetic opioids were a primary driver.

The current Mass General analysis provides a more timely and detailed dive, senior author Mohammad Jalali, PhD, who is a senior scientist at Mass General’s Institute for Technology Assessment, told this news organization.

The findings, which have not yet been peer reviewed, were published in MedRxiv.
 

Shifting sands of opioid use disorder

Dr. Jalali and colleagues used a decision analysis approach to study opioid data in the hopes of providing better tools for policymakers to analyze and project trends and also to be better prepared to address the shifting sands of opioid use disorder in the United States.

They attempted to collect data on confirmed opioid overdose deaths from all 50 states and Washington, D.C. to assess what might have changed during the COVID-19 pandemic. Only nine states provided enough data for the analysis, which has been submitted to a peer reviewed publication.

These states were Alaska, Connecticut, Indiana, Massachusetts, North Carolina, Rhode Island, Colorado, Utah, and Wyoming.

“Drug overdose data are collected and reported more slowly than COVID-19 data,” Dr. Jalali said in a press release. The data reflected a lag time of about 4 to 8 months in Massachusetts and North Carolina to more than a year in Maryland and Ohio, he noted.

The reporting lag “has clouded the understanding of the effects of the COVID-19 pandemic on opioid-related overdose deaths,” said Dr. Jalali.

Commenting on the findings, Brandon Marshall, PhD, associate professor of epidemiology at Brown University, Providence, R.I, said that “the overall pattern of what’s being reported here is not surprising,” given the national trends seen in the CDC data.

“This paper adds a deeper dive into some of the sociodemographic trends that we’re starting to observe in specific states,” Dr. Marshall said.

Also commenting for this news organization, Brian Fuehrlein, MD, PhD, director of the psychiatric emergency department at the VA Connecticut Healthcare System in West Haven, Connecticut, noted that the current study “highlights things that we are currently seeing at VA Connecticut.”
 

Decrease in heroin, rise in fentanyl

The investigators found a significant reduction in overdose deaths that involved heroin in Alaska, Connecticut, Indiana, Massachusetts, North Carolina, and Rhode Island. That was a new trend for Alaska, Indiana, and Rhode Island, although with only 3 years of data, it’s hard to say whether it will continue, Dr. Jalali noted.

The decrease in heroin involvement seemed to continue a trend previously observed in Colorado, Connecticut, Massachusetts, and North Carolina.

In Connecticut, heroin was involved in 36% of deaths in 2018, 30% in 2019, and 16% in 2020, according to the study.

“We have begun seeing more and more heroin-negative, fentanyl-positive drug screens,” said Dr. Fuehrlein, who is also associate professor of psychiatry at Yale University, New Haven, Conn.

“There is a shift from fentanyl being an adulterant to fentanyl being what is sold and used exclusively,” he added.

In 2020, 92% (n = 887) of deaths in Connecticut involved synthetic opioids, continuing a trend. In Alaska, however, synthetic opioids were involved in 60% (44) of deaths, which is a big jump from 23% (9) in 2018.

Synthetic opioids were involved in the largest percentage of overdoses in all of the states studied. The fewest deaths, 17 (49%), occurred in Wyoming.

Cocaine is also increasingly found in addition to other substances in decedents. In Alaska, about 14% of individuals who overdosed in 2020 also had cocaine in their system, which was a jump from 2% in the prior year.

In Colorado, 19% (94) of those who died also had taken cocaine, up from 13% in 2019. Cocaine was also frequently found in those who died in the northeast: 39% (467) of those who died in Massachusetts, 29% (280) in Connecticut, and 47% (109) in Rhode Island.

There was also an increase in psychostimulants found in those who had died in Massachusetts in 2020.
 

More male overdoses in 2020

Results also showed that, compared to 2019, significantly more men died from overdoses in 2020 in Colorado (61% vs. 70%, P = .017) and Indiana (62% vs. 70%, P = .026).

This finding was unexpected, said Dr. Marshall, who has observed the same phenomenon in Rhode Island. He is the scientific director of PreventOverdoseRI, Rhode Island’s drug overdose surveillance and information dashboard.

Dr. Marshall and his colleagues conducted a study that also found disproportionate increases in overdoses among men. The findings of that study will be published in September.

“We’re still trying to wrap our head around why that is,” he said. He added that a deeper dive into the Rhode Island data showed that the deaths were increased especially among middle-aged men who had been diagnosed with depression and anxiety.

The same patterns were not seen among women in either Dr. Jalali’s study or his own analysis of the Rhode Island data, said Dr. Marshall.

“That suggests the COVID-19 pandemic impacted men who are at risk for overdose in some particularly severe way,” he noted.

Dr. Fuehrlein said he believes a variety of factors have led to an increase in overdose deaths during the pandemic, including the fact that many patients who would normally seek help avoided care or dropped out of treatment because of COVID fears. In addition, other support systems, such as group therapy and Narcotics Anonymous, were unavailable.

The pandemic increased stress, which can lead to worsening substance use, said Dr. Fuehrlein. He also noted that regular opioid suppliers were often not available, which led some to buy from different dealers, “which can lead to overdose if the fentanyl content is different.”
 

Identifying at-risk individuals

Dr. Jalali and colleagues note that clinicians and policymakers could use the new study to help identify and treat at-risk individuals.

“Practitioners and policy makers can use our findings to help them anticipate which groups of people might be most affected by opioid overdose and which types of policy interventions might be most effective given each state’s unique situation,” said lead study author Gian-Gabriel P. Garcia, PhD, in a press release. At the time of the study, Dr. Garcia was a postdoctoral fellow at Mass General and Harvard Medical School. He is currently an assistant professor at Georgia Tech, Atlanta.

Dr. Marshall pointed out that Dr. Jalali’s study is also relevant for emergency departments.

ED clinicians “are and will be seeing patients coming in who have no idea they were exposed to an opioid, nevermind fentanyl,” he said. ED clinicians can discuss with patients various harm reduction techniques, including the use of naloxone as well as test strips that can detect fentanyl in the drug supply, he added.

“Given the increasing use of fentanyl, which is very dangerous in overdose, clinicians need to be well versed in a harm reduction/overdose prevention approach to patient care,” Dr. Fuehrlein agreed.

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

Emerging evidence suggests that autoimmunity plays a role in postinfectious myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and that targeting autoantibodies could be a promising treatment approach.

The same may also apply to many cases of “long COVID,” in which many of the symptoms overlap with those of ME/CFS, Carmen Scheibenbogen, MD, professor of clinical immunology and director of the Institute for Medical Immunology, Charité University Medicine, Berlin, said during the annual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis.

Several groups, including Dr. Scheibenbogen’s, have reported finding autoantibodies against neurotransmitter receptor antigens in people with ME/CFS. And, in a paper published in the Journal of Clinical Medicine the day that Dr. Scheibenbogen spoke at the meeting, her team reported significant correlations between autoantibodies to vasoregulative G-protein–coupled receptors and symptom severity, autonomic dysfunction, and disability among 116 patients with infection-triggered ME/CFS who were diagnosed using the symptom-based 2003 Canadian consensus criteria.

People with ME/CFS are also more likely to have genetic risk factors associated with autoimmunity and personal and/or family histories of autoimmune conditions. And, clinical trials have demonstrated early success with various immunomodulatory treatments in subsets of people with ME/CFS, including endoxan, rituximab, and immunoadsorption.

“We have evidence that ME/CFS is an autoantibody-mediated disease, and we have evidence that autoantibody targeting is effective in this disease. So far ... we have few and underfinanced clinical studies, but the good news is we have promising emerging treatment options,” Dr. Scheibenbogen said.

Asked to comment, ME/CFS expert Anthony L. Komaroff, MD, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said: “There is already strong evidence that there are autoantibodies in ME/CFS. Dr. Scheibenbogen’s work is the latest and employs the latest technology. ... I would bet that autoantibodies to neural targets are likely to cause some of the symptoms of ME/CFS and some of the symptoms of long COVID.”

However, he cautioned, “that has not been proven, and even if it were proven you would have to demonstrate that treatments based on that theory worked.”

Dr. Komaroff said he views autoimmunity as a likely component of the ME/CFS spectrum, but not the only one. “My current view of this illness is that there’s a final common pathway in the brain that leads to the symptoms of the illness. But that final common pathway can be triggered by a variety of different things, one of which could be autoantibodies while another could be infection or inflammation in the brain.”
 

Emerging evidence points to autoimmunity

Dr. Scheibenbogen summarized the work published in this area over the past few years by her group and others.

In a comparison of ME/CFS patients with 201 healthy controls, significant associations were seen with two specific autoimmunity-related risk alleles only in the ME/CFS patients who reported acute onset of disease with an infection but not in those with ME/CFS without infection-triggered onset or the controls. Both genes play roles in regulating B- and T-cell activation.

Another recent study found associations with ME/CFS and major histocompatibility complex class II molecules, a typical feature of autoimmune diseases, in a comparison between 426 adult Norwegian ME/CFS patients who were diagnosed with the Canadian consensus criteria and 4,511 healthy, ethnically matched controls.

In a 2020 paper, Dr. Scheibenbogen and pharmacologist Klaus Wirth presented a “unifying hypothesis” of ME/CFS pathophysiology based on the finding of elevations in autoantibodies against beta₂-adrenergic receptors and muscarinic acetylcholine receptors in some individuals with the condition. Since both of those receptors are important vasodilators, their functional disturbance would be expected to cause vasoconstriction and hypoxemia, which would explain many of the symptoms of ME/CFS. This mechanism would align with other findings of muscular and cerebral hypoperfusion that correlate with fatigue, particularly post exertion, as well as metabolic changes that are in line with the concepts of hypoxemia and ischemia.

Further evidence for vascular dysfunction in ME/CFS came from her group’s study finding evidence of peripheral endothelial dysfunction that was associated with symptom severity in 35 adult patients. “Vasoconstriction, hypovolemia, and release of vasoactive and algesic mediators is probably a key pathomechanism of the disease,” Dr. Scheibenbogen said.
 

Treatments: Will targeting autoantibodies work?

In the second part of her talk, Dr. Scheibenbogen summarized clinical trials of the following treatment approaches that involve targeting autoantibodies as a way to alleviate ME/CFS symptoms:

Rituximab: Work on infusions of the B-cell depleting agent has been conducted by Norwegian researchers beginning in 2011 with a small randomized trial and an open-label, phase 2 study in 2015, both showing clinical responses in ME/CFS. However, a subsequent phase 3, randomized clinical trial of 151 patients, again diagnosed using the Canadian criteria, was negative.

There are several possible explanations for this, Dr. Scheibenbogen noted. For one, the maintenance dose had to be reduced because of a lack of financial support. “This was probably critical. The lower dose was insufficient to adequately deplete B cells.” Also, there may have been a strong placebo response in the control group since they were being given better care than they normally would receive during the trial. “I think probably nobody will again do a rituximab trial. This was very disappointing for all of us. But, we still have other opportunities to follow this path,” she said.

Dr. Komaroff agreed. “I don’t think the failure of one drug that hits malignant B cells is proof against the autoimmune hypothesis per se. I think the evidence is that rituximab doesn’t work, but that doesn’t invalidate the autoimmunity hypothesis.”

Cyclophosphamide: The same Norwegian group also showed positive findings in an open-label, phase 2 trial of the immune-modifying drug cyclophosphamide in 22 of 40 patients. Interestingly, HLA risk alleles were much more common in responders than nonresponders, Dr. Scheibenbogen noted.

Immunoadsorption: This technique, similar to dialysis, involves separating out the blood plasma by centrifugation and removing IgG autoantibodies by a binding column, then returning the plasma back to the patient. It is used, primarily in Europe, to treat severe autoimmune diseases including dilative cardiomyopathy and refractory systemic lupus erythematosus (SLE).

Dr. Scheibenbogen’s group has conducted two studies of immunoadsorption in ME/CFS. In one, a 5-day procedure led to rapid symptom improvement in 7 of 10 patients, with sustained improvement in 3 patients after 2 years. Autoantibodies decreased rapidly in 9 of the 10 patients. In a follow-up study of five of the responders 2 years later, retreatment with a modified immunoadsorption protocol led to rapid and sustained improvement in four. Further study has been on hold because of the pandemic.

Next-gen IgG-targeting therapies: Another approach that could offer promise for ME/CFS involves therapies that block the Fc receptors of IgG. Several are in phase 1-3 trials for autoimmune conditions. One candidate drug, the Fc fragment efgartigimod, is currently in phase 3 trials for several conditions, including generalized myasthenia gravis, primary immune thrombocytopenia, and chronic inflammatory demyelinating polyneuropathy. Phase 3 trials are planned for the monoclonal antibody rozanolixizumab in those same conditions.

Newer-generation monoclonal antibodies targeting CD19 or CD20 that show benefit in various autoimmune conditions are another possibility for ME/CFS. These include ocrelizumab (Ocrevus), approved in the United States for treating relapsing and progressive multiple sclerosis and in trials for SLE; obinutuzumab (Gazyva), approved for treating lymphoma and also in development for SLE; and ublituximab, in phase 3 trials for multiple sclerosis.

“Most of them are more effective than rituximab,” Dr. Scheibenbogen noted, adding that “currently the data look quite promising. They are effective in different autoimmune diseases and they are quite well tolerated. There’s great hope now with COVID-19 that we can convince some companies to do such trials in ME/CFS as well.”

Dr. Scheibenbogen’s institution, the Charité Fatigue Center, has a patent for beta₂-adrenergic receptor antibodies for diagnosing ME/CFS under her name together with Celltrend. Dr. Komaroff has received personal fees from Serimmune.

Emerging evidence suggests that autoimmunity plays a role in postinfectious myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and that targeting autoantibodies could be a promising treatment approach.

The same may also apply to many cases of “long COVID,” in which many of the symptoms overlap with those of ME/CFS, Carmen Scheibenbogen, MD, professor of clinical immunology and director of the Institute for Medical Immunology, Charité University Medicine, Berlin, said during the annual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis.

Several groups, including Dr. Scheibenbogen’s, have reported finding autoantibodies against neurotransmitter receptor antigens in people with ME/CFS. And, in a paper published in the Journal of Clinical Medicine the day that Dr. Scheibenbogen spoke at the meeting, her team reported significant correlations between autoantibodies to vasoregulative G-protein–coupled receptors and symptom severity, autonomic dysfunction, and disability among 116 patients with infection-triggered ME/CFS who were diagnosed using the symptom-based 2003 Canadian consensus criteria.

People with ME/CFS are also more likely to have genetic risk factors associated with autoimmunity and personal and/or family histories of autoimmune conditions. And, clinical trials have demonstrated early success with various immunomodulatory treatments in subsets of people with ME/CFS, including endoxan, rituximab, and immunoadsorption.

“We have evidence that ME/CFS is an autoantibody-mediated disease, and we have evidence that autoantibody targeting is effective in this disease. So far ... we have few and underfinanced clinical studies, but the good news is we have promising emerging treatment options,” Dr. Scheibenbogen said.

Asked to comment, ME/CFS expert Anthony L. Komaroff, MD, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said: “There is already strong evidence that there are autoantibodies in ME/CFS. Dr. Scheibenbogen’s work is the latest and employs the latest technology. ... I would bet that autoantibodies to neural targets are likely to cause some of the symptoms of ME/CFS and some of the symptoms of long COVID.”

However, he cautioned, “that has not been proven, and even if it were proven you would have to demonstrate that treatments based on that theory worked.”

Dr. Komaroff said he views autoimmunity as a likely component of the ME/CFS spectrum, but not the only one. “My current view of this illness is that there’s a final common pathway in the brain that leads to the symptoms of the illness. But that final common pathway can be triggered by a variety of different things, one of which could be autoantibodies while another could be infection or inflammation in the brain.”
 

Emerging evidence points to autoimmunity

Dr. Scheibenbogen summarized the work published in this area over the past few years by her group and others.

In a comparison of ME/CFS patients with 201 healthy controls, significant associations were seen with two specific autoimmunity-related risk alleles only in the ME/CFS patients who reported acute onset of disease with an infection but not in those with ME/CFS without infection-triggered onset or the controls. Both genes play roles in regulating B- and T-cell activation.

Another recent study found associations with ME/CFS and major histocompatibility complex class II molecules, a typical feature of autoimmune diseases, in a comparison between 426 adult Norwegian ME/CFS patients who were diagnosed with the Canadian consensus criteria and 4,511 healthy, ethnically matched controls.

In a 2020 paper, Dr. Scheibenbogen and pharmacologist Klaus Wirth presented a “unifying hypothesis” of ME/CFS pathophysiology based on the finding of elevations in autoantibodies against beta₂-adrenergic receptors and muscarinic acetylcholine receptors in some individuals with the condition. Since both of those receptors are important vasodilators, their functional disturbance would be expected to cause vasoconstriction and hypoxemia, which would explain many of the symptoms of ME/CFS. This mechanism would align with other findings of muscular and cerebral hypoperfusion that correlate with fatigue, particularly post exertion, as well as metabolic changes that are in line with the concepts of hypoxemia and ischemia.

Further evidence for vascular dysfunction in ME/CFS came from her group’s study finding evidence of peripheral endothelial dysfunction that was associated with symptom severity in 35 adult patients. “Vasoconstriction, hypovolemia, and release of vasoactive and algesic mediators is probably a key pathomechanism of the disease,” Dr. Scheibenbogen said.
 

Treatments: Will targeting autoantibodies work?

In the second part of her talk, Dr. Scheibenbogen summarized clinical trials of the following treatment approaches that involve targeting autoantibodies as a way to alleviate ME/CFS symptoms:

Rituximab: Work on infusions of the B-cell depleting agent has been conducted by Norwegian researchers beginning in 2011 with a small randomized trial and an open-label, phase 2 study in 2015, both showing clinical responses in ME/CFS. However, a subsequent phase 3, randomized clinical trial of 151 patients, again diagnosed using the Canadian criteria, was negative.

There are several possible explanations for this, Dr. Scheibenbogen noted. For one, the maintenance dose had to be reduced because of a lack of financial support. “This was probably critical. The lower dose was insufficient to adequately deplete B cells.” Also, there may have been a strong placebo response in the control group since they were being given better care than they normally would receive during the trial. “I think probably nobody will again do a rituximab trial. This was very disappointing for all of us. But, we still have other opportunities to follow this path,” she said.

Dr. Komaroff agreed. “I don’t think the failure of one drug that hits malignant B cells is proof against the autoimmune hypothesis per se. I think the evidence is that rituximab doesn’t work, but that doesn’t invalidate the autoimmunity hypothesis.”

Cyclophosphamide: The same Norwegian group also showed positive findings in an open-label, phase 2 trial of the immune-modifying drug cyclophosphamide in 22 of 40 patients. Interestingly, HLA risk alleles were much more common in responders than nonresponders, Dr. Scheibenbogen noted.

Immunoadsorption: This technique, similar to dialysis, involves separating out the blood plasma by centrifugation and removing IgG autoantibodies by a binding column, then returning the plasma back to the patient. It is used, primarily in Europe, to treat severe autoimmune diseases including dilative cardiomyopathy and refractory systemic lupus erythematosus (SLE).

Dr. Scheibenbogen’s group has conducted two studies of immunoadsorption in ME/CFS. In one, a 5-day procedure led to rapid symptom improvement in 7 of 10 patients, with sustained improvement in 3 patients after 2 years. Autoantibodies decreased rapidly in 9 of the 10 patients. In a follow-up study of five of the responders 2 years later, retreatment with a modified immunoadsorption protocol led to rapid and sustained improvement in four. Further study has been on hold because of the pandemic.

Next-gen IgG-targeting therapies: Another approach that could offer promise for ME/CFS involves therapies that block the Fc receptors of IgG. Several are in phase 1-3 trials for autoimmune conditions. One candidate drug, the Fc fragment efgartigimod, is currently in phase 3 trials for several conditions, including generalized myasthenia gravis, primary immune thrombocytopenia, and chronic inflammatory demyelinating polyneuropathy. Phase 3 trials are planned for the monoclonal antibody rozanolixizumab in those same conditions.

Newer-generation monoclonal antibodies targeting CD19 or CD20 that show benefit in various autoimmune conditions are another possibility for ME/CFS. These include ocrelizumab (Ocrevus), approved in the United States for treating relapsing and progressive multiple sclerosis and in trials for SLE; obinutuzumab (Gazyva), approved for treating lymphoma and also in development for SLE; and ublituximab, in phase 3 trials for multiple sclerosis.

“Most of them are more effective than rituximab,” Dr. Scheibenbogen noted, adding that “currently the data look quite promising. They are effective in different autoimmune diseases and they are quite well tolerated. There’s great hope now with COVID-19 that we can convince some companies to do such trials in ME/CFS as well.”

Dr. Scheibenbogen’s institution, the Charité Fatigue Center, has a patent for beta₂-adrenergic receptor antibodies for diagnosing ME/CFS under her name together with Celltrend. Dr. Komaroff has received personal fees from Serimmune.

Emerging evidence suggests that autoimmunity plays a role in postinfectious myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and that targeting autoantibodies could be a promising treatment approach.

The same may also apply to many cases of “long COVID,” in which many of the symptoms overlap with those of ME/CFS, Carmen Scheibenbogen, MD, professor of clinical immunology and director of the Institute for Medical Immunology, Charité University Medicine, Berlin, said during the annual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis.

Several groups, including Dr. Scheibenbogen’s, have reported finding autoantibodies against neurotransmitter receptor antigens in people with ME/CFS. And, in a paper published in the Journal of Clinical Medicine the day that Dr. Scheibenbogen spoke at the meeting, her team reported significant correlations between autoantibodies to vasoregulative G-protein–coupled receptors and symptom severity, autonomic dysfunction, and disability among 116 patients with infection-triggered ME/CFS who were diagnosed using the symptom-based 2003 Canadian consensus criteria.

People with ME/CFS are also more likely to have genetic risk factors associated with autoimmunity and personal and/or family histories of autoimmune conditions. And, clinical trials have demonstrated early success with various immunomodulatory treatments in subsets of people with ME/CFS, including endoxan, rituximab, and immunoadsorption.

“We have evidence that ME/CFS is an autoantibody-mediated disease, and we have evidence that autoantibody targeting is effective in this disease. So far ... we have few and underfinanced clinical studies, but the good news is we have promising emerging treatment options,” Dr. Scheibenbogen said.

Asked to comment, ME/CFS expert Anthony L. Komaroff, MD, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said: “There is already strong evidence that there are autoantibodies in ME/CFS. Dr. Scheibenbogen’s work is the latest and employs the latest technology. ... I would bet that autoantibodies to neural targets are likely to cause some of the symptoms of ME/CFS and some of the symptoms of long COVID.”

However, he cautioned, “that has not been proven, and even if it were proven you would have to demonstrate that treatments based on that theory worked.”

Dr. Komaroff said he views autoimmunity as a likely component of the ME/CFS spectrum, but not the only one. “My current view of this illness is that there’s a final common pathway in the brain that leads to the symptoms of the illness. But that final common pathway can be triggered by a variety of different things, one of which could be autoantibodies while another could be infection or inflammation in the brain.”
 

Emerging evidence points to autoimmunity

Dr. Scheibenbogen summarized the work published in this area over the past few years by her group and others.

In a comparison of ME/CFS patients with 201 healthy controls, significant associations were seen with two specific autoimmunity-related risk alleles only in the ME/CFS patients who reported acute onset of disease with an infection but not in those with ME/CFS without infection-triggered onset or the controls. Both genes play roles in regulating B- and T-cell activation.

Another recent study found associations with ME/CFS and major histocompatibility complex class II molecules, a typical feature of autoimmune diseases, in a comparison between 426 adult Norwegian ME/CFS patients who were diagnosed with the Canadian consensus criteria and 4,511 healthy, ethnically matched controls.

In a 2020 paper, Dr. Scheibenbogen and pharmacologist Klaus Wirth presented a “unifying hypothesis” of ME/CFS pathophysiology based on the finding of elevations in autoantibodies against beta₂-adrenergic receptors and muscarinic acetylcholine receptors in some individuals with the condition. Since both of those receptors are important vasodilators, their functional disturbance would be expected to cause vasoconstriction and hypoxemia, which would explain many of the symptoms of ME/CFS. This mechanism would align with other findings of muscular and cerebral hypoperfusion that correlate with fatigue, particularly post exertion, as well as metabolic changes that are in line with the concepts of hypoxemia and ischemia.

Further evidence for vascular dysfunction in ME/CFS came from her group’s study finding evidence of peripheral endothelial dysfunction that was associated with symptom severity in 35 adult patients. “Vasoconstriction, hypovolemia, and release of vasoactive and algesic mediators is probably a key pathomechanism of the disease,” Dr. Scheibenbogen said.
 

Treatments: Will targeting autoantibodies work?

In the second part of her talk, Dr. Scheibenbogen summarized clinical trials of the following treatment approaches that involve targeting autoantibodies as a way to alleviate ME/CFS symptoms:

Rituximab: Work on infusions of the B-cell depleting agent has been conducted by Norwegian researchers beginning in 2011 with a small randomized trial and an open-label, phase 2 study in 2015, both showing clinical responses in ME/CFS. However, a subsequent phase 3, randomized clinical trial of 151 patients, again diagnosed using the Canadian criteria, was negative.

There are several possible explanations for this, Dr. Scheibenbogen noted. For one, the maintenance dose had to be reduced because of a lack of financial support. “This was probably critical. The lower dose was insufficient to adequately deplete B cells.” Also, there may have been a strong placebo response in the control group since they were being given better care than they normally would receive during the trial. “I think probably nobody will again do a rituximab trial. This was very disappointing for all of us. But, we still have other opportunities to follow this path,” she said.

Dr. Komaroff agreed. “I don’t think the failure of one drug that hits malignant B cells is proof against the autoimmune hypothesis per se. I think the evidence is that rituximab doesn’t work, but that doesn’t invalidate the autoimmunity hypothesis.”

Cyclophosphamide: The same Norwegian group also showed positive findings in an open-label, phase 2 trial of the immune-modifying drug cyclophosphamide in 22 of 40 patients. Interestingly, HLA risk alleles were much more common in responders than nonresponders, Dr. Scheibenbogen noted.

Immunoadsorption: This technique, similar to dialysis, involves separating out the blood plasma by centrifugation and removing IgG autoantibodies by a binding column, then returning the plasma back to the patient. It is used, primarily in Europe, to treat severe autoimmune diseases including dilative cardiomyopathy and refractory systemic lupus erythematosus (SLE).

Dr. Scheibenbogen’s group has conducted two studies of immunoadsorption in ME/CFS. In one, a 5-day procedure led to rapid symptom improvement in 7 of 10 patients, with sustained improvement in 3 patients after 2 years. Autoantibodies decreased rapidly in 9 of the 10 patients. In a follow-up study of five of the responders 2 years later, retreatment with a modified immunoadsorption protocol led to rapid and sustained improvement in four. Further study has been on hold because of the pandemic.

Next-gen IgG-targeting therapies: Another approach that could offer promise for ME/CFS involves therapies that block the Fc receptors of IgG. Several are in phase 1-3 trials for autoimmune conditions. One candidate drug, the Fc fragment efgartigimod, is currently in phase 3 trials for several conditions, including generalized myasthenia gravis, primary immune thrombocytopenia, and chronic inflammatory demyelinating polyneuropathy. Phase 3 trials are planned for the monoclonal antibody rozanolixizumab in those same conditions.

Newer-generation monoclonal antibodies targeting CD19 or CD20 that show benefit in various autoimmune conditions are another possibility for ME/CFS. These include ocrelizumab (Ocrevus), approved in the United States for treating relapsing and progressive multiple sclerosis and in trials for SLE; obinutuzumab (Gazyva), approved for treating lymphoma and also in development for SLE; and ublituximab, in phase 3 trials for multiple sclerosis.

“Most of them are more effective than rituximab,” Dr. Scheibenbogen noted, adding that “currently the data look quite promising. They are effective in different autoimmune diseases and they are quite well tolerated. There’s great hope now with COVID-19 that we can convince some companies to do such trials in ME/CFS as well.”

Dr. Scheibenbogen’s institution, the Charité Fatigue Center, has a patent for beta₂-adrenergic receptor antibodies for diagnosing ME/CFS under her name together with Celltrend. Dr. Komaroff has received personal fees from Serimmune.

Identifying risk factors for onset of Psoriatic Arthritis (PsA) is a major unmet need. Comparing potential risk factors for the diagnosis of PsA, rheumatoid arthritis (RA), and ankylosing spondylitis (AS) is of interest. Such studies may help us identify shared and unique risk factors of onset of chronic inflammatory arthritis. Meer E et al compared potential risk factors for the diagnosis of PsA, psoriasis, RA, and AS. They conducted four parallel case-control studies using data collected between 1994 and 2015 in The Health Improvement Network, an anonymized longitudinal patient dataset collected at primary care clinics throughout the United Kingdom. PsA was associated with obesity, pharyngitis, skin infections, moderate alcohol intake, gout, and uveitis. As expected, PsA and AS were associated with uveitis. Interestingly, PsA and RA were associated with preceding gout. Smoking was a risk factor for all disease and statin use was inversely associated with all 4 diseases. This study has identified potential risk factors for inflammatory diseases including PsA and may help in early identification as well as risk mitigation.

Most patients develop psoriatic arthritis (PsA) after or simultaneously with cutaneous psoriasis. The mechanisms underlying progression from cutaneous psoriasis to arthritis psoriasis are currently unclear. An important question is whether modern targeted treatment of cutaneous psoriasis reduces the risk of developing PsA. To address this, Acosta Felquer ML et al  conducted a retrospective cohort study to compare the incidence of PsA in 1719 patients with psoriasis (14,721 patient/years of follow up) grouped according to different treatments for their skin psoriasis: topicals, phototherapy or no treatment (n= 1387), conventional disease-modifying antirheumatic drugs (cDMARDs) or biological DMARDs (bDMARDs). During follow-up, 239 patients (14%) developed PsA. The risk of developing PsA in patients treated with bDMARDs was significantly lower (incidence rate ratio (IRR)=0.26; 95% CI 0.03 to 0.94), compared with topicals, but not compared with cDMARDs (IRR=0.35; 95% CI 0.035 to 1.96). Male sex, nail involvement and higher body mass index were associated with increased risk of developing PsA, while bDMARD use was protective. Thus, this study provides some evidence that systemic treatment might ‘protect’ against development if PsA. Appropriately designed prospective studies are required.

One important clinical question is whether patients with oligoarthritis (involvement of <5 joints) progress to polyarthritis. In an observational study Gladman DD et al  reported that in 407 patients evaluated within 12 months of diagnosis, 192 (47%) presented with oligoarthritis. More patients with polyarthritis presented with dactylitis, enthesitis, higher HAQ and lower SF-36 scores. Of the 192 patients with oligoarthritis, 75 (39%) progressed to polyarthritis. Lower SF-36 mental component summary score was the predictor for progressing to polyarthritis. Thus, except for the burden of musculoskeletal involvement, oligoarticular PsA resembles polyarticular PsA and therefore the two PsA subclasses should simply be classified together as peripheral arthritis.

Identifying risk factors for onset of Psoriatic Arthritis (PsA) is a major unmet need. Comparing potential risk factors for the diagnosis of PsA, rheumatoid arthritis (RA), and ankylosing spondylitis (AS) is of interest. Such studies may help us identify shared and unique risk factors of onset of chronic inflammatory arthritis. Meer E et al compared potential risk factors for the diagnosis of PsA, psoriasis, RA, and AS. They conducted four parallel case-control studies using data collected between 1994 and 2015 in The Health Improvement Network, an anonymized longitudinal patient dataset collected at primary care clinics throughout the United Kingdom. PsA was associated with obesity, pharyngitis, skin infections, moderate alcohol intake, gout, and uveitis. As expected, PsA and AS were associated with uveitis. Interestingly, PsA and RA were associated with preceding gout. Smoking was a risk factor for all disease and statin use was inversely associated with all 4 diseases. This study has identified potential risk factors for inflammatory diseases including PsA and may help in early identification as well as risk mitigation.

Most patients develop psoriatic arthritis (PsA) after or simultaneously with cutaneous psoriasis. The mechanisms underlying progression from cutaneous psoriasis to arthritis psoriasis are currently unclear. An important question is whether modern targeted treatment of cutaneous psoriasis reduces the risk of developing PsA. To address this, Acosta Felquer ML et al  conducted a retrospective cohort study to compare the incidence of PsA in 1719 patients with psoriasis (14,721 patient/years of follow up) grouped according to different treatments for their skin psoriasis: topicals, phototherapy or no treatment (n= 1387), conventional disease-modifying antirheumatic drugs (cDMARDs) or biological DMARDs (bDMARDs). During follow-up, 239 patients (14%) developed PsA. The risk of developing PsA in patients treated with bDMARDs was significantly lower (incidence rate ratio (IRR)=0.26; 95% CI 0.03 to 0.94), compared with topicals, but not compared with cDMARDs (IRR=0.35; 95% CI 0.035 to 1.96). Male sex, nail involvement and higher body mass index were associated with increased risk of developing PsA, while bDMARD use was protective. Thus, this study provides some evidence that systemic treatment might ‘protect’ against development if PsA. Appropriately designed prospective studies are required.

One important clinical question is whether patients with oligoarthritis (involvement of <5 joints) progress to polyarthritis. In an observational study Gladman DD et al  reported that in 407 patients evaluated within 12 months of diagnosis, 192 (47%) presented with oligoarthritis. More patients with polyarthritis presented with dactylitis, enthesitis, higher HAQ and lower SF-36 scores. Of the 192 patients with oligoarthritis, 75 (39%) progressed to polyarthritis. Lower SF-36 mental component summary score was the predictor for progressing to polyarthritis. Thus, except for the burden of musculoskeletal involvement, oligoarticular PsA resembles polyarticular PsA and therefore the two PsA subclasses should simply be classified together as peripheral arthritis.

Identifying risk factors for onset of Psoriatic Arthritis (PsA) is a major unmet need. Comparing potential risk factors for the diagnosis of PsA, rheumatoid arthritis (RA), and ankylosing spondylitis (AS) is of interest. Such studies may help us identify shared and unique risk factors of onset of chronic inflammatory arthritis. Meer E et al compared potential risk factors for the diagnosis of PsA, psoriasis, RA, and AS. They conducted four parallel case-control studies using data collected between 1994 and 2015 in The Health Improvement Network, an anonymized longitudinal patient dataset collected at primary care clinics throughout the United Kingdom. PsA was associated with obesity, pharyngitis, skin infections, moderate alcohol intake, gout, and uveitis. As expected, PsA and AS were associated with uveitis. Interestingly, PsA and RA were associated with preceding gout. Smoking was a risk factor for all disease and statin use was inversely associated with all 4 diseases. This study has identified potential risk factors for inflammatory diseases including PsA and may help in early identification as well as risk mitigation.

Most patients develop psoriatic arthritis (PsA) after or simultaneously with cutaneous psoriasis. The mechanisms underlying progression from cutaneous psoriasis to arthritis psoriasis are currently unclear. An important question is whether modern targeted treatment of cutaneous psoriasis reduces the risk of developing PsA. To address this, Acosta Felquer ML et al  conducted a retrospective cohort study to compare the incidence of PsA in 1719 patients with psoriasis (14,721 patient/years of follow up) grouped according to different treatments for their skin psoriasis: topicals, phototherapy or no treatment (n= 1387), conventional disease-modifying antirheumatic drugs (cDMARDs) or biological DMARDs (bDMARDs). During follow-up, 239 patients (14%) developed PsA. The risk of developing PsA in patients treated with bDMARDs was significantly lower (incidence rate ratio (IRR)=0.26; 95% CI 0.03 to 0.94), compared with topicals, but not compared with cDMARDs (IRR=0.35; 95% CI 0.035 to 1.96). Male sex, nail involvement and higher body mass index were associated with increased risk of developing PsA, while bDMARD use was protective. Thus, this study provides some evidence that systemic treatment might ‘protect’ against development if PsA. Appropriately designed prospective studies are required.

One important clinical question is whether patients with oligoarthritis (involvement of <5 joints) progress to polyarthritis. In an observational study Gladman DD et al  reported that in 407 patients evaluated within 12 months of diagnosis, 192 (47%) presented with oligoarthritis. More patients with polyarthritis presented with dactylitis, enthesitis, higher HAQ and lower SF-36 scores. Of the 192 patients with oligoarthritis, 75 (39%) progressed to polyarthritis. Lower SF-36 mental component summary score was the predictor for progressing to polyarthritis. Thus, except for the burden of musculoskeletal involvement, oligoarticular PsA resembles polyarticular PsA and therefore the two PsA subclasses should simply be classified together as peripheral arthritis.

In a year when emergency department visits dropped by almost 18%, visits for benzodiazepine overdoses did the opposite, according to a report from the Centers for Disease Control and Prevention.

The actual increase in the number of overdose visits for benzodiazepine overdoses was quite small – from 15,547 in 2019 to 15,830 in 2020 (1.8%) – but the 11 million fewer ED visits magnified its effect, Stephen Liu, PhD, and associates said in the Morbidity and Mortality Weekly Report.

The rate of benzodiazepine overdose visits to all visits increased by 23.7% from 2019 (24.22 per 100,000 ED visits) to 2020 (29.97 per 100,000), with the larger share going to those involving opioids, which were up by 34.4%, compared with overdose visits not involving opioids (21.0%), the investigators said, based on data reported by 32 states and the District of Columbia to the CDC’s Drug Overdose Surveillance and Epidemiology system. All of the rate changes are statistically significant.

The number of overdose visits without opioid coinvolvement actually dropped, from 2019 (12,276) to 2020 (12,218), but not by enough to offset the decline in total visits, noted Dr. Liu, of the CDC’s National Center for Injury Prevention and Control and associates.

The number of deaths from benzodiazepine overdose, on the other hand, did not drop in 2020. Those data, coming from 23 states participating in the CDC’s State Unintentional Drug Overdose Reporting System, were available only for the first half of the year.

In those 6 months, benzodiazepines were involved in more than 2,700 overdose deaths, with second-quarter deaths increasing by 43% from 2019 (1,004) to 2020 (1,435). The first quarter of 2020 also showed an increase, but exact numbers were not provided in the report. Overdose deaths rose by 22% for prescription forms of benzodiazepine and 520% for illicit forms in Q2 of 2020, compared with 2019, the researchers said.

Almost all of the benzodiazepine deaths (93%) in the first half of 2020 also involved opioids, mostly in the form of illicitly manufactured fentanyls (67% of all deaths). Between Q2 of 2019 and Q2 of 2020, involvement of illicit fentanyls in benzodiazepine overdose deaths increased from almost 57% to 71%, Dr. Liu and associates reported.

“Despite progress in reducing coprescribing [of opioids and benzodiazepines] before 2019, this study suggests a reversal in the decline in benzodiazepine deaths from 2017 to 2019, driven in part by increasing involvement of [illicitly manufactured fentanyls] in benzodiazepine deaths and influxes of illicit benzodiazepines,” they wrote.

[email protected]

In a year when emergency department visits dropped by almost 18%, visits for benzodiazepine overdoses did the opposite, according to a report from the Centers for Disease Control and Prevention.

The actual increase in the number of overdose visits for benzodiazepine overdoses was quite small – from 15,547 in 2019 to 15,830 in 2020 (1.8%) – but the 11 million fewer ED visits magnified its effect, Stephen Liu, PhD, and associates said in the Morbidity and Mortality Weekly Report.

The rate of benzodiazepine overdose visits to all visits increased by 23.7% from 2019 (24.22 per 100,000 ED visits) to 2020 (29.97 per 100,000), with the larger share going to those involving opioids, which were up by 34.4%, compared with overdose visits not involving opioids (21.0%), the investigators said, based on data reported by 32 states and the District of Columbia to the CDC’s Drug Overdose Surveillance and Epidemiology system. All of the rate changes are statistically significant.

The number of overdose visits without opioid coinvolvement actually dropped, from 2019 (12,276) to 2020 (12,218), but not by enough to offset the decline in total visits, noted Dr. Liu, of the CDC’s National Center for Injury Prevention and Control and associates.

The number of deaths from benzodiazepine overdose, on the other hand, did not drop in 2020. Those data, coming from 23 states participating in the CDC’s State Unintentional Drug Overdose Reporting System, were available only for the first half of the year.

In those 6 months, benzodiazepines were involved in more than 2,700 overdose deaths, with second-quarter deaths increasing by 43% from 2019 (1,004) to 2020 (1,435). The first quarter of 2020 also showed an increase, but exact numbers were not provided in the report. Overdose deaths rose by 22% for prescription forms of benzodiazepine and 520% for illicit forms in Q2 of 2020, compared with 2019, the researchers said.

Almost all of the benzodiazepine deaths (93%) in the first half of 2020 also involved opioids, mostly in the form of illicitly manufactured fentanyls (67% of all deaths). Between Q2 of 2019 and Q2 of 2020, involvement of illicit fentanyls in benzodiazepine overdose deaths increased from almost 57% to 71%, Dr. Liu and associates reported.

“Despite progress in reducing coprescribing [of opioids and benzodiazepines] before 2019, this study suggests a reversal in the decline in benzodiazepine deaths from 2017 to 2019, driven in part by increasing involvement of [illicitly manufactured fentanyls] in benzodiazepine deaths and influxes of illicit benzodiazepines,” they wrote.

[email protected]

In a year when emergency department visits dropped by almost 18%, visits for benzodiazepine overdoses did the opposite, according to a report from the Centers for Disease Control and Prevention.

The actual increase in the number of overdose visits for benzodiazepine overdoses was quite small – from 15,547 in 2019 to 15,830 in 2020 (1.8%) – but the 11 million fewer ED visits magnified its effect, Stephen Liu, PhD, and associates said in the Morbidity and Mortality Weekly Report.

The rate of benzodiazepine overdose visits to all visits increased by 23.7% from 2019 (24.22 per 100,000 ED visits) to 2020 (29.97 per 100,000), with the larger share going to those involving opioids, which were up by 34.4%, compared with overdose visits not involving opioids (21.0%), the investigators said, based on data reported by 32 states and the District of Columbia to the CDC’s Drug Overdose Surveillance and Epidemiology system. All of the rate changes are statistically significant.

The number of overdose visits without opioid coinvolvement actually dropped, from 2019 (12,276) to 2020 (12,218), but not by enough to offset the decline in total visits, noted Dr. Liu, of the CDC’s National Center for Injury Prevention and Control and associates.

The number of deaths from benzodiazepine overdose, on the other hand, did not drop in 2020. Those data, coming from 23 states participating in the CDC’s State Unintentional Drug Overdose Reporting System, were available only for the first half of the year.

In those 6 months, benzodiazepines were involved in more than 2,700 overdose deaths, with second-quarter deaths increasing by 43% from 2019 (1,004) to 2020 (1,435). The first quarter of 2020 also showed an increase, but exact numbers were not provided in the report. Overdose deaths rose by 22% for prescription forms of benzodiazepine and 520% for illicit forms in Q2 of 2020, compared with 2019, the researchers said.

Almost all of the benzodiazepine deaths (93%) in the first half of 2020 also involved opioids, mostly in the form of illicitly manufactured fentanyls (67% of all deaths). Between Q2 of 2019 and Q2 of 2020, involvement of illicit fentanyls in benzodiazepine overdose deaths increased from almost 57% to 71%, Dr. Liu and associates reported.

“Despite progress in reducing coprescribing [of opioids and benzodiazepines] before 2019, this study suggests a reversal in the decline in benzodiazepine deaths from 2017 to 2019, driven in part by increasing involvement of [illicitly manufactured fentanyls] in benzodiazepine deaths and influxes of illicit benzodiazepines,” they wrote.

[email protected]

Most children who develop multisystemic inflammatory syndrome (MIS-C) after infection with SARS-CoV-2 recover relatively quickly and without significant sequelae, according to a research letter published online in JAMA Pediatrics.

“The results of this research letter offer some reassurance as has been the case with other longitudinal reports, that children with MIS-C largely recover from the illness with minimal sequelae,” said Kanwal M. Farooqi, MD, a pediatric cardiologist from Columbia University Irving Medical Center, New York.

“This is despite the severity of the initial clinical presentation, which can be quite significant with signs of systemic inflammation, hypotension, and need for ICU-level care,” continued Dr. Farooqi, who was not involved in the study.

Given that little is known about the medium- and long-term effects of MIS-C following infection with COVID-19, Patrick Davies, MRCPCH, Nottingham (England) University Hospitals NHS Trust, and colleagues reviewed data from one of the earliest multicenter national cohorts of children in the United Kingdom. The cohort included children admitted to the hospital prior to May 10, 2020, and the analysis was based on data from 68 of 76 (89%) patients of the initial surviving cohort. Information regarding critical care readmissions and outpatient follow-up visits up to April 1, 2021 (1-year post admission), was included in the analysis.

Overall laboratory results appeared normal for most children at 50 days post admission, including neutrophils, platelets, ferritin, creatinine, and alanine transaminase. Just 3% (2/65 test results) of children showed elevated levels of C-reactive protein, 3% (2/59 test results) for D-dimer, and 2% (1/60 test results) for troponin.

Based on echocardiographic data, 14 of the 19 patients who presented with aneurysms had resolution. Nine of 10 patients who presented with “bright” coronary arteries had resolution and only one progressed to having unresolved coronary artery aneurysms with the latest follow-up at 86 days post admission. All of the 38 patients who presented with impaired function without aneurysm had recovered by day 74.

Of the six patients with ongoing echocardiographic abnormalities, all had aneurysmal changes noted on echocardiograms performed between 86 and 336 days post admission. The authors were surprised to find that troponin levels in this group were lower when compared with others in the cohort (0.06 ng/mL [interquartile range, 0.02-0.418 ng/mL] vs. 0.157 ng/mL [0.033-0.81 ng/mL]; P = .02).

These six patients ranged in age from 0 to 13 years (median age, 8.75 years); five were Afro Caribbean boys and one was a White girl.

The researchers acknowledged that, despite coming from a nationwide data set, the interpretation of this data is limited given the small size of the cohort and the lack of standardized follow-up protocol available at the time.

When asked how this data might inform follow-up guidance for children post COVID infection, Dr. Farooqi said, “although it appears from the data that we have seen in the last few months that the patients recover relatively quickly from MIS-C, I believe it is reasonable to evaluate them at 6-month intervals for the second year until we have more information regarding longer-term outcomes.”

The study authors and Dr. Farooqi disclosed no relevant financial relationships.

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

Most children who develop multisystemic inflammatory syndrome (MIS-C) after infection with SARS-CoV-2 recover relatively quickly and without significant sequelae, according to a research letter published online in JAMA Pediatrics.

“The results of this research letter offer some reassurance as has been the case with other longitudinal reports, that children with MIS-C largely recover from the illness with minimal sequelae,” said Kanwal M. Farooqi, MD, a pediatric cardiologist from Columbia University Irving Medical Center, New York.

“This is despite the severity of the initial clinical presentation, which can be quite significant with signs of systemic inflammation, hypotension, and need for ICU-level care,” continued Dr. Farooqi, who was not involved in the study.

Given that little is known about the medium- and long-term effects of MIS-C following infection with COVID-19, Patrick Davies, MRCPCH, Nottingham (England) University Hospitals NHS Trust, and colleagues reviewed data from one of the earliest multicenter national cohorts of children in the United Kingdom. The cohort included children admitted to the hospital prior to May 10, 2020, and the analysis was based on data from 68 of 76 (89%) patients of the initial surviving cohort. Information regarding critical care readmissions and outpatient follow-up visits up to April 1, 2021 (1-year post admission), was included in the analysis.

Overall laboratory results appeared normal for most children at 50 days post admission, including neutrophils, platelets, ferritin, creatinine, and alanine transaminase. Just 3% (2/65 test results) of children showed elevated levels of C-reactive protein, 3% (2/59 test results) for D-dimer, and 2% (1/60 test results) for troponin.

Based on echocardiographic data, 14 of the 19 patients who presented with aneurysms had resolution. Nine of 10 patients who presented with “bright” coronary arteries had resolution and only one progressed to having unresolved coronary artery aneurysms with the latest follow-up at 86 days post admission. All of the 38 patients who presented with impaired function without aneurysm had recovered by day 74.

Of the six patients with ongoing echocardiographic abnormalities, all had aneurysmal changes noted on echocardiograms performed between 86 and 336 days post admission. The authors were surprised to find that troponin levels in this group were lower when compared with others in the cohort (0.06 ng/mL [interquartile range, 0.02-0.418 ng/mL] vs. 0.157 ng/mL [0.033-0.81 ng/mL]; P = .02).

These six patients ranged in age from 0 to 13 years (median age, 8.75 years); five were Afro Caribbean boys and one was a White girl.

The researchers acknowledged that, despite coming from a nationwide data set, the interpretation of this data is limited given the small size of the cohort and the lack of standardized follow-up protocol available at the time.

When asked how this data might inform follow-up guidance for children post COVID infection, Dr. Farooqi said, “although it appears from the data that we have seen in the last few months that the patients recover relatively quickly from MIS-C, I believe it is reasonable to evaluate them at 6-month intervals for the second year until we have more information regarding longer-term outcomes.”

The study authors and Dr. Farooqi disclosed no relevant financial relationships.

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

Most children who develop multisystemic inflammatory syndrome (MIS-C) after infection with SARS-CoV-2 recover relatively quickly and without significant sequelae, according to a research letter published online in JAMA Pediatrics.

“The results of this research letter offer some reassurance as has been the case with other longitudinal reports, that children with MIS-C largely recover from the illness with minimal sequelae,” said Kanwal M. Farooqi, MD, a pediatric cardiologist from Columbia University Irving Medical Center, New York.

“This is despite the severity of the initial clinical presentation, which can be quite significant with signs of systemic inflammation, hypotension, and need for ICU-level care,” continued Dr. Farooqi, who was not involved in the study.

Given that little is known about the medium- and long-term effects of MIS-C following infection with COVID-19, Patrick Davies, MRCPCH, Nottingham (England) University Hospitals NHS Trust, and colleagues reviewed data from one of the earliest multicenter national cohorts of children in the United Kingdom. The cohort included children admitted to the hospital prior to May 10, 2020, and the analysis was based on data from 68 of 76 (89%) patients of the initial surviving cohort. Information regarding critical care readmissions and outpatient follow-up visits up to April 1, 2021 (1-year post admission), was included in the analysis.

Overall laboratory results appeared normal for most children at 50 days post admission, including neutrophils, platelets, ferritin, creatinine, and alanine transaminase. Just 3% (2/65 test results) of children showed elevated levels of C-reactive protein, 3% (2/59 test results) for D-dimer, and 2% (1/60 test results) for troponin.

Based on echocardiographic data, 14 of the 19 patients who presented with aneurysms had resolution. Nine of 10 patients who presented with “bright” coronary arteries had resolution and only one progressed to having unresolved coronary artery aneurysms with the latest follow-up at 86 days post admission. All of the 38 patients who presented with impaired function without aneurysm had recovered by day 74.

Of the six patients with ongoing echocardiographic abnormalities, all had aneurysmal changes noted on echocardiograms performed between 86 and 336 days post admission. The authors were surprised to find that troponin levels in this group were lower when compared with others in the cohort (0.06 ng/mL [interquartile range, 0.02-0.418 ng/mL] vs. 0.157 ng/mL [0.033-0.81 ng/mL]; P = .02).

These six patients ranged in age from 0 to 13 years (median age, 8.75 years); five were Afro Caribbean boys and one was a White girl.

The researchers acknowledged that, despite coming from a nationwide data set, the interpretation of this data is limited given the small size of the cohort and the lack of standardized follow-up protocol available at the time.

When asked how this data might inform follow-up guidance for children post COVID infection, Dr. Farooqi said, “although it appears from the data that we have seen in the last few months that the patients recover relatively quickly from MIS-C, I believe it is reasonable to evaluate them at 6-month intervals for the second year until we have more information regarding longer-term outcomes.”

The study authors and Dr. Farooqi disclosed no relevant financial relationships.

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

Nearly half of people who are hospitalized with COVID-19 suffer at least one lingering symptom 1 year after discharge, according to the largest study yet to assess the dynamic recovery of a group of COVID-19 survivors 12 months after the illness.

The most common lingering symptoms are fatigue and muscle weakness. One-third continue to have shortness of breath.

Overall, at 12 months, COVID-19 survivors had more problems with mobility, pain or discomfort, and anxiety or depression, and had lower self-assessment scores of quality of life than matched COVID-free peers, the investigators report. 

The study was published online Aug. 28 in The Lancet.

“While most had made a good recovery, health problems persisted in some patients, especially those who had been critically ill during their hospital stay,” Bin Cao, MD, from the National Center for Respiratory Medicine at the China-Japan Friendship Hospital and Capital Medical University, both in Beijing, said in a Lancet news release.

“Our findings suggest that recovery for some patients will take longer than 1 year, and this should be taken into account when planning delivery of health care services post pandemic,” Dr. Cao said.

“As the COVID-19 pandemic continues, the need to understand and respond to long COVID is increasingly pressing,” says a Lancet editorial.

“Symptoms such as persistent fatigue, breathlessness, brain fog, and depression could debilitate many millions of people globally. Long COVID is a modern medical challenge of the first order,” it reads.
 

Study details

Dr. Cao and colleagues studied 1,276 COVID-19 patients (median age 59; 53% men) discharged from a hospital in Wuhan, China, between Jan. 7 and May 29, 2020. The patients were assessed at 6 and 12 months from the date they first experienced COVID-19 symptoms.

Many symptoms resolved over time, regardless of the severity of illness. Yet 49% of patients still had at least one symptom 12 months after their acute illness, down from 68% at the 6-month mark, the authors report.

Fatigue and muscle weakness were the most commonly reported symptoms seen in 52% of patients at 6 months and 20% at 12 months. Compared with men, women were 1.4 times more likely to report fatigue or muscle weakness.

Patients treated with corticosteroids during the acute phase of COVID-19 were 1.5 times as likely to experience fatigue or muscle weakness after 12 months, compared with those who had not received corticosteroids.

Thirty percent of patients reported dyspnea at 12 months, slightly more than at 6 months (26%). Dyspnea was more common in the most severely ill patients needing a ventilator during their hospital stay (39%), compared with those who did not need oxygen treatment (25%).

At the 6-month check, 349 study participants underwent pulmonary function tests and 244 of those patients completed the same test at 12 months.

Spirometric and lung volume parameters of most of these patients were within normal limits at 12 months. But lung diffusion impairment was observed in about 20%-30% of patients who had been moderately ill with COVID-19 and as high as 54% in critically ill patients. 

Compared with men, women were almost three times as likely to have lung diffusion impairment after 12 months.

Of 186 patients with abnormal lung CT scan at 6 months, 118 patients had a repeat CT scan at 12 months. The lung imaging abnormality gradually recovered during follow-up, yet 76% of the most critically ill patients still had ground glass opacity at 12 months.

Mental health hit

Among those patients who had been employed full- or part-time before catching COVID, the majority had returned to their original job (88%) and most had returned to their pre-COVID-19 level of work (76%) within 12 months.

Among those who did not return to their original work, 32% cited decreased physical function, 25% were unwilling to do their previous job, and 18% were unemployed.

As shown in multiple other studies, COVID-19 can take a toll on mental health. In this cohort, slightly more patients reported anxiety or depression at 12 months than at 6 months (23% vs. 26%), and the proportion was much greater than in matched community-dwelling adults without COVID-19 (5%).

Compared with men, women were twice as likely to report anxiety or depression.

“We do not yet fully understand why psychiatric symptoms are slightly more common at 1 year than at 6 months in COVID-19 survivors,” study author Xiaoying Gu, PhD, from the Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, said in the news release.

“These could be caused by a biological process linked to the virus infection itself, or the body’s immune response to it. Or they could be linked to reduced social contact, loneliness, incomplete recovery of physical health, or loss of employment associated with illness. Large, long-term studies of COVID-19 survivors are needed so that we can better understand the long-term physical and mental health consequences of COVID-19,” Dr. Gu said.

The authors caution that the findings represent a group of patients from a single hospital in China and the cohort included only a small number of patients who had been admitted to intensive care (94 of 1,276; 7.4%).

The Lancet editorial urges the scientific and medical community to “collaborate to explore the mechanism and pathogenesis of long COVID, estimate the global and regional disease burdens, better delineate who is most at risk, understand how vaccines might affect the condition, and find effective treatments via randomized controlled trials.”

“At the same time, health care providers must acknowledge and validate the toll of the persistent symptoms of long COVID on patients, and health systems need to be prepared to meet individualized, patient-oriented goals, with an appropriately trained workforce involving physical, cognitive, social, and occupational elements,” the editorial states.

“Answering these research questions while providing compassionate and multidisciplinary care will require the full breadth of scientific and medical ingenuity. It is a challenge to which the whole health community must rise,” the editorialists conclude.

The study was funded by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, the National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, the China Evergrande Group, the Jack Ma Foundation, Sino Biopharmaceutical, the Ping An Insurance (Group), and the New Sunshine Charity Foundation. The full list of author disclosures is available with the original article.

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

Nearly half of people who are hospitalized with COVID-19 suffer at least one lingering symptom 1 year after discharge, according to the largest study yet to assess the dynamic recovery of a group of COVID-19 survivors 12 months after the illness.

The most common lingering symptoms are fatigue and muscle weakness. One-third continue to have shortness of breath.

Overall, at 12 months, COVID-19 survivors had more problems with mobility, pain or discomfort, and anxiety or depression, and had lower self-assessment scores of quality of life than matched COVID-free peers, the investigators report. 

The study was published online Aug. 28 in The Lancet.

“While most had made a good recovery, health problems persisted in some patients, especially those who had been critically ill during their hospital stay,” Bin Cao, MD, from the National Center for Respiratory Medicine at the China-Japan Friendship Hospital and Capital Medical University, both in Beijing, said in a Lancet news release.

“Our findings suggest that recovery for some patients will take longer than 1 year, and this should be taken into account when planning delivery of health care services post pandemic,” Dr. Cao said.

“As the COVID-19 pandemic continues, the need to understand and respond to long COVID is increasingly pressing,” says a Lancet editorial.

“Symptoms such as persistent fatigue, breathlessness, brain fog, and depression could debilitate many millions of people globally. Long COVID is a modern medical challenge of the first order,” it reads.
 

Study details

Dr. Cao and colleagues studied 1,276 COVID-19 patients (median age 59; 53% men) discharged from a hospital in Wuhan, China, between Jan. 7 and May 29, 2020. The patients were assessed at 6 and 12 months from the date they first experienced COVID-19 symptoms.

Many symptoms resolved over time, regardless of the severity of illness. Yet 49% of patients still had at least one symptom 12 months after their acute illness, down from 68% at the 6-month mark, the authors report.

Fatigue and muscle weakness were the most commonly reported symptoms seen in 52% of patients at 6 months and 20% at 12 months. Compared with men, women were 1.4 times more likely to report fatigue or muscle weakness.

Patients treated with corticosteroids during the acute phase of COVID-19 were 1.5 times as likely to experience fatigue or muscle weakness after 12 months, compared with those who had not received corticosteroids.

Thirty percent of patients reported dyspnea at 12 months, slightly more than at 6 months (26%). Dyspnea was more common in the most severely ill patients needing a ventilator during their hospital stay (39%), compared with those who did not need oxygen treatment (25%).

At the 6-month check, 349 study participants underwent pulmonary function tests and 244 of those patients completed the same test at 12 months.

Spirometric and lung volume parameters of most of these patients were within normal limits at 12 months. But lung diffusion impairment was observed in about 20%-30% of patients who had been moderately ill with COVID-19 and as high as 54% in critically ill patients. 

Compared with men, women were almost three times as likely to have lung diffusion impairment after 12 months.

Of 186 patients with abnormal lung CT scan at 6 months, 118 patients had a repeat CT scan at 12 months. The lung imaging abnormality gradually recovered during follow-up, yet 76% of the most critically ill patients still had ground glass opacity at 12 months.

Mental health hit

Among those patients who had been employed full- or part-time before catching COVID, the majority had returned to their original job (88%) and most had returned to their pre-COVID-19 level of work (76%) within 12 months.

Among those who did not return to their original work, 32% cited decreased physical function, 25% were unwilling to do their previous job, and 18% were unemployed.

As shown in multiple other studies, COVID-19 can take a toll on mental health. In this cohort, slightly more patients reported anxiety or depression at 12 months than at 6 months (23% vs. 26%), and the proportion was much greater than in matched community-dwelling adults without COVID-19 (5%).

Compared with men, women were twice as likely to report anxiety or depression.

“We do not yet fully understand why psychiatric symptoms are slightly more common at 1 year than at 6 months in COVID-19 survivors,” study author Xiaoying Gu, PhD, from the Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, said in the news release.

“These could be caused by a biological process linked to the virus infection itself, or the body’s immune response to it. Or they could be linked to reduced social contact, loneliness, incomplete recovery of physical health, or loss of employment associated with illness. Large, long-term studies of COVID-19 survivors are needed so that we can better understand the long-term physical and mental health consequences of COVID-19,” Dr. Gu said.

The authors caution that the findings represent a group of patients from a single hospital in China and the cohort included only a small number of patients who had been admitted to intensive care (94 of 1,276; 7.4%).

The Lancet editorial urges the scientific and medical community to “collaborate to explore the mechanism and pathogenesis of long COVID, estimate the global and regional disease burdens, better delineate who is most at risk, understand how vaccines might affect the condition, and find effective treatments via randomized controlled trials.”

“At the same time, health care providers must acknowledge and validate the toll of the persistent symptoms of long COVID on patients, and health systems need to be prepared to meet individualized, patient-oriented goals, with an appropriately trained workforce involving physical, cognitive, social, and occupational elements,” the editorial states.

“Answering these research questions while providing compassionate and multidisciplinary care will require the full breadth of scientific and medical ingenuity. It is a challenge to which the whole health community must rise,” the editorialists conclude.

The study was funded by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, the National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, the China Evergrande Group, the Jack Ma Foundation, Sino Biopharmaceutical, the Ping An Insurance (Group), and the New Sunshine Charity Foundation. The full list of author disclosures is available with the original article.

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

Nearly half of people who are hospitalized with COVID-19 suffer at least one lingering symptom 1 year after discharge, according to the largest study yet to assess the dynamic recovery of a group of COVID-19 survivors 12 months after the illness.

The most common lingering symptoms are fatigue and muscle weakness. One-third continue to have shortness of breath.

Overall, at 12 months, COVID-19 survivors had more problems with mobility, pain or discomfort, and anxiety or depression, and had lower self-assessment scores of quality of life than matched COVID-free peers, the investigators report. 

The study was published online Aug. 28 in The Lancet.

“While most had made a good recovery, health problems persisted in some patients, especially those who had been critically ill during their hospital stay,” Bin Cao, MD, from the National Center for Respiratory Medicine at the China-Japan Friendship Hospital and Capital Medical University, both in Beijing, said in a Lancet news release.

“Our findings suggest that recovery for some patients will take longer than 1 year, and this should be taken into account when planning delivery of health care services post pandemic,” Dr. Cao said.

“As the COVID-19 pandemic continues, the need to understand and respond to long COVID is increasingly pressing,” says a Lancet editorial.

“Symptoms such as persistent fatigue, breathlessness, brain fog, and depression could debilitate many millions of people globally. Long COVID is a modern medical challenge of the first order,” it reads.
 

Study details

Dr. Cao and colleagues studied 1,276 COVID-19 patients (median age 59; 53% men) discharged from a hospital in Wuhan, China, between Jan. 7 and May 29, 2020. The patients were assessed at 6 and 12 months from the date they first experienced COVID-19 symptoms.

Many symptoms resolved over time, regardless of the severity of illness. Yet 49% of patients still had at least one symptom 12 months after their acute illness, down from 68% at the 6-month mark, the authors report.

Fatigue and muscle weakness were the most commonly reported symptoms seen in 52% of patients at 6 months and 20% at 12 months. Compared with men, women were 1.4 times more likely to report fatigue or muscle weakness.

Patients treated with corticosteroids during the acute phase of COVID-19 were 1.5 times as likely to experience fatigue or muscle weakness after 12 months, compared with those who had not received corticosteroids.

Thirty percent of patients reported dyspnea at 12 months, slightly more than at 6 months (26%). Dyspnea was more common in the most severely ill patients needing a ventilator during their hospital stay (39%), compared with those who did not need oxygen treatment (25%).

At the 6-month check, 349 study participants underwent pulmonary function tests and 244 of those patients completed the same test at 12 months.

Spirometric and lung volume parameters of most of these patients were within normal limits at 12 months. But lung diffusion impairment was observed in about 20%-30% of patients who had been moderately ill with COVID-19 and as high as 54% in critically ill patients. 

Compared with men, women were almost three times as likely to have lung diffusion impairment after 12 months.

Of 186 patients with abnormal lung CT scan at 6 months, 118 patients had a repeat CT scan at 12 months. The lung imaging abnormality gradually recovered during follow-up, yet 76% of the most critically ill patients still had ground glass opacity at 12 months.

Mental health hit

Among those patients who had been employed full- or part-time before catching COVID, the majority had returned to their original job (88%) and most had returned to their pre-COVID-19 level of work (76%) within 12 months.

Among those who did not return to their original work, 32% cited decreased physical function, 25% were unwilling to do their previous job, and 18% were unemployed.

As shown in multiple other studies, COVID-19 can take a toll on mental health. In this cohort, slightly more patients reported anxiety or depression at 12 months than at 6 months (23% vs. 26%), and the proportion was much greater than in matched community-dwelling adults without COVID-19 (5%).

Compared with men, women were twice as likely to report anxiety or depression.

“We do not yet fully understand why psychiatric symptoms are slightly more common at 1 year than at 6 months in COVID-19 survivors,” study author Xiaoying Gu, PhD, from the Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, said in the news release.

“These could be caused by a biological process linked to the virus infection itself, or the body’s immune response to it. Or they could be linked to reduced social contact, loneliness, incomplete recovery of physical health, or loss of employment associated with illness. Large, long-term studies of COVID-19 survivors are needed so that we can better understand the long-term physical and mental health consequences of COVID-19,” Dr. Gu said.

The authors caution that the findings represent a group of patients from a single hospital in China and the cohort included only a small number of patients who had been admitted to intensive care (94 of 1,276; 7.4%).

The Lancet editorial urges the scientific and medical community to “collaborate to explore the mechanism and pathogenesis of long COVID, estimate the global and regional disease burdens, better delineate who is most at risk, understand how vaccines might affect the condition, and find effective treatments via randomized controlled trials.”

“At the same time, health care providers must acknowledge and validate the toll of the persistent symptoms of long COVID on patients, and health systems need to be prepared to meet individualized, patient-oriented goals, with an appropriately trained workforce involving physical, cognitive, social, and occupational elements,” the editorial states.

“Answering these research questions while providing compassionate and multidisciplinary care will require the full breadth of scientific and medical ingenuity. It is a challenge to which the whole health community must rise,” the editorialists conclude.

The study was funded by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, the National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, the China Evergrande Group, the Jack Ma Foundation, Sino Biopharmaceutical, the Ping An Insurance (Group), and the New Sunshine Charity Foundation. The full list of author disclosures is available with the original article.

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

The transition from undergraduate medical education (UME) to graduate medical education in the United States needs comprehensive reform, says a new report from the Graduate Medical Education Review Committee (UGRC) of the Coalition for Physician Accountability.

The 275-page report presents preliminary findings that were released in April 2021 and a long list of stakeholder comments. According to the report, the coalition will meet soon to discuss the final recommendations and consider next steps toward implementation.

The UGRC includes representatives of national medical organizations, medical schools, and residency programs. Among the organizations that participated in the report’s creation are the American Medical Association, the National Board of Medical Examiners, the American Osteopathic Association, the National Board of Osteopathic Medical Examiners, the Educational Commission for Foreign Medical Graduates, and the Association of American Medical Colleges.

The report identifies a list of challenges that affect the transition of medical students into residency programs and beyond. They include:

• Too much focus on finding and filling residency positions instead of “assuring learner competence and readiness for residency training”
• Inattention to assuring congruence between applicant goals and program missions
• Overreliance on licensure exam scores rather than “valid, trustworthy measures of students’ competence and clinical abilities”
• Increasing financial costs to students
• Individual and systemic biases in the UME-GME transition, as well as inequities related to international medical graduates

Seeking a common framework for competence

Overall, the report calls for increased standardization of how students are evaluated in medical school and how residency programs evaluate students. Less reliance should be placed on the numerical scores of the U.S. Medical Licensing Examination (USMLE), the report says, and more attention should be paid to the direct observation of student performance in clinical situations. In addition, the various organizations involved in the UME-GME transition process are asked to work better together.

To develop better methods of evaluating medical students and residents, UME and GME educators should jointly define and implement a common framework and set of competencies to apply to learners across the UME-GME transition, the report suggests.

While emphasizing the need for a broader student assessment framework, the report says, USMLE scores should also continue to be used in judging residency applicants. “Assessment information should be shared in residency applications and a postmatch learner handover. Licensing examinations should be used for their intended purpose to ensure requisite competence.”

Among the committee’s three dozen recommendations are the following:

• The Centers for Medicare & Medicaid Services should change the GME funding structure so that the initial residency period is calculated starting with the second year of postgraduate training. This change would allow residents to reconsider their career choices. Currently, if a resident decides to switch to another program or specialty after beginning training, the hospital may not receive full GME funding, so may be less likely to approve the change.
• Residency programs should improve recruitment practices to increase specialty-specific diversity of residents. Medical educators should also receive additional training regarding antiracism, avoiding bias, and ensuring equity.
• The self-reported demographic information of applicants to residency programs should be measured and shared with stakeholders, including the programs and medical schools, to promote equity. “A residency program that finds bias in its selection process could go back in real time to find qualified applicants who may have been missed, potentially improving outcomes,” the report notes.
• An interactive database of GME program and specialty track information should be created and made available to all applicants, medical schools, and residency programs at no cost to applicants. “Applicants and their advisors should be able to sort the information according to demographic and educational features that may significantly impact the likelihood of matching at a program.”

Less than half of applicants get in-depth reviews

The 2020 National Resident Matching Program Program Director Survey found that only 49% of applications received in-depth review. In light of this, the report suggests that the application system be updated to use modern information technology, including discrete fields for key data to expedite application reviews.

Many applications have been discarded because of various filters used to block consideration of certain applications. The report suggests that new filters be designed to ensure that each detects meaningful differences among applicants and promotes review based on mission alignment and likelihood of success in a program. Filters should be improved to decrease the likelihood of random exclusions of qualified applicants.

Specialty-specific, just-in-time training for all incoming first-year residents is also suggested to support the transition from the role of student to a physician ready to assume increased responsibility for patient care. In addition, the report urges adequate time be allowed between medical school graduation and residency to enable new residents to relocate and find homes.

The report also calls for a standardized process in the United States for initial licensing of doctors at entrance to residency in order to streamline the process of credentialing for both residency training and continuing practice.
 

Osteopathic students’ dilemma

To promote equitable treatment of applicants regardless of licensure examination requirements, comparable exams with different scales (COMLEX-USA and USMLE) should be reported within the electronic application system in a single field, the report said.

Osteopathic students, who make up 25% of U.S. medical students, must take the COMLEX-USA exam, but residency programs may filter them out if they don’t also take the USMLE exam. Thus, many osteopathic students take both exams, incurring extra time, cost, and stress.

The UGRC recommends creating a combined field in the electronic residency application service that normalizes the scores between the two exams. Residency programs could then filter applications based only on the single normalized score.

This approach makes sense from the viewpoint that it would reduce the pressure on osteopathic students to take the USMLE, Bryan Carmody, MD, an outspoken critic of various current training policies, said in an interview. But it could also have serious disadvantages.

For one thing, only osteopathic students can take the COMLEX-USA exam, he noted. If they don’t like their score, they can then take the USMLE test to get a higher score – an option that allopathic students don’t have. It’s not clear that they’d be prevented from doing this under the UGRC recommendation.

Second, he said, osteopathic students, on average, don’t do as well as allopathic students on the UMSLE exam. If they only take the COMLEX-USA test, they’re competing against other students who don’t do as well on tests as allopathic students do. If their scores were normalized with those of the USMLE test takers, they’d gain an unfair advantage against students who can only take the USMLE, including international medical graduates.

Although Dr. Carmody admitted that osteopathic students face a harder challenge than allopathic students in matching to residency programs, he said that the UGRC approach to the licensing exams might actually penalize them further. As a result of the scores of the two exams being averaged, residency program directors might discount the scores of all osteopathic students.

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

The transition from undergraduate medical education (UME) to graduate medical education in the United States needs comprehensive reform, says a new report from the Graduate Medical Education Review Committee (UGRC) of the Coalition for Physician Accountability.

The 275-page report presents preliminary findings that were released in April 2021 and a long list of stakeholder comments. According to the report, the coalition will meet soon to discuss the final recommendations and consider next steps toward implementation.

The UGRC includes representatives of national medical organizations, medical schools, and residency programs. Among the organizations that participated in the report’s creation are the American Medical Association, the National Board of Medical Examiners, the American Osteopathic Association, the National Board of Osteopathic Medical Examiners, the Educational Commission for Foreign Medical Graduates, and the Association of American Medical Colleges.

The report identifies a list of challenges that affect the transition of medical students into residency programs and beyond. They include:

• Too much focus on finding and filling residency positions instead of “assuring learner competence and readiness for residency training”
• Inattention to assuring congruence between applicant goals and program missions
• Overreliance on licensure exam scores rather than “valid, trustworthy measures of students’ competence and clinical abilities”
• Increasing financial costs to students
• Individual and systemic biases in the UME-GME transition, as well as inequities related to international medical graduates

Seeking a common framework for competence

Overall, the report calls for increased standardization of how students are evaluated in medical school and how residency programs evaluate students. Less reliance should be placed on the numerical scores of the U.S. Medical Licensing Examination (USMLE), the report says, and more attention should be paid to the direct observation of student performance in clinical situations. In addition, the various organizations involved in the UME-GME transition process are asked to work better together.

To develop better methods of evaluating medical students and residents, UME and GME educators should jointly define and implement a common framework and set of competencies to apply to learners across the UME-GME transition, the report suggests.

While emphasizing the need for a broader student assessment framework, the report says, USMLE scores should also continue to be used in judging residency applicants. “Assessment information should be shared in residency applications and a postmatch learner handover. Licensing examinations should be used for their intended purpose to ensure requisite competence.”

Among the committee’s three dozen recommendations are the following:

• The Centers for Medicare & Medicaid Services should change the GME funding structure so that the initial residency period is calculated starting with the second year of postgraduate training. This change would allow residents to reconsider their career choices. Currently, if a resident decides to switch to another program or specialty after beginning training, the hospital may not receive full GME funding, so may be less likely to approve the change.
• Residency programs should improve recruitment practices to increase specialty-specific diversity of residents. Medical educators should also receive additional training regarding antiracism, avoiding bias, and ensuring equity.
• The self-reported demographic information of applicants to residency programs should be measured and shared with stakeholders, including the programs and medical schools, to promote equity. “A residency program that finds bias in its selection process could go back in real time to find qualified applicants who may have been missed, potentially improving outcomes,” the report notes.
• An interactive database of GME program and specialty track information should be created and made available to all applicants, medical schools, and residency programs at no cost to applicants. “Applicants and their advisors should be able to sort the information according to demographic and educational features that may significantly impact the likelihood of matching at a program.”

Less than half of applicants get in-depth reviews

The 2020 National Resident Matching Program Program Director Survey found that only 49% of applications received in-depth review. In light of this, the report suggests that the application system be updated to use modern information technology, including discrete fields for key data to expedite application reviews.

Many applications have been discarded because of various filters used to block consideration of certain applications. The report suggests that new filters be designed to ensure that each detects meaningful differences among applicants and promotes review based on mission alignment and likelihood of success in a program. Filters should be improved to decrease the likelihood of random exclusions of qualified applicants.

Specialty-specific, just-in-time training for all incoming first-year residents is also suggested to support the transition from the role of student to a physician ready to assume increased responsibility for patient care. In addition, the report urges adequate time be allowed between medical school graduation and residency to enable new residents to relocate and find homes.

The report also calls for a standardized process in the United States for initial licensing of doctors at entrance to residency in order to streamline the process of credentialing for both residency training and continuing practice.
 

Osteopathic students’ dilemma

To promote equitable treatment of applicants regardless of licensure examination requirements, comparable exams with different scales (COMLEX-USA and USMLE) should be reported within the electronic application system in a single field, the report said.

Osteopathic students, who make up 25% of U.S. medical students, must take the COMLEX-USA exam, but residency programs may filter them out if they don’t also take the USMLE exam. Thus, many osteopathic students take both exams, incurring extra time, cost, and stress.

The UGRC recommends creating a combined field in the electronic residency application service that normalizes the scores between the two exams. Residency programs could then filter applications based only on the single normalized score.

This approach makes sense from the viewpoint that it would reduce the pressure on osteopathic students to take the USMLE, Bryan Carmody, MD, an outspoken critic of various current training policies, said in an interview. But it could also have serious disadvantages.

For one thing, only osteopathic students can take the COMLEX-USA exam, he noted. If they don’t like their score, they can then take the USMLE test to get a higher score – an option that allopathic students don’t have. It’s not clear that they’d be prevented from doing this under the UGRC recommendation.

Second, he said, osteopathic students, on average, don’t do as well as allopathic students on the UMSLE exam. If they only take the COMLEX-USA test, they’re competing against other students who don’t do as well on tests as allopathic students do. If their scores were normalized with those of the USMLE test takers, they’d gain an unfair advantage against students who can only take the USMLE, including international medical graduates.

Although Dr. Carmody admitted that osteopathic students face a harder challenge than allopathic students in matching to residency programs, he said that the UGRC approach to the licensing exams might actually penalize them further. As a result of the scores of the two exams being averaged, residency program directors might discount the scores of all osteopathic students.

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

The transition from undergraduate medical education (UME) to graduate medical education in the United States needs comprehensive reform, says a new report from the Graduate Medical Education Review Committee (UGRC) of the Coalition for Physician Accountability.

The 275-page report presents preliminary findings that were released in April 2021 and a long list of stakeholder comments. According to the report, the coalition will meet soon to discuss the final recommendations and consider next steps toward implementation.

The UGRC includes representatives of national medical organizations, medical schools, and residency programs. Among the organizations that participated in the report’s creation are the American Medical Association, the National Board of Medical Examiners, the American Osteopathic Association, the National Board of Osteopathic Medical Examiners, the Educational Commission for Foreign Medical Graduates, and the Association of American Medical Colleges.

The report identifies a list of challenges that affect the transition of medical students into residency programs and beyond. They include:

• Too much focus on finding and filling residency positions instead of “assuring learner competence and readiness for residency training”
• Inattention to assuring congruence between applicant goals and program missions
• Overreliance on licensure exam scores rather than “valid, trustworthy measures of students’ competence and clinical abilities”
• Increasing financial costs to students
• Individual and systemic biases in the UME-GME transition, as well as inequities related to international medical graduates

Seeking a common framework for competence

Overall, the report calls for increased standardization of how students are evaluated in medical school and how residency programs evaluate students. Less reliance should be placed on the numerical scores of the U.S. Medical Licensing Examination (USMLE), the report says, and more attention should be paid to the direct observation of student performance in clinical situations. In addition, the various organizations involved in the UME-GME transition process are asked to work better together.

To develop better methods of evaluating medical students and residents, UME and GME educators should jointly define and implement a common framework and set of competencies to apply to learners across the UME-GME transition, the report suggests.

While emphasizing the need for a broader student assessment framework, the report says, USMLE scores should also continue to be used in judging residency applicants. “Assessment information should be shared in residency applications and a postmatch learner handover. Licensing examinations should be used for their intended purpose to ensure requisite competence.”

Among the committee’s three dozen recommendations are the following:

• The Centers for Medicare & Medicaid Services should change the GME funding structure so that the initial residency period is calculated starting with the second year of postgraduate training. This change would allow residents to reconsider their career choices. Currently, if a resident decides to switch to another program or specialty after beginning training, the hospital may not receive full GME funding, so may be less likely to approve the change.
• Residency programs should improve recruitment practices to increase specialty-specific diversity of residents. Medical educators should also receive additional training regarding antiracism, avoiding bias, and ensuring equity.
• The self-reported demographic information of applicants to residency programs should be measured and shared with stakeholders, including the programs and medical schools, to promote equity. “A residency program that finds bias in its selection process could go back in real time to find qualified applicants who may have been missed, potentially improving outcomes,” the report notes.
• An interactive database of GME program and specialty track information should be created and made available to all applicants, medical schools, and residency programs at no cost to applicants. “Applicants and their advisors should be able to sort the information according to demographic and educational features that may significantly impact the likelihood of matching at a program.”

Less than half of applicants get in-depth reviews

The 2020 National Resident Matching Program Program Director Survey found that only 49% of applications received in-depth review. In light of this, the report suggests that the application system be updated to use modern information technology, including discrete fields for key data to expedite application reviews.

Many applications have been discarded because of various filters used to block consideration of certain applications. The report suggests that new filters be designed to ensure that each detects meaningful differences among applicants and promotes review based on mission alignment and likelihood of success in a program. Filters should be improved to decrease the likelihood of random exclusions of qualified applicants.

Specialty-specific, just-in-time training for all incoming first-year residents is also suggested to support the transition from the role of student to a physician ready to assume increased responsibility for patient care. In addition, the report urges adequate time be allowed between medical school graduation and residency to enable new residents to relocate and find homes.

The report also calls for a standardized process in the United States for initial licensing of doctors at entrance to residency in order to streamline the process of credentialing for both residency training and continuing practice.
 

Osteopathic students’ dilemma

To promote equitable treatment of applicants regardless of licensure examination requirements, comparable exams with different scales (COMLEX-USA and USMLE) should be reported within the electronic application system in a single field, the report said.

Osteopathic students, who make up 25% of U.S. medical students, must take the COMLEX-USA exam, but residency programs may filter them out if they don’t also take the USMLE exam. Thus, many osteopathic students take both exams, incurring extra time, cost, and stress.

The UGRC recommends creating a combined field in the electronic residency application service that normalizes the scores between the two exams. Residency programs could then filter applications based only on the single normalized score.

This approach makes sense from the viewpoint that it would reduce the pressure on osteopathic students to take the USMLE, Bryan Carmody, MD, an outspoken critic of various current training policies, said in an interview. But it could also have serious disadvantages.

For one thing, only osteopathic students can take the COMLEX-USA exam, he noted. If they don’t like their score, they can then take the USMLE test to get a higher score – an option that allopathic students don’t have. It’s not clear that they’d be prevented from doing this under the UGRC recommendation.

Second, he said, osteopathic students, on average, don’t do as well as allopathic students on the UMSLE exam. If they only take the COMLEX-USA test, they’re competing against other students who don’t do as well on tests as allopathic students do. If their scores were normalized with those of the USMLE test takers, they’d gain an unfair advantage against students who can only take the USMLE, including international medical graduates.

Although Dr. Carmody admitted that osteopathic students face a harder challenge than allopathic students in matching to residency programs, he said that the UGRC approach to the licensing exams might actually penalize them further. As a result of the scores of the two exams being averaged, residency program directors might discount the scores of all osteopathic students.

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