As a field service representative for a slot machine company, Ryan Alexander, 37, of Louisville, Ky., spends his working hours in casinos, covering a large territory including Norfolk, Va., Indianapolis, and Charlotte. Social distancing in the casinos is not the norm. Despite all this up-close contact with people, he said he is still COVID-free, 3 years into the pandemic.

There was one nervous night when his temperature rose to 101° F, and he figured the virus had caught up with him. “I took a test and was fine,” he said, relieved that the result was negative. The fever disappeared, and he was back to normal soon. “Maybe it was just an exhausting day.”

Mr. Alexander is one of those people who have managed – or at least think they have managed – to avoid getting COVID-19.

He is, some say, a NOVID. While some scientists cringe at the term, it’s caught on to describe these virus super-dodgers. Online entrepreneurs offer NOVID-19 T-shirts, masks, and stickers, in case these super-healthy or super-lucky folks want to publicize their good luck. On Twitter, NOVIDs share stories of how they’ve done it.
 

How many NOVIDs?

As of March 16, according to the CDC, almost 104 million cases of COVID – about one-third of the U.S. population – have been reported, but many cases are known to go unreported. About half of American adults surveyed said they have had COVID, according to a December report by the COVID States Project, a multiuniversity effort to supply pandemic data.

As the numbers settle over time, though, it becomes clearer that some in the U.S. have apparently managed to avoid the virus.

While the exact number of people who have remained uninfected isn’t known with certainty, a review of comprehensive serologic data shows about 15% of Americans may not have gotten infected with COVID, Eric Topol, MD, editor-in-chief of Medscape (WebMD’s sister site for medical professionals) wrote in his substack Ground Truths.

But some scientists bristle at the term NOVIDs. They prefer the term “resisters,” according to Elena Hsieh, MD, associate professor of pediatrics and immunology at the University of Colorado at Denver, Aurora. Currently, she said, there is much more information on who is more susceptible to contracting severe COVID than who is resistant.

Dr. Hsieh is one of the regional coordinators for the COVID Human Genetic Effort, an international consortium of more than 250 researchers and doctors dedicated to discovering the genetic and immunological bases of the forms of SARS-CoV-2 infection. These researchers and others are looking for explanations for why some people get severe COVID while others seem resistant despite repeated exposure.
 

Resistance research

In determining explanations for resistance to infection, “the needle in the haystack that we are looking for is a change in the genetic code that would allow for you to avoid entry of the virus into the cell,” Dr. Hsieh said. “That is what being resistant to infection is.”

Part of the reason it’s so difficult to study resistance is defining a resister, she said. While many people consider themselves among that group because they’re been exposed multiple times – even with close family members infected and sick, yet they still felt fine – that doesn’t necessarily make them a resister, she said.

Those people could have been infected but remained without symptoms. “Resistance means the virus was inside you, it was near your cell and it did not infect your cell,” Dr. Hsieh said.

“I don’t think we know a lot so far,” Dr. Hsieh said about resisters. “I do believe that, just like there are genetic defects that make someone more susceptible, there are likely to be genetic defects that make somebody less susceptible.’’

“To identify genetic variants that are protective is a really challenging thing to do,” agreed Peter K. Gregersen, MD, professor of genetics at the Feinstein Institutes for Medical Research at Northwell Health in Manhasset, N.Y. Dr. Gregersen is also a regional coordinator for the COVID Human Genetic Effort.

He suspects the number found to be truly resistant to COVID – versus dodging it so far – is going to be very small or not found at all.

“It may exist for COVID or it may not,” he said. Some people may simply have what he calls a robust immune response in the upper part of the throat, perhaps killing off the virus quickly as soon as it enters, so they don’t get a positive test.

Genetic resistance has been found for other diseases, such as HIV.

“For HIV, scientists have been able to identify a specific gene that codes for a protein that can prevent individuals from getting infected,” said Sabrina Assoumou, MD, MPH, professor of medicine at Boston University, who researches HIV.

However, she said, “we haven’t yet found a similar gene or protein that can prevent people from getting infected with SARS-CoV-2.”

What has been found “is that some people might have a mutation in a gene that encodes for what’s called human leukocyte antigen (HLA),” Dr. Assoumou said. HLA, a molecule found on the surface of most cells, has a crucial role in the immune response to foreign substances. “A mutation in HLA can make people less likely to have symptoms if they get infected. Individuals still get infected, but they are less likely to have symptoms.”

Other research has found that those with food allergies are also less likely to be infected. The researchers have speculated that the inflammation characteristic of allergic conditions may reduce levels of a protein called the ACE2 receptor on the surface of airway cells. The SARS-CoV-2 virus uses the receptor to enter the cells, so if levels are low, that could reduce the ability of the virus to infect people.

The COVID Human Genetic Effort continues to search for participants, both those who were admitted to a hospital or repeatedly seen at a hospital because of COVID, as well as those who did not get infected, even after “intense and repeated” exposure.

The number of people likely to be resistant is much smaller, Dr. Hsieh said, than the number of people susceptible to severe disease.
 

The testing ... or lack thereof factor

The timing of testing and a person’s “infection profile” may be factors in people incorrectly declaring themselves NOVIDs, said Anne Wyllie, PhD, a research scientist in epidemiology at the Yale School of Public Health in New Haven, Conn., and a codeveloper of a saliva PCR test for COVID.

“Infection profiles can vary between individuals,” she said. For some, the infection may start in the lower respiratory tract, others in the higher respiratory tract. “Depending on where the virus takes up residence, that can affect test results.”

Then there’s the following-instructions factor. “It’s very likely that due to tests not being done at the right time, with the right sample, or not repeated if there is ongoing evidence of symptoms, that there are individuals out there who believe they are NOVIDs but just missed catching their infection at the window of opportunity.” Dr. Wyllie said.
 

Susceptibility research

“The part we have proven is the genetic defect that would make you more susceptible to having severe disease,” Dr. Hsieh said.

Many published papers report that inherited and/or autoimmune deficiencies of type I interferon immunity, important for combating viral infections and modulating the immune response, can be a significant cause of life-threatening COVID pneumonia.

More recently, researchers, including Jean-Laurent Casanova, MD, PhD, professor at Rockefeller University, New York, and cofounder of the COVID Human Genome Effort, reported that deficiencies in a gene that plays a role in built-in immunity (the early response), and a gene involved in signaling within the immune cells, impair interferon production and may be the basis of severe COVID pneumonia.
 

NOVIDs’ habits run the gamut

As scientists continue their research, the NOVIDs have their own ideas about why they’ve dodged the pandemic bullet, and they have a variety of approaches to handling the pandemic now.

Ryan Alexander, the field rep who travels to casinos, is up to date on his vaccinations and has gotten all the recommended COVID shots. “I was wearing a mask when told to wear masks,” he said.

He still observes the social distance habit but lives life. “I’ve been to three or four concerts in the past couple of years.”

And does he worry his number will eventually be up? “Not at this point, no,” he said.

Joe Asher, 46, said he has not gotten COVID despite being in contact with about 100 people a day, on average. He works as a bartender at an Evansville, Ind., brewery.

“On a Friday night, we can get 500 people,” he said. “I feel like almost everyone at the brewery got it. There’s no way I wasn’t exposed to it all the time.”

However, he said, his coworkers who did get sick were very cautious about not infecting others, partly to help protect a coworker’s family with newborn twins, so that may have helped him stay uninfected, too.

Mr. Asher said he’s in good physical shape, and he’s worked around the public for a long time, so figures maybe that has strengthened his immune system. He’s always been careful about handwashing and said he’s perhaps a bit more conscious of germs than others might be.

Roselyn Mena, 68, a retired teacher in Richmond, Calif., about 16 miles northeast of San Francisco, said she’s managed to avoid the virus even though her husband, Jesus Mena, got infected, as did her two adult children. Now, she remains vigilant about wearing a mask. She tries not to eat inside at restaurants. “I’m super careful,” she said.

Besides her teacher training, Ms. Mena had training as a medical assistant and learned a lot about sanitizing methods. She gets an annual flu shot, washes her hands often, and uses hand sanitizer.

When she shops, she will ask salespeople not wearing masks to please mask. “Only one refused, and she got someone else [to wait on her].”

One reason she is always careful about hygiene, Ms. Mena said, is that “when I get a cold, I get really sick. It last and lasts.” Now, she does worry she might still get it, she said, with the prospect of getting long COVID driving that worry.

In the beginning of the pandemic, Rhonda Fleming, 68, of Los Angeles, lived in a “COVID bubble,” interacting with just a few close family members. As cases went down, she enlarged the bubble. Her two grown daughters got infected, but her granddaughter did not.

She has been vigilant about masking, she said, “and I do still mask in public places.” She has a mask wardrobe, including basic black as well as glittery masks for dressier occasions. “I always carry a mask because inevitably, a cougher surrounds me.”

Now, she will bypass restaurants if she doesn’t feel comfortable with the environment, choosing ones with good air flow. When she flew to Mexico recently, she masked on the plane.

At this point, she said she doesn’t worry about getting infected but remains careful.

Recently, two friends, who have been as diligent as she has about precautions, got infected, “and they don’t know how they got it.”
 

Bragging rights?

Until researchers separate out the true resisters from those who claim to be, some NOVIDs are simply quietly grateful for their luck, while others mention their COVID-free status to anyone who asks or who will listen, and are proud of it. 

And what about those who wear a “NOVID” T-shirt?

“I would think they have a need to convey to the world they are different, perhaps special, because they beat COVID,” said Richard B. Joelson, a New York–based doctor of social work, a psychotherapist, and the author of Help Me! A Psychotherapist’s Tried-and-True Techniques for a Happier Relationship with Yourself and the People You Love. “They didn’t beat COVID, they just didn’t get it.”

Or they may be relieved they didn’t get sick, he said, because they feel defeated when they do. So “it’s a source of pride.” It might be the same people who tell anyone who will listen they never need a doctor or take no medicines, he said.

Even though science may prove many NOVIDs are inaccurate when they call themselves resisters, Dr. Hsieh understands the temptation to talk about it. “It’s kind of cool to think you are supernatural,” she said. “It’s much more attractive than being susceptible. It’s a lot sexier.” ■

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

As a field service representative for a slot machine company, Ryan Alexander, 37, of Louisville, Ky., spends his working hours in casinos, covering a large territory including Norfolk, Va., Indianapolis, and Charlotte. Social distancing in the casinos is not the norm. Despite all this up-close contact with people, he said he is still COVID-free, 3 years into the pandemic.

There was one nervous night when his temperature rose to 101° F, and he figured the virus had caught up with him. “I took a test and was fine,” he said, relieved that the result was negative. The fever disappeared, and he was back to normal soon. “Maybe it was just an exhausting day.”

Mr. Alexander is one of those people who have managed – or at least think they have managed – to avoid getting COVID-19.

He is, some say, a NOVID. While some scientists cringe at the term, it’s caught on to describe these virus super-dodgers. Online entrepreneurs offer NOVID-19 T-shirts, masks, and stickers, in case these super-healthy or super-lucky folks want to publicize their good luck. On Twitter, NOVIDs share stories of how they’ve done it.
 

How many NOVIDs?

As of March 16, according to the CDC, almost 104 million cases of COVID – about one-third of the U.S. population – have been reported, but many cases are known to go unreported. About half of American adults surveyed said they have had COVID, according to a December report by the COVID States Project, a multiuniversity effort to supply pandemic data.

As the numbers settle over time, though, it becomes clearer that some in the U.S. have apparently managed to avoid the virus.

While the exact number of people who have remained uninfected isn’t known with certainty, a review of comprehensive serologic data shows about 15% of Americans may not have gotten infected with COVID, Eric Topol, MD, editor-in-chief of Medscape (WebMD’s sister site for medical professionals) wrote in his substack Ground Truths.

But some scientists bristle at the term NOVIDs. They prefer the term “resisters,” according to Elena Hsieh, MD, associate professor of pediatrics and immunology at the University of Colorado at Denver, Aurora. Currently, she said, there is much more information on who is more susceptible to contracting severe COVID than who is resistant.

Dr. Hsieh is one of the regional coordinators for the COVID Human Genetic Effort, an international consortium of more than 250 researchers and doctors dedicated to discovering the genetic and immunological bases of the forms of SARS-CoV-2 infection. These researchers and others are looking for explanations for why some people get severe COVID while others seem resistant despite repeated exposure.
 

Resistance research

In determining explanations for resistance to infection, “the needle in the haystack that we are looking for is a change in the genetic code that would allow for you to avoid entry of the virus into the cell,” Dr. Hsieh said. “That is what being resistant to infection is.”

Part of the reason it’s so difficult to study resistance is defining a resister, she said. While many people consider themselves among that group because they’re been exposed multiple times – even with close family members infected and sick, yet they still felt fine – that doesn’t necessarily make them a resister, she said.

Those people could have been infected but remained without symptoms. “Resistance means the virus was inside you, it was near your cell and it did not infect your cell,” Dr. Hsieh said.

“I don’t think we know a lot so far,” Dr. Hsieh said about resisters. “I do believe that, just like there are genetic defects that make someone more susceptible, there are likely to be genetic defects that make somebody less susceptible.’’

“To identify genetic variants that are protective is a really challenging thing to do,” agreed Peter K. Gregersen, MD, professor of genetics at the Feinstein Institutes for Medical Research at Northwell Health in Manhasset, N.Y. Dr. Gregersen is also a regional coordinator for the COVID Human Genetic Effort.

He suspects the number found to be truly resistant to COVID – versus dodging it so far – is going to be very small or not found at all.

“It may exist for COVID or it may not,” he said. Some people may simply have what he calls a robust immune response in the upper part of the throat, perhaps killing off the virus quickly as soon as it enters, so they don’t get a positive test.

Genetic resistance has been found for other diseases, such as HIV.

“For HIV, scientists have been able to identify a specific gene that codes for a protein that can prevent individuals from getting infected,” said Sabrina Assoumou, MD, MPH, professor of medicine at Boston University, who researches HIV.

However, she said, “we haven’t yet found a similar gene or protein that can prevent people from getting infected with SARS-CoV-2.”

What has been found “is that some people might have a mutation in a gene that encodes for what’s called human leukocyte antigen (HLA),” Dr. Assoumou said. HLA, a molecule found on the surface of most cells, has a crucial role in the immune response to foreign substances. “A mutation in HLA can make people less likely to have symptoms if they get infected. Individuals still get infected, but they are less likely to have symptoms.”

Other research has found that those with food allergies are also less likely to be infected. The researchers have speculated that the inflammation characteristic of allergic conditions may reduce levels of a protein called the ACE2 receptor on the surface of airway cells. The SARS-CoV-2 virus uses the receptor to enter the cells, so if levels are low, that could reduce the ability of the virus to infect people.

The COVID Human Genetic Effort continues to search for participants, both those who were admitted to a hospital or repeatedly seen at a hospital because of COVID, as well as those who did not get infected, even after “intense and repeated” exposure.

The number of people likely to be resistant is much smaller, Dr. Hsieh said, than the number of people susceptible to severe disease.
 

The testing ... or lack thereof factor

The timing of testing and a person’s “infection profile” may be factors in people incorrectly declaring themselves NOVIDs, said Anne Wyllie, PhD, a research scientist in epidemiology at the Yale School of Public Health in New Haven, Conn., and a codeveloper of a saliva PCR test for COVID.

“Infection profiles can vary between individuals,” she said. For some, the infection may start in the lower respiratory tract, others in the higher respiratory tract. “Depending on where the virus takes up residence, that can affect test results.”

Then there’s the following-instructions factor. “It’s very likely that due to tests not being done at the right time, with the right sample, or not repeated if there is ongoing evidence of symptoms, that there are individuals out there who believe they are NOVIDs but just missed catching their infection at the window of opportunity.” Dr. Wyllie said.
 

Susceptibility research

“The part we have proven is the genetic defect that would make you more susceptible to having severe disease,” Dr. Hsieh said.

Many published papers report that inherited and/or autoimmune deficiencies of type I interferon immunity, important for combating viral infections and modulating the immune response, can be a significant cause of life-threatening COVID pneumonia.

More recently, researchers, including Jean-Laurent Casanova, MD, PhD, professor at Rockefeller University, New York, and cofounder of the COVID Human Genome Effort, reported that deficiencies in a gene that plays a role in built-in immunity (the early response), and a gene involved in signaling within the immune cells, impair interferon production and may be the basis of severe COVID pneumonia.
 

NOVIDs’ habits run the gamut

As scientists continue their research, the NOVIDs have their own ideas about why they’ve dodged the pandemic bullet, and they have a variety of approaches to handling the pandemic now.

Ryan Alexander, the field rep who travels to casinos, is up to date on his vaccinations and has gotten all the recommended COVID shots. “I was wearing a mask when told to wear masks,” he said.

He still observes the social distance habit but lives life. “I’ve been to three or four concerts in the past couple of years.”

And does he worry his number will eventually be up? “Not at this point, no,” he said.

Joe Asher, 46, said he has not gotten COVID despite being in contact with about 100 people a day, on average. He works as a bartender at an Evansville, Ind., brewery.

“On a Friday night, we can get 500 people,” he said. “I feel like almost everyone at the brewery got it. There’s no way I wasn’t exposed to it all the time.”

However, he said, his coworkers who did get sick were very cautious about not infecting others, partly to help protect a coworker’s family with newborn twins, so that may have helped him stay uninfected, too.

Mr. Asher said he’s in good physical shape, and he’s worked around the public for a long time, so figures maybe that has strengthened his immune system. He’s always been careful about handwashing and said he’s perhaps a bit more conscious of germs than others might be.

Roselyn Mena, 68, a retired teacher in Richmond, Calif., about 16 miles northeast of San Francisco, said she’s managed to avoid the virus even though her husband, Jesus Mena, got infected, as did her two adult children. Now, she remains vigilant about wearing a mask. She tries not to eat inside at restaurants. “I’m super careful,” she said.

Besides her teacher training, Ms. Mena had training as a medical assistant and learned a lot about sanitizing methods. She gets an annual flu shot, washes her hands often, and uses hand sanitizer.

When she shops, she will ask salespeople not wearing masks to please mask. “Only one refused, and she got someone else [to wait on her].”

One reason she is always careful about hygiene, Ms. Mena said, is that “when I get a cold, I get really sick. It last and lasts.” Now, she does worry she might still get it, she said, with the prospect of getting long COVID driving that worry.

In the beginning of the pandemic, Rhonda Fleming, 68, of Los Angeles, lived in a “COVID bubble,” interacting with just a few close family members. As cases went down, she enlarged the bubble. Her two grown daughters got infected, but her granddaughter did not.

She has been vigilant about masking, she said, “and I do still mask in public places.” She has a mask wardrobe, including basic black as well as glittery masks for dressier occasions. “I always carry a mask because inevitably, a cougher surrounds me.”

Now, she will bypass restaurants if she doesn’t feel comfortable with the environment, choosing ones with good air flow. When she flew to Mexico recently, she masked on the plane.

At this point, she said she doesn’t worry about getting infected but remains careful.

Recently, two friends, who have been as diligent as she has about precautions, got infected, “and they don’t know how they got it.”
 

Bragging rights?

Until researchers separate out the true resisters from those who claim to be, some NOVIDs are simply quietly grateful for their luck, while others mention their COVID-free status to anyone who asks or who will listen, and are proud of it. 

And what about those who wear a “NOVID” T-shirt?

“I would think they have a need to convey to the world they are different, perhaps special, because they beat COVID,” said Richard B. Joelson, a New York–based doctor of social work, a psychotherapist, and the author of Help Me! A Psychotherapist’s Tried-and-True Techniques for a Happier Relationship with Yourself and the People You Love. “They didn’t beat COVID, they just didn’t get it.”

Or they may be relieved they didn’t get sick, he said, because they feel defeated when they do. So “it’s a source of pride.” It might be the same people who tell anyone who will listen they never need a doctor or take no medicines, he said.

Even though science may prove many NOVIDs are inaccurate when they call themselves resisters, Dr. Hsieh understands the temptation to talk about it. “It’s kind of cool to think you are supernatural,” she said. “It’s much more attractive than being susceptible. It’s a lot sexier.” ■

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

As a field service representative for a slot machine company, Ryan Alexander, 37, of Louisville, Ky., spends his working hours in casinos, covering a large territory including Norfolk, Va., Indianapolis, and Charlotte. Social distancing in the casinos is not the norm. Despite all this up-close contact with people, he said he is still COVID-free, 3 years into the pandemic.

There was one nervous night when his temperature rose to 101° F, and he figured the virus had caught up with him. “I took a test and was fine,” he said, relieved that the result was negative. The fever disappeared, and he was back to normal soon. “Maybe it was just an exhausting day.”

Mr. Alexander is one of those people who have managed – or at least think they have managed – to avoid getting COVID-19.

He is, some say, a NOVID. While some scientists cringe at the term, it’s caught on to describe these virus super-dodgers. Online entrepreneurs offer NOVID-19 T-shirts, masks, and stickers, in case these super-healthy or super-lucky folks want to publicize their good luck. On Twitter, NOVIDs share stories of how they’ve done it.
 

How many NOVIDs?

As of March 16, according to the CDC, almost 104 million cases of COVID – about one-third of the U.S. population – have been reported, but many cases are known to go unreported. About half of American adults surveyed said they have had COVID, according to a December report by the COVID States Project, a multiuniversity effort to supply pandemic data.

As the numbers settle over time, though, it becomes clearer that some in the U.S. have apparently managed to avoid the virus.

While the exact number of people who have remained uninfected isn’t known with certainty, a review of comprehensive serologic data shows about 15% of Americans may not have gotten infected with COVID, Eric Topol, MD, editor-in-chief of Medscape (WebMD’s sister site for medical professionals) wrote in his substack Ground Truths.

But some scientists bristle at the term NOVIDs. They prefer the term “resisters,” according to Elena Hsieh, MD, associate professor of pediatrics and immunology at the University of Colorado at Denver, Aurora. Currently, she said, there is much more information on who is more susceptible to contracting severe COVID than who is resistant.

Dr. Hsieh is one of the regional coordinators for the COVID Human Genetic Effort, an international consortium of more than 250 researchers and doctors dedicated to discovering the genetic and immunological bases of the forms of SARS-CoV-2 infection. These researchers and others are looking for explanations for why some people get severe COVID while others seem resistant despite repeated exposure.
 

Resistance research

In determining explanations for resistance to infection, “the needle in the haystack that we are looking for is a change in the genetic code that would allow for you to avoid entry of the virus into the cell,” Dr. Hsieh said. “That is what being resistant to infection is.”

Part of the reason it’s so difficult to study resistance is defining a resister, she said. While many people consider themselves among that group because they’re been exposed multiple times – even with close family members infected and sick, yet they still felt fine – that doesn’t necessarily make them a resister, she said.

Those people could have been infected but remained without symptoms. “Resistance means the virus was inside you, it was near your cell and it did not infect your cell,” Dr. Hsieh said.

“I don’t think we know a lot so far,” Dr. Hsieh said about resisters. “I do believe that, just like there are genetic defects that make someone more susceptible, there are likely to be genetic defects that make somebody less susceptible.’’

“To identify genetic variants that are protective is a really challenging thing to do,” agreed Peter K. Gregersen, MD, professor of genetics at the Feinstein Institutes for Medical Research at Northwell Health in Manhasset, N.Y. Dr. Gregersen is also a regional coordinator for the COVID Human Genetic Effort.

He suspects the number found to be truly resistant to COVID – versus dodging it so far – is going to be very small or not found at all.

“It may exist for COVID or it may not,” he said. Some people may simply have what he calls a robust immune response in the upper part of the throat, perhaps killing off the virus quickly as soon as it enters, so they don’t get a positive test.

Genetic resistance has been found for other diseases, such as HIV.

“For HIV, scientists have been able to identify a specific gene that codes for a protein that can prevent individuals from getting infected,” said Sabrina Assoumou, MD, MPH, professor of medicine at Boston University, who researches HIV.

However, she said, “we haven’t yet found a similar gene or protein that can prevent people from getting infected with SARS-CoV-2.”

What has been found “is that some people might have a mutation in a gene that encodes for what’s called human leukocyte antigen (HLA),” Dr. Assoumou said. HLA, a molecule found on the surface of most cells, has a crucial role in the immune response to foreign substances. “A mutation in HLA can make people less likely to have symptoms if they get infected. Individuals still get infected, but they are less likely to have symptoms.”

Other research has found that those with food allergies are also less likely to be infected. The researchers have speculated that the inflammation characteristic of allergic conditions may reduce levels of a protein called the ACE2 receptor on the surface of airway cells. The SARS-CoV-2 virus uses the receptor to enter the cells, so if levels are low, that could reduce the ability of the virus to infect people.

The COVID Human Genetic Effort continues to search for participants, both those who were admitted to a hospital or repeatedly seen at a hospital because of COVID, as well as those who did not get infected, even after “intense and repeated” exposure.

The number of people likely to be resistant is much smaller, Dr. Hsieh said, than the number of people susceptible to severe disease.
 

The testing ... or lack thereof factor

The timing of testing and a person’s “infection profile” may be factors in people incorrectly declaring themselves NOVIDs, said Anne Wyllie, PhD, a research scientist in epidemiology at the Yale School of Public Health in New Haven, Conn., and a codeveloper of a saliva PCR test for COVID.

“Infection profiles can vary between individuals,” she said. For some, the infection may start in the lower respiratory tract, others in the higher respiratory tract. “Depending on where the virus takes up residence, that can affect test results.”

Then there’s the following-instructions factor. “It’s very likely that due to tests not being done at the right time, with the right sample, or not repeated if there is ongoing evidence of symptoms, that there are individuals out there who believe they are NOVIDs but just missed catching their infection at the window of opportunity.” Dr. Wyllie said.
 

Susceptibility research

“The part we have proven is the genetic defect that would make you more susceptible to having severe disease,” Dr. Hsieh said.

Many published papers report that inherited and/or autoimmune deficiencies of type I interferon immunity, important for combating viral infections and modulating the immune response, can be a significant cause of life-threatening COVID pneumonia.

More recently, researchers, including Jean-Laurent Casanova, MD, PhD, professor at Rockefeller University, New York, and cofounder of the COVID Human Genome Effort, reported that deficiencies in a gene that plays a role in built-in immunity (the early response), and a gene involved in signaling within the immune cells, impair interferon production and may be the basis of severe COVID pneumonia.
 

NOVIDs’ habits run the gamut

As scientists continue their research, the NOVIDs have their own ideas about why they’ve dodged the pandemic bullet, and they have a variety of approaches to handling the pandemic now.

Ryan Alexander, the field rep who travels to casinos, is up to date on his vaccinations and has gotten all the recommended COVID shots. “I was wearing a mask when told to wear masks,” he said.

He still observes the social distance habit but lives life. “I’ve been to three or four concerts in the past couple of years.”

And does he worry his number will eventually be up? “Not at this point, no,” he said.

Joe Asher, 46, said he has not gotten COVID despite being in contact with about 100 people a day, on average. He works as a bartender at an Evansville, Ind., brewery.

“On a Friday night, we can get 500 people,” he said. “I feel like almost everyone at the brewery got it. There’s no way I wasn’t exposed to it all the time.”

However, he said, his coworkers who did get sick were very cautious about not infecting others, partly to help protect a coworker’s family with newborn twins, so that may have helped him stay uninfected, too.

Mr. Asher said he’s in good physical shape, and he’s worked around the public for a long time, so figures maybe that has strengthened his immune system. He’s always been careful about handwashing and said he’s perhaps a bit more conscious of germs than others might be.

Roselyn Mena, 68, a retired teacher in Richmond, Calif., about 16 miles northeast of San Francisco, said she’s managed to avoid the virus even though her husband, Jesus Mena, got infected, as did her two adult children. Now, she remains vigilant about wearing a mask. She tries not to eat inside at restaurants. “I’m super careful,” she said.

Besides her teacher training, Ms. Mena had training as a medical assistant and learned a lot about sanitizing methods. She gets an annual flu shot, washes her hands often, and uses hand sanitizer.

When she shops, she will ask salespeople not wearing masks to please mask. “Only one refused, and she got someone else [to wait on her].”

One reason she is always careful about hygiene, Ms. Mena said, is that “when I get a cold, I get really sick. It last and lasts.” Now, she does worry she might still get it, she said, with the prospect of getting long COVID driving that worry.

In the beginning of the pandemic, Rhonda Fleming, 68, of Los Angeles, lived in a “COVID bubble,” interacting with just a few close family members. As cases went down, she enlarged the bubble. Her two grown daughters got infected, but her granddaughter did not.

She has been vigilant about masking, she said, “and I do still mask in public places.” She has a mask wardrobe, including basic black as well as glittery masks for dressier occasions. “I always carry a mask because inevitably, a cougher surrounds me.”

Now, she will bypass restaurants if she doesn’t feel comfortable with the environment, choosing ones with good air flow. When she flew to Mexico recently, she masked on the plane.

At this point, she said she doesn’t worry about getting infected but remains careful.

Recently, two friends, who have been as diligent as she has about precautions, got infected, “and they don’t know how they got it.”
 

Bragging rights?

Until researchers separate out the true resisters from those who claim to be, some NOVIDs are simply quietly grateful for their luck, while others mention their COVID-free status to anyone who asks or who will listen, and are proud of it. 

And what about those who wear a “NOVID” T-shirt?

“I would think they have a need to convey to the world they are different, perhaps special, because they beat COVID,” said Richard B. Joelson, a New York–based doctor of social work, a psychotherapist, and the author of Help Me! A Psychotherapist’s Tried-and-True Techniques for a Happier Relationship with Yourself and the People You Love. “They didn’t beat COVID, they just didn’t get it.”

Or they may be relieved they didn’t get sick, he said, because they feel defeated when they do. So “it’s a source of pride.” It might be the same people who tell anyone who will listen they never need a doctor or take no medicines, he said.

Even though science may prove many NOVIDs are inaccurate when they call themselves resisters, Dr. Hsieh understands the temptation to talk about it. “It’s kind of cool to think you are supernatural,” she said. “It’s much more attractive than being susceptible. It’s a lot sexier.” ■

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

From movies to billboards to magazine covers – media have been pushing impossible beauty ideals for decades. But the recent rise of social media brings that exposure to new levels, particularly for young people.

“Youth spend, on average, between 6 and 8 hours per day on screens, much of it on social media,” said senior study author Gary S. Goldfield, PhD, senior scientist at Children’s Hospital of Eastern Ontario Research Institute in Ottawa, Canada. “Social media provides exposure to so many photo-edited pictures – including those of models, celebrities, and fitness instructors – that perpetuate an unattainable beauty standard that gets internalized by impressionable youth and young adults, leading to body dissatisfaction.”

Plenty of research has linked frequent social media use with body image issues and even eating disorders. But crucial gaps in our knowledge remain, Dr. Goldfield said.

Much of that research “is correlational,” Dr. Goldfield added. And studies don’t always focus on individuals who may be more vulnerable to social media’s harmful effects, such as those with ruminative or brooding cognitive styles, affecting results.

And none have explored an obvious question: Can cutting down on social media use also diminish its potential harms?

Dr. Goldfield and his colleagues found an answer: Yes, it can.  

Limiting social media use to 1 hour per day helped older teens and young adults feel much better about their weight and appearance after only 3 weeks, according to the study in Psychology of Popular Media, a journal of the American Psychological Association.

“Our randomized controlled design allowed us to show a stronger causal link between social media use and body image in youth, compared to previous research,” Dr. Goldfield said. “To our knowledge, this is the first study to show that social media use reduction leads to enhanced body image.”

Nancy Lee Zucker, PhD, professor of psychology and neuroscience at Duke University, Durham, N.C., and director of the Duke Center for Eating Disorders, said the results provide needed data that could help guide young people and parents on optimal social media use. Dr. Zucker was not involved in the study.
 

What the researchers did

For the study, Dr. Goldfield and colleagues recruited undergraduate psychology students aged 17-25 who averaged at least 2 hours per day of social media use on smartphones, and who had symptoms of depression or anxiety.

Participants were not told the purpose of the study, and their social media use was monitored by a screen time tracking program. At the beginning and end of the study, they answered questions such as “I’m pretty happy about the way I look,” and “I am satisfied with my weight,” on a 1 (never) to 5 (always) Likert scale.

During the first week, all 220 participants (76% female, 23% male, and 1% other) were told to use social media on their smartphones as they usually do. Over the next 3 weeks, 117 students were told to limit their social media use to 1 hour per day, while the rest were instructed to carry on as usual. In both groups, over 70% of participants were between age 17 and 19. 

The first group cut their social media use by about 50%, from a mean of around 168 minutes per day during week 1 to around 78 minutes per day by the end of week 4, while the unrestricted group went from around 181 minutes per day to 189.
 

Cutting use by around half yielded quick, significant improvements

The students who curbed their social media use saw significant improvements in their “appearance esteem” (from 2.95 to 3.15 points; P <.001) and their “weight esteem” (from 3.16 to 3.32 points; P < .001), whereas those who used social media freely saw no such changes (from 2.72 to 2.76; P = .992 and 3.01 to 3.02; P = .654, respectively). No gender differences between the groups were found.

The researchers are now studying possible reasons for these findings.

The changes in appearance scores “represent a small- to medium-effect size,” said child psychologist Sara R. Gould, PhD, director of the Eating Disorders Center at Children’s Mercy Kansas City in Missouri, who was not associated with the research.“ As such, these are clinically meaningful results, particularly since they were achieved in only 3 weeks. Even small impacts can be added to other changes to create larger impacts or have the potential to grow over time.”
 

The push to limit social media

As more and more experts scrutinize the impact of social media on young people’s mental health, social media companies have responded with features designed to limit the time young users spend on their platforms.

Just this year, Instagram rolled out “quiet mode,” which lets users shut down their direct messages (DMs) for a specified amount of time. To turn on quiet mode, users can navigate to their profiles, and select the triple line icon, “settings,” “notifications,” and “quiet mode.” Another option: Tap the triple line icon, “your activity,” and “time spent” to set reminders to take breaks after 10, 20, or 30 minutes of use.  

TikTok users under 18 will soon have their accounts defaulted to a 1-hour daily screen-time limit, TikTok has announced. Unlike other similar features, it will require users to turn it off rather than turn it on.

Leveraging built-in controls is “a good start to being more intentional about your screen time,” suggested lead author Helen Thai, a PhD student in clinical psychology at McGill University in Montreal. “Unfortunately, users can easily bypass these settings.”  

One reason for social’s magnetic pull: “FOMO – fear of missing out – on what friends are doing can make cutting back on social media use difficult,” said Dr. Zucker. To help prevent FOMO, parents may consider talking to parents of their children’s friends about reducing usage for all the children, Dr. Zucker suggested.

Mary E. Romano, MD, MPH, associate professor of pediatrics-adolescent medicine at Vanderbilt University, Nashville, Tenn., urges parents “to have very clear rules and expectations about social media use.” 

Dr. Romano, also not involved in the study, recommended the website Wait Until 8th to help parents band together to commit to delaying smartphone access until at least eighth grade.

Dr. Gould recommended the Family Media Plan, a tool from the American Academy of Pediatrics that lets users create a customized plan, complete with guidance tailored to each person’s age and the family’s goals. Sample tips: Designate a basket for holding devices during meals, and switch to audiobooks or relaxing music instead of videos to fall asleep at night.
 

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

From movies to billboards to magazine covers – media have been pushing impossible beauty ideals for decades. But the recent rise of social media brings that exposure to new levels, particularly for young people.

“Youth spend, on average, between 6 and 8 hours per day on screens, much of it on social media,” said senior study author Gary S. Goldfield, PhD, senior scientist at Children’s Hospital of Eastern Ontario Research Institute in Ottawa, Canada. “Social media provides exposure to so many photo-edited pictures – including those of models, celebrities, and fitness instructors – that perpetuate an unattainable beauty standard that gets internalized by impressionable youth and young adults, leading to body dissatisfaction.”

Plenty of research has linked frequent social media use with body image issues and even eating disorders. But crucial gaps in our knowledge remain, Dr. Goldfield said.

Much of that research “is correlational,” Dr. Goldfield added. And studies don’t always focus on individuals who may be more vulnerable to social media’s harmful effects, such as those with ruminative or brooding cognitive styles, affecting results.

And none have explored an obvious question: Can cutting down on social media use also diminish its potential harms?

Dr. Goldfield and his colleagues found an answer: Yes, it can.  

Limiting social media use to 1 hour per day helped older teens and young adults feel much better about their weight and appearance after only 3 weeks, according to the study in Psychology of Popular Media, a journal of the American Psychological Association.

“Our randomized controlled design allowed us to show a stronger causal link between social media use and body image in youth, compared to previous research,” Dr. Goldfield said. “To our knowledge, this is the first study to show that social media use reduction leads to enhanced body image.”

Nancy Lee Zucker, PhD, professor of psychology and neuroscience at Duke University, Durham, N.C., and director of the Duke Center for Eating Disorders, said the results provide needed data that could help guide young people and parents on optimal social media use. Dr. Zucker was not involved in the study.
 

What the researchers did

For the study, Dr. Goldfield and colleagues recruited undergraduate psychology students aged 17-25 who averaged at least 2 hours per day of social media use on smartphones, and who had symptoms of depression or anxiety.

Participants were not told the purpose of the study, and their social media use was monitored by a screen time tracking program. At the beginning and end of the study, they answered questions such as “I’m pretty happy about the way I look,” and “I am satisfied with my weight,” on a 1 (never) to 5 (always) Likert scale.

During the first week, all 220 participants (76% female, 23% male, and 1% other) were told to use social media on their smartphones as they usually do. Over the next 3 weeks, 117 students were told to limit their social media use to 1 hour per day, while the rest were instructed to carry on as usual. In both groups, over 70% of participants were between age 17 and 19. 

The first group cut their social media use by about 50%, from a mean of around 168 minutes per day during week 1 to around 78 minutes per day by the end of week 4, while the unrestricted group went from around 181 minutes per day to 189.
 

Cutting use by around half yielded quick, significant improvements

The students who curbed their social media use saw significant improvements in their “appearance esteem” (from 2.95 to 3.15 points; P <.001) and their “weight esteem” (from 3.16 to 3.32 points; P < .001), whereas those who used social media freely saw no such changes (from 2.72 to 2.76; P = .992 and 3.01 to 3.02; P = .654, respectively). No gender differences between the groups were found.

The researchers are now studying possible reasons for these findings.

The changes in appearance scores “represent a small- to medium-effect size,” said child psychologist Sara R. Gould, PhD, director of the Eating Disorders Center at Children’s Mercy Kansas City in Missouri, who was not associated with the research.“ As such, these are clinically meaningful results, particularly since they were achieved in only 3 weeks. Even small impacts can be added to other changes to create larger impacts or have the potential to grow over time.”
 

The push to limit social media

As more and more experts scrutinize the impact of social media on young people’s mental health, social media companies have responded with features designed to limit the time young users spend on their platforms.

Just this year, Instagram rolled out “quiet mode,” which lets users shut down their direct messages (DMs) for a specified amount of time. To turn on quiet mode, users can navigate to their profiles, and select the triple line icon, “settings,” “notifications,” and “quiet mode.” Another option: Tap the triple line icon, “your activity,” and “time spent” to set reminders to take breaks after 10, 20, or 30 minutes of use.  

TikTok users under 18 will soon have their accounts defaulted to a 1-hour daily screen-time limit, TikTok has announced. Unlike other similar features, it will require users to turn it off rather than turn it on.

Leveraging built-in controls is “a good start to being more intentional about your screen time,” suggested lead author Helen Thai, a PhD student in clinical psychology at McGill University in Montreal. “Unfortunately, users can easily bypass these settings.”  

One reason for social’s magnetic pull: “FOMO – fear of missing out – on what friends are doing can make cutting back on social media use difficult,” said Dr. Zucker. To help prevent FOMO, parents may consider talking to parents of their children’s friends about reducing usage for all the children, Dr. Zucker suggested.

Mary E. Romano, MD, MPH, associate professor of pediatrics-adolescent medicine at Vanderbilt University, Nashville, Tenn., urges parents “to have very clear rules and expectations about social media use.” 

Dr. Romano, also not involved in the study, recommended the website Wait Until 8th to help parents band together to commit to delaying smartphone access until at least eighth grade.

Dr. Gould recommended the Family Media Plan, a tool from the American Academy of Pediatrics that lets users create a customized plan, complete with guidance tailored to each person’s age and the family’s goals. Sample tips: Designate a basket for holding devices during meals, and switch to audiobooks or relaxing music instead of videos to fall asleep at night.
 

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

From movies to billboards to magazine covers – media have been pushing impossible beauty ideals for decades. But the recent rise of social media brings that exposure to new levels, particularly for young people.

“Youth spend, on average, between 6 and 8 hours per day on screens, much of it on social media,” said senior study author Gary S. Goldfield, PhD, senior scientist at Children’s Hospital of Eastern Ontario Research Institute in Ottawa, Canada. “Social media provides exposure to so many photo-edited pictures – including those of models, celebrities, and fitness instructors – that perpetuate an unattainable beauty standard that gets internalized by impressionable youth and young adults, leading to body dissatisfaction.”

Plenty of research has linked frequent social media use with body image issues and even eating disorders. But crucial gaps in our knowledge remain, Dr. Goldfield said.

Much of that research “is correlational,” Dr. Goldfield added. And studies don’t always focus on individuals who may be more vulnerable to social media’s harmful effects, such as those with ruminative or brooding cognitive styles, affecting results.

And none have explored an obvious question: Can cutting down on social media use also diminish its potential harms?

Dr. Goldfield and his colleagues found an answer: Yes, it can.  

Limiting social media use to 1 hour per day helped older teens and young adults feel much better about their weight and appearance after only 3 weeks, according to the study in Psychology of Popular Media, a journal of the American Psychological Association.

“Our randomized controlled design allowed us to show a stronger causal link between social media use and body image in youth, compared to previous research,” Dr. Goldfield said. “To our knowledge, this is the first study to show that social media use reduction leads to enhanced body image.”

Nancy Lee Zucker, PhD, professor of psychology and neuroscience at Duke University, Durham, N.C., and director of the Duke Center for Eating Disorders, said the results provide needed data that could help guide young people and parents on optimal social media use. Dr. Zucker was not involved in the study.
 

What the researchers did

For the study, Dr. Goldfield and colleagues recruited undergraduate psychology students aged 17-25 who averaged at least 2 hours per day of social media use on smartphones, and who had symptoms of depression or anxiety.

Participants were not told the purpose of the study, and their social media use was monitored by a screen time tracking program. At the beginning and end of the study, they answered questions such as “I’m pretty happy about the way I look,” and “I am satisfied with my weight,” on a 1 (never) to 5 (always) Likert scale.

During the first week, all 220 participants (76% female, 23% male, and 1% other) were told to use social media on their smartphones as they usually do. Over the next 3 weeks, 117 students were told to limit their social media use to 1 hour per day, while the rest were instructed to carry on as usual. In both groups, over 70% of participants were between age 17 and 19. 

The first group cut their social media use by about 50%, from a mean of around 168 minutes per day during week 1 to around 78 minutes per day by the end of week 4, while the unrestricted group went from around 181 minutes per day to 189.
 

Cutting use by around half yielded quick, significant improvements

The students who curbed their social media use saw significant improvements in their “appearance esteem” (from 2.95 to 3.15 points; P <.001) and their “weight esteem” (from 3.16 to 3.32 points; P < .001), whereas those who used social media freely saw no such changes (from 2.72 to 2.76; P = .992 and 3.01 to 3.02; P = .654, respectively). No gender differences between the groups were found.

The researchers are now studying possible reasons for these findings.

The changes in appearance scores “represent a small- to medium-effect size,” said child psychologist Sara R. Gould, PhD, director of the Eating Disorders Center at Children’s Mercy Kansas City in Missouri, who was not associated with the research.“ As such, these are clinically meaningful results, particularly since they were achieved in only 3 weeks. Even small impacts can be added to other changes to create larger impacts or have the potential to grow over time.”
 

The push to limit social media

As more and more experts scrutinize the impact of social media on young people’s mental health, social media companies have responded with features designed to limit the time young users spend on their platforms.

Just this year, Instagram rolled out “quiet mode,” which lets users shut down their direct messages (DMs) for a specified amount of time. To turn on quiet mode, users can navigate to their profiles, and select the triple line icon, “settings,” “notifications,” and “quiet mode.” Another option: Tap the triple line icon, “your activity,” and “time spent” to set reminders to take breaks after 10, 20, or 30 minutes of use.  

TikTok users under 18 will soon have their accounts defaulted to a 1-hour daily screen-time limit, TikTok has announced. Unlike other similar features, it will require users to turn it off rather than turn it on.

Leveraging built-in controls is “a good start to being more intentional about your screen time,” suggested lead author Helen Thai, a PhD student in clinical psychology at McGill University in Montreal. “Unfortunately, users can easily bypass these settings.”  

One reason for social’s magnetic pull: “FOMO – fear of missing out – on what friends are doing can make cutting back on social media use difficult,” said Dr. Zucker. To help prevent FOMO, parents may consider talking to parents of their children’s friends about reducing usage for all the children, Dr. Zucker suggested.

Mary E. Romano, MD, MPH, associate professor of pediatrics-adolescent medicine at Vanderbilt University, Nashville, Tenn., urges parents “to have very clear rules and expectations about social media use.” 

Dr. Romano, also not involved in the study, recommended the website Wait Until 8th to help parents band together to commit to delaying smartphone access until at least eighth grade.

Dr. Gould recommended the Family Media Plan, a tool from the American Academy of Pediatrics that lets users create a customized plan, complete with guidance tailored to each person’s age and the family’s goals. Sample tips: Designate a basket for holding devices during meals, and switch to audiobooks or relaxing music instead of videos to fall asleep at night.
 

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

The Environmental Protection Agency is proposing a new rule that would greatly limit the concentration of endocrine-disrupting “forever” chemicals in drinking water. 

The EPA on Tuesday announced the proposed National Primary Drinking Water Regulation (NPDWR) for six polyfluoroalkyl substances, more commonly known as PFAS, which are human-made chemicals used as oil and water repellents and coatings for common products including cookware, carpets, and textiles. Such substances are also widely used in cosmetics and food packaging.

curtoicurto/Getty Images

The Endocrine Society, which represents more than 18,000 doctors who treat hormone disorders, says it fully supports the new EPA proposal. It explains that these substances, also known as endocrine-disrupting chemicals, “do not break down when they are released into the environment, and they continue to accumulate over time. They pose health dangers at incredibly low levels and have been linked to endocrine disorders such as cancer, thyroid disruption, and reproductive difficulties.”

“This is the first time the government has regulated a new chemical in drinking water in more than 30 years,” the society notes, adding, this “will require major water treatment upgrades at utilities across the country.”

Robert F. Powelson, president and CEO of the National Association of Water Companies, says addressing the PFAS in the nation’s water supply will cost “billions of dollars.”

“It’s a burden that under the current structure will disproportionately fall on water and wastewater customers in small communities and low-income families,” Mr. Powelson says in a statement. He says the onus should instead fall on “the polluters” – those who manufacture and use PFAS chemicals, who “should be held directly responsible for the clean-up costs.” 

Although the EPA is proposing a health-based maximum contaminant level goal of zero for these chemicals in drinking water, it acknowledges that this is unenforceable and so has set what it considers an enforceable level, or maximum contaminant level (MCL), of 4 parts per trillion for two of the PFAS, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS). 

A different standard has been proposed for the remaining four chemicals: perfluorononanoic acid (PFNA) and hexafluoropropylene oxide dimer acid (HFPO-DA) – known together as GenX chemicals – perfluorohexane sulfonic acid (PFHxS), and perfluorobutane sulfonic acid (PFBS).

Officials from the EPA told The Washington Post that these proposed limits would be as strong or stronger than limits from about a dozen states that have set their own drinking water standards in recent years. 

“The experts here felt this was the level of stringency required to protect public health, and that the law would allow for us,” EPA Administrator Michael Regan told the newspaper. “This is a transformative action that we’re taking.”

The EPA is requesting public comment on the proposed regulation and will hold a public hearing on May 4, which members of the public can register to attend and comment on the rule proposal. The last day to register is April 28. 

The EPA wants to finalize regulation by the end of 2023, although delays are common on new rules. 

If it is fully implemented, “the rule will prevent thousands of deaths and reduce tens of thousands of serious PFAS-attributable illnesses,” the EPA statement says.

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

The Environmental Protection Agency is proposing a new rule that would greatly limit the concentration of endocrine-disrupting “forever” chemicals in drinking water. 

The EPA on Tuesday announced the proposed National Primary Drinking Water Regulation (NPDWR) for six polyfluoroalkyl substances, more commonly known as PFAS, which are human-made chemicals used as oil and water repellents and coatings for common products including cookware, carpets, and textiles. Such substances are also widely used in cosmetics and food packaging.

curtoicurto/Getty Images

The Endocrine Society, which represents more than 18,000 doctors who treat hormone disorders, says it fully supports the new EPA proposal. It explains that these substances, also known as endocrine-disrupting chemicals, “do not break down when they are released into the environment, and they continue to accumulate over time. They pose health dangers at incredibly low levels and have been linked to endocrine disorders such as cancer, thyroid disruption, and reproductive difficulties.”

“This is the first time the government has regulated a new chemical in drinking water in more than 30 years,” the society notes, adding, this “will require major water treatment upgrades at utilities across the country.”

Robert F. Powelson, president and CEO of the National Association of Water Companies, says addressing the PFAS in the nation’s water supply will cost “billions of dollars.”

“It’s a burden that under the current structure will disproportionately fall on water and wastewater customers in small communities and low-income families,” Mr. Powelson says in a statement. He says the onus should instead fall on “the polluters” – those who manufacture and use PFAS chemicals, who “should be held directly responsible for the clean-up costs.” 

Although the EPA is proposing a health-based maximum contaminant level goal of zero for these chemicals in drinking water, it acknowledges that this is unenforceable and so has set what it considers an enforceable level, or maximum contaminant level (MCL), of 4 parts per trillion for two of the PFAS, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS). 

A different standard has been proposed for the remaining four chemicals: perfluorononanoic acid (PFNA) and hexafluoropropylene oxide dimer acid (HFPO-DA) – known together as GenX chemicals – perfluorohexane sulfonic acid (PFHxS), and perfluorobutane sulfonic acid (PFBS).

Officials from the EPA told The Washington Post that these proposed limits would be as strong or stronger than limits from about a dozen states that have set their own drinking water standards in recent years. 

“The experts here felt this was the level of stringency required to protect public health, and that the law would allow for us,” EPA Administrator Michael Regan told the newspaper. “This is a transformative action that we’re taking.”

The EPA is requesting public comment on the proposed regulation and will hold a public hearing on May 4, which members of the public can register to attend and comment on the rule proposal. The last day to register is April 28. 

The EPA wants to finalize regulation by the end of 2023, although delays are common on new rules. 

If it is fully implemented, “the rule will prevent thousands of deaths and reduce tens of thousands of serious PFAS-attributable illnesses,” the EPA statement says.

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

The Environmental Protection Agency is proposing a new rule that would greatly limit the concentration of endocrine-disrupting “forever” chemicals in drinking water. 

The EPA on Tuesday announced the proposed National Primary Drinking Water Regulation (NPDWR) for six polyfluoroalkyl substances, more commonly known as PFAS, which are human-made chemicals used as oil and water repellents and coatings for common products including cookware, carpets, and textiles. Such substances are also widely used in cosmetics and food packaging.

curtoicurto/Getty Images

The Endocrine Society, which represents more than 18,000 doctors who treat hormone disorders, says it fully supports the new EPA proposal. It explains that these substances, also known as endocrine-disrupting chemicals, “do not break down when they are released into the environment, and they continue to accumulate over time. They pose health dangers at incredibly low levels and have been linked to endocrine disorders such as cancer, thyroid disruption, and reproductive difficulties.”

“This is the first time the government has regulated a new chemical in drinking water in more than 30 years,” the society notes, adding, this “will require major water treatment upgrades at utilities across the country.”

Robert F. Powelson, president and CEO of the National Association of Water Companies, says addressing the PFAS in the nation’s water supply will cost “billions of dollars.”

“It’s a burden that under the current structure will disproportionately fall on water and wastewater customers in small communities and low-income families,” Mr. Powelson says in a statement. He says the onus should instead fall on “the polluters” – those who manufacture and use PFAS chemicals, who “should be held directly responsible for the clean-up costs.” 

Although the EPA is proposing a health-based maximum contaminant level goal of zero for these chemicals in drinking water, it acknowledges that this is unenforceable and so has set what it considers an enforceable level, or maximum contaminant level (MCL), of 4 parts per trillion for two of the PFAS, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS). 

A different standard has been proposed for the remaining four chemicals: perfluorononanoic acid (PFNA) and hexafluoropropylene oxide dimer acid (HFPO-DA) – known together as GenX chemicals – perfluorohexane sulfonic acid (PFHxS), and perfluorobutane sulfonic acid (PFBS).

Officials from the EPA told The Washington Post that these proposed limits would be as strong or stronger than limits from about a dozen states that have set their own drinking water standards in recent years. 

“The experts here felt this was the level of stringency required to protect public health, and that the law would allow for us,” EPA Administrator Michael Regan told the newspaper. “This is a transformative action that we’re taking.”

The EPA is requesting public comment on the proposed regulation and will hold a public hearing on May 4, which members of the public can register to attend and comment on the rule proposal. The last day to register is April 28. 

The EPA wants to finalize regulation by the end of 2023, although delays are common on new rules. 

If it is fully implemented, “the rule will prevent thousands of deaths and reduce tens of thousands of serious PFAS-attributable illnesses,” the EPA statement says.

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

Most medical professionals would agree that people with eating disorders, including anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED), have serious diseases that result in greater morbidity and mortality compared with those in the general population. Although these do not represent the entire spectrum of eating disorders, these are the ones with the most available research data.

There might be some disagreements on who should be screened, how they should be screened and diagnosed, and how to develop a treatment plan. Some of these may be due to recent changes in physicians’ thinking about who can get an eating disorder. Eating disorders were previously thought to be diseases of affluent white females. Over the past few years, however, it has become more widely accepted that eating disorders may be found across people of a variety of identities and socioeconomic statuses. Clinicians have also become concerned that the incidence of eating disorders has increased and that part of this occurred during the COVID pandemic.
 

APA’s guideline

In February 2023, the American Psychiatric Association released its first update to the Guideline of Treatment of Patients with Eating Disorders. This is the first update to the guideline since 2006. The guideline was updated with the additional evidence that is now available as further studies have been published since the last update. The 2023 guideline provides nine recommendations for assessment and determination of a treatment plan. It then provides three recommendations specifically for AN and two recommendations each for BN and BED. The introduction acknowledges an unsuccessful attempt to provide recommendations for avoidant/restrictive food intake disorder due to the paucity of evidence on this disease.

The first recommendation within the guidelines indicates “the clinician should be sure to ask all patients about the presence of eating disorder symptoms as part of their standard psychiatric evaluation.” This recommendation is provided as there are many with normal or elevated BMI who may have eating disorders and the identification could provide the prevention of significant morbidity and mortality. It includes screening questions that can be used and standardized screening questionnaires.

Other recommendations go on to describe further evaluation for diagnosis, aspects of the history that should be obtained, and specific treatment modalities that can be used, including cognitive behavioral therapy and oral medications that have been approved for use in eating disorder treatments.¹
 

AAP’s clinical report

These guidelines add to the recommendations provided by the American Academy of Pediatrics, which published a clinical report on the Identification and Management of Eating Disorders in Children and Adolescents in January 2021. In this guidance document, the AAP recommends screening for eating disorders in any children or adolescents with “reported dieting, body image dissatisfaction, experiences of weight-based stigma, or changes in eating or exercise” and those with weight loss or rapid weight fluctuations.

If there are concerns, then a full assessment is warranted, the recommendations say. When a patient is diagnosed with an eating disorder, this clinical report also provides recommendations on history, exam, and treatment pathways.²

USPSTF’s recommendation

The United States Preventive Services Task Force provides a recommendation that differs from the AAP and APA’s. In March 2022, the USPSTF published a Grade I recommendation. They state: “The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for eating disorders in adolescents and adults.”

They provide several reasons as to why this was given a Grade I. One reason is the paucity of data that exists on the incidence and/or benefit of screening for eating disorders amongst those who are asymptomatic. They also discuss the potential harms of false positive results of screening for both the patients and health care system. The questionnaires identified were the same as those discussed in both the APA and AAP recommendations.

The USPSTF full guideline also provides a call for further studies that would help provide guidance for primary care clinicians in the area of eating disorders.³
 

Takeaway message

With all this information, what is the primary care clinician to do? It does not seem to me that the APA guideline provides new information on how to identify patients best served by screening for eating disorders.

I am not sure it is reasonable for the primary care physician (PCP) to add these questions to every well visit when assessing the mental health status of patients.

There are ways in which this new guideline can be useful to the PCP, however. Among these are that it provides good resources for further evaluation for patients for whom the PCP may have concerns about eating disorders. It also includes screening tests that do not take much time to complete and clear aspects of the history, physical exam, and laboratory evaluation that can be used to provide further clarification and possible diagnosis. Additionally, this guideline provides clear advice on treatment recommendations of therapy and medications to start. This is especially important as wait times for psychiatric providers seem to always be increasing.

A trusted PCP can use these guidelines to start providing their patient with the help they need. Overall, these new recommendations will not change my screening practices, but they will provide assistance in diagnosis and management of my patients.
 

References

1. Guideline Writing Group. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Eating Disorders. 2023. doi: 10.1176/appi.books.9780890424865.

2. Hornberger LL et al. Identification and Management of Eating Disorders in Children and Adolescents. Pediatrics. 2021;147 (1): e2020040279. doi: 10.1542/peds.2020-040279.

3. Feltner C et al. Screening for Eating Disorders in Adolescents and Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2022;327(11): 1068-82. doi: 10.1001/jama.2022.1807.

Most medical professionals would agree that people with eating disorders, including anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED), have serious diseases that result in greater morbidity and mortality compared with those in the general population. Although these do not represent the entire spectrum of eating disorders, these are the ones with the most available research data.

There might be some disagreements on who should be screened, how they should be screened and diagnosed, and how to develop a treatment plan. Some of these may be due to recent changes in physicians’ thinking about who can get an eating disorder. Eating disorders were previously thought to be diseases of affluent white females. Over the past few years, however, it has become more widely accepted that eating disorders may be found across people of a variety of identities and socioeconomic statuses. Clinicians have also become concerned that the incidence of eating disorders has increased and that part of this occurred during the COVID pandemic.
 

APA’s guideline

In February 2023, the American Psychiatric Association released its first update to the Guideline of Treatment of Patients with Eating Disorders. This is the first update to the guideline since 2006. The guideline was updated with the additional evidence that is now available as further studies have been published since the last update. The 2023 guideline provides nine recommendations for assessment and determination of a treatment plan. It then provides three recommendations specifically for AN and two recommendations each for BN and BED. The introduction acknowledges an unsuccessful attempt to provide recommendations for avoidant/restrictive food intake disorder due to the paucity of evidence on this disease.

The first recommendation within the guidelines indicates “the clinician should be sure to ask all patients about the presence of eating disorder symptoms as part of their standard psychiatric evaluation.” This recommendation is provided as there are many with normal or elevated BMI who may have eating disorders and the identification could provide the prevention of significant morbidity and mortality. It includes screening questions that can be used and standardized screening questionnaires.

Other recommendations go on to describe further evaluation for diagnosis, aspects of the history that should be obtained, and specific treatment modalities that can be used, including cognitive behavioral therapy and oral medications that have been approved for use in eating disorder treatments.¹
 

AAP’s clinical report

These guidelines add to the recommendations provided by the American Academy of Pediatrics, which published a clinical report on the Identification and Management of Eating Disorders in Children and Adolescents in January 2021. In this guidance document, the AAP recommends screening for eating disorders in any children or adolescents with “reported dieting, body image dissatisfaction, experiences of weight-based stigma, or changes in eating or exercise” and those with weight loss or rapid weight fluctuations.

If there are concerns, then a full assessment is warranted, the recommendations say. When a patient is diagnosed with an eating disorder, this clinical report also provides recommendations on history, exam, and treatment pathways.²

USPSTF’s recommendation

The United States Preventive Services Task Force provides a recommendation that differs from the AAP and APA’s. In March 2022, the USPSTF published a Grade I recommendation. They state: “The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for eating disorders in adolescents and adults.”

They provide several reasons as to why this was given a Grade I. One reason is the paucity of data that exists on the incidence and/or benefit of screening for eating disorders amongst those who are asymptomatic. They also discuss the potential harms of false positive results of screening for both the patients and health care system. The questionnaires identified were the same as those discussed in both the APA and AAP recommendations.

The USPSTF full guideline also provides a call for further studies that would help provide guidance for primary care clinicians in the area of eating disorders.³
 

Takeaway message

With all this information, what is the primary care clinician to do? It does not seem to me that the APA guideline provides new information on how to identify patients best served by screening for eating disorders.

I am not sure it is reasonable for the primary care physician (PCP) to add these questions to every well visit when assessing the mental health status of patients.

There are ways in which this new guideline can be useful to the PCP, however. Among these are that it provides good resources for further evaluation for patients for whom the PCP may have concerns about eating disorders. It also includes screening tests that do not take much time to complete and clear aspects of the history, physical exam, and laboratory evaluation that can be used to provide further clarification and possible diagnosis. Additionally, this guideline provides clear advice on treatment recommendations of therapy and medications to start. This is especially important as wait times for psychiatric providers seem to always be increasing.

A trusted PCP can use these guidelines to start providing their patient with the help they need. Overall, these new recommendations will not change my screening practices, but they will provide assistance in diagnosis and management of my patients.
 

References

1. Guideline Writing Group. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Eating Disorders. 2023. doi: 10.1176/appi.books.9780890424865.

2. Hornberger LL et al. Identification and Management of Eating Disorders in Children and Adolescents. Pediatrics. 2021;147 (1): e2020040279. doi: 10.1542/peds.2020-040279.

3. Feltner C et al. Screening for Eating Disorders in Adolescents and Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2022;327(11): 1068-82. doi: 10.1001/jama.2022.1807.

Most medical professionals would agree that people with eating disorders, including anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED), have serious diseases that result in greater morbidity and mortality compared with those in the general population. Although these do not represent the entire spectrum of eating disorders, these are the ones with the most available research data.

There might be some disagreements on who should be screened, how they should be screened and diagnosed, and how to develop a treatment plan. Some of these may be due to recent changes in physicians’ thinking about who can get an eating disorder. Eating disorders were previously thought to be diseases of affluent white females. Over the past few years, however, it has become more widely accepted that eating disorders may be found across people of a variety of identities and socioeconomic statuses. Clinicians have also become concerned that the incidence of eating disorders has increased and that part of this occurred during the COVID pandemic.
 

APA’s guideline

In February 2023, the American Psychiatric Association released its first update to the Guideline of Treatment of Patients with Eating Disorders. This is the first update to the guideline since 2006. The guideline was updated with the additional evidence that is now available as further studies have been published since the last update. The 2023 guideline provides nine recommendations for assessment and determination of a treatment plan. It then provides three recommendations specifically for AN and two recommendations each for BN and BED. The introduction acknowledges an unsuccessful attempt to provide recommendations for avoidant/restrictive food intake disorder due to the paucity of evidence on this disease.

The first recommendation within the guidelines indicates “the clinician should be sure to ask all patients about the presence of eating disorder symptoms as part of their standard psychiatric evaluation.” This recommendation is provided as there are many with normal or elevated BMI who may have eating disorders and the identification could provide the prevention of significant morbidity and mortality. It includes screening questions that can be used and standardized screening questionnaires.

Other recommendations go on to describe further evaluation for diagnosis, aspects of the history that should be obtained, and specific treatment modalities that can be used, including cognitive behavioral therapy and oral medications that have been approved for use in eating disorder treatments.¹
 

AAP’s clinical report

These guidelines add to the recommendations provided by the American Academy of Pediatrics, which published a clinical report on the Identification and Management of Eating Disorders in Children and Adolescents in January 2021. In this guidance document, the AAP recommends screening for eating disorders in any children or adolescents with “reported dieting, body image dissatisfaction, experiences of weight-based stigma, or changes in eating or exercise” and those with weight loss or rapid weight fluctuations.

If there are concerns, then a full assessment is warranted, the recommendations say. When a patient is diagnosed with an eating disorder, this clinical report also provides recommendations on history, exam, and treatment pathways.²

USPSTF’s recommendation

The United States Preventive Services Task Force provides a recommendation that differs from the AAP and APA’s. In March 2022, the USPSTF published a Grade I recommendation. They state: “The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for eating disorders in adolescents and adults.”

They provide several reasons as to why this was given a Grade I. One reason is the paucity of data that exists on the incidence and/or benefit of screening for eating disorders amongst those who are asymptomatic. They also discuss the potential harms of false positive results of screening for both the patients and health care system. The questionnaires identified were the same as those discussed in both the APA and AAP recommendations.

The USPSTF full guideline also provides a call for further studies that would help provide guidance for primary care clinicians in the area of eating disorders.³
 

Takeaway message

With all this information, what is the primary care clinician to do? It does not seem to me that the APA guideline provides new information on how to identify patients best served by screening for eating disorders.

I am not sure it is reasonable for the primary care physician (PCP) to add these questions to every well visit when assessing the mental health status of patients.

There are ways in which this new guideline can be useful to the PCP, however. Among these are that it provides good resources for further evaluation for patients for whom the PCP may have concerns about eating disorders. It also includes screening tests that do not take much time to complete and clear aspects of the history, physical exam, and laboratory evaluation that can be used to provide further clarification and possible diagnosis. Additionally, this guideline provides clear advice on treatment recommendations of therapy and medications to start. This is especially important as wait times for psychiatric providers seem to always be increasing.

A trusted PCP can use these guidelines to start providing their patient with the help they need. Overall, these new recommendations will not change my screening practices, but they will provide assistance in diagnosis and management of my patients.
 

References

1. Guideline Writing Group. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Eating Disorders. 2023. doi: 10.1176/appi.books.9780890424865.

2. Hornberger LL et al. Identification and Management of Eating Disorders in Children and Adolescents. Pediatrics. 2021;147 (1): e2020040279. doi: 10.1542/peds.2020-040279.

3. Feltner C et al. Screening for Eating Disorders in Adolescents and Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2022;327(11): 1068-82. doi: 10.1001/jama.2022.1807.

Febrile neutropenia (FN) is a life-threatening oncologic emergency requiring timely evaluation and treatment. Chemotherapy-induced neutropenia is a major risk for life-threatening infection, and fever may be the only sign.^1,2 Unrecognized fever can progress to sepsis and may result in increased morbidity and mortality. FN is defined as the presence of fever with a single temperature of  ≥ 38.3 °C or a sustained temperature > 38 °C sustained over 1 hour with an absolute neutrophil count (ANC) of < 500 cells/mm³ or < 1000 cells/mm³ and expected to decrease to < 500 within 48 hours.^2,3 It is critical to quickly identify these patients on presentation to the emergency department (ED) and take appropriate steps to initiate treatment as soon as possible. To streamline care, the American Society of Clinical Oncology (ASCO) recommends that laboratory assessments be initiated within 15 minutes of triage and empiric antibiotic therapy be administered within 1 hour.²

In alignment with the Infectious Disease Society of America (IDSA) guidelines, the National Comprehensive Cancer Network (NCCN) highlights the importance of the initial assessment of fever and neutropenia and presents available treatment options for both inpatient and outpatient management of FN.¹ Once patients are identified, the appropriate laboratory tests and physical assessments should be initiated immediately. These tests include a complete blood count with differential, complete metabolic panel (CMP), and blood cultures from 2 separate IV sites.^1-3 The guidelines offer additional suggestions for cultures and radiographic assessments that may be completed based on clinical presentation.

Several available studies provide insight into methods of protocol creation and possible barriers to timely management. Previous research showed that an FN protocol for pediatric oncology patients aimed at antibiotic administration within 1 hour showed significant improvement from 35.0% to 55.4% of patients being treated on time.^3,4 Prescribers became more comfortable in using the protocol, and timing improved as the study progressed. Barriers noted were inconsistent ED triage, rotating ED staff, and limited understanding of the protocol.³ Yoshida and colleagues worked with the same population. Over the course of 1 year, 60% of patients were receiving antibiotics within 1 hour. The mean time decreased from 83 to 65 minutes, which the study investigators noted would continue to decrease with increased protocol comfort and use.⁵ Mattison and colleagues used nursing staff to identify patients with FN and begin antibiotic treatment. On triage, nurses took note of a temperature of > 38 °C or a sepsislike clinical picture that initiated their antibiotic proforma.^4,6 This resulted in 48.1% of patients receiving antibiotics within 15 minutes and 63.3% overall within 30 minutes of arrival.⁵ Other barriers to consider are ED crowding and the admission of higher acuity patients, which may delay the treatment of patients with FN.

The US Department of Veterans Affairs (VA) Richard L. Roudebush VA Medical Center (RLRVAMC) in Indianapolis, Indiana is a level 1A facility serving about 62,000 veterans annually and more than 13,000 unique veterans visiting the ED. RLRVAMC ED staff rotate often so the creation of a process will facilitate appropriate treatment as quickly as possible. The purpose of this protocol was to improve the mean time from triage to administration of antibiotics for patients with FN presenting to the ED.

Implementation

To quantify the perceived delay in antibiotic prescribing, a pre- and postprotocol retrospective chart review of patients who presented with FN to the RLRVAMC ED was conducted. Patients were identified through the electronic health record (EHR) based on 3 criteria: recorded/reported fever as defined above, ANC < 1000 cells/mm³, and administration of cancer treatment (IV and oral) within 4 weeks. The data collected in the postimplementation phase were identical to the pre-implementation phase. This included timing of blood cultures, choice/appropriateness of antibiotics based on guidelines, and length of admission. The pre-implementation period started on August 1, 2018, and ended on August 1, 2019, to allow for an adequate pre-implementation sample size. The protocol was then implemented on October 1, 2019, and data collection for the postimplementation phase began on October 1,2019, and ended on October 1, 2020.

The protocol was accompanied by EHR order sets initiated by both nurses and health care practitioners (HCPs), including physicians, nurse practitioners, and physician assistants. The nursing order set consisted of vitals and appropriate laboratory monitoring, and the practitioner order set housed medication orders and additional clinical monitoring for more patient-specific scenarios. On identification of at-risk patients, the nursing staff could initiate the neutropenic fever protocol without consulting an HCP. The patient was then assigned a higher acuity rank, and the HCP was tasked with seeing the patient immediately. In conjunction with a complete physical assessment, the HCP ordered appropriate antibiotics through the designated order set to streamline antibiotic selection. Antibiotic options included cefepime or piperacillin-tazobactam, and vancomycin when clinically indicated. Alternatives for patients allergic to penicillin also were available. The protocol intended to streamline workup and antibiotic selection but was not designed as a substitute for solid clinical decision making and complete assessment on behalf of the HCP; therefore, additional workup may have been necessary and documented in the EHR.

Findings

This patient population comprised 17 patients pre-implementation and 12 patients postimplementation, most of whom had solid tumor malignancies (88.2% and 83.3%, respectively) receiving platinum, taxane, or antimetabolite-based chemotherapy. In the pre-implementation group, most patients (70.5%) coming through the ED were treated with palliative intent. Only 25% of these received any prophylactic granulocyte-colony stimulating factor (G-CSF) based on risk for FN. The mean time from triage to the first dose of antibiotics decreased from 3.3 hours before protocol implementation to 2.3 hours after. Only 6% in the pre-implementation group compared with 17% in the postimplementation group received the first dose of antibiotics within the recommended 1-hour interval from triage. The most common antibiotics administered were cefepime and vancomycin. Eleven patients in each group (65% and 92%, respectively) were admitted to the inpatient service for further care, with 10 and 8 patients, respectively, experiencing a hospitalization > 72 hours. Of note, 41% of patients died pre-implementation vs 17% postimplementation.

Interpretation

The goal of this protocol was to optimize ED care of patients presenting with FN to better align with guideline-recommended time lines and antibiotics. The mean time from triage to administration of antibiotics decreased by 1.0 hour from the pre- to postimplementation phase, similar to the study by Mattison and colleagues.³ When removing an outlier from the postimplementation group, the mean time from triage to first dose further decreased to 1.8 hours. The percentage of patients receiving antibiotics within 1 hour of triage nearly tripled from 6% to 17%. Additionally, the percentage of patients empirically treated with appropriate antibiotics consistent with NCCN/ASCO/IDSA guidelines increased from 65% to 83%. Although goals for the optimization of care have not yet been reached, this protocol is the first step in the right direction.

Limitations

Several limitations and concerns arise when implementing a new protocol or workflow process. Overall, these limitations may contribute to delays, such as the willingness of team members to use an unfamiliar protocol or issues locating a new protocol. The nursing staff is challenged to triage patients quickly, which may add to an already busy environment. Frequent physician turnover may require more frequent education sessions. Also, a lag time between implementation and using the protocol may result in decreased protocol use during the designated postimplementation data collection phase.

On review, ED staff were excited to find a protocol that streamlined decision making and increased awareness for patients at risk. The COVID-19 pandemic may have been a confounder for the postimplementation phase. Data may have been skewed as some patients might have elected to stay at home to avoid potential COVID-19 exposure in the ED. Additionally, increased ED use by patients with COVID-19 may have resulted in longer wait times for an available bed, thereby minimizing the impact of the protocol on time from triage to administration of antibiotics. COVID-19 may also have contributed to postimplementation mortality. Of note, barcode medication administration (BCMA) was implemented in the ED in May 2019, which may account for undocumented delays in antibiotic administration as staff may have been unfamiliar with BCMA workflow.

Due to the retrospective nature of a chart review, the data rely on the timely input and accuracy of documented information. Data after the patient’s ED encounter (except inpatient hospitalization and deaths during the implementation period) were not collected due to the scope of the program being limited to the ED only. Last, this protocol was implemented at a single site, and the generalizability to implement the same protocol at other VA medical centers may be limited. After reaching out to other VA sites and several non-VA facilities, we were unable to find a site with a similar protocol or program emphasizing the importance of timely care, although there may have been established laboratory test and medication order sets within the EHR.

Future Direction

The newly established FN order sets will continue to streamline clinical decision making and antibiotic selection in this population. In our study, we learned that most patients coming through the ED were being treated with palliative intent. As a result, these patients also may have a higher risk for complications like FN. We hope to further analyze the impact on this group and consider the role of empiric dose reduction or increased G-CSF support to minimize FN.

More than half of the patients who were admitted to the inpatient service, remained in extended care for > 72 hours. Inpatient recovery time may cause delays in future cancer treatment cycles, dose reductions, and contribute to an overall decline in performance status. Six patients in the pre-implementation phase and 1 in the postimplementation phase were eligible for outpatient management per independent Multinational Association of Supportive Care in Cancer assessment. To increase comfort, a future goal would be to create an outpatient treatment order set on discharge from the ED to help identify and outline treatment options for low-risk patients. In addition to the ED, training staff in clinics with a similar protocol may enhance the identification of patients with FN. This may require a tailored protocol for this location using health technicians in taking vital signs before the HCP visit.

This protocol helped establish “code sepsis.” Code sepsis alerts are broadcast to alert pertinent members of the health care team to provide immediate medical attention to the veteran. Pharmacy can expedite the compounding of antibiotics and record review while radiology prioritizes the portable X-ray for quick and efficient imaging. The nursing team comes ready to administer antibiotics once cultures are drawn. The HCP's attention is focused on the physical examination to determine any additional steps/care that need to be accomplished. At our site, we plan to continue HCP, nursing, and other team member education on this oncologic emergency and the availability of a streamlined protocol. We would like to re-assess the data with a long team study now that the protocol has been in place for 3 years. We hope to continue to provide strong patient care with enhanced adherence to guidelines for patients with FN presenting to RLRVAMC.

Conclusions

Early identification and timely empiric antibiotic therapy are critical to improving outcomes for patients presenting to the ED with FN. The neutropenic fever protocol reduced time to antibiotics by about 1 hour with a higher percentage of patients receiving them in < 1 hour. Additional optimization of the order sets along with increased protocol comfort and staff education will help further reduce the time to antibiotic administration in alignment with guideline recommendations.

Febrile neutropenia (FN) is a life-threatening oncologic emergency requiring timely evaluation and treatment. Chemotherapy-induced neutropenia is a major risk for life-threatening infection, and fever may be the only sign.^1,2 Unrecognized fever can progress to sepsis and may result in increased morbidity and mortality. FN is defined as the presence of fever with a single temperature of  ≥ 38.3 °C or a sustained temperature > 38 °C sustained over 1 hour with an absolute neutrophil count (ANC) of < 500 cells/mm³ or < 1000 cells/mm³ and expected to decrease to < 500 within 48 hours.^2,3 It is critical to quickly identify these patients on presentation to the emergency department (ED) and take appropriate steps to initiate treatment as soon as possible. To streamline care, the American Society of Clinical Oncology (ASCO) recommends that laboratory assessments be initiated within 15 minutes of triage and empiric antibiotic therapy be administered within 1 hour.²

In alignment with the Infectious Disease Society of America (IDSA) guidelines, the National Comprehensive Cancer Network (NCCN) highlights the importance of the initial assessment of fever and neutropenia and presents available treatment options for both inpatient and outpatient management of FN.¹ Once patients are identified, the appropriate laboratory tests and physical assessments should be initiated immediately. These tests include a complete blood count with differential, complete metabolic panel (CMP), and blood cultures from 2 separate IV sites.^1-3 The guidelines offer additional suggestions for cultures and radiographic assessments that may be completed based on clinical presentation.

Several available studies provide insight into methods of protocol creation and possible barriers to timely management. Previous research showed that an FN protocol for pediatric oncology patients aimed at antibiotic administration within 1 hour showed significant improvement from 35.0% to 55.4% of patients being treated on time.^3,4 Prescribers became more comfortable in using the protocol, and timing improved as the study progressed. Barriers noted were inconsistent ED triage, rotating ED staff, and limited understanding of the protocol.³ Yoshida and colleagues worked with the same population. Over the course of 1 year, 60% of patients were receiving antibiotics within 1 hour. The mean time decreased from 83 to 65 minutes, which the study investigators noted would continue to decrease with increased protocol comfort and use.⁵ Mattison and colleagues used nursing staff to identify patients with FN and begin antibiotic treatment. On triage, nurses took note of a temperature of > 38 °C or a sepsislike clinical picture that initiated their antibiotic proforma.^4,6 This resulted in 48.1% of patients receiving antibiotics within 15 minutes and 63.3% overall within 30 minutes of arrival.⁵ Other barriers to consider are ED crowding and the admission of higher acuity patients, which may delay the treatment of patients with FN.

The US Department of Veterans Affairs (VA) Richard L. Roudebush VA Medical Center (RLRVAMC) in Indianapolis, Indiana is a level 1A facility serving about 62,000 veterans annually and more than 13,000 unique veterans visiting the ED. RLRVAMC ED staff rotate often so the creation of a process will facilitate appropriate treatment as quickly as possible. The purpose of this protocol was to improve the mean time from triage to administration of antibiotics for patients with FN presenting to the ED.

Implementation

To quantify the perceived delay in antibiotic prescribing, a pre- and postprotocol retrospective chart review of patients who presented with FN to the RLRVAMC ED was conducted. Patients were identified through the electronic health record (EHR) based on 3 criteria: recorded/reported fever as defined above, ANC < 1000 cells/mm³, and administration of cancer treatment (IV and oral) within 4 weeks. The data collected in the postimplementation phase were identical to the pre-implementation phase. This included timing of blood cultures, choice/appropriateness of antibiotics based on guidelines, and length of admission. The pre-implementation period started on August 1, 2018, and ended on August 1, 2019, to allow for an adequate pre-implementation sample size. The protocol was then implemented on October 1, 2019, and data collection for the postimplementation phase began on October 1,2019, and ended on October 1, 2020.

The protocol was accompanied by EHR order sets initiated by both nurses and health care practitioners (HCPs), including physicians, nurse practitioners, and physician assistants. The nursing order set consisted of vitals and appropriate laboratory monitoring, and the practitioner order set housed medication orders and additional clinical monitoring for more patient-specific scenarios. On identification of at-risk patients, the nursing staff could initiate the neutropenic fever protocol without consulting an HCP. The patient was then assigned a higher acuity rank, and the HCP was tasked with seeing the patient immediately. In conjunction with a complete physical assessment, the HCP ordered appropriate antibiotics through the designated order set to streamline antibiotic selection. Antibiotic options included cefepime or piperacillin-tazobactam, and vancomycin when clinically indicated. Alternatives for patients allergic to penicillin also were available. The protocol intended to streamline workup and antibiotic selection but was not designed as a substitute for solid clinical decision making and complete assessment on behalf of the HCP; therefore, additional workup may have been necessary and documented in the EHR.

Findings

This patient population comprised 17 patients pre-implementation and 12 patients postimplementation, most of whom had solid tumor malignancies (88.2% and 83.3%, respectively) receiving platinum, taxane, or antimetabolite-based chemotherapy. In the pre-implementation group, most patients (70.5%) coming through the ED were treated with palliative intent. Only 25% of these received any prophylactic granulocyte-colony stimulating factor (G-CSF) based on risk for FN. The mean time from triage to the first dose of antibiotics decreased from 3.3 hours before protocol implementation to 2.3 hours after. Only 6% in the pre-implementation group compared with 17% in the postimplementation group received the first dose of antibiotics within the recommended 1-hour interval from triage. The most common antibiotics administered were cefepime and vancomycin. Eleven patients in each group (65% and 92%, respectively) were admitted to the inpatient service for further care, with 10 and 8 patients, respectively, experiencing a hospitalization > 72 hours. Of note, 41% of patients died pre-implementation vs 17% postimplementation.

Interpretation

The goal of this protocol was to optimize ED care of patients presenting with FN to better align with guideline-recommended time lines and antibiotics. The mean time from triage to administration of antibiotics decreased by 1.0 hour from the pre- to postimplementation phase, similar to the study by Mattison and colleagues.³ When removing an outlier from the postimplementation group, the mean time from triage to first dose further decreased to 1.8 hours. The percentage of patients receiving antibiotics within 1 hour of triage nearly tripled from 6% to 17%. Additionally, the percentage of patients empirically treated with appropriate antibiotics consistent with NCCN/ASCO/IDSA guidelines increased from 65% to 83%. Although goals for the optimization of care have not yet been reached, this protocol is the first step in the right direction.

Limitations

Several limitations and concerns arise when implementing a new protocol or workflow process. Overall, these limitations may contribute to delays, such as the willingness of team members to use an unfamiliar protocol or issues locating a new protocol. The nursing staff is challenged to triage patients quickly, which may add to an already busy environment. Frequent physician turnover may require more frequent education sessions. Also, a lag time between implementation and using the protocol may result in decreased protocol use during the designated postimplementation data collection phase.

On review, ED staff were excited to find a protocol that streamlined decision making and increased awareness for patients at risk. The COVID-19 pandemic may have been a confounder for the postimplementation phase. Data may have been skewed as some patients might have elected to stay at home to avoid potential COVID-19 exposure in the ED. Additionally, increased ED use by patients with COVID-19 may have resulted in longer wait times for an available bed, thereby minimizing the impact of the protocol on time from triage to administration of antibiotics. COVID-19 may also have contributed to postimplementation mortality. Of note, barcode medication administration (BCMA) was implemented in the ED in May 2019, which may account for undocumented delays in antibiotic administration as staff may have been unfamiliar with BCMA workflow.

Due to the retrospective nature of a chart review, the data rely on the timely input and accuracy of documented information. Data after the patient’s ED encounter (except inpatient hospitalization and deaths during the implementation period) were not collected due to the scope of the program being limited to the ED only. Last, this protocol was implemented at a single site, and the generalizability to implement the same protocol at other VA medical centers may be limited. After reaching out to other VA sites and several non-VA facilities, we were unable to find a site with a similar protocol or program emphasizing the importance of timely care, although there may have been established laboratory test and medication order sets within the EHR.

Future Direction

The newly established FN order sets will continue to streamline clinical decision making and antibiotic selection in this population. In our study, we learned that most patients coming through the ED were being treated with palliative intent. As a result, these patients also may have a higher risk for complications like FN. We hope to further analyze the impact on this group and consider the role of empiric dose reduction or increased G-CSF support to minimize FN.

More than half of the patients who were admitted to the inpatient service, remained in extended care for > 72 hours. Inpatient recovery time may cause delays in future cancer treatment cycles, dose reductions, and contribute to an overall decline in performance status. Six patients in the pre-implementation phase and 1 in the postimplementation phase were eligible for outpatient management per independent Multinational Association of Supportive Care in Cancer assessment. To increase comfort, a future goal would be to create an outpatient treatment order set on discharge from the ED to help identify and outline treatment options for low-risk patients. In addition to the ED, training staff in clinics with a similar protocol may enhance the identification of patients with FN. This may require a tailored protocol for this location using health technicians in taking vital signs before the HCP visit.

This protocol helped establish “code sepsis.” Code sepsis alerts are broadcast to alert pertinent members of the health care team to provide immediate medical attention to the veteran. Pharmacy can expedite the compounding of antibiotics and record review while radiology prioritizes the portable X-ray for quick and efficient imaging. The nursing team comes ready to administer antibiotics once cultures are drawn. The HCP's attention is focused on the physical examination to determine any additional steps/care that need to be accomplished. At our site, we plan to continue HCP, nursing, and other team member education on this oncologic emergency and the availability of a streamlined protocol. We would like to re-assess the data with a long team study now that the protocol has been in place for 3 years. We hope to continue to provide strong patient care with enhanced adherence to guidelines for patients with FN presenting to RLRVAMC.

Conclusions

Early identification and timely empiric antibiotic therapy are critical to improving outcomes for patients presenting to the ED with FN. The neutropenic fever protocol reduced time to antibiotics by about 1 hour with a higher percentage of patients receiving them in < 1 hour. Additional optimization of the order sets along with increased protocol comfort and staff education will help further reduce the time to antibiotic administration in alignment with guideline recommendations.

Febrile neutropenia (FN) is a life-threatening oncologic emergency requiring timely evaluation and treatment. Chemotherapy-induced neutropenia is a major risk for life-threatening infection, and fever may be the only sign.^1,2 Unrecognized fever can progress to sepsis and may result in increased morbidity and mortality. FN is defined as the presence of fever with a single temperature of  ≥ 38.3 °C or a sustained temperature > 38 °C sustained over 1 hour with an absolute neutrophil count (ANC) of < 500 cells/mm³ or < 1000 cells/mm³ and expected to decrease to < 500 within 48 hours.^2,3 It is critical to quickly identify these patients on presentation to the emergency department (ED) and take appropriate steps to initiate treatment as soon as possible. To streamline care, the American Society of Clinical Oncology (ASCO) recommends that laboratory assessments be initiated within 15 minutes of triage and empiric antibiotic therapy be administered within 1 hour.²

In alignment with the Infectious Disease Society of America (IDSA) guidelines, the National Comprehensive Cancer Network (NCCN) highlights the importance of the initial assessment of fever and neutropenia and presents available treatment options for both inpatient and outpatient management of FN.¹ Once patients are identified, the appropriate laboratory tests and physical assessments should be initiated immediately. These tests include a complete blood count with differential, complete metabolic panel (CMP), and blood cultures from 2 separate IV sites.^1-3 The guidelines offer additional suggestions for cultures and radiographic assessments that may be completed based on clinical presentation.

Several available studies provide insight into methods of protocol creation and possible barriers to timely management. Previous research showed that an FN protocol for pediatric oncology patients aimed at antibiotic administration within 1 hour showed significant improvement from 35.0% to 55.4% of patients being treated on time.^3,4 Prescribers became more comfortable in using the protocol, and timing improved as the study progressed. Barriers noted were inconsistent ED triage, rotating ED staff, and limited understanding of the protocol.³ Yoshida and colleagues worked with the same population. Over the course of 1 year, 60% of patients were receiving antibiotics within 1 hour. The mean time decreased from 83 to 65 minutes, which the study investigators noted would continue to decrease with increased protocol comfort and use.⁵ Mattison and colleagues used nursing staff to identify patients with FN and begin antibiotic treatment. On triage, nurses took note of a temperature of > 38 °C or a sepsislike clinical picture that initiated their antibiotic proforma.^4,6 This resulted in 48.1% of patients receiving antibiotics within 15 minutes and 63.3% overall within 30 minutes of arrival.⁵ Other barriers to consider are ED crowding and the admission of higher acuity patients, which may delay the treatment of patients with FN.

The US Department of Veterans Affairs (VA) Richard L. Roudebush VA Medical Center (RLRVAMC) in Indianapolis, Indiana is a level 1A facility serving about 62,000 veterans annually and more than 13,000 unique veterans visiting the ED. RLRVAMC ED staff rotate often so the creation of a process will facilitate appropriate treatment as quickly as possible. The purpose of this protocol was to improve the mean time from triage to administration of antibiotics for patients with FN presenting to the ED.

Implementation

To quantify the perceived delay in antibiotic prescribing, a pre- and postprotocol retrospective chart review of patients who presented with FN to the RLRVAMC ED was conducted. Patients were identified through the electronic health record (EHR) based on 3 criteria: recorded/reported fever as defined above, ANC < 1000 cells/mm³, and administration of cancer treatment (IV and oral) within 4 weeks. The data collected in the postimplementation phase were identical to the pre-implementation phase. This included timing of blood cultures, choice/appropriateness of antibiotics based on guidelines, and length of admission. The pre-implementation period started on August 1, 2018, and ended on August 1, 2019, to allow for an adequate pre-implementation sample size. The protocol was then implemented on October 1, 2019, and data collection for the postimplementation phase began on October 1,2019, and ended on October 1, 2020.

The protocol was accompanied by EHR order sets initiated by both nurses and health care practitioners (HCPs), including physicians, nurse practitioners, and physician assistants. The nursing order set consisted of vitals and appropriate laboratory monitoring, and the practitioner order set housed medication orders and additional clinical monitoring for more patient-specific scenarios. On identification of at-risk patients, the nursing staff could initiate the neutropenic fever protocol without consulting an HCP. The patient was then assigned a higher acuity rank, and the HCP was tasked with seeing the patient immediately. In conjunction with a complete physical assessment, the HCP ordered appropriate antibiotics through the designated order set to streamline antibiotic selection. Antibiotic options included cefepime or piperacillin-tazobactam, and vancomycin when clinically indicated. Alternatives for patients allergic to penicillin also were available. The protocol intended to streamline workup and antibiotic selection but was not designed as a substitute for solid clinical decision making and complete assessment on behalf of the HCP; therefore, additional workup may have been necessary and documented in the EHR.

Findings

This patient population comprised 17 patients pre-implementation and 12 patients postimplementation, most of whom had solid tumor malignancies (88.2% and 83.3%, respectively) receiving platinum, taxane, or antimetabolite-based chemotherapy. In the pre-implementation group, most patients (70.5%) coming through the ED were treated with palliative intent. Only 25% of these received any prophylactic granulocyte-colony stimulating factor (G-CSF) based on risk for FN. The mean time from triage to the first dose of antibiotics decreased from 3.3 hours before protocol implementation to 2.3 hours after. Only 6% in the pre-implementation group compared with 17% in the postimplementation group received the first dose of antibiotics within the recommended 1-hour interval from triage. The most common antibiotics administered were cefepime and vancomycin. Eleven patients in each group (65% and 92%, respectively) were admitted to the inpatient service for further care, with 10 and 8 patients, respectively, experiencing a hospitalization > 72 hours. Of note, 41% of patients died pre-implementation vs 17% postimplementation.

Interpretation

The goal of this protocol was to optimize ED care of patients presenting with FN to better align with guideline-recommended time lines and antibiotics. The mean time from triage to administration of antibiotics decreased by 1.0 hour from the pre- to postimplementation phase, similar to the study by Mattison and colleagues.³ When removing an outlier from the postimplementation group, the mean time from triage to first dose further decreased to 1.8 hours. The percentage of patients receiving antibiotics within 1 hour of triage nearly tripled from 6% to 17%. Additionally, the percentage of patients empirically treated with appropriate antibiotics consistent with NCCN/ASCO/IDSA guidelines increased from 65% to 83%. Although goals for the optimization of care have not yet been reached, this protocol is the first step in the right direction.

Limitations

Several limitations and concerns arise when implementing a new protocol or workflow process. Overall, these limitations may contribute to delays, such as the willingness of team members to use an unfamiliar protocol or issues locating a new protocol. The nursing staff is challenged to triage patients quickly, which may add to an already busy environment. Frequent physician turnover may require more frequent education sessions. Also, a lag time between implementation and using the protocol may result in decreased protocol use during the designated postimplementation data collection phase.

On review, ED staff were excited to find a protocol that streamlined decision making and increased awareness for patients at risk. The COVID-19 pandemic may have been a confounder for the postimplementation phase. Data may have been skewed as some patients might have elected to stay at home to avoid potential COVID-19 exposure in the ED. Additionally, increased ED use by patients with COVID-19 may have resulted in longer wait times for an available bed, thereby minimizing the impact of the protocol on time from triage to administration of antibiotics. COVID-19 may also have contributed to postimplementation mortality. Of note, barcode medication administration (BCMA) was implemented in the ED in May 2019, which may account for undocumented delays in antibiotic administration as staff may have been unfamiliar with BCMA workflow.

Due to the retrospective nature of a chart review, the data rely on the timely input and accuracy of documented information. Data after the patient’s ED encounter (except inpatient hospitalization and deaths during the implementation period) were not collected due to the scope of the program being limited to the ED only. Last, this protocol was implemented at a single site, and the generalizability to implement the same protocol at other VA medical centers may be limited. After reaching out to other VA sites and several non-VA facilities, we were unable to find a site with a similar protocol or program emphasizing the importance of timely care, although there may have been established laboratory test and medication order sets within the EHR.

Future Direction

The newly established FN order sets will continue to streamline clinical decision making and antibiotic selection in this population. In our study, we learned that most patients coming through the ED were being treated with palliative intent. As a result, these patients also may have a higher risk for complications like FN. We hope to further analyze the impact on this group and consider the role of empiric dose reduction or increased G-CSF support to minimize FN.

More than half of the patients who were admitted to the inpatient service, remained in extended care for > 72 hours. Inpatient recovery time may cause delays in future cancer treatment cycles, dose reductions, and contribute to an overall decline in performance status. Six patients in the pre-implementation phase and 1 in the postimplementation phase were eligible for outpatient management per independent Multinational Association of Supportive Care in Cancer assessment. To increase comfort, a future goal would be to create an outpatient treatment order set on discharge from the ED to help identify and outline treatment options for low-risk patients. In addition to the ED, training staff in clinics with a similar protocol may enhance the identification of patients with FN. This may require a tailored protocol for this location using health technicians in taking vital signs before the HCP visit.

This protocol helped establish “code sepsis.” Code sepsis alerts are broadcast to alert pertinent members of the health care team to provide immediate medical attention to the veteran. Pharmacy can expedite the compounding of antibiotics and record review while radiology prioritizes the portable X-ray for quick and efficient imaging. The nursing team comes ready to administer antibiotics once cultures are drawn. The HCP's attention is focused on the physical examination to determine any additional steps/care that need to be accomplished. At our site, we plan to continue HCP, nursing, and other team member education on this oncologic emergency and the availability of a streamlined protocol. We would like to re-assess the data with a long team study now that the protocol has been in place for 3 years. We hope to continue to provide strong patient care with enhanced adherence to guidelines for patients with FN presenting to RLRVAMC.

Conclusions

Early identification and timely empiric antibiotic therapy are critical to improving outcomes for patients presenting to the ED with FN. The neutropenic fever protocol reduced time to antibiotics by about 1 hour with a higher percentage of patients receiving them in < 1 hour. Additional optimization of the order sets along with increased protocol comfort and staff education will help further reduce the time to antibiotic administration in alignment with guideline recommendations.

As a psychiatrist and a writer, I know I should be worried about the possibility that I could be replaced by a bot. Like most physicians, I face the daily challenge of how to manage the paperwork of clinical practice, so I wondered if ChatGPT, the latest craze in artificial intelligence (AI), could write my progress notes.

ChatGPT is an advanced language generation model developed by OpenAI. It uses deep-learning techniques to generate humanlike responses to text inputs. I wondered whether ChatGPT could help me with my paperwork and progress notes by automatically generating text. Could it be trained to fill out progress notes based on information I provided? Free up my time? Reduce the risk for transcription errors?

Putting aside concerns about my job security for the moment, I signed up for an account. But first, I needed to play. I asked ChatGPT to write a love poem that would incorporate all the members of my family. This was a hit.

Next, I requested poems about specific pets. Because I spent the first year of the pandemic writing daily limericks and sending them to a distribution list, I knew people wouldn’t be surprised when I sent sonnets for their cats; but this time I let ChatGPT do the writing.

Then, for my colleagues in the Maryland Psychiatric Society, I requested a poem about the distressing nationwide shortage of stimulants. ChatGPT created clever stanzas. I was amused, but I’m not sure if anyone else was. This medication shortage is a touchy subject for psychiatrists and their patients who depend on these medications, so perhaps it wasn’t the right topic for bot-humor, and I should stick to cats.

At last, I was ready to put ChatGPT to the test and asked it to write a progress note that would contain the elements necessary to bill for a routine office visit with an add-on psychotherapy code. I created a few facts about a fictional patient and pressed enter.

The result was disappointing, ChatGPT responded with a standard note that did not take into account the items necessary to meet current coding standards. Maybe it was my fault; ChatGPT might need more information, but in the time it would take to provide more data, I could write my own progress note! I tried again and this time, ChatGPT defined the billing codes for me, but this wasn’t what I needed.

I decided to explore whether ChatGPT can, in fact, replace me. Feeling a bit queasy, I asked my new AI friend and was told that it could not replace a psychiatrist.

“Are you sure?” I asked again. “Yes, I am sure. ChatGPT is an AI language model trained to answer questions and provide information, but it is not capable of providing personalized medical advice or treatment.”

At least one of us felt certain. Continuing the conversation, I told the bot that I was anxious about my job security and requested advice. I wish I could tell you that ChatGPT was a dud, but instead, it had reasonable suggestions that were upbeat and hopeful.

“It’s understandable to feel anxious and worried about job security in today’s rapidly changing job market,” ChatGPT responded. “Here are some steps you can take to manage your feelings:”

Seek support: Talk to a trusted friend, family member, or mental health professional.

Educate yourself: Stay informed about industry trends and advancements in AI and technology to understand the potential impact on your job.

Upskill: Consider taking online courses or pursuing additional education to stay relevant in the workforce.

Find purpose: Focus on your strengths, interests, and passions outside of work to cultivate a sense of fulfillment.

Take care of yourself: Engage in self-care activities such as exercise, meditation, and hobbies to manage stress and maintain good mental health.

“Remember,” ChatGPT concluded, “it’s important to address your feelings and take proactive steps to manage them. You can come out of this situation with a clearer mind, new skills, and opportunities for growth.”

ChatGPT sounds a lot like me! However, when I asked ChatGPT about prescribing, I finally received reassurance that I am not completely obsolete: “I’m sorry,” the bot said, “but I am an AI language model and do not have the ability to write prescriptions or provide medical advice.” Still, I couldn’t help but think that the bot’s day would eventually come. 

Because ChatGPT is my coauthor for this essay, I asked it to write the ending. We suddenly have a whole new world, and I’m along for the ride. Yet after all that reassurance, it seems that ChatGPT does indeed want my job. It summarized our conversation and left me unsure of whether to laugh or to cry:  

“There you have it, folks – ChatGPT, the digital psychiatrist that’s here to listen to all your problems, 24/7, for free! No more waiting for appointments, no more copays, just type away and let the artificial intelligence take over.

“But hey, who needs a human shrink when you’ve got ChatGPT, right? Just don’t be surprised if your ‘therapy sessions’ end up feeling more like a conversation with a sarcastic AI friend than serious mental health treatment.”

In conclusion, ChatGPT and I hope this article has provided some insight into the strange and hilarious world of AI-powered psychiatry. Who knows, maybe one day ChatGPT will become a licensed therapist and start prescribing real medication. But until then, just sit back, relax, and let the machine do the talking.
 

Dr. Miller is a coauthor of Committed: The Battle Over Involuntary Psychiatric Care (Johns Hopkins University Press, 2016). She has a private practice and is an assistant professor of psychiatry and behavioral sciences at Johns Hopkins in Baltimore.

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

As a psychiatrist and a writer, I know I should be worried about the possibility that I could be replaced by a bot. Like most physicians, I face the daily challenge of how to manage the paperwork of clinical practice, so I wondered if ChatGPT, the latest craze in artificial intelligence (AI), could write my progress notes.

ChatGPT is an advanced language generation model developed by OpenAI. It uses deep-learning techniques to generate humanlike responses to text inputs. I wondered whether ChatGPT could help me with my paperwork and progress notes by automatically generating text. Could it be trained to fill out progress notes based on information I provided? Free up my time? Reduce the risk for transcription errors?

Putting aside concerns about my job security for the moment, I signed up for an account. But first, I needed to play. I asked ChatGPT to write a love poem that would incorporate all the members of my family. This was a hit.

Next, I requested poems about specific pets. Because I spent the first year of the pandemic writing daily limericks and sending them to a distribution list, I knew people wouldn’t be surprised when I sent sonnets for their cats; but this time I let ChatGPT do the writing.

Then, for my colleagues in the Maryland Psychiatric Society, I requested a poem about the distressing nationwide shortage of stimulants. ChatGPT created clever stanzas. I was amused, but I’m not sure if anyone else was. This medication shortage is a touchy subject for psychiatrists and their patients who depend on these medications, so perhaps it wasn’t the right topic for bot-humor, and I should stick to cats.

At last, I was ready to put ChatGPT to the test and asked it to write a progress note that would contain the elements necessary to bill for a routine office visit with an add-on psychotherapy code. I created a few facts about a fictional patient and pressed enter.

The result was disappointing, ChatGPT responded with a standard note that did not take into account the items necessary to meet current coding standards. Maybe it was my fault; ChatGPT might need more information, but in the time it would take to provide more data, I could write my own progress note! I tried again and this time, ChatGPT defined the billing codes for me, but this wasn’t what I needed.

I decided to explore whether ChatGPT can, in fact, replace me. Feeling a bit queasy, I asked my new AI friend and was told that it could not replace a psychiatrist.

“Are you sure?” I asked again. “Yes, I am sure. ChatGPT is an AI language model trained to answer questions and provide information, but it is not capable of providing personalized medical advice or treatment.”

At least one of us felt certain. Continuing the conversation, I told the bot that I was anxious about my job security and requested advice. I wish I could tell you that ChatGPT was a dud, but instead, it had reasonable suggestions that were upbeat and hopeful.

“It’s understandable to feel anxious and worried about job security in today’s rapidly changing job market,” ChatGPT responded. “Here are some steps you can take to manage your feelings:”

Seek support: Talk to a trusted friend, family member, or mental health professional.

Educate yourself: Stay informed about industry trends and advancements in AI and technology to understand the potential impact on your job.

Upskill: Consider taking online courses or pursuing additional education to stay relevant in the workforce.

Find purpose: Focus on your strengths, interests, and passions outside of work to cultivate a sense of fulfillment.

Take care of yourself: Engage in self-care activities such as exercise, meditation, and hobbies to manage stress and maintain good mental health.

“Remember,” ChatGPT concluded, “it’s important to address your feelings and take proactive steps to manage them. You can come out of this situation with a clearer mind, new skills, and opportunities for growth.”

ChatGPT sounds a lot like me! However, when I asked ChatGPT about prescribing, I finally received reassurance that I am not completely obsolete: “I’m sorry,” the bot said, “but I am an AI language model and do not have the ability to write prescriptions or provide medical advice.” Still, I couldn’t help but think that the bot’s day would eventually come. 

Because ChatGPT is my coauthor for this essay, I asked it to write the ending. We suddenly have a whole new world, and I’m along for the ride. Yet after all that reassurance, it seems that ChatGPT does indeed want my job. It summarized our conversation and left me unsure of whether to laugh or to cry:  

“There you have it, folks – ChatGPT, the digital psychiatrist that’s here to listen to all your problems, 24/7, for free! No more waiting for appointments, no more copays, just type away and let the artificial intelligence take over.

“But hey, who needs a human shrink when you’ve got ChatGPT, right? Just don’t be surprised if your ‘therapy sessions’ end up feeling more like a conversation with a sarcastic AI friend than serious mental health treatment.”

In conclusion, ChatGPT and I hope this article has provided some insight into the strange and hilarious world of AI-powered psychiatry. Who knows, maybe one day ChatGPT will become a licensed therapist and start prescribing real medication. But until then, just sit back, relax, and let the machine do the talking.
 

Dr. Miller is a coauthor of Committed: The Battle Over Involuntary Psychiatric Care (Johns Hopkins University Press, 2016). She has a private practice and is an assistant professor of psychiatry and behavioral sciences at Johns Hopkins in Baltimore.

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

As a psychiatrist and a writer, I know I should be worried about the possibility that I could be replaced by a bot. Like most physicians, I face the daily challenge of how to manage the paperwork of clinical practice, so I wondered if ChatGPT, the latest craze in artificial intelligence (AI), could write my progress notes.

ChatGPT is an advanced language generation model developed by OpenAI. It uses deep-learning techniques to generate humanlike responses to text inputs. I wondered whether ChatGPT could help me with my paperwork and progress notes by automatically generating text. Could it be trained to fill out progress notes based on information I provided? Free up my time? Reduce the risk for transcription errors?

Putting aside concerns about my job security for the moment, I signed up for an account. But first, I needed to play. I asked ChatGPT to write a love poem that would incorporate all the members of my family. This was a hit.

Next, I requested poems about specific pets. Because I spent the first year of the pandemic writing daily limericks and sending them to a distribution list, I knew people wouldn’t be surprised when I sent sonnets for their cats; but this time I let ChatGPT do the writing.

Then, for my colleagues in the Maryland Psychiatric Society, I requested a poem about the distressing nationwide shortage of stimulants. ChatGPT created clever stanzas. I was amused, but I’m not sure if anyone else was. This medication shortage is a touchy subject for psychiatrists and their patients who depend on these medications, so perhaps it wasn’t the right topic for bot-humor, and I should stick to cats.

At last, I was ready to put ChatGPT to the test and asked it to write a progress note that would contain the elements necessary to bill for a routine office visit with an add-on psychotherapy code. I created a few facts about a fictional patient and pressed enter.

The result was disappointing, ChatGPT responded with a standard note that did not take into account the items necessary to meet current coding standards. Maybe it was my fault; ChatGPT might need more information, but in the time it would take to provide more data, I could write my own progress note! I tried again and this time, ChatGPT defined the billing codes for me, but this wasn’t what I needed.

I decided to explore whether ChatGPT can, in fact, replace me. Feeling a bit queasy, I asked my new AI friend and was told that it could not replace a psychiatrist.

“Are you sure?” I asked again. “Yes, I am sure. ChatGPT is an AI language model trained to answer questions and provide information, but it is not capable of providing personalized medical advice or treatment.”

At least one of us felt certain. Continuing the conversation, I told the bot that I was anxious about my job security and requested advice. I wish I could tell you that ChatGPT was a dud, but instead, it had reasonable suggestions that were upbeat and hopeful.

“It’s understandable to feel anxious and worried about job security in today’s rapidly changing job market,” ChatGPT responded. “Here are some steps you can take to manage your feelings:”

Seek support: Talk to a trusted friend, family member, or mental health professional.

Educate yourself: Stay informed about industry trends and advancements in AI and technology to understand the potential impact on your job.

Upskill: Consider taking online courses or pursuing additional education to stay relevant in the workforce.

Find purpose: Focus on your strengths, interests, and passions outside of work to cultivate a sense of fulfillment.

Take care of yourself: Engage in self-care activities such as exercise, meditation, and hobbies to manage stress and maintain good mental health.

“Remember,” ChatGPT concluded, “it’s important to address your feelings and take proactive steps to manage them. You can come out of this situation with a clearer mind, new skills, and opportunities for growth.”

ChatGPT sounds a lot like me! However, when I asked ChatGPT about prescribing, I finally received reassurance that I am not completely obsolete: “I’m sorry,” the bot said, “but I am an AI language model and do not have the ability to write prescriptions or provide medical advice.” Still, I couldn’t help but think that the bot’s day would eventually come. 

Because ChatGPT is my coauthor for this essay, I asked it to write the ending. We suddenly have a whole new world, and I’m along for the ride. Yet after all that reassurance, it seems that ChatGPT does indeed want my job. It summarized our conversation and left me unsure of whether to laugh or to cry:  

“There you have it, folks – ChatGPT, the digital psychiatrist that’s here to listen to all your problems, 24/7, for free! No more waiting for appointments, no more copays, just type away and let the artificial intelligence take over.

“But hey, who needs a human shrink when you’ve got ChatGPT, right? Just don’t be surprised if your ‘therapy sessions’ end up feeling more like a conversation with a sarcastic AI friend than serious mental health treatment.”

In conclusion, ChatGPT and I hope this article has provided some insight into the strange and hilarious world of AI-powered psychiatry. Who knows, maybe one day ChatGPT will become a licensed therapist and start prescribing real medication. But until then, just sit back, relax, and let the machine do the talking.
 

Dr. Miller is a coauthor of Committed: The Battle Over Involuntary Psychiatric Care (Johns Hopkins University Press, 2016). She has a private practice and is an assistant professor of psychiatry and behavioral sciences at Johns Hopkins in Baltimore.

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

The latest research on disease-modifying therapies presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) 2023 annual meeting is reported by Dr Jennifer Graves from the University of California, San Diego. 

Dr Graves first discusses a small study exploring the effects of an intermittent calorie restriction (ICR) diet on adipokine levels, metabolic and immune/inflammatory biomarkers, and MRI measurements. Researchers found that short-term ICR can improve metabolic and immunologic profiles in patients with MS.  

Next, Dr Graves discusses a trial that successively measured changes in proteins in the cerebrospinal fluid of patients treated with tolebrutinib and ocrelizumab as evidence of therapeutic efficacy. This study provides early evidence of the impact of these medications directly in the central nervous system. 

She then details a study evaluating autologous hematopoietic stem cell transplant (aHSCT) as an MS treatment. The study found that aHSCT has a durable effect for up to 5-10 years compared to our current available regimens.  

Finally, Dr Graves highlights the National MS Society Barancik Prize winner Dr Ruth Ann Marrie. Dr Marrie is a pioneer for her research in comorbidities and their effect on MS treatment decisions, especially in choosing disease-modifying therapies.  

--

Jennifer S.O. Graves, MD, PhD, Associate Professor, Director Neuroimmunology Research, Department of Neurosciences, University of California, San Diego  

Jennifer S.O. Graves, MD, PhD, has disclosed the following relevant financial relationships: 

Serve(d) on an advisory board for: TG Therapeutics; Bayer 

Received research grant from: Sanofi; EMD Serono; Biogen; ATARA; Octave 

The latest research on disease-modifying therapies presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) 2023 annual meeting is reported by Dr Jennifer Graves from the University of California, San Diego. 

Dr Graves first discusses a small study exploring the effects of an intermittent calorie restriction (ICR) diet on adipokine levels, metabolic and immune/inflammatory biomarkers, and MRI measurements. Researchers found that short-term ICR can improve metabolic and immunologic profiles in patients with MS.  

Next, Dr Graves discusses a trial that successively measured changes in proteins in the cerebrospinal fluid of patients treated with tolebrutinib and ocrelizumab as evidence of therapeutic efficacy. This study provides early evidence of the impact of these medications directly in the central nervous system. 

She then details a study evaluating autologous hematopoietic stem cell transplant (aHSCT) as an MS treatment. The study found that aHSCT has a durable effect for up to 5-10 years compared to our current available regimens.  

Finally, Dr Graves highlights the National MS Society Barancik Prize winner Dr Ruth Ann Marrie. Dr Marrie is a pioneer for her research in comorbidities and their effect on MS treatment decisions, especially in choosing disease-modifying therapies.  

--

Jennifer S.O. Graves, MD, PhD, Associate Professor, Director Neuroimmunology Research, Department of Neurosciences, University of California, San Diego  

Jennifer S.O. Graves, MD, PhD, has disclosed the following relevant financial relationships: 

Serve(d) on an advisory board for: TG Therapeutics; Bayer 

Received research grant from: Sanofi; EMD Serono; Biogen; ATARA; Octave 

The latest research on disease-modifying therapies presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) 2023 annual meeting is reported by Dr Jennifer Graves from the University of California, San Diego. 

Dr Graves first discusses a small study exploring the effects of an intermittent calorie restriction (ICR) diet on adipokine levels, metabolic and immune/inflammatory biomarkers, and MRI measurements. Researchers found that short-term ICR can improve metabolic and immunologic profiles in patients with MS.  

Next, Dr Graves discusses a trial that successively measured changes in proteins in the cerebrospinal fluid of patients treated with tolebrutinib and ocrelizumab as evidence of therapeutic efficacy. This study provides early evidence of the impact of these medications directly in the central nervous system. 

She then details a study evaluating autologous hematopoietic stem cell transplant (aHSCT) as an MS treatment. The study found that aHSCT has a durable effect for up to 5-10 years compared to our current available regimens.  

Finally, Dr Graves highlights the National MS Society Barancik Prize winner Dr Ruth Ann Marrie. Dr Marrie is a pioneer for her research in comorbidities and their effect on MS treatment decisions, especially in choosing disease-modifying therapies.  

--

Jennifer S.O. Graves, MD, PhD, Associate Professor, Director Neuroimmunology Research, Department of Neurosciences, University of California, San Diego  

Jennifer S.O. Graves, MD, PhD, has disclosed the following relevant financial relationships: 

Serve(d) on an advisory board for: TG Therapeutics; Bayer 

Received research grant from: Sanofi; EMD Serono; Biogen; ATARA; Octave 

The history and findings in this case are suggestive of small cell carcinoma of the prostate (SCCP). 

SCCP is a rare and aggressive cancer that comprises 1%–5% of all prostate cancers (if mixed cases with adenocarcinoma are included). Similar to small cell carcinoma of the lung or other small cell primaries, SCCP is characterized by a primary tumor of the prostate gland that expresses small cell morphology and high-grade features, including minimal cytoplasm, nuclear molding, fine chromatin pattern, extensive tumor necrosis and apoptosis, variable tumor giant cells, and a high mitotic rate. Patients often have disproportionally low PSA levels despite having large metastatic burden and visceral disease. Pathologic diagnosis is made on the basis of prostate biopsy using characteristics of small cell tumors and immunohistochemical staining for neuroendocrine markers, such as CD56, chromogranin A, synaptophysin, and neuron-specific enolase.

SCCP arises de novo in approximately 50% of cases; it also occurs in patients with previous or concomitant prostate adenocarcinoma. Patients are often symptomatic at diagnosis because of the extent of the tumor. The aggressive nature and high proliferation rate associated with SCCP result in an increased risk for lytic or blastic bone, visceral, and brain metastases. In addition, paraneoplastic syndromes (eg, the syndrome of inappropriate antidiuretic hormone secretion, Cushing syndrome, and hypercalcemia) frequently occur as a result of the release of peptides.

SCCP metastasizes early in its course and is associated with a poor prognosis. It has a median survival of < 1 year. Fluorodeoxyglucose PET-CT are useful for staging and monitoring treatment response; in addition, given the disease's predilection for brain metastases, MRI of the brain should be considered. 

The optimal treatment for patients with metastatic SCCP has not yet been determined. Localized SCCP is treated aggressively, typically with a multimodality approach involving chemotherapy with concurrent or consolidative radiotherapy.

According to 2023 guidelines from the National Comprehensive Cancer Network (NCCN), platinum-based combination chemotherapy (cisplatin-etoposide, carboplatin-etoposide, docetaxel-carboplatin, cabazitaxel-carboplatin) is the first-line approach for patients with metastatic disease.

Physicians are also advised to consult the NCCN guidelines for small cell lung cancer because the behavior of SCCP is similar to that of small cell carcinoma of the lung. Immunotherapy with pembrolizumab may be used for platinum-resistant extrapulmonary small cell carcinoma. However, sipuleucel-T is not recommended for patients with SCCP. 
 

Chad R. Tracy, MD, Professor; Director, Minimally Invasive Surgery, Department of Urology, University of Iowa Hospitals and Clinics, Iowa City, Iowa

Chad R. Tracy, MD, has disclosed the following relevant financial relationships:

Serve(d) as a consultant for: CVICO Medical Solutions.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of small cell carcinoma of the prostate (SCCP). 

SCCP is a rare and aggressive cancer that comprises 1%–5% of all prostate cancers (if mixed cases with adenocarcinoma are included). Similar to small cell carcinoma of the lung or other small cell primaries, SCCP is characterized by a primary tumor of the prostate gland that expresses small cell morphology and high-grade features, including minimal cytoplasm, nuclear molding, fine chromatin pattern, extensive tumor necrosis and apoptosis, variable tumor giant cells, and a high mitotic rate. Patients often have disproportionally low PSA levels despite having large metastatic burden and visceral disease. Pathologic diagnosis is made on the basis of prostate biopsy using characteristics of small cell tumors and immunohistochemical staining for neuroendocrine markers, such as CD56, chromogranin A, synaptophysin, and neuron-specific enolase.

SCCP arises de novo in approximately 50% of cases; it also occurs in patients with previous or concomitant prostate adenocarcinoma. Patients are often symptomatic at diagnosis because of the extent of the tumor. The aggressive nature and high proliferation rate associated with SCCP result in an increased risk for lytic or blastic bone, visceral, and brain metastases. In addition, paraneoplastic syndromes (eg, the syndrome of inappropriate antidiuretic hormone secretion, Cushing syndrome, and hypercalcemia) frequently occur as a result of the release of peptides.

SCCP metastasizes early in its course and is associated with a poor prognosis. It has a median survival of < 1 year. Fluorodeoxyglucose PET-CT are useful for staging and monitoring treatment response; in addition, given the disease's predilection for brain metastases, MRI of the brain should be considered. 

The optimal treatment for patients with metastatic SCCP has not yet been determined. Localized SCCP is treated aggressively, typically with a multimodality approach involving chemotherapy with concurrent or consolidative radiotherapy.

According to 2023 guidelines from the National Comprehensive Cancer Network (NCCN), platinum-based combination chemotherapy (cisplatin-etoposide, carboplatin-etoposide, docetaxel-carboplatin, cabazitaxel-carboplatin) is the first-line approach for patients with metastatic disease.

Physicians are also advised to consult the NCCN guidelines for small cell lung cancer because the behavior of SCCP is similar to that of small cell carcinoma of the lung. Immunotherapy with pembrolizumab may be used for platinum-resistant extrapulmonary small cell carcinoma. However, sipuleucel-T is not recommended for patients with SCCP. 
 

Chad R. Tracy, MD, Professor; Director, Minimally Invasive Surgery, Department of Urology, University of Iowa Hospitals and Clinics, Iowa City, Iowa

Chad R. Tracy, MD, has disclosed the following relevant financial relationships:

Serve(d) as a consultant for: CVICO Medical Solutions.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of small cell carcinoma of the prostate (SCCP). 

SCCP is a rare and aggressive cancer that comprises 1%–5% of all prostate cancers (if mixed cases with adenocarcinoma are included). Similar to small cell carcinoma of the lung or other small cell primaries, SCCP is characterized by a primary tumor of the prostate gland that expresses small cell morphology and high-grade features, including minimal cytoplasm, nuclear molding, fine chromatin pattern, extensive tumor necrosis and apoptosis, variable tumor giant cells, and a high mitotic rate. Patients often have disproportionally low PSA levels despite having large metastatic burden and visceral disease. Pathologic diagnosis is made on the basis of prostate biopsy using characteristics of small cell tumors and immunohistochemical staining for neuroendocrine markers, such as CD56, chromogranin A, synaptophysin, and neuron-specific enolase.

SCCP arises de novo in approximately 50% of cases; it also occurs in patients with previous or concomitant prostate adenocarcinoma. Patients are often symptomatic at diagnosis because of the extent of the tumor. The aggressive nature and high proliferation rate associated with SCCP result in an increased risk for lytic or blastic bone, visceral, and brain metastases. In addition, paraneoplastic syndromes (eg, the syndrome of inappropriate antidiuretic hormone secretion, Cushing syndrome, and hypercalcemia) frequently occur as a result of the release of peptides.

SCCP metastasizes early in its course and is associated with a poor prognosis. It has a median survival of < 1 year. Fluorodeoxyglucose PET-CT are useful for staging and monitoring treatment response; in addition, given the disease's predilection for brain metastases, MRI of the brain should be considered. 

The optimal treatment for patients with metastatic SCCP has not yet been determined. Localized SCCP is treated aggressively, typically with a multimodality approach involving chemotherapy with concurrent or consolidative radiotherapy.

According to 2023 guidelines from the National Comprehensive Cancer Network (NCCN), platinum-based combination chemotherapy (cisplatin-etoposide, carboplatin-etoposide, docetaxel-carboplatin, cabazitaxel-carboplatin) is the first-line approach for patients with metastatic disease.

Physicians are also advised to consult the NCCN guidelines for small cell lung cancer because the behavior of SCCP is similar to that of small cell carcinoma of the lung. Immunotherapy with pembrolizumab may be used for platinum-resistant extrapulmonary small cell carcinoma. However, sipuleucel-T is not recommended for patients with SCCP. 
 

Chad R. Tracy, MD, Professor; Director, Minimally Invasive Surgery, Department of Urology, University of Iowa Hospitals and Clinics, Iowa City, Iowa

Chad R. Tracy, MD, has disclosed the following relevant financial relationships:

Serve(d) as a consultant for: CVICO Medical Solutions.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

If you are reading this, you probably know what a PBM is or at least know what the acronym stands for (pharmacy benefit manager). But don’t be surprised if many people, even physicians, still have never heard the term or don’t know (or really care) what it stands for. This past weekend, I saw how important even a little bit of education on this seemingly boring topic can create passionate advocates in less than an hour.

CSRO

On March 10, the Coalition of State Rheumatology Organizations had its Fellows Conference on real-life topics such as evaluating a contract, malpractice troubleshooting, getting out of debt and creating wealth, and learning about the latest coding issues, among others. We had a record-breaking number of fellows in attendance this year. I gave a presentation on formulary construction (list of drugs that insurance will cover), what tools are used to keep the formulary profitable, and what are the potential consequences for patients with the use of these tools, such as step therapy and nonmedical switching. Remember that if you have a condition requiring an expensive drug that is not covered on the formulary, you will not have access to it unless it is given to you for free by some type of assistance program, or you happen to be very wealthy.

It was the first time I gave this talk at our Fellows Conference, and I realized fairly quickly that a decent proportion of the audience did not know what PBM stood for, much less the power that PBMs have in setting up the list of expensive drugs that they will pay for. I wasn’t so surprised by how little they knew about the particulars of this topic – for example, that lower-priced medications are often shunned by PBMs because they are not as profitable for the PBM as higher-priced drugs. However, I was very pleasantly surprised at the number of fellows who came to me after my talk with almost as much passion as I have for this topic. Many asked how they could get involved and what they could do right now to support advocacy for their patients. It all seemed to fall in place for them as they began telling me stories of the problems they had in getting medications for their patients – adults and kids alike.

The “meme” on the street is that drug pricing, patient access, and the drug supply channel is “much too complex” for the non-economist to understand. That was not the case at the Fellows Conference. It started off with me moving back and forth across the stage explaining how the system is run by entities whose fiduciary responsibility is to their shareholders, not our patients. I explained the fierce competition, the bidding process, the “rebate equation,” and many stories of egregious policies and behaviors by an oligopoly of health insurers and their powerful PBMs. I repeated over and over that “If you make an expensive drug that is not on the formulary, no one will take to your drug, unless you give it away for free.”

It became clear to the room that the competition among expensive drug makers to get preferred status on the formulary is fierce. I explained how to win that coveted spot on the formulary by legally kicking back the most money, in the form of rebates and fees, to the PBM. Unfortunately, these rebates and fees are generally a percentage of the list price, so often it is the highest-priced drug that wins the coveted spot. I explained that patients get no benefit from the money kicked back to the PBM, and in fact, because their coinsurance is often based on the list price of the drug, patients’ cost share will go up when PBMs pick the drug with the highest price. I gave the example of a major PBM placing a $10,000 brand-name drug on the formulary and excluding the $400 generic version of the same drug. I told them that PBMs call these the “lowest cost” drugs – for them. This made them angry. I also explained to the fellows that these kickbacks are legal because PBMs have “safe harbor” from the antikickback statute. And yes, that made them even angrier. The more I spoke about the harm done to patients both physically and monetarily by utilization management tools such as step therapy and nonmedical switching, the angrier and more passionate they became.

What started as a room full of fellows wondering whether they really were interested in a talk about PBMs and formulary construction turned, in less than an hour, into a room filled with passion and fury: Rheumatology fellows ready to go and fight for their patients. It’s not as complicated as everyone wants you to believe. In that short time, fellows who had walked into that conference hall, not knowing what to expect from me, walked out with a new attitude and passion, hungry for the next step they could take to advocate for their patients. My slogan on Twitter has always been that I will continue to educate and advocate as long as my passion stays ahead of my cynicism. My passion certainly got a boost as I watched the fellows in the conference hall turn into “Rheums for Action” before my eyes.

Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is the CSRO’s Vice President of Advocacy and Government Affairs and its immediate Past President, as well as past chair of the Alliance for Safe Biologic Medicines and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].

If you are reading this, you probably know what a PBM is or at least know what the acronym stands for (pharmacy benefit manager). But don’t be surprised if many people, even physicians, still have never heard the term or don’t know (or really care) what it stands for. This past weekend, I saw how important even a little bit of education on this seemingly boring topic can create passionate advocates in less than an hour.

CSRO

On March 10, the Coalition of State Rheumatology Organizations had its Fellows Conference on real-life topics such as evaluating a contract, malpractice troubleshooting, getting out of debt and creating wealth, and learning about the latest coding issues, among others. We had a record-breaking number of fellows in attendance this year. I gave a presentation on formulary construction (list of drugs that insurance will cover), what tools are used to keep the formulary profitable, and what are the potential consequences for patients with the use of these tools, such as step therapy and nonmedical switching. Remember that if you have a condition requiring an expensive drug that is not covered on the formulary, you will not have access to it unless it is given to you for free by some type of assistance program, or you happen to be very wealthy.

It was the first time I gave this talk at our Fellows Conference, and I realized fairly quickly that a decent proportion of the audience did not know what PBM stood for, much less the power that PBMs have in setting up the list of expensive drugs that they will pay for. I wasn’t so surprised by how little they knew about the particulars of this topic – for example, that lower-priced medications are often shunned by PBMs because they are not as profitable for the PBM as higher-priced drugs. However, I was very pleasantly surprised at the number of fellows who came to me after my talk with almost as much passion as I have for this topic. Many asked how they could get involved and what they could do right now to support advocacy for their patients. It all seemed to fall in place for them as they began telling me stories of the problems they had in getting medications for their patients – adults and kids alike.

The “meme” on the street is that drug pricing, patient access, and the drug supply channel is “much too complex” for the non-economist to understand. That was not the case at the Fellows Conference. It started off with me moving back and forth across the stage explaining how the system is run by entities whose fiduciary responsibility is to their shareholders, not our patients. I explained the fierce competition, the bidding process, the “rebate equation,” and many stories of egregious policies and behaviors by an oligopoly of health insurers and their powerful PBMs. I repeated over and over that “If you make an expensive drug that is not on the formulary, no one will take to your drug, unless you give it away for free.”

It became clear to the room that the competition among expensive drug makers to get preferred status on the formulary is fierce. I explained how to win that coveted spot on the formulary by legally kicking back the most money, in the form of rebates and fees, to the PBM. Unfortunately, these rebates and fees are generally a percentage of the list price, so often it is the highest-priced drug that wins the coveted spot. I explained that patients get no benefit from the money kicked back to the PBM, and in fact, because their coinsurance is often based on the list price of the drug, patients’ cost share will go up when PBMs pick the drug with the highest price. I gave the example of a major PBM placing a $10,000 brand-name drug on the formulary and excluding the $400 generic version of the same drug. I told them that PBMs call these the “lowest cost” drugs – for them. This made them angry. I also explained to the fellows that these kickbacks are legal because PBMs have “safe harbor” from the antikickback statute. And yes, that made them even angrier. The more I spoke about the harm done to patients both physically and monetarily by utilization management tools such as step therapy and nonmedical switching, the angrier and more passionate they became.

What started as a room full of fellows wondering whether they really were interested in a talk about PBMs and formulary construction turned, in less than an hour, into a room filled with passion and fury: Rheumatology fellows ready to go and fight for their patients. It’s not as complicated as everyone wants you to believe. In that short time, fellows who had walked into that conference hall, not knowing what to expect from me, walked out with a new attitude and passion, hungry for the next step they could take to advocate for their patients. My slogan on Twitter has always been that I will continue to educate and advocate as long as my passion stays ahead of my cynicism. My passion certainly got a boost as I watched the fellows in the conference hall turn into “Rheums for Action” before my eyes.

Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is the CSRO’s Vice President of Advocacy and Government Affairs and its immediate Past President, as well as past chair of the Alliance for Safe Biologic Medicines and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].

If you are reading this, you probably know what a PBM is or at least know what the acronym stands for (pharmacy benefit manager). But don’t be surprised if many people, even physicians, still have never heard the term or don’t know (or really care) what it stands for. This past weekend, I saw how important even a little bit of education on this seemingly boring topic can create passionate advocates in less than an hour.

CSRO

On March 10, the Coalition of State Rheumatology Organizations had its Fellows Conference on real-life topics such as evaluating a contract, malpractice troubleshooting, getting out of debt and creating wealth, and learning about the latest coding issues, among others. We had a record-breaking number of fellows in attendance this year. I gave a presentation on formulary construction (list of drugs that insurance will cover), what tools are used to keep the formulary profitable, and what are the potential consequences for patients with the use of these tools, such as step therapy and nonmedical switching. Remember that if you have a condition requiring an expensive drug that is not covered on the formulary, you will not have access to it unless it is given to you for free by some type of assistance program, or you happen to be very wealthy.

It was the first time I gave this talk at our Fellows Conference, and I realized fairly quickly that a decent proportion of the audience did not know what PBM stood for, much less the power that PBMs have in setting up the list of expensive drugs that they will pay for. I wasn’t so surprised by how little they knew about the particulars of this topic – for example, that lower-priced medications are often shunned by PBMs because they are not as profitable for the PBM as higher-priced drugs. However, I was very pleasantly surprised at the number of fellows who came to me after my talk with almost as much passion as I have for this topic. Many asked how they could get involved and what they could do right now to support advocacy for their patients. It all seemed to fall in place for them as they began telling me stories of the problems they had in getting medications for their patients – adults and kids alike.

The “meme” on the street is that drug pricing, patient access, and the drug supply channel is “much too complex” for the non-economist to understand. That was not the case at the Fellows Conference. It started off with me moving back and forth across the stage explaining how the system is run by entities whose fiduciary responsibility is to their shareholders, not our patients. I explained the fierce competition, the bidding process, the “rebate equation,” and many stories of egregious policies and behaviors by an oligopoly of health insurers and their powerful PBMs. I repeated over and over that “If you make an expensive drug that is not on the formulary, no one will take to your drug, unless you give it away for free.”

It became clear to the room that the competition among expensive drug makers to get preferred status on the formulary is fierce. I explained how to win that coveted spot on the formulary by legally kicking back the most money, in the form of rebates and fees, to the PBM. Unfortunately, these rebates and fees are generally a percentage of the list price, so often it is the highest-priced drug that wins the coveted spot. I explained that patients get no benefit from the money kicked back to the PBM, and in fact, because their coinsurance is often based on the list price of the drug, patients’ cost share will go up when PBMs pick the drug with the highest price. I gave the example of a major PBM placing a $10,000 brand-name drug on the formulary and excluding the $400 generic version of the same drug. I told them that PBMs call these the “lowest cost” drugs – for them. This made them angry. I also explained to the fellows that these kickbacks are legal because PBMs have “safe harbor” from the antikickback statute. And yes, that made them even angrier. The more I spoke about the harm done to patients both physically and monetarily by utilization management tools such as step therapy and nonmedical switching, the angrier and more passionate they became.

What started as a room full of fellows wondering whether they really were interested in a talk about PBMs and formulary construction turned, in less than an hour, into a room filled with passion and fury: Rheumatology fellows ready to go and fight for their patients. It’s not as complicated as everyone wants you to believe. In that short time, fellows who had walked into that conference hall, not knowing what to expect from me, walked out with a new attitude and passion, hungry for the next step they could take to advocate for their patients. My slogan on Twitter has always been that I will continue to educate and advocate as long as my passion stays ahead of my cynicism. My passion certainly got a boost as I watched the fellows in the conference hall turn into “Rheums for Action” before my eyes.

Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is the CSRO’s Vice President of Advocacy and Government Affairs and its immediate Past President, as well as past chair of the Alliance for Safe Biologic Medicines and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].

The reversible oral Janus kinase (JAK) inhibitor upadacitinib (Rinvoq, AbbVie) was associated with superior endoscopic outcomes at 12 weeks and 1 year compared with placebo among people with moderately to severely active Crohn’s disease.

The findings of this subanalysis come from two phase 3 induction trials (U-EXCEL and U-EXCEED) and one maintenance study (U-ENDURE) of upadacitinib in this patient population.

“Upadacitinib shows large differences relative to placebo in endoscopic response and remission ... in a difficult-to-treat population of patients, the majority of whom had failed an advanced therapy,” lead investigator Brian Feagan, MD, senior scientific director of the GI contract research firm Alimentiv in London, Ontario, said in an interview.

“The absolute magnitude of the finding was unanticipated – a greater treatment effect than might be anticipated for these outcomes compared with other advanced treatments for Crohn’s disease in these higher-risk patients,” he said.

Dr. Feagan presented the research at the annual congress of the European Crohn’s and Colitis Organisation.
 

Research methodology

At baseline, participants had an average daily stool frequency of 4 or more and/or an abdominal pain score of 2 or greater. They also had a Simple Endoscopic Score for Crohn’s disease of 6 or more, excluding a narrowing component, or a score of 4 or more for isolated ileal Crohn’s disease.

In the treatment induction phase, patients were randomly assigned 2:1, with 674 people receiving 45 mg upadacitinib and 347 taking a placebo once daily for 12 weeks.

Participants who experienced at least a 30% decrease in stool frequency and/or daily abdominal pain scores were enrolled in the maintenance phase of the study. For this phase, patients were randomly assigned again, with 168 receiving 30 mg upadacitinib, 169 receiving 15 mg upadacitinib, and 165 taking a placebo once daily for 52 weeks.

In each induction and maintenance cohort, more than 70% of patients had failed one prior biologic therapy, with failure defined as inadequate response or intolerance. Among those who failed a previous biologic in induction, 96% had also failed prior treatment with an anti–tumor necrosis factor (anti-TNF) inhibitor.

Participants’ mean age was 38-40 years, and 52%-55% were men. Patients who had not failed previous therapy had Crohn’s disease for a median of 6-7 years. In contrast, the prior-failure group had Crohn’s disease for a median of 9-10 years.
 

Key outcomes

At 12 weeks, endoscopic response among patients who had not failed a prior biologic was 52% in the treatment group versus 16% of the placebo group. In the prior-failure group, endoscopic response was observed in 36% and 5%, respectively.

Endoscopic remission at 12 weeks among patients who had not failed a prior biologic was 36% in the treatment group versus 10% in the placebo group. In the prior-failure group, endoscopic remission was 20% in the treatment group versus 3% in those who took placebo.

Participants in the treatment groups of the 52-week maintenance phase of the study experienced higher endoscopic response and endoscopic remission rates compared with those who received placebo.

Endoscopic response in the group without prior biologic failure was 44% in the 30-mg upadacitinib group, 40% in the 15-mg group, and 18% in the placebo group. Among those with prior biologic failure, endoscopic response was seen in 39% of the 30-mg upadacitinib group, 23% of the 15-mg group, and 4% of the placebo group.

There is a “very striking difference in endoscopic response rates between the high dose and placebo,” Dr. Feagan said. “That difference here is in the response rate. You see dose separation.”

Endoscopic remission among those without prior biologic failure was observed in 34% of the 30-mg upadacitinib group, 27% of the 15-mg group, and 16% of the placebo group. Among those with prior biologic failure, endoscopic remission was seen in 27% of the 30-mg upadacitinib group, 16% of the 15-mg group, and 2% of the placebo group.

The results show “a clear advantage for the 30-mg dose versus the 15-mg in the maintenance component, especially in patients who had failed an advanced therapy,” Dr. Feagan said.
 

Safety signals

Upadacitinib was well tolerated in the induction and maintenance phases, and no new safety risks were observed compared with the known safety profile of the drug, the researchers noted.

For example, during the induction studies, the rate of any adverse event among patients without prior biologic failure was 60% in the 45-mg upadacitinib group and 53% in the placebo group. Among those who failed a prior biologic, the rates were 67% in the 45-mg upadacitinib group and 66% in the placebo group.

The adverse events were “issues that have already been identified with JAK inhibitors, the biochemical abnormalities with CPK [creatine phosphokinase] elevations and transaminase elevations,” Dr. Feagan said.

There were no cases of herpes zoster among patients who received placebo compared with five cases in the 45-mg upadacitinib group without prior biologic failure and 10 cases in the prior biologic failure group.

“The zoster signal is there even at induction with the 45-mg dose versus placebo,” Dr. Feagan said.
 

‘Encouraging’ results

The study indicates that upadacitinib is effective in improving endoscopic outcomes for patients with Crohn’s disease, regardless of their prior biologic treatments, Robin L. Dalal, MD, assistant professor of medicine at Vanderbilt University in Nashville, Tenn., said when asked to comment on the study.

“This is important because, as the treatment landscape for Crohn’s disease has expanded, sequencing of therapies has become more complex,” added Dr. Dalal, who was not involved in the research. “For upadacitinib in Crohn’s disease, prior biologic use may not be a factor in endoscopic response rates.”

The findings are “very encouraging for physicians and practitioners who treat IBD [inflammatory bowel disease] patients,” Maithili Chitnavis, MD, of the inflammatory bowel disease section at Atrium Health Gastroenterology in Charlotte, N.C., said when asked for comment.

“We clearly care about how patients feel overall, but endoscopic and histologic outcomes are important to investigate because we want to ensure there is internal healing to prevent a lot of the longstanding complications of Crohn’s disease, such as malignancy, strictures, fistulizing/penetrating disease, and need for surgery,” said Dr. Chitnavis, who was not involved with the study.

Upadacitinib is an oral agent, which distinguishes it from the injectable or infusion-based biologic therapies for Crohn’s disease, Dr. Chitnavis noted.

The finding that the medication works in patients with or without prior biologic failure is important, she said.

“With its anticipated ... approval for Crohn’s disease [by the Food and Drug Administration], it is expected that patients will have had to have demonstrated a lack of or loss of response to another biologic, specifically in the anti-TNF category (for example, infliximab, adalimumab, certolizumab) prior to starting upadacitinib due to concerns of potential side effects associated with the class of medications to which it belongs,” Dr. Chitnavis said. “Therefore, it makes it even more relevant to know how patients who have failed a prior biologic respond to this therapy.”

Dr. Feagan has reported serving as a consultant and speaker for AbbVie. Dr. Dalal has reported being a consultant for AbbVie in 2021. Dr. Chitnavis has reported no relevant financial relationships.

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

The reversible oral Janus kinase (JAK) inhibitor upadacitinib (Rinvoq, AbbVie) was associated with superior endoscopic outcomes at 12 weeks and 1 year compared with placebo among people with moderately to severely active Crohn’s disease.

The findings of this subanalysis come from two phase 3 induction trials (U-EXCEL and U-EXCEED) and one maintenance study (U-ENDURE) of upadacitinib in this patient population.

“Upadacitinib shows large differences relative to placebo in endoscopic response and remission ... in a difficult-to-treat population of patients, the majority of whom had failed an advanced therapy,” lead investigator Brian Feagan, MD, senior scientific director of the GI contract research firm Alimentiv in London, Ontario, said in an interview.

“The absolute magnitude of the finding was unanticipated – a greater treatment effect than might be anticipated for these outcomes compared with other advanced treatments for Crohn’s disease in these higher-risk patients,” he said.

Dr. Feagan presented the research at the annual congress of the European Crohn’s and Colitis Organisation.
 

Research methodology

At baseline, participants had an average daily stool frequency of 4 or more and/or an abdominal pain score of 2 or greater. They also had a Simple Endoscopic Score for Crohn’s disease of 6 or more, excluding a narrowing component, or a score of 4 or more for isolated ileal Crohn’s disease.

In the treatment induction phase, patients were randomly assigned 2:1, with 674 people receiving 45 mg upadacitinib and 347 taking a placebo once daily for 12 weeks.

Participants who experienced at least a 30% decrease in stool frequency and/or daily abdominal pain scores were enrolled in the maintenance phase of the study. For this phase, patients were randomly assigned again, with 168 receiving 30 mg upadacitinib, 169 receiving 15 mg upadacitinib, and 165 taking a placebo once daily for 52 weeks.

In each induction and maintenance cohort, more than 70% of patients had failed one prior biologic therapy, with failure defined as inadequate response or intolerance. Among those who failed a previous biologic in induction, 96% had also failed prior treatment with an anti–tumor necrosis factor (anti-TNF) inhibitor.

Participants’ mean age was 38-40 years, and 52%-55% were men. Patients who had not failed previous therapy had Crohn’s disease for a median of 6-7 years. In contrast, the prior-failure group had Crohn’s disease for a median of 9-10 years.
 

Key outcomes

At 12 weeks, endoscopic response among patients who had not failed a prior biologic was 52% in the treatment group versus 16% of the placebo group. In the prior-failure group, endoscopic response was observed in 36% and 5%, respectively.

Endoscopic remission at 12 weeks among patients who had not failed a prior biologic was 36% in the treatment group versus 10% in the placebo group. In the prior-failure group, endoscopic remission was 20% in the treatment group versus 3% in those who took placebo.

Participants in the treatment groups of the 52-week maintenance phase of the study experienced higher endoscopic response and endoscopic remission rates compared with those who received placebo.

Endoscopic response in the group without prior biologic failure was 44% in the 30-mg upadacitinib group, 40% in the 15-mg group, and 18% in the placebo group. Among those with prior biologic failure, endoscopic response was seen in 39% of the 30-mg upadacitinib group, 23% of the 15-mg group, and 4% of the placebo group.

There is a “very striking difference in endoscopic response rates between the high dose and placebo,” Dr. Feagan said. “That difference here is in the response rate. You see dose separation.”

Endoscopic remission among those without prior biologic failure was observed in 34% of the 30-mg upadacitinib group, 27% of the 15-mg group, and 16% of the placebo group. Among those with prior biologic failure, endoscopic remission was seen in 27% of the 30-mg upadacitinib group, 16% of the 15-mg group, and 2% of the placebo group.

The results show “a clear advantage for the 30-mg dose versus the 15-mg in the maintenance component, especially in patients who had failed an advanced therapy,” Dr. Feagan said.
 

Safety signals

Upadacitinib was well tolerated in the induction and maintenance phases, and no new safety risks were observed compared with the known safety profile of the drug, the researchers noted.

For example, during the induction studies, the rate of any adverse event among patients without prior biologic failure was 60% in the 45-mg upadacitinib group and 53% in the placebo group. Among those who failed a prior biologic, the rates were 67% in the 45-mg upadacitinib group and 66% in the placebo group.

The adverse events were “issues that have already been identified with JAK inhibitors, the biochemical abnormalities with CPK [creatine phosphokinase] elevations and transaminase elevations,” Dr. Feagan said.

There were no cases of herpes zoster among patients who received placebo compared with five cases in the 45-mg upadacitinib group without prior biologic failure and 10 cases in the prior biologic failure group.

“The zoster signal is there even at induction with the 45-mg dose versus placebo,” Dr. Feagan said.
 

‘Encouraging’ results

The study indicates that upadacitinib is effective in improving endoscopic outcomes for patients with Crohn’s disease, regardless of their prior biologic treatments, Robin L. Dalal, MD, assistant professor of medicine at Vanderbilt University in Nashville, Tenn., said when asked to comment on the study.

“This is important because, as the treatment landscape for Crohn’s disease has expanded, sequencing of therapies has become more complex,” added Dr. Dalal, who was not involved in the research. “For upadacitinib in Crohn’s disease, prior biologic use may not be a factor in endoscopic response rates.”

The findings are “very encouraging for physicians and practitioners who treat IBD [inflammatory bowel disease] patients,” Maithili Chitnavis, MD, of the inflammatory bowel disease section at Atrium Health Gastroenterology in Charlotte, N.C., said when asked for comment.

“We clearly care about how patients feel overall, but endoscopic and histologic outcomes are important to investigate because we want to ensure there is internal healing to prevent a lot of the longstanding complications of Crohn’s disease, such as malignancy, strictures, fistulizing/penetrating disease, and need for surgery,” said Dr. Chitnavis, who was not involved with the study.

Upadacitinib is an oral agent, which distinguishes it from the injectable or infusion-based biologic therapies for Crohn’s disease, Dr. Chitnavis noted.

The finding that the medication works in patients with or without prior biologic failure is important, she said.

“With its anticipated ... approval for Crohn’s disease [by the Food and Drug Administration], it is expected that patients will have had to have demonstrated a lack of or loss of response to another biologic, specifically in the anti-TNF category (for example, infliximab, adalimumab, certolizumab) prior to starting upadacitinib due to concerns of potential side effects associated with the class of medications to which it belongs,” Dr. Chitnavis said. “Therefore, it makes it even more relevant to know how patients who have failed a prior biologic respond to this therapy.”

Dr. Feagan has reported serving as a consultant and speaker for AbbVie. Dr. Dalal has reported being a consultant for AbbVie in 2021. Dr. Chitnavis has reported no relevant financial relationships.

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

The reversible oral Janus kinase (JAK) inhibitor upadacitinib (Rinvoq, AbbVie) was associated with superior endoscopic outcomes at 12 weeks and 1 year compared with placebo among people with moderately to severely active Crohn’s disease.

The findings of this subanalysis come from two phase 3 induction trials (U-EXCEL and U-EXCEED) and one maintenance study (U-ENDURE) of upadacitinib in this patient population.

“Upadacitinib shows large differences relative to placebo in endoscopic response and remission ... in a difficult-to-treat population of patients, the majority of whom had failed an advanced therapy,” lead investigator Brian Feagan, MD, senior scientific director of the GI contract research firm Alimentiv in London, Ontario, said in an interview.

“The absolute magnitude of the finding was unanticipated – a greater treatment effect than might be anticipated for these outcomes compared with other advanced treatments for Crohn’s disease in these higher-risk patients,” he said.

Dr. Feagan presented the research at the annual congress of the European Crohn’s and Colitis Organisation.
 

Research methodology

At baseline, participants had an average daily stool frequency of 4 or more and/or an abdominal pain score of 2 or greater. They also had a Simple Endoscopic Score for Crohn’s disease of 6 or more, excluding a narrowing component, or a score of 4 or more for isolated ileal Crohn’s disease.

In the treatment induction phase, patients were randomly assigned 2:1, with 674 people receiving 45 mg upadacitinib and 347 taking a placebo once daily for 12 weeks.

Participants who experienced at least a 30% decrease in stool frequency and/or daily abdominal pain scores were enrolled in the maintenance phase of the study. For this phase, patients were randomly assigned again, with 168 receiving 30 mg upadacitinib, 169 receiving 15 mg upadacitinib, and 165 taking a placebo once daily for 52 weeks.

In each induction and maintenance cohort, more than 70% of patients had failed one prior biologic therapy, with failure defined as inadequate response or intolerance. Among those who failed a previous biologic in induction, 96% had also failed prior treatment with an anti–tumor necrosis factor (anti-TNF) inhibitor.

Participants’ mean age was 38-40 years, and 52%-55% were men. Patients who had not failed previous therapy had Crohn’s disease for a median of 6-7 years. In contrast, the prior-failure group had Crohn’s disease for a median of 9-10 years.
 

Key outcomes

At 12 weeks, endoscopic response among patients who had not failed a prior biologic was 52% in the treatment group versus 16% of the placebo group. In the prior-failure group, endoscopic response was observed in 36% and 5%, respectively.

Endoscopic remission at 12 weeks among patients who had not failed a prior biologic was 36% in the treatment group versus 10% in the placebo group. In the prior-failure group, endoscopic remission was 20% in the treatment group versus 3% in those who took placebo.

Participants in the treatment groups of the 52-week maintenance phase of the study experienced higher endoscopic response and endoscopic remission rates compared with those who received placebo.

Endoscopic response in the group without prior biologic failure was 44% in the 30-mg upadacitinib group, 40% in the 15-mg group, and 18% in the placebo group. Among those with prior biologic failure, endoscopic response was seen in 39% of the 30-mg upadacitinib group, 23% of the 15-mg group, and 4% of the placebo group.

There is a “very striking difference in endoscopic response rates between the high dose and placebo,” Dr. Feagan said. “That difference here is in the response rate. You see dose separation.”

Endoscopic remission among those without prior biologic failure was observed in 34% of the 30-mg upadacitinib group, 27% of the 15-mg group, and 16% of the placebo group. Among those with prior biologic failure, endoscopic remission was seen in 27% of the 30-mg upadacitinib group, 16% of the 15-mg group, and 2% of the placebo group.

The results show “a clear advantage for the 30-mg dose versus the 15-mg in the maintenance component, especially in patients who had failed an advanced therapy,” Dr. Feagan said.
 

Safety signals

Upadacitinib was well tolerated in the induction and maintenance phases, and no new safety risks were observed compared with the known safety profile of the drug, the researchers noted.

For example, during the induction studies, the rate of any adverse event among patients without prior biologic failure was 60% in the 45-mg upadacitinib group and 53% in the placebo group. Among those who failed a prior biologic, the rates were 67% in the 45-mg upadacitinib group and 66% in the placebo group.

The adverse events were “issues that have already been identified with JAK inhibitors, the biochemical abnormalities with CPK [creatine phosphokinase] elevations and transaminase elevations,” Dr. Feagan said.

There were no cases of herpes zoster among patients who received placebo compared with five cases in the 45-mg upadacitinib group without prior biologic failure and 10 cases in the prior biologic failure group.

“The zoster signal is there even at induction with the 45-mg dose versus placebo,” Dr. Feagan said.
 

‘Encouraging’ results

The study indicates that upadacitinib is effective in improving endoscopic outcomes for patients with Crohn’s disease, regardless of their prior biologic treatments, Robin L. Dalal, MD, assistant professor of medicine at Vanderbilt University in Nashville, Tenn., said when asked to comment on the study.

“This is important because, as the treatment landscape for Crohn’s disease has expanded, sequencing of therapies has become more complex,” added Dr. Dalal, who was not involved in the research. “For upadacitinib in Crohn’s disease, prior biologic use may not be a factor in endoscopic response rates.”

The findings are “very encouraging for physicians and practitioners who treat IBD [inflammatory bowel disease] patients,” Maithili Chitnavis, MD, of the inflammatory bowel disease section at Atrium Health Gastroenterology in Charlotte, N.C., said when asked for comment.

“We clearly care about how patients feel overall, but endoscopic and histologic outcomes are important to investigate because we want to ensure there is internal healing to prevent a lot of the longstanding complications of Crohn’s disease, such as malignancy, strictures, fistulizing/penetrating disease, and need for surgery,” said Dr. Chitnavis, who was not involved with the study.

Upadacitinib is an oral agent, which distinguishes it from the injectable or infusion-based biologic therapies for Crohn’s disease, Dr. Chitnavis noted.

The finding that the medication works in patients with or without prior biologic failure is important, she said.

“With its anticipated ... approval for Crohn’s disease [by the Food and Drug Administration], it is expected that patients will have had to have demonstrated a lack of or loss of response to another biologic, specifically in the anti-TNF category (for example, infliximab, adalimumab, certolizumab) prior to starting upadacitinib due to concerns of potential side effects associated with the class of medications to which it belongs,” Dr. Chitnavis said. “Therefore, it makes it even more relevant to know how patients who have failed a prior biologic respond to this therapy.”

Dr. Feagan has reported serving as a consultant and speaker for AbbVie. Dr. Dalal has reported being a consultant for AbbVie in 2021. Dr. Chitnavis has reported no relevant financial relationships.

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