Journal of Clinical Outcomes Management

We all have friends or relatives who, somehow, have managed to avoid catching COVID-19, which has infected more than 91.5 million Americans. You may even be one of the lucky ones yourself.

But health experts are saying: Not so fast. A mounting pile of scientific evidence suggests millions of Americans have been infected with the virus without ever even knowing it because they didn’t have symptoms or had mild cases they mistook for a cold or allergies.

The upshot: These silent COVID-19 cases reflect a hidden side of the pandemic that may be helping to drive new surges and viral variants.

Still, infectious disease experts say there is little doubt that some people have indeed managed to avoid COVID-19 infection altogether, and they are trying to understand why.

Several recent studies have suggested certain genetic and immune system traits may better protect this group of people against the coronavirus, making them less likely than others to be infected or seriously sickened. Researchers around the world are now studying these seemingly super-immune people for clues to what makes them so special, with an eye toward better vaccines, treatments, and prevention strategies.

Infectious disease specialists say both types of cases – those unknowingly infected by COVID-19 and people who’ve avoided the virus altogether – matter greatly to public health, more than 2 years into the pandemic.

“It’s definitely true that some people have had COVID and don’t realize it,” says Stephen Kissler, PhD, an infectious disease researcher with the Harvard T.H. Chan School of Public Health, Boston. “It is potentially good news if there’s more immunity in the population than we realize.”

But he says that being able to identify genetic and other factors that may offer some people protection against COVID-19 is an “exciting prospect” that could help find out who’s most at risk and improve efforts to get the pandemic under control.

Some studies have found a person’s genetic profile, past exposure to other COVID-like viruses, allergies, and even drugs they take for other conditions may all provide some defense – even for people who have not been vaccinated, don’t use masks, or don’t practice social distancing.

A person’s medical history and genetics may help decide their risk from new diseases, meaning “we may be able to help identify people who are at especially high risk from infection,” Dr. Kissler says. “That knowledge could help those people better shield themselves from infection and get quicker access to treatment and vaccines, if necessary. … We don’t yet know, but studies are ongoing for these things.”

Amesh Adalja, MD, an infectious disease specialist with the Johns Hopkins Center for Health Security, Baltimore, agrees that emerging research on people who’ve avoided infection offers the chance of new public health strategies to combat COVID-19.

“I’m sure there is some subset of people who are [COVID] negative,” he says. “So what explains that phenomenon, especially if that person was out there getting significant exposures?”
 

Have you had COVID without knowing it?

In a media briefing late last month, White House COVID-19 Response Coordinator Ashish Jha, MD, said more than 70% of the U.S. population has had the virus, according to the latest CDC data. That’s up from 33.5% in December.

But the actual number of people in the U.S. who have been infected with SARS-CoV-2, the scientific name for the virus that causes COVID-19, is likely to be much higher due to cases without symptoms that are unreported, experts say.

Since the early days of the pandemic, researchers have tried to put a number on these hidden cases, but that figure has been evolving and a clear consensus has not emerged.

In September 2020, a study published in the Annals of Internal Medicine said “approximately 40% to 45% of those infected with SARS-CoV-2 will remain asymptomatic.”

A follow-up analysis of 95 studies, published last December, reached similar findings, estimating that more than 40% of COVID-19 infections didn’t come with symptoms.

To get a better handle on the issue, CDC officials have been working with the American Red Cross and other blood banks to track COVID-19 antibodies – proteins your body makes after exposure to the virus to fight off an infection – in donors who said they have never had COVID-19.

While that joint effort is still ongoing, early findings say the number of donors with antibodies from COVID-19 infection increased in blood donors from 3.5% in July 2020 to at least 20.2% in May 2021. Since then, those percentages have soared, in part due to the introduction of vaccines, which also make the body produce COVID-19 antibodies.

The most current findings show that 83.3% of donors have combined COVID infection– and vaccine-induced antibodies in their blood. Those findings are based on 1.4 million blood donations.

Health experts say all of these studies are strong evidence that many COVID-19 cases continue to go undetected. In fact, the University of Washington Institute for Health Metrics and Evaluation estimates that only 7% of positive COVID-19 cases in the U.S. are being detected. That means case rates are actually 14.5 times higher than the official count of 131,000 new COVID infections each day, according to the Centers for Disease Control and Prevention, which reports the virus is still killing about 440 Americans daily.

So, why is all this important, in terms of public health?

Experts say people are more likely to be cautious if they know COVID-19 cases are high where they live, work, and play. On the other hand, if they believe case rates in their communities are lower than they actually are, they may be less likely to get vaccinated and boosted, wear masks indoors, avoid crowded indoor spaces, and take other precautions to fend off infection.
 

How do some avoid infection altogether?

In addition to tracking cases that go unreported and don’t have symptoms, infectious disease experts have also been trying to figure out why some people have managed to avoid getting the highly contagious virus.

Several leading lines of research have produced promising early results – suggesting that a person’s genetic makeup, past exposure to less-lethal coronaviruses, allergies, and even certain drugs they take for other conditions may all provide at least some protection against COVID.

“Our study showed that there are many human genes – hundreds of genes – that can impact SARS-CoV-2 infection,” says Neville Sanjana, PhD, a geneticist at New York University and the New York Genome Center who co-led the study. “With a better understanding of host genetic factors, we can find new kinds of therapies that target these host factors to block infection.”

In addition, he says several studies show some drugs that regulate genes, such as the breast cancer drug tamoxifen, also appear to knock down COVID-19 risk. He suggests such drugs, already approved by the Food and Drug Administration, might be “repurposed” to target the virus.

Studies in other countries show that patients taking tamoxifen before the pandemic were protected against severe COVID-19, Dr. Sanjana says. “That was a really cool thing, highlighting the power of harnessing host genetics. The virus critically depends on our genes to complete key parts of its life cycle.”

The NYU research findings echo other studies that have been published in recent months.

In July, a team of researchers led by the National Cancer Institute identified a genetic factor that appears to determine how severe an infection will be. In a study involving 3,000 people, they found that two gene changes, or mutations, that decrease the expression of a gene called OAS1 boosted the risk of hospitalization from COVID-19. OAS1 is part of the immune system’s response to viral infections.

As a result, developing a genetic therapy designed to increase the OAS1 gene’s expression might reduce the risk of severe disease.

“It’s very natural to get infected once you are exposed. There’s no magic bullet for that. But after you get infected, how you’re going to respond to this infection, that’s what is going to be affected by your genetic variants,” said Ludmila Prokunina-Olsson, PhD, the study’s lead researcher and chief of the National Cancer Institute’s Laboratory of Translational Genomics, Bethesda, Md., in an interview with NBC News.

Benjamin tenOever, PhD, a New York University virologist who co-authored the 2020 research, says the new genetic research is promising, but he believes it’s unlikely scientists will be able to identify a single gene responsible for actually preventing a COVID-19 infection.

“On the flip side, we have identified many genes that makes the disease worse,” he says.
 

T cells ‘remember’ past viral infections

As Dr. tenOever and Dr. Sanjana suggest, another intriguing line of research has found that prior viral infections may prime the body’s immune system to fight COVID-19.

Four other common coronaviruses – aside from SARS-CoV-2 – infect people worldwide, typically causing mild to moderate upper respiratory illnesses like the common cold, says Alessandro Sette, PhD, an infectious disease expert and vaccine researcher with the La Jolla (Calif.) Institute for Immunology.

In a recent study published in Science, he and his team found past infection with these other coronaviruses may give some protection against SARS-CoV-2.

T cells – white blood cells that act like immunological ninjas to ferret out and fight infections – appear to maintain a kind of “biological memory” of coronaviruses they have seen before and can mount an attack on similar pathogens, such SARS-CoV-2, Dr. Sette says.

The new work builds on a prior research he helped lead that found 40%-60% of people never exposed to SARS-CoV-2 had T cells that reacted to the virus – with their immune systems recognizing fragments of a virus they had never seen before.

Dr. Sette says his research shows that people whose T cells have this “preexisting memory” of past coronavirus exposures also tend to respond better to vaccination for reasons not yet well understood.

“The question is, at which point will there be enough immunity from vaccination, repeated infections from other coronaviruses, but also some of the variants of the SARS-CoV-2 … where infections become less frequent? We’re not there yet,” he says.

In addition to these exciting genetic and T-cell findings, other research has suggested low-grade inflammation from allergies – a key part of the body’s immune response to foreign substances – may also give some people an extra leg up, in terms of avoiding COVID infection.

Last May, a study of 1,400 households published in The Journal of Allergy and Clinical Immunology found that having a food allergy cut the risk of COVID-19 infection in half.

The researchers said it’s unclear why allergies may reduce the risk of infection, but they noted that people with food allergies express fewer ACE2 receptors on the surface of their airway cells, making it harder for the virus to enter cells.
 

The big picture: Prevention still your best bet

So, what’s the takeaway from all of this emerging research?

New York University’s Dr. tenOever says that while genes, T cells and allergies may offer some protection against COVID, tried-and-true precautions – vaccination, wearing masks, avoiding crowded indoor spaces, and social distancing – are likely to provide a greater defense.

He believes these precautions are likely why he and his family have never contracted COVID-19.

“I was tested weekly, as were my kids at school,” he says. “We definitely never got COVID, despite the fact that we live in New York City and I worked in a hospital every single day of the pandemic.”

Ziyad Al-Aly, MD, an infectious disease specialist and director of clinical epidemiology at Washington University in St. Louis, agrees that the new research on COVID-19 is intriguing but won’t likely result in practical changes in the approach to fighting the virus in the near term.

“Getting a deeper understanding of potential genetic factors or other characteristics – that could really help us understand why the virus just comes and goes without any ill effects in some people, and in other people it produces really serious disease,” he says. “That will really help us eventually to design better vaccines to prevent it or reduce severity or even [treat] people who get severe disease.”

In the meantime, Dr. Al-Aly says, “it’s still best to do everything you can to avoid infection in the first place – even if you’re vaccinated or previously infected, you should really try to avoid reinfection.”

That means sit outside if you can when visiting a restaurant. Wear a mask on a plane, even though it’s not required. And get vaccinated and boosted.

“In the future, there may be more tools to address this pandemic, but that’s really the best advice for now,” Dr. Al-Aly says.

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

We all have friends or relatives who, somehow, have managed to avoid catching COVID-19, which has infected more than 91.5 million Americans. You may even be one of the lucky ones yourself.

But health experts are saying: Not so fast. A mounting pile of scientific evidence suggests millions of Americans have been infected with the virus without ever even knowing it because they didn’t have symptoms or had mild cases they mistook for a cold or allergies.

The upshot: These silent COVID-19 cases reflect a hidden side of the pandemic that may be helping to drive new surges and viral variants.

Still, infectious disease experts say there is little doubt that some people have indeed managed to avoid COVID-19 infection altogether, and they are trying to understand why.

Several recent studies have suggested certain genetic and immune system traits may better protect this group of people against the coronavirus, making them less likely than others to be infected or seriously sickened. Researchers around the world are now studying these seemingly super-immune people for clues to what makes them so special, with an eye toward better vaccines, treatments, and prevention strategies.

Infectious disease specialists say both types of cases – those unknowingly infected by COVID-19 and people who’ve avoided the virus altogether – matter greatly to public health, more than 2 years into the pandemic.

“It’s definitely true that some people have had COVID and don’t realize it,” says Stephen Kissler, PhD, an infectious disease researcher with the Harvard T.H. Chan School of Public Health, Boston. “It is potentially good news if there’s more immunity in the population than we realize.”

But he says that being able to identify genetic and other factors that may offer some people protection against COVID-19 is an “exciting prospect” that could help find out who’s most at risk and improve efforts to get the pandemic under control.

Some studies have found a person’s genetic profile, past exposure to other COVID-like viruses, allergies, and even drugs they take for other conditions may all provide some defense – even for people who have not been vaccinated, don’t use masks, or don’t practice social distancing.

A person’s medical history and genetics may help decide their risk from new diseases, meaning “we may be able to help identify people who are at especially high risk from infection,” Dr. Kissler says. “That knowledge could help those people better shield themselves from infection and get quicker access to treatment and vaccines, if necessary. … We don’t yet know, but studies are ongoing for these things.”

Amesh Adalja, MD, an infectious disease specialist with the Johns Hopkins Center for Health Security, Baltimore, agrees that emerging research on people who’ve avoided infection offers the chance of new public health strategies to combat COVID-19.

“I’m sure there is some subset of people who are [COVID] negative,” he says. “So what explains that phenomenon, especially if that person was out there getting significant exposures?”
 

Have you had COVID without knowing it?

In a media briefing late last month, White House COVID-19 Response Coordinator Ashish Jha, MD, said more than 70% of the U.S. population has had the virus, according to the latest CDC data. That’s up from 33.5% in December.

But the actual number of people in the U.S. who have been infected with SARS-CoV-2, the scientific name for the virus that causes COVID-19, is likely to be much higher due to cases without symptoms that are unreported, experts say.

Since the early days of the pandemic, researchers have tried to put a number on these hidden cases, but that figure has been evolving and a clear consensus has not emerged.

In September 2020, a study published in the Annals of Internal Medicine said “approximately 40% to 45% of those infected with SARS-CoV-2 will remain asymptomatic.”

A follow-up analysis of 95 studies, published last December, reached similar findings, estimating that more than 40% of COVID-19 infections didn’t come with symptoms.

To get a better handle on the issue, CDC officials have been working with the American Red Cross and other blood banks to track COVID-19 antibodies – proteins your body makes after exposure to the virus to fight off an infection – in donors who said they have never had COVID-19.

While that joint effort is still ongoing, early findings say the number of donors with antibodies from COVID-19 infection increased in blood donors from 3.5% in July 2020 to at least 20.2% in May 2021. Since then, those percentages have soared, in part due to the introduction of vaccines, which also make the body produce COVID-19 antibodies.

The most current findings show that 83.3% of donors have combined COVID infection– and vaccine-induced antibodies in their blood. Those findings are based on 1.4 million blood donations.

Health experts say all of these studies are strong evidence that many COVID-19 cases continue to go undetected. In fact, the University of Washington Institute for Health Metrics and Evaluation estimates that only 7% of positive COVID-19 cases in the U.S. are being detected. That means case rates are actually 14.5 times higher than the official count of 131,000 new COVID infections each day, according to the Centers for Disease Control and Prevention, which reports the virus is still killing about 440 Americans daily.

So, why is all this important, in terms of public health?

Experts say people are more likely to be cautious if they know COVID-19 cases are high where they live, work, and play. On the other hand, if they believe case rates in their communities are lower than they actually are, they may be less likely to get vaccinated and boosted, wear masks indoors, avoid crowded indoor spaces, and take other precautions to fend off infection.
 

How do some avoid infection altogether?

In addition to tracking cases that go unreported and don’t have symptoms, infectious disease experts have also been trying to figure out why some people have managed to avoid getting the highly contagious virus.

Several leading lines of research have produced promising early results – suggesting that a person’s genetic makeup, past exposure to less-lethal coronaviruses, allergies, and even certain drugs they take for other conditions may all provide at least some protection against COVID.

“Our study showed that there are many human genes – hundreds of genes – that can impact SARS-CoV-2 infection,” says Neville Sanjana, PhD, a geneticist at New York University and the New York Genome Center who co-led the study. “With a better understanding of host genetic factors, we can find new kinds of therapies that target these host factors to block infection.”

In addition, he says several studies show some drugs that regulate genes, such as the breast cancer drug tamoxifen, also appear to knock down COVID-19 risk. He suggests such drugs, already approved by the Food and Drug Administration, might be “repurposed” to target the virus.

Studies in other countries show that patients taking tamoxifen before the pandemic were protected against severe COVID-19, Dr. Sanjana says. “That was a really cool thing, highlighting the power of harnessing host genetics. The virus critically depends on our genes to complete key parts of its life cycle.”

The NYU research findings echo other studies that have been published in recent months.

In July, a team of researchers led by the National Cancer Institute identified a genetic factor that appears to determine how severe an infection will be. In a study involving 3,000 people, they found that two gene changes, or mutations, that decrease the expression of a gene called OAS1 boosted the risk of hospitalization from COVID-19. OAS1 is part of the immune system’s response to viral infections.

As a result, developing a genetic therapy designed to increase the OAS1 gene’s expression might reduce the risk of severe disease.

“It’s very natural to get infected once you are exposed. There’s no magic bullet for that. But after you get infected, how you’re going to respond to this infection, that’s what is going to be affected by your genetic variants,” said Ludmila Prokunina-Olsson, PhD, the study’s lead researcher and chief of the National Cancer Institute’s Laboratory of Translational Genomics, Bethesda, Md., in an interview with NBC News.

Benjamin tenOever, PhD, a New York University virologist who co-authored the 2020 research, says the new genetic research is promising, but he believes it’s unlikely scientists will be able to identify a single gene responsible for actually preventing a COVID-19 infection.

“On the flip side, we have identified many genes that makes the disease worse,” he says.
 

T cells ‘remember’ past viral infections

As Dr. tenOever and Dr. Sanjana suggest, another intriguing line of research has found that prior viral infections may prime the body’s immune system to fight COVID-19.

Four other common coronaviruses – aside from SARS-CoV-2 – infect people worldwide, typically causing mild to moderate upper respiratory illnesses like the common cold, says Alessandro Sette, PhD, an infectious disease expert and vaccine researcher with the La Jolla (Calif.) Institute for Immunology.

In a recent study published in Science, he and his team found past infection with these other coronaviruses may give some protection against SARS-CoV-2.

T cells – white blood cells that act like immunological ninjas to ferret out and fight infections – appear to maintain a kind of “biological memory” of coronaviruses they have seen before and can mount an attack on similar pathogens, such SARS-CoV-2, Dr. Sette says.

The new work builds on a prior research he helped lead that found 40%-60% of people never exposed to SARS-CoV-2 had T cells that reacted to the virus – with their immune systems recognizing fragments of a virus they had never seen before.

Dr. Sette says his research shows that people whose T cells have this “preexisting memory” of past coronavirus exposures also tend to respond better to vaccination for reasons not yet well understood.

“The question is, at which point will there be enough immunity from vaccination, repeated infections from other coronaviruses, but also some of the variants of the SARS-CoV-2 … where infections become less frequent? We’re not there yet,” he says.

In addition to these exciting genetic and T-cell findings, other research has suggested low-grade inflammation from allergies – a key part of the body’s immune response to foreign substances – may also give some people an extra leg up, in terms of avoiding COVID infection.

Last May, a study of 1,400 households published in The Journal of Allergy and Clinical Immunology found that having a food allergy cut the risk of COVID-19 infection in half.

The researchers said it’s unclear why allergies may reduce the risk of infection, but they noted that people with food allergies express fewer ACE2 receptors on the surface of their airway cells, making it harder for the virus to enter cells.
 

The big picture: Prevention still your best bet

So, what’s the takeaway from all of this emerging research?

New York University’s Dr. tenOever says that while genes, T cells and allergies may offer some protection against COVID, tried-and-true precautions – vaccination, wearing masks, avoiding crowded indoor spaces, and social distancing – are likely to provide a greater defense.

He believes these precautions are likely why he and his family have never contracted COVID-19.

“I was tested weekly, as were my kids at school,” he says. “We definitely never got COVID, despite the fact that we live in New York City and I worked in a hospital every single day of the pandemic.”

Ziyad Al-Aly, MD, an infectious disease specialist and director of clinical epidemiology at Washington University in St. Louis, agrees that the new research on COVID-19 is intriguing but won’t likely result in practical changes in the approach to fighting the virus in the near term.

“Getting a deeper understanding of potential genetic factors or other characteristics – that could really help us understand why the virus just comes and goes without any ill effects in some people, and in other people it produces really serious disease,” he says. “That will really help us eventually to design better vaccines to prevent it or reduce severity or even [treat] people who get severe disease.”

In the meantime, Dr. Al-Aly says, “it’s still best to do everything you can to avoid infection in the first place – even if you’re vaccinated or previously infected, you should really try to avoid reinfection.”

That means sit outside if you can when visiting a restaurant. Wear a mask on a plane, even though it’s not required. And get vaccinated and boosted.

“In the future, there may be more tools to address this pandemic, but that’s really the best advice for now,” Dr. Al-Aly says.

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

We all have friends or relatives who, somehow, have managed to avoid catching COVID-19, which has infected more than 91.5 million Americans. You may even be one of the lucky ones yourself.

But health experts are saying: Not so fast. A mounting pile of scientific evidence suggests millions of Americans have been infected with the virus without ever even knowing it because they didn’t have symptoms or had mild cases they mistook for a cold or allergies.

The upshot: These silent COVID-19 cases reflect a hidden side of the pandemic that may be helping to drive new surges and viral variants.

Still, infectious disease experts say there is little doubt that some people have indeed managed to avoid COVID-19 infection altogether, and they are trying to understand why.

Several recent studies have suggested certain genetic and immune system traits may better protect this group of people against the coronavirus, making them less likely than others to be infected or seriously sickened. Researchers around the world are now studying these seemingly super-immune people for clues to what makes them so special, with an eye toward better vaccines, treatments, and prevention strategies.

Infectious disease specialists say both types of cases – those unknowingly infected by COVID-19 and people who’ve avoided the virus altogether – matter greatly to public health, more than 2 years into the pandemic.

“It’s definitely true that some people have had COVID and don’t realize it,” says Stephen Kissler, PhD, an infectious disease researcher with the Harvard T.H. Chan School of Public Health, Boston. “It is potentially good news if there’s more immunity in the population than we realize.”

But he says that being able to identify genetic and other factors that may offer some people protection against COVID-19 is an “exciting prospect” that could help find out who’s most at risk and improve efforts to get the pandemic under control.

Some studies have found a person’s genetic profile, past exposure to other COVID-like viruses, allergies, and even drugs they take for other conditions may all provide some defense – even for people who have not been vaccinated, don’t use masks, or don’t practice social distancing.

A person’s medical history and genetics may help decide their risk from new diseases, meaning “we may be able to help identify people who are at especially high risk from infection,” Dr. Kissler says. “That knowledge could help those people better shield themselves from infection and get quicker access to treatment and vaccines, if necessary. … We don’t yet know, but studies are ongoing for these things.”

Amesh Adalja, MD, an infectious disease specialist with the Johns Hopkins Center for Health Security, Baltimore, agrees that emerging research on people who’ve avoided infection offers the chance of new public health strategies to combat COVID-19.

“I’m sure there is some subset of people who are [COVID] negative,” he says. “So what explains that phenomenon, especially if that person was out there getting significant exposures?”
 

Have you had COVID without knowing it?

In a media briefing late last month, White House COVID-19 Response Coordinator Ashish Jha, MD, said more than 70% of the U.S. population has had the virus, according to the latest CDC data. That’s up from 33.5% in December.

But the actual number of people in the U.S. who have been infected with SARS-CoV-2, the scientific name for the virus that causes COVID-19, is likely to be much higher due to cases without symptoms that are unreported, experts say.

Since the early days of the pandemic, researchers have tried to put a number on these hidden cases, but that figure has been evolving and a clear consensus has not emerged.

In September 2020, a study published in the Annals of Internal Medicine said “approximately 40% to 45% of those infected with SARS-CoV-2 will remain asymptomatic.”

A follow-up analysis of 95 studies, published last December, reached similar findings, estimating that more than 40% of COVID-19 infections didn’t come with symptoms.

To get a better handle on the issue, CDC officials have been working with the American Red Cross and other blood banks to track COVID-19 antibodies – proteins your body makes after exposure to the virus to fight off an infection – in donors who said they have never had COVID-19.

While that joint effort is still ongoing, early findings say the number of donors with antibodies from COVID-19 infection increased in blood donors from 3.5% in July 2020 to at least 20.2% in May 2021. Since then, those percentages have soared, in part due to the introduction of vaccines, which also make the body produce COVID-19 antibodies.

The most current findings show that 83.3% of donors have combined COVID infection– and vaccine-induced antibodies in their blood. Those findings are based on 1.4 million blood donations.

Health experts say all of these studies are strong evidence that many COVID-19 cases continue to go undetected. In fact, the University of Washington Institute for Health Metrics and Evaluation estimates that only 7% of positive COVID-19 cases in the U.S. are being detected. That means case rates are actually 14.5 times higher than the official count of 131,000 new COVID infections each day, according to the Centers for Disease Control and Prevention, which reports the virus is still killing about 440 Americans daily.

So, why is all this important, in terms of public health?

Experts say people are more likely to be cautious if they know COVID-19 cases are high where they live, work, and play. On the other hand, if they believe case rates in their communities are lower than they actually are, they may be less likely to get vaccinated and boosted, wear masks indoors, avoid crowded indoor spaces, and take other precautions to fend off infection.
 

How do some avoid infection altogether?

In addition to tracking cases that go unreported and don’t have symptoms, infectious disease experts have also been trying to figure out why some people have managed to avoid getting the highly contagious virus.

Several leading lines of research have produced promising early results – suggesting that a person’s genetic makeup, past exposure to less-lethal coronaviruses, allergies, and even certain drugs they take for other conditions may all provide at least some protection against COVID.

“Our study showed that there are many human genes – hundreds of genes – that can impact SARS-CoV-2 infection,” says Neville Sanjana, PhD, a geneticist at New York University and the New York Genome Center who co-led the study. “With a better understanding of host genetic factors, we can find new kinds of therapies that target these host factors to block infection.”

In addition, he says several studies show some drugs that regulate genes, such as the breast cancer drug tamoxifen, also appear to knock down COVID-19 risk. He suggests such drugs, already approved by the Food and Drug Administration, might be “repurposed” to target the virus.

Studies in other countries show that patients taking tamoxifen before the pandemic were protected against severe COVID-19, Dr. Sanjana says. “That was a really cool thing, highlighting the power of harnessing host genetics. The virus critically depends on our genes to complete key parts of its life cycle.”

The NYU research findings echo other studies that have been published in recent months.

In July, a team of researchers led by the National Cancer Institute identified a genetic factor that appears to determine how severe an infection will be. In a study involving 3,000 people, they found that two gene changes, or mutations, that decrease the expression of a gene called OAS1 boosted the risk of hospitalization from COVID-19. OAS1 is part of the immune system’s response to viral infections.

As a result, developing a genetic therapy designed to increase the OAS1 gene’s expression might reduce the risk of severe disease.

“It’s very natural to get infected once you are exposed. There’s no magic bullet for that. But after you get infected, how you’re going to respond to this infection, that’s what is going to be affected by your genetic variants,” said Ludmila Prokunina-Olsson, PhD, the study’s lead researcher and chief of the National Cancer Institute’s Laboratory of Translational Genomics, Bethesda, Md., in an interview with NBC News.

Benjamin tenOever, PhD, a New York University virologist who co-authored the 2020 research, says the new genetic research is promising, but he believes it’s unlikely scientists will be able to identify a single gene responsible for actually preventing a COVID-19 infection.

“On the flip side, we have identified many genes that makes the disease worse,” he says.
 

T cells ‘remember’ past viral infections

As Dr. tenOever and Dr. Sanjana suggest, another intriguing line of research has found that prior viral infections may prime the body’s immune system to fight COVID-19.

Four other common coronaviruses – aside from SARS-CoV-2 – infect people worldwide, typically causing mild to moderate upper respiratory illnesses like the common cold, says Alessandro Sette, PhD, an infectious disease expert and vaccine researcher with the La Jolla (Calif.) Institute for Immunology.

In a recent study published in Science, he and his team found past infection with these other coronaviruses may give some protection against SARS-CoV-2.

T cells – white blood cells that act like immunological ninjas to ferret out and fight infections – appear to maintain a kind of “biological memory” of coronaviruses they have seen before and can mount an attack on similar pathogens, such SARS-CoV-2, Dr. Sette says.

The new work builds on a prior research he helped lead that found 40%-60% of people never exposed to SARS-CoV-2 had T cells that reacted to the virus – with their immune systems recognizing fragments of a virus they had never seen before.

Dr. Sette says his research shows that people whose T cells have this “preexisting memory” of past coronavirus exposures also tend to respond better to vaccination for reasons not yet well understood.

“The question is, at which point will there be enough immunity from vaccination, repeated infections from other coronaviruses, but also some of the variants of the SARS-CoV-2 … where infections become less frequent? We’re not there yet,” he says.

In addition to these exciting genetic and T-cell findings, other research has suggested low-grade inflammation from allergies – a key part of the body’s immune response to foreign substances – may also give some people an extra leg up, in terms of avoiding COVID infection.

Last May, a study of 1,400 households published in The Journal of Allergy and Clinical Immunology found that having a food allergy cut the risk of COVID-19 infection in half.

The researchers said it’s unclear why allergies may reduce the risk of infection, but they noted that people with food allergies express fewer ACE2 receptors on the surface of their airway cells, making it harder for the virus to enter cells.
 

The big picture: Prevention still your best bet

So, what’s the takeaway from all of this emerging research?

New York University’s Dr. tenOever says that while genes, T cells and allergies may offer some protection against COVID, tried-and-true precautions – vaccination, wearing masks, avoiding crowded indoor spaces, and social distancing – are likely to provide a greater defense.

He believes these precautions are likely why he and his family have never contracted COVID-19.

“I was tested weekly, as were my kids at school,” he says. “We definitely never got COVID, despite the fact that we live in New York City and I worked in a hospital every single day of the pandemic.”

Ziyad Al-Aly, MD, an infectious disease specialist and director of clinical epidemiology at Washington University in St. Louis, agrees that the new research on COVID-19 is intriguing but won’t likely result in practical changes in the approach to fighting the virus in the near term.

“Getting a deeper understanding of potential genetic factors or other characteristics – that could really help us understand why the virus just comes and goes without any ill effects in some people, and in other people it produces really serious disease,” he says. “That will really help us eventually to design better vaccines to prevent it or reduce severity or even [treat] people who get severe disease.”

In the meantime, Dr. Al-Aly says, “it’s still best to do everything you can to avoid infection in the first place – even if you’re vaccinated or previously infected, you should really try to avoid reinfection.”

That means sit outside if you can when visiting a restaurant. Wear a mask on a plane, even though it’s not required. And get vaccinated and boosted.

“In the future, there may be more tools to address this pandemic, but that’s really the best advice for now,” Dr. Al-Aly says.

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

Scientists have found three types of long COVID, which have their own symptoms and seem to appear across several coronavirus variants, according to a new preprint study published on MedRxiv that hasn’t yet been peer-reviewed.

Long COVID has been hard to define due to its large number of symptoms, but researchers at King’s College London have identified three distinct profiles – with long-term symptoms focused on neurological, respiratory, or physical conditions. So far, they also found patterns among people infected with the original coronavirus strain, the Alpha variant, and the Delta variant.

“These data show clearly that post-COVID syndrome is not just one condition but appears to have several subtypes,” Claire Steves, PhD, one of the study authors and a senior clinical lecturer in King’s College London’s School of Life Course & Population Sciences, said in a statement.

“Understanding the root causes of these subtypes may help in finding treatment strategies,” she said. “Moreover, these data emphasize the need for long-COVID services to incorporate a personalized approach sensitive to the issues of each individual.”

The research team analyzed ZOE COVID app data for 1,459 people who have had symptoms for more than 84 days, or 12 weeks, according to their definition of long COVID or post-COVID syndrome.

They found that the largest group had a cluster of symptoms in the nervous system, such as fatigue, brain fog, and headaches. It was the most common subtype among the Alpha variant, which was dominant in winter 2020-2021, and the Delta variant, which was dominant in 2021.

The second group had respiratory symptoms, such as chest pain and severe shortness of breath, which could suggest lung damage, the researchers wrote. It was the largest cluster for the original coronavirus strain in spring 2020, when people were unvaccinated.

The third group included people who reported a diverse range of physical symptoms, including heart palpitations, muscle aches and pain, and changes to their skin and hair. This group had some of the “most severe and debilitating multi-organ symptoms,” the researchers wrote.

The researchers found that the subtypes were similar in vaccinated and unvaccinated people based on the variants investigated so far. But the data showed that the risk of long COVID was reduced by vaccination.

In addition, although the three subtypes were present in all the variants, other symptom clusters had subtle differences among the variants, such as symptoms in the stomach and intestines. The differences could be due to other things that changed during the pandemic, such as the time of year, social behaviors, and treatments, the researchers said.

“Machine learning approaches, such as clustering analysis, have made it possible to start exploring and identifying different profiles of post-COVID syndrome,” Marc Modat, PhD, who led the analysis and is a senior lecturer at King’s College London’s School of Biomedical Engineering & Imaging Sciences, said in the statement.

“This opens new avenues of research to better understand COVID-19 and to motivate clinical research that might mitigate the long-term effects of the disease,” he said.

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

Scientists have found three types of long COVID, which have their own symptoms and seem to appear across several coronavirus variants, according to a new preprint study published on MedRxiv that hasn’t yet been peer-reviewed.

Long COVID has been hard to define due to its large number of symptoms, but researchers at King’s College London have identified three distinct profiles – with long-term symptoms focused on neurological, respiratory, or physical conditions. So far, they also found patterns among people infected with the original coronavirus strain, the Alpha variant, and the Delta variant.

“These data show clearly that post-COVID syndrome is not just one condition but appears to have several subtypes,” Claire Steves, PhD, one of the study authors and a senior clinical lecturer in King’s College London’s School of Life Course & Population Sciences, said in a statement.

“Understanding the root causes of these subtypes may help in finding treatment strategies,” she said. “Moreover, these data emphasize the need for long-COVID services to incorporate a personalized approach sensitive to the issues of each individual.”

The research team analyzed ZOE COVID app data for 1,459 people who have had symptoms for more than 84 days, or 12 weeks, according to their definition of long COVID or post-COVID syndrome.

They found that the largest group had a cluster of symptoms in the nervous system, such as fatigue, brain fog, and headaches. It was the most common subtype among the Alpha variant, which was dominant in winter 2020-2021, and the Delta variant, which was dominant in 2021.

The second group had respiratory symptoms, such as chest pain and severe shortness of breath, which could suggest lung damage, the researchers wrote. It was the largest cluster for the original coronavirus strain in spring 2020, when people were unvaccinated.

The third group included people who reported a diverse range of physical symptoms, including heart palpitations, muscle aches and pain, and changes to their skin and hair. This group had some of the “most severe and debilitating multi-organ symptoms,” the researchers wrote.

The researchers found that the subtypes were similar in vaccinated and unvaccinated people based on the variants investigated so far. But the data showed that the risk of long COVID was reduced by vaccination.

In addition, although the three subtypes were present in all the variants, other symptom clusters had subtle differences among the variants, such as symptoms in the stomach and intestines. The differences could be due to other things that changed during the pandemic, such as the time of year, social behaviors, and treatments, the researchers said.

“Machine learning approaches, such as clustering analysis, have made it possible to start exploring and identifying different profiles of post-COVID syndrome,” Marc Modat, PhD, who led the analysis and is a senior lecturer at King’s College London’s School of Biomedical Engineering & Imaging Sciences, said in the statement.

“This opens new avenues of research to better understand COVID-19 and to motivate clinical research that might mitigate the long-term effects of the disease,” he said.

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

Scientists have found three types of long COVID, which have their own symptoms and seem to appear across several coronavirus variants, according to a new preprint study published on MedRxiv that hasn’t yet been peer-reviewed.

Long COVID has been hard to define due to its large number of symptoms, but researchers at King’s College London have identified three distinct profiles – with long-term symptoms focused on neurological, respiratory, or physical conditions. So far, they also found patterns among people infected with the original coronavirus strain, the Alpha variant, and the Delta variant.

“These data show clearly that post-COVID syndrome is not just one condition but appears to have several subtypes,” Claire Steves, PhD, one of the study authors and a senior clinical lecturer in King’s College London’s School of Life Course & Population Sciences, said in a statement.

“Understanding the root causes of these subtypes may help in finding treatment strategies,” she said. “Moreover, these data emphasize the need for long-COVID services to incorporate a personalized approach sensitive to the issues of each individual.”

The research team analyzed ZOE COVID app data for 1,459 people who have had symptoms for more than 84 days, or 12 weeks, according to their definition of long COVID or post-COVID syndrome.

They found that the largest group had a cluster of symptoms in the nervous system, such as fatigue, brain fog, and headaches. It was the most common subtype among the Alpha variant, which was dominant in winter 2020-2021, and the Delta variant, which was dominant in 2021.

The second group had respiratory symptoms, such as chest pain and severe shortness of breath, which could suggest lung damage, the researchers wrote. It was the largest cluster for the original coronavirus strain in spring 2020, when people were unvaccinated.

The third group included people who reported a diverse range of physical symptoms, including heart palpitations, muscle aches and pain, and changes to their skin and hair. This group had some of the “most severe and debilitating multi-organ symptoms,” the researchers wrote.

The researchers found that the subtypes were similar in vaccinated and unvaccinated people based on the variants investigated so far. But the data showed that the risk of long COVID was reduced by vaccination.

In addition, although the three subtypes were present in all the variants, other symptom clusters had subtle differences among the variants, such as symptoms in the stomach and intestines. The differences could be due to other things that changed during the pandemic, such as the time of year, social behaviors, and treatments, the researchers said.

“Machine learning approaches, such as clustering analysis, have made it possible to start exploring and identifying different profiles of post-COVID syndrome,” Marc Modat, PhD, who led the analysis and is a senior lecturer at King’s College London’s School of Biomedical Engineering & Imaging Sciences, said in the statement.

“This opens new avenues of research to better understand COVID-19 and to motivate clinical research that might mitigate the long-term effects of the disease,” he said.

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

More research suggests that a diet high in ultraprocessed foods (UPFs) is harmful for the aging brain.

Results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), which included participants aged 35 and older, showed that higher intake of UPFs was significantly associated with a faster rate of decline in both executive and global cognitive function.

“Based on these findings, doctors might counsel patients to prefer cooking at home [and] choosing fresher ingredients instead of buying ready-made meals and snacks,” said coinvestigator Natalia Gonçalves, PhD, University of São Paulo, Brazil.

Presented at the Alzheimer’s Association International Conference, the findings align with those from a recent study in Neurology. That study linked a diet high in UPFs to an increased risk for dementia.
 

Increasing worldwide consumption

UPFs are highly manipulated, are packed with added ingredients, including sugar, fat, and salt, and are low in protein and fiber. Examples of UPFs include soft drinks, chips, chocolate, candy, ice cream, sweetened breakfast cereals, packaged soups, chicken nuggets, hot dogs, fries, and many more.

Over the past 30 years, there has been a steady increase in consumption of UPFs worldwide. They are thought to induce systemic inflammation and oxidative stress and have been linked to a variety of ailments, such as overweight/obesity, cardiovascular disease, and cancer.

UPFs may also be a risk factor for cognitive decline, although data are scarce as to their effects on the brain.

To investigate, Dr. Gonçalves and colleagues evaluated longitudinal data on 10,775 adults (mean age, 50.6 years; 56% women; 55% White) who participated in the ELSA-Brasil study. They were evaluated in three waves (2008-2010, 2012-2014, and 2017-2019).

Information on diet was obtained via food frequency questionnaires and included information regarding consumption of unprocessed foods, minimally processed foods, and UPFs.

Participants were grouped according to UPF consumption quartiles (lowest to highest). Cognitive performance was evaluated by use of a standardized battery of tests.
 

Significant decline

Using linear mixed effects models that were adjusted for sociodemographic, lifestyle, and clinical variables, the investigators assessed the association of dietary UPFs as a percentage of total daily calories with cognitive performance over time.

During a median follow-up of 8 years, UPF intake in quartiles 2 to 4 (vs. quartile 1) was associated with a significant decline in global cognition (P = .003) and executive function (P = .015).

“Participants who reported consumption of more than 20% of daily calories from ultraprocessed foods had a 28% faster rate of global cognitive decline and a 25% faster decrease of the executive function compared to those who reported eating less than 20% of daily calories from ultraprocessed foods,” Dr. Gonçalves reported.

“Considering a person who eats a total of 2,000 kcal per day, 20% of daily calories from ultraprocessed foods are about two 1.5-ounce bars of KitKat, or five slices of bread, or about a third of an 8.5-ounce package of chips,” she explained.

Dr. Gonçalves noted that the reasons UPFs may harm the brain remain a “very relevant but not yet well-studied topic.”

Hypotheses include secondary effects from cerebrovascular lesions or chronic inflammation processes. More studies are needed to investigate the possible mechanisms that might explain the harm of UPFs to the brain, she said.
 

‘Troubling but not surprising’

Commenting on the study, Percy Griffin, PhD, director of scientific engagement for the Alzheimer’s Association, said there is “growing evidence that what we eat can impact our brains as we age.”

He added that many previous studies have suggested it is best for the brain for one to eat a heart-healthy, balanced diet that is low in processed foods and high in whole, nutritional foods, such as vegetables and fruits.

“These new data from the Alzheimer’s Association International Conference suggest eating a large amount of ultraprocessed food can significantly accelerate cognitive decline,” said Dr. Griffin, who was not involved with the research.

He noted that an increase in the availability and consumption of fast foods, processed foods, and UPFs is due to a number of socioeconomic factors, including low access to healthy foods, less time to prepare foods from scratch, and an inability to afford whole foods.

“Ultraprocessed foods make up more than half of American diets. It’s troubling but not surprising to see new data suggesting these foods can significantly accelerate cognitive decline,” Dr. Griffin said.

“The good news is there are steps we can take to reduce risk of cognitive decline as we age. These include eating a balanced diet, exercising regularly, getting good sleep, staying cognitively engaged, protecting from head injury, not smoking, and managing heart health,” he added.

Past research has suggested that the greatest benefit is from engaging in combinations of these lifestyle changes and that they are beneficial at any age, he noted.

“Even if you begin with one or two healthful actions, you’re moving in the right direction. It’s never too early or too late to incorporate these habits into your life,” Dr. Griffin said.

The study had no specific funding. Dr. Gonçalves and Dr. Griffin have reported no relevant financial relationships.

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

More research suggests that a diet high in ultraprocessed foods (UPFs) is harmful for the aging brain.

Results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), which included participants aged 35 and older, showed that higher intake of UPFs was significantly associated with a faster rate of decline in both executive and global cognitive function.

“Based on these findings, doctors might counsel patients to prefer cooking at home [and] choosing fresher ingredients instead of buying ready-made meals and snacks,” said coinvestigator Natalia Gonçalves, PhD, University of São Paulo, Brazil.

Presented at the Alzheimer’s Association International Conference, the findings align with those from a recent study in Neurology. That study linked a diet high in UPFs to an increased risk for dementia.
 

Increasing worldwide consumption

UPFs are highly manipulated, are packed with added ingredients, including sugar, fat, and salt, and are low in protein and fiber. Examples of UPFs include soft drinks, chips, chocolate, candy, ice cream, sweetened breakfast cereals, packaged soups, chicken nuggets, hot dogs, fries, and many more.

Over the past 30 years, there has been a steady increase in consumption of UPFs worldwide. They are thought to induce systemic inflammation and oxidative stress and have been linked to a variety of ailments, such as overweight/obesity, cardiovascular disease, and cancer.

UPFs may also be a risk factor for cognitive decline, although data are scarce as to their effects on the brain.

To investigate, Dr. Gonçalves and colleagues evaluated longitudinal data on 10,775 adults (mean age, 50.6 years; 56% women; 55% White) who participated in the ELSA-Brasil study. They were evaluated in three waves (2008-2010, 2012-2014, and 2017-2019).

Information on diet was obtained via food frequency questionnaires and included information regarding consumption of unprocessed foods, minimally processed foods, and UPFs.

Participants were grouped according to UPF consumption quartiles (lowest to highest). Cognitive performance was evaluated by use of a standardized battery of tests.
 

Significant decline

Using linear mixed effects models that were adjusted for sociodemographic, lifestyle, and clinical variables, the investigators assessed the association of dietary UPFs as a percentage of total daily calories with cognitive performance over time.

During a median follow-up of 8 years, UPF intake in quartiles 2 to 4 (vs. quartile 1) was associated with a significant decline in global cognition (P = .003) and executive function (P = .015).

“Participants who reported consumption of more than 20% of daily calories from ultraprocessed foods had a 28% faster rate of global cognitive decline and a 25% faster decrease of the executive function compared to those who reported eating less than 20% of daily calories from ultraprocessed foods,” Dr. Gonçalves reported.

“Considering a person who eats a total of 2,000 kcal per day, 20% of daily calories from ultraprocessed foods are about two 1.5-ounce bars of KitKat, or five slices of bread, or about a third of an 8.5-ounce package of chips,” she explained.

Dr. Gonçalves noted that the reasons UPFs may harm the brain remain a “very relevant but not yet well-studied topic.”

Hypotheses include secondary effects from cerebrovascular lesions or chronic inflammation processes. More studies are needed to investigate the possible mechanisms that might explain the harm of UPFs to the brain, she said.
 

‘Troubling but not surprising’

Commenting on the study, Percy Griffin, PhD, director of scientific engagement for the Alzheimer’s Association, said there is “growing evidence that what we eat can impact our brains as we age.”

He added that many previous studies have suggested it is best for the brain for one to eat a heart-healthy, balanced diet that is low in processed foods and high in whole, nutritional foods, such as vegetables and fruits.

“These new data from the Alzheimer’s Association International Conference suggest eating a large amount of ultraprocessed food can significantly accelerate cognitive decline,” said Dr. Griffin, who was not involved with the research.

He noted that an increase in the availability and consumption of fast foods, processed foods, and UPFs is due to a number of socioeconomic factors, including low access to healthy foods, less time to prepare foods from scratch, and an inability to afford whole foods.

“Ultraprocessed foods make up more than half of American diets. It’s troubling but not surprising to see new data suggesting these foods can significantly accelerate cognitive decline,” Dr. Griffin said.

“The good news is there are steps we can take to reduce risk of cognitive decline as we age. These include eating a balanced diet, exercising regularly, getting good sleep, staying cognitively engaged, protecting from head injury, not smoking, and managing heart health,” he added.

Past research has suggested that the greatest benefit is from engaging in combinations of these lifestyle changes and that they are beneficial at any age, he noted.

“Even if you begin with one or two healthful actions, you’re moving in the right direction. It’s never too early or too late to incorporate these habits into your life,” Dr. Griffin said.

The study had no specific funding. Dr. Gonçalves and Dr. Griffin have reported no relevant financial relationships.

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

More research suggests that a diet high in ultraprocessed foods (UPFs) is harmful for the aging brain.

Results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), which included participants aged 35 and older, showed that higher intake of UPFs was significantly associated with a faster rate of decline in both executive and global cognitive function.

“Based on these findings, doctors might counsel patients to prefer cooking at home [and] choosing fresher ingredients instead of buying ready-made meals and snacks,” said coinvestigator Natalia Gonçalves, PhD, University of São Paulo, Brazil.

Presented at the Alzheimer’s Association International Conference, the findings align with those from a recent study in Neurology. That study linked a diet high in UPFs to an increased risk for dementia.
 

Increasing worldwide consumption

UPFs are highly manipulated, are packed with added ingredients, including sugar, fat, and salt, and are low in protein and fiber. Examples of UPFs include soft drinks, chips, chocolate, candy, ice cream, sweetened breakfast cereals, packaged soups, chicken nuggets, hot dogs, fries, and many more.

Over the past 30 years, there has been a steady increase in consumption of UPFs worldwide. They are thought to induce systemic inflammation and oxidative stress and have been linked to a variety of ailments, such as overweight/obesity, cardiovascular disease, and cancer.

UPFs may also be a risk factor for cognitive decline, although data are scarce as to their effects on the brain.

To investigate, Dr. Gonçalves and colleagues evaluated longitudinal data on 10,775 adults (mean age, 50.6 years; 56% women; 55% White) who participated in the ELSA-Brasil study. They were evaluated in three waves (2008-2010, 2012-2014, and 2017-2019).

Information on diet was obtained via food frequency questionnaires and included information regarding consumption of unprocessed foods, minimally processed foods, and UPFs.

Participants were grouped according to UPF consumption quartiles (lowest to highest). Cognitive performance was evaluated by use of a standardized battery of tests.
 

Significant decline

Using linear mixed effects models that were adjusted for sociodemographic, lifestyle, and clinical variables, the investigators assessed the association of dietary UPFs as a percentage of total daily calories with cognitive performance over time.

During a median follow-up of 8 years, UPF intake in quartiles 2 to 4 (vs. quartile 1) was associated with a significant decline in global cognition (P = .003) and executive function (P = .015).

“Participants who reported consumption of more than 20% of daily calories from ultraprocessed foods had a 28% faster rate of global cognitive decline and a 25% faster decrease of the executive function compared to those who reported eating less than 20% of daily calories from ultraprocessed foods,” Dr. Gonçalves reported.

“Considering a person who eats a total of 2,000 kcal per day, 20% of daily calories from ultraprocessed foods are about two 1.5-ounce bars of KitKat, or five slices of bread, or about a third of an 8.5-ounce package of chips,” she explained.

Dr. Gonçalves noted that the reasons UPFs may harm the brain remain a “very relevant but not yet well-studied topic.”

Hypotheses include secondary effects from cerebrovascular lesions or chronic inflammation processes. More studies are needed to investigate the possible mechanisms that might explain the harm of UPFs to the brain, she said.
 

‘Troubling but not surprising’

Commenting on the study, Percy Griffin, PhD, director of scientific engagement for the Alzheimer’s Association, said there is “growing evidence that what we eat can impact our brains as we age.”

He added that many previous studies have suggested it is best for the brain for one to eat a heart-healthy, balanced diet that is low in processed foods and high in whole, nutritional foods, such as vegetables and fruits.

“These new data from the Alzheimer’s Association International Conference suggest eating a large amount of ultraprocessed food can significantly accelerate cognitive decline,” said Dr. Griffin, who was not involved with the research.

He noted that an increase in the availability and consumption of fast foods, processed foods, and UPFs is due to a number of socioeconomic factors, including low access to healthy foods, less time to prepare foods from scratch, and an inability to afford whole foods.

“Ultraprocessed foods make up more than half of American diets. It’s troubling but not surprising to see new data suggesting these foods can significantly accelerate cognitive decline,” Dr. Griffin said.

“The good news is there are steps we can take to reduce risk of cognitive decline as we age. These include eating a balanced diet, exercising regularly, getting good sleep, staying cognitively engaged, protecting from head injury, not smoking, and managing heart health,” he added.

Past research has suggested that the greatest benefit is from engaging in combinations of these lifestyle changes and that they are beneficial at any age, he noted.

“Even if you begin with one or two healthful actions, you’re moving in the right direction. It’s never too early or too late to incorporate these habits into your life,” Dr. Griffin said.

The study had no specific funding. Dr. Gonçalves and Dr. Griffin have reported no relevant financial relationships.

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

It is generally understood that racism, whether structural or personal, harms the well-being of the individual who experiences it. It has harmful health effects, and it contributes to ethnic inequality. New evidence shows that the experience of racism is associated with worse cognitive function in later life.

That was the fundamental message behind two studies presented at a press conference at the Alzheimer’s Association International Conference.

“We know that there are communities like black African Americans and Hispanic Latinos who are at greater risk for developing Alzheimer’s or another dementia,” said Carl Hill, PhD, who served as a moderator during the press conference. He pointed out that the genetic and lifestyle factors linked to dementia tell only part of the story. “It’s important that the science also examines the unique experiences of those at greater risk for dementia in our society,” said Dr. Hill, who is Alzheimer’s Association Chief Diversity Equity and Inclusion Officer.
 

Racism, memory, and cognition in middle-aged patients

Jennifer J. Manly, PhD, professor of neuropsychology at Columbia University, New York, presented a study of experience of racism and memory scores among a highly diverse, middle-aged cohort.

“There’s little understanding of how the multiple levels of racism – including intrapersonal, institutional, and structural racism – influence cognitive aging and dementia risk,” Dr. Manly said during the press conference.

Among 1,095 participants, 19.5% were non-Latinx White (61% female, mean age 57), 26.0% were non-Latinx Black (63% female, mean age 56), 32.3% were English-speaking Latinx (66% female, mean age 50), and 21.2% were Spanish-speaking Latinx (68% female, mean age 58).

The researchers used the Everyday Discrimination (ED) scale to measure experience of individual racism, the Major Discrimination (MD) scale to measure experience of institutional racism, and residential segregation of the census block group for an individual’s parents to measure residential segregation. Outcome measures included the Digit Span to assess attention and working memory, and the Selective Reminding Test to assess episodic memory.

The study found a clear association between racism and cognition. “The association of interpersonal racism to memory corresponds to 3 years of chronological age, and was driven by non-Hispanic black participants. Next, there was a reliable relationship between institutional racism and memory scores among non-Hispanic black participants, such that each reported civil rights violation corresponded to the effect of about 4.5 years of age on memory,” said Dr. Manly.

“The bottom line is that our results suggest that exposure to racism is a substantial driver of later life memory function, even in middle age, and especially for Black people,” Dr. Manly added.

The results should alert physicians to the complexities of racism and its impact. “Health providers need to be aware that many accumulated risks are historical and structural, and not controlled by the individual. Maybe more importantly, the medical system itself may perpetuate discriminatory experiences that contribute to worse health,” said Dr. Manly.
 

Latinx concerns

Also at the press conference, Adriana Perez, PhD, emphasized the challenges that Spanish-speaking Latinxs have with health care. Just 5%-7% of nurses are Latinx. “The same could be said for physicians, for clinical psychologists ... as you look at the really critical positions to address brain health equity, we are not represented there,” said Dr. Perez, an assistant professor and senior fellow at the University of Pennsylvania School of Nursing in Philadelphia.

She also pointed out that Latinx representation in clinical trials is very low, even though surveys performed by the Alzheimer’s Association show that this population values medical science and is willing to participate. In fact, 85% said they would participate if invited. The trouble is that many clinical trial announcements state that participants must speak English. Even the many Latinos who are bilingual may be put off by that wording: “That is a message that you’re not invited. That’s how it’s perceived,” said Dr. Perez.
 

Racism and cognition in the elderly

At the press conference, Kristen George, PhD, presented results from a study of individuals over age 90. “Racial disparities in dementia have been well characterized, particularly among those people who are aged 65 and older, but we don’t know very much about the oldest old individuals who are aged 90 and older. This group is one of the fastest growing segments of the population, and it’s becoming increasingly diverse,” said Dr. George, assistant professor of epidemiology at the University of California, Davis.

The group enrolled 445 Asian, Black, Latinx, White, and multiracial individuals who were members of Kaiser Permanente Northern California, with a mean age of 92.7 years. They used the Major Experiences of Discrimination Scale to assess discrimination.

The researchers divided them into three groups based on gender, race, and responses to the 10-item scale. Class 1 included largely White men who had reported workplace discrimination, with an average of two major discrimination experiences. Class 2 was made up of White women and non-Whites who reported little or no discrimination, with an average of 0 experiences. Class 3 included all non-White participants, and they reported a mean of four discrimination experiences.

Using class 2 as a reference, executive function was better among class 1 individuals (beta = 0.28; 95% CI, 0.03-0.52) but there was no significant difference between class 3 and class 2. Class 1 had better baseline semantic memory than class 2 (beta = 0.33; 95% CI, 0.07-0.58), and those in class 3 performed significantly worse than class 2 (beta = –0.24; 95% CI, –0.48 to –0.00). There were no between-group differences in baseline verbal or episodic memory.

Dr. Perez, Dr. Manly, Dr. George, and Dr. Hill have no relevant financial disclosures.

It is generally understood that racism, whether structural or personal, harms the well-being of the individual who experiences it. It has harmful health effects, and it contributes to ethnic inequality. New evidence shows that the experience of racism is associated with worse cognitive function in later life.

That was the fundamental message behind two studies presented at a press conference at the Alzheimer’s Association International Conference.

“We know that there are communities like black African Americans and Hispanic Latinos who are at greater risk for developing Alzheimer’s or another dementia,” said Carl Hill, PhD, who served as a moderator during the press conference. He pointed out that the genetic and lifestyle factors linked to dementia tell only part of the story. “It’s important that the science also examines the unique experiences of those at greater risk for dementia in our society,” said Dr. Hill, who is Alzheimer’s Association Chief Diversity Equity and Inclusion Officer.
 

Racism, memory, and cognition in middle-aged patients

Jennifer J. Manly, PhD, professor of neuropsychology at Columbia University, New York, presented a study of experience of racism and memory scores among a highly diverse, middle-aged cohort.

“There’s little understanding of how the multiple levels of racism – including intrapersonal, institutional, and structural racism – influence cognitive aging and dementia risk,” Dr. Manly said during the press conference.

Among 1,095 participants, 19.5% were non-Latinx White (61% female, mean age 57), 26.0% were non-Latinx Black (63% female, mean age 56), 32.3% were English-speaking Latinx (66% female, mean age 50), and 21.2% were Spanish-speaking Latinx (68% female, mean age 58).

The researchers used the Everyday Discrimination (ED) scale to measure experience of individual racism, the Major Discrimination (MD) scale to measure experience of institutional racism, and residential segregation of the census block group for an individual’s parents to measure residential segregation. Outcome measures included the Digit Span to assess attention and working memory, and the Selective Reminding Test to assess episodic memory.

The study found a clear association between racism and cognition. “The association of interpersonal racism to memory corresponds to 3 years of chronological age, and was driven by non-Hispanic black participants. Next, there was a reliable relationship between institutional racism and memory scores among non-Hispanic black participants, such that each reported civil rights violation corresponded to the effect of about 4.5 years of age on memory,” said Dr. Manly.

“The bottom line is that our results suggest that exposure to racism is a substantial driver of later life memory function, even in middle age, and especially for Black people,” Dr. Manly added.

The results should alert physicians to the complexities of racism and its impact. “Health providers need to be aware that many accumulated risks are historical and structural, and not controlled by the individual. Maybe more importantly, the medical system itself may perpetuate discriminatory experiences that contribute to worse health,” said Dr. Manly.
 

Latinx concerns

Also at the press conference, Adriana Perez, PhD, emphasized the challenges that Spanish-speaking Latinxs have with health care. Just 5%-7% of nurses are Latinx. “The same could be said for physicians, for clinical psychologists ... as you look at the really critical positions to address brain health equity, we are not represented there,” said Dr. Perez, an assistant professor and senior fellow at the University of Pennsylvania School of Nursing in Philadelphia.

She also pointed out that Latinx representation in clinical trials is very low, even though surveys performed by the Alzheimer’s Association show that this population values medical science and is willing to participate. In fact, 85% said they would participate if invited. The trouble is that many clinical trial announcements state that participants must speak English. Even the many Latinos who are bilingual may be put off by that wording: “That is a message that you’re not invited. That’s how it’s perceived,” said Dr. Perez.
 

Racism and cognition in the elderly

At the press conference, Kristen George, PhD, presented results from a study of individuals over age 90. “Racial disparities in dementia have been well characterized, particularly among those people who are aged 65 and older, but we don’t know very much about the oldest old individuals who are aged 90 and older. This group is one of the fastest growing segments of the population, and it’s becoming increasingly diverse,” said Dr. George, assistant professor of epidemiology at the University of California, Davis.

The group enrolled 445 Asian, Black, Latinx, White, and multiracial individuals who were members of Kaiser Permanente Northern California, with a mean age of 92.7 years. They used the Major Experiences of Discrimination Scale to assess discrimination.

The researchers divided them into three groups based on gender, race, and responses to the 10-item scale. Class 1 included largely White men who had reported workplace discrimination, with an average of two major discrimination experiences. Class 2 was made up of White women and non-Whites who reported little or no discrimination, with an average of 0 experiences. Class 3 included all non-White participants, and they reported a mean of four discrimination experiences.

Using class 2 as a reference, executive function was better among class 1 individuals (beta = 0.28; 95% CI, 0.03-0.52) but there was no significant difference between class 3 and class 2. Class 1 had better baseline semantic memory than class 2 (beta = 0.33; 95% CI, 0.07-0.58), and those in class 3 performed significantly worse than class 2 (beta = –0.24; 95% CI, –0.48 to –0.00). There were no between-group differences in baseline verbal or episodic memory.

Dr. Perez, Dr. Manly, Dr. George, and Dr. Hill have no relevant financial disclosures.

It is generally understood that racism, whether structural or personal, harms the well-being of the individual who experiences it. It has harmful health effects, and it contributes to ethnic inequality. New evidence shows that the experience of racism is associated with worse cognitive function in later life.

That was the fundamental message behind two studies presented at a press conference at the Alzheimer’s Association International Conference.

“We know that there are communities like black African Americans and Hispanic Latinos who are at greater risk for developing Alzheimer’s or another dementia,” said Carl Hill, PhD, who served as a moderator during the press conference. He pointed out that the genetic and lifestyle factors linked to dementia tell only part of the story. “It’s important that the science also examines the unique experiences of those at greater risk for dementia in our society,” said Dr. Hill, who is Alzheimer’s Association Chief Diversity Equity and Inclusion Officer.
 

Racism, memory, and cognition in middle-aged patients

Jennifer J. Manly, PhD, professor of neuropsychology at Columbia University, New York, presented a study of experience of racism and memory scores among a highly diverse, middle-aged cohort.

“There’s little understanding of how the multiple levels of racism – including intrapersonal, institutional, and structural racism – influence cognitive aging and dementia risk,” Dr. Manly said during the press conference.

Among 1,095 participants, 19.5% were non-Latinx White (61% female, mean age 57), 26.0% were non-Latinx Black (63% female, mean age 56), 32.3% were English-speaking Latinx (66% female, mean age 50), and 21.2% were Spanish-speaking Latinx (68% female, mean age 58).

The researchers used the Everyday Discrimination (ED) scale to measure experience of individual racism, the Major Discrimination (MD) scale to measure experience of institutional racism, and residential segregation of the census block group for an individual’s parents to measure residential segregation. Outcome measures included the Digit Span to assess attention and working memory, and the Selective Reminding Test to assess episodic memory.

The study found a clear association between racism and cognition. “The association of interpersonal racism to memory corresponds to 3 years of chronological age, and was driven by non-Hispanic black participants. Next, there was a reliable relationship between institutional racism and memory scores among non-Hispanic black participants, such that each reported civil rights violation corresponded to the effect of about 4.5 years of age on memory,” said Dr. Manly.

“The bottom line is that our results suggest that exposure to racism is a substantial driver of later life memory function, even in middle age, and especially for Black people,” Dr. Manly added.

The results should alert physicians to the complexities of racism and its impact. “Health providers need to be aware that many accumulated risks are historical and structural, and not controlled by the individual. Maybe more importantly, the medical system itself may perpetuate discriminatory experiences that contribute to worse health,” said Dr. Manly.
 

Latinx concerns

Also at the press conference, Adriana Perez, PhD, emphasized the challenges that Spanish-speaking Latinxs have with health care. Just 5%-7% of nurses are Latinx. “The same could be said for physicians, for clinical psychologists ... as you look at the really critical positions to address brain health equity, we are not represented there,” said Dr. Perez, an assistant professor and senior fellow at the University of Pennsylvania School of Nursing in Philadelphia.

She also pointed out that Latinx representation in clinical trials is very low, even though surveys performed by the Alzheimer’s Association show that this population values medical science and is willing to participate. In fact, 85% said they would participate if invited. The trouble is that many clinical trial announcements state that participants must speak English. Even the many Latinos who are bilingual may be put off by that wording: “That is a message that you’re not invited. That’s how it’s perceived,” said Dr. Perez.
 

Racism and cognition in the elderly

At the press conference, Kristen George, PhD, presented results from a study of individuals over age 90. “Racial disparities in dementia have been well characterized, particularly among those people who are aged 65 and older, but we don’t know very much about the oldest old individuals who are aged 90 and older. This group is one of the fastest growing segments of the population, and it’s becoming increasingly diverse,” said Dr. George, assistant professor of epidemiology at the University of California, Davis.

The group enrolled 445 Asian, Black, Latinx, White, and multiracial individuals who were members of Kaiser Permanente Northern California, with a mean age of 92.7 years. They used the Major Experiences of Discrimination Scale to assess discrimination.

The researchers divided them into three groups based on gender, race, and responses to the 10-item scale. Class 1 included largely White men who had reported workplace discrimination, with an average of two major discrimination experiences. Class 2 was made up of White women and non-Whites who reported little or no discrimination, with an average of 0 experiences. Class 3 included all non-White participants, and they reported a mean of four discrimination experiences.

Using class 2 as a reference, executive function was better among class 1 individuals (beta = 0.28; 95% CI, 0.03-0.52) but there was no significant difference between class 3 and class 2. Class 1 had better baseline semantic memory than class 2 (beta = 0.33; 95% CI, 0.07-0.58), and those in class 3 performed significantly worse than class 2 (beta = –0.24; 95% CI, –0.48 to –0.00). There were no between-group differences in baseline verbal or episodic memory.

Dr. Perez, Dr. Manly, Dr. George, and Dr. Hill have no relevant financial disclosures.

Loss of smell, not disease severity, predicts persistent cognitive impairment 1 year after SARS-CoV-2 infection, preliminary results of new research suggest.

The findings provide important insight into the long-term cognitive impact of COVID-19, said study investigator Gabriela Gonzalez-Alemán, PhD, professor at Pontifical Catholic University of Argentina, Buenos Aires.

The more information that can be gathered on factors increasing risks for this cognitive impact, “the better we can track it and begin to develop methods to prevent it,” she said.

The findings were presented at the Alzheimer’s Association International Conference.
 

Memory, attention problems

COVID-19 has infected more than 570 million people worldwide. Related infections may result in long-term sequelae, including neuropsychiatric symptoms, said Dr. Gonzalez-Alemán.

In older adults, COVID-19 sequelae may resemble early Alzheimer’s disease, and the two conditions may share risk factors and blood biomarkers.

The new study highlighted 1-year results from a large, prospective cohort study from Argentina. Researchers used measures to evaluate long-term consequences of COVID-19 in older adults recommended by the Alzheimer’s Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 infection (CNS SC2).

Harmonizing definitions and methodologies for studying COVID-19’s impact on the brain allows consortium members to compare study results, said Dr. Gonzalez-Alemán.

The investigators used the health registry in the province of Jujuy, situated in the extreme northwestern part of Argentina. The registry includes all SARS-CoV-2 testing data for the entire region.

The investigators randomly invited adults aged 60 years and older from the registry to participate in the study. The current analysis included 766 adults aged 55-95 years (mean age 66.9 years; 57% female) with an average of 10.4 years of education. The education system in Argentina includes 12 years of school before university.

Investigators stratified subjects by polymerase chain reaction testing status. Of the total, 88.4% were infected with COVID and 11.6% were controls (subjects without COVID).

The neurocognitive assessment of participants included four cognitive domains: memory, attention, language, and executive function, and an olfactory test that determined degree of olfactory dysfunction. Cognitive impairment was defined as z scores below –2.

Researchers divided participants into groups according to cognitive performance. These included normal cognition, memory-only impairment (single domain; 11.7%), impairment in attention and executive function without memory impairment (two domains; 8.3%), and multiple domain impairment (11.6%).

“Our participants showed a predominance of memory impairment as would be seen in Alzheimer’s disease,” noted Dr. Gonzalez-Alemán. “And a large group showed a combination of memory and attention problems.”

About 40% of the study sample – but no controls – had olfactory dysfunction.

“All the subjects that had a severe cognitive impairment also had anosmia [loss of smell],” said Dr. Gonzalez-Alemán. “We established an association between olfactory dysfunction and cognitive performance and impairment.”

The analysis showed that severity of anosmia, but not clinical status, significantly predicted cognitive impairment. “So, anosmia could be a good predictor of cognitive impairment after COVID-19 infection,” said Dr. Gonzalez-Alemán.

For individuals older than 60 years, cognitive impairment can be persistent, as can be olfactory dysfunction, she added.

Results of a 1-year phone survey showed about 71.8% of subjects had received three vaccine doses and 24.9% two doses. About 12.5% of those with three doses were reinfected and 23.3% of those with two doses were reinfected.
 

Longest follow-up to date

Commenting on the research, Heather Snyder, PhD, vice president, medical and scientific relations at the Alzheimer’s Association, noted the study is “the longest follow-up we’ve seen” looking at the connection between persistent loss of smell and cognitive changes after a COVID-19 infection.

The study included a “fairly large” sample size and was “unique” in that it was set up in a part of the country with centralized testing, said Dr. Snyder.

The Argentinian group is among the most advanced of those connected to the CNS SC2, said Dr. Snyder.

Members of this Alzheimer’s Association consortium, said Dr. Snyder, regularly share updates of ongoing studies, which are at different stages and looking at various neuropsychiatric impacts of COVID-19. It is important to bring these groups together to determine what those impacts are “because no one group will be able to do this on their own,” she said. “We saw pretty early on that some individuals had changes in the brain, or changes in cognition, and loss of sense of smell or taste, which indicates there’s a connection to the brain.”

However, she added, “there’s still a lot we don’t know” about this connection.

The study was funded by Alzheimer’s Association and FULTRA.

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

Loss of smell, not disease severity, predicts persistent cognitive impairment 1 year after SARS-CoV-2 infection, preliminary results of new research suggest.

The findings provide important insight into the long-term cognitive impact of COVID-19, said study investigator Gabriela Gonzalez-Alemán, PhD, professor at Pontifical Catholic University of Argentina, Buenos Aires.

The more information that can be gathered on factors increasing risks for this cognitive impact, “the better we can track it and begin to develop methods to prevent it,” she said.

The findings were presented at the Alzheimer’s Association International Conference.
 

Memory, attention problems

COVID-19 has infected more than 570 million people worldwide. Related infections may result in long-term sequelae, including neuropsychiatric symptoms, said Dr. Gonzalez-Alemán.

In older adults, COVID-19 sequelae may resemble early Alzheimer’s disease, and the two conditions may share risk factors and blood biomarkers.

The new study highlighted 1-year results from a large, prospective cohort study from Argentina. Researchers used measures to evaluate long-term consequences of COVID-19 in older adults recommended by the Alzheimer’s Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 infection (CNS SC2).

Harmonizing definitions and methodologies for studying COVID-19’s impact on the brain allows consortium members to compare study results, said Dr. Gonzalez-Alemán.

The investigators used the health registry in the province of Jujuy, situated in the extreme northwestern part of Argentina. The registry includes all SARS-CoV-2 testing data for the entire region.

The investigators randomly invited adults aged 60 years and older from the registry to participate in the study. The current analysis included 766 adults aged 55-95 years (mean age 66.9 years; 57% female) with an average of 10.4 years of education. The education system in Argentina includes 12 years of school before university.

Investigators stratified subjects by polymerase chain reaction testing status. Of the total, 88.4% were infected with COVID and 11.6% were controls (subjects without COVID).

The neurocognitive assessment of participants included four cognitive domains: memory, attention, language, and executive function, and an olfactory test that determined degree of olfactory dysfunction. Cognitive impairment was defined as z scores below –2.

Researchers divided participants into groups according to cognitive performance. These included normal cognition, memory-only impairment (single domain; 11.7%), impairment in attention and executive function without memory impairment (two domains; 8.3%), and multiple domain impairment (11.6%).

“Our participants showed a predominance of memory impairment as would be seen in Alzheimer’s disease,” noted Dr. Gonzalez-Alemán. “And a large group showed a combination of memory and attention problems.”

About 40% of the study sample – but no controls – had olfactory dysfunction.

“All the subjects that had a severe cognitive impairment also had anosmia [loss of smell],” said Dr. Gonzalez-Alemán. “We established an association between olfactory dysfunction and cognitive performance and impairment.”

The analysis showed that severity of anosmia, but not clinical status, significantly predicted cognitive impairment. “So, anosmia could be a good predictor of cognitive impairment after COVID-19 infection,” said Dr. Gonzalez-Alemán.

For individuals older than 60 years, cognitive impairment can be persistent, as can be olfactory dysfunction, she added.

Results of a 1-year phone survey showed about 71.8% of subjects had received three vaccine doses and 24.9% two doses. About 12.5% of those with three doses were reinfected and 23.3% of those with two doses were reinfected.
 

Longest follow-up to date

Commenting on the research, Heather Snyder, PhD, vice president, medical and scientific relations at the Alzheimer’s Association, noted the study is “the longest follow-up we’ve seen” looking at the connection between persistent loss of smell and cognitive changes after a COVID-19 infection.

The study included a “fairly large” sample size and was “unique” in that it was set up in a part of the country with centralized testing, said Dr. Snyder.

The Argentinian group is among the most advanced of those connected to the CNS SC2, said Dr. Snyder.

Members of this Alzheimer’s Association consortium, said Dr. Snyder, regularly share updates of ongoing studies, which are at different stages and looking at various neuropsychiatric impacts of COVID-19. It is important to bring these groups together to determine what those impacts are “because no one group will be able to do this on their own,” she said. “We saw pretty early on that some individuals had changes in the brain, or changes in cognition, and loss of sense of smell or taste, which indicates there’s a connection to the brain.”

However, she added, “there’s still a lot we don’t know” about this connection.

The study was funded by Alzheimer’s Association and FULTRA.

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

Loss of smell, not disease severity, predicts persistent cognitive impairment 1 year after SARS-CoV-2 infection, preliminary results of new research suggest.

The findings provide important insight into the long-term cognitive impact of COVID-19, said study investigator Gabriela Gonzalez-Alemán, PhD, professor at Pontifical Catholic University of Argentina, Buenos Aires.

The more information that can be gathered on factors increasing risks for this cognitive impact, “the better we can track it and begin to develop methods to prevent it,” she said.

The findings were presented at the Alzheimer’s Association International Conference.
 

Memory, attention problems

COVID-19 has infected more than 570 million people worldwide. Related infections may result in long-term sequelae, including neuropsychiatric symptoms, said Dr. Gonzalez-Alemán.

In older adults, COVID-19 sequelae may resemble early Alzheimer’s disease, and the two conditions may share risk factors and blood biomarkers.

The new study highlighted 1-year results from a large, prospective cohort study from Argentina. Researchers used measures to evaluate long-term consequences of COVID-19 in older adults recommended by the Alzheimer’s Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 infection (CNS SC2).

Harmonizing definitions and methodologies for studying COVID-19’s impact on the brain allows consortium members to compare study results, said Dr. Gonzalez-Alemán.

The investigators used the health registry in the province of Jujuy, situated in the extreme northwestern part of Argentina. The registry includes all SARS-CoV-2 testing data for the entire region.

The investigators randomly invited adults aged 60 years and older from the registry to participate in the study. The current analysis included 766 adults aged 55-95 years (mean age 66.9 years; 57% female) with an average of 10.4 years of education. The education system in Argentina includes 12 years of school before university.

Investigators stratified subjects by polymerase chain reaction testing status. Of the total, 88.4% were infected with COVID and 11.6% were controls (subjects without COVID).

The neurocognitive assessment of participants included four cognitive domains: memory, attention, language, and executive function, and an olfactory test that determined degree of olfactory dysfunction. Cognitive impairment was defined as z scores below –2.

Researchers divided participants into groups according to cognitive performance. These included normal cognition, memory-only impairment (single domain; 11.7%), impairment in attention and executive function without memory impairment (two domains; 8.3%), and multiple domain impairment (11.6%).

“Our participants showed a predominance of memory impairment as would be seen in Alzheimer’s disease,” noted Dr. Gonzalez-Alemán. “And a large group showed a combination of memory and attention problems.”

About 40% of the study sample – but no controls – had olfactory dysfunction.

“All the subjects that had a severe cognitive impairment also had anosmia [loss of smell],” said Dr. Gonzalez-Alemán. “We established an association between olfactory dysfunction and cognitive performance and impairment.”

The analysis showed that severity of anosmia, but not clinical status, significantly predicted cognitive impairment. “So, anosmia could be a good predictor of cognitive impairment after COVID-19 infection,” said Dr. Gonzalez-Alemán.

For individuals older than 60 years, cognitive impairment can be persistent, as can be olfactory dysfunction, she added.

Results of a 1-year phone survey showed about 71.8% of subjects had received three vaccine doses and 24.9% two doses. About 12.5% of those with three doses were reinfected and 23.3% of those with two doses were reinfected.
 

Longest follow-up to date

Commenting on the research, Heather Snyder, PhD, vice president, medical and scientific relations at the Alzheimer’s Association, noted the study is “the longest follow-up we’ve seen” looking at the connection between persistent loss of smell and cognitive changes after a COVID-19 infection.

The study included a “fairly large” sample size and was “unique” in that it was set up in a part of the country with centralized testing, said Dr. Snyder.

The Argentinian group is among the most advanced of those connected to the CNS SC2, said Dr. Snyder.

Members of this Alzheimer’s Association consortium, said Dr. Snyder, regularly share updates of ongoing studies, which are at different stages and looking at various neuropsychiatric impacts of COVID-19. It is important to bring these groups together to determine what those impacts are “because no one group will be able to do this on their own,” she said. “We saw pretty early on that some individuals had changes in the brain, or changes in cognition, and loss of sense of smell or taste, which indicates there’s a connection to the brain.”

However, she added, “there’s still a lot we don’t know” about this connection.

The study was funded by Alzheimer’s Association and FULTRA.

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

New pediatric COVID-19 cases increased for the third straight week as a substantial number of children under age 5 years started to receive their second doses of the vaccine.

Despite the 3-week trend, however, there are some positive signs. The new-case count for the latest reporting week (July 22-28) was over 95,000, but the 3.9% increase over the previous week’s 92,000 cases is much smaller than that week’s (July 15-21) corresponding jump of almost 22% over the July 8-14 total (75,000), according to the American Academy of Pediatrics and the Children’s Hospital Association.

On the not-so-positive side is the trend in admissions among children aged 0-17 years, which continue to climb steadily and have nearly equaled the highest rate seen during the Delta surge in 2021. The rate on July 29 was 0.46 admissions per 100,000 population, and the highest rate over the course of the Delta surge was 0.47 per 100,000, but the all-time high from the Omicron surge – 1.25 per 100,000 in mid-January – is still a long way off, based on data from the Centers for Disease Control and Prevention.

A similar situation is occurring with emergency department visits, but there is differentiation by age group. Among those aged 0-11 years, visits with diagnosed COVID made up 6.5% of all their ED visits on July 25, which was well above the high (4.0%) during the Delta surge, the CDC said.

That is not the case, however, for the older children, for whom rates are rising more slowly. Those aged 12-15 have reached 3.4% so far this summer, as have the 16- to 17-years-olds, versus Delta highs last year of around 7%, the CDC said on its COVID Data Tracker. As with admissions, though, current rates are well below the all-time Omicron high points, the CDC data show.
 

Joining the ranks of the fully vaccinated

Over the last 2 weeks, the first children to receive the COVID vaccine after its approval for those under age 5 years have been coming back for their second doses. Almost 50,000, about 0.3% of all those in that age group, had done so by July 27. Just over 662,000, about 3.4% of the total under-5 population, have received at least one dose, the CDC said.

Meanwhile, analysis of “data from the first several weeks following availability of the vaccine in this age group indicate high variability across states,” the AAP said in its weekly vaccination report. In the District of Columbia, 20.7% of all children under age 5 have received an initial dose as of July 27, as have 15.5% of those in Vermont and 12.5% in Massachusetts. No other state was above 10%, but Mississippi, at 0.7%, was the only one below 1%.

The older children, obviously, have a head start, so their numbers are much higher. At the state level, Vermont has the highest initial dose rate, 69%, for those aged 5-11 years, while Alabama, Mississippi, and Wyoming, at 17%, are looking up at everyone else in the country. Among children aged 12-17 years, D.C. is the highest with 100% vaccination – Massachusetts and Rhode Island are at 98% – and Wyoming is the lowest with 40%, the AAP said.

[email protected]

New pediatric COVID-19 cases increased for the third straight week as a substantial number of children under age 5 years started to receive their second doses of the vaccine.

Despite the 3-week trend, however, there are some positive signs. The new-case count for the latest reporting week (July 22-28) was over 95,000, but the 3.9% increase over the previous week’s 92,000 cases is much smaller than that week’s (July 15-21) corresponding jump of almost 22% over the July 8-14 total (75,000), according to the American Academy of Pediatrics and the Children’s Hospital Association.

On the not-so-positive side is the trend in admissions among children aged 0-17 years, which continue to climb steadily and have nearly equaled the highest rate seen during the Delta surge in 2021. The rate on July 29 was 0.46 admissions per 100,000 population, and the highest rate over the course of the Delta surge was 0.47 per 100,000, but the all-time high from the Omicron surge – 1.25 per 100,000 in mid-January – is still a long way off, based on data from the Centers for Disease Control and Prevention.

A similar situation is occurring with emergency department visits, but there is differentiation by age group. Among those aged 0-11 years, visits with diagnosed COVID made up 6.5% of all their ED visits on July 25, which was well above the high (4.0%) during the Delta surge, the CDC said.

That is not the case, however, for the older children, for whom rates are rising more slowly. Those aged 12-15 have reached 3.4% so far this summer, as have the 16- to 17-years-olds, versus Delta highs last year of around 7%, the CDC said on its COVID Data Tracker. As with admissions, though, current rates are well below the all-time Omicron high points, the CDC data show.
 

Joining the ranks of the fully vaccinated

Over the last 2 weeks, the first children to receive the COVID vaccine after its approval for those under age 5 years have been coming back for their second doses. Almost 50,000, about 0.3% of all those in that age group, had done so by July 27. Just over 662,000, about 3.4% of the total under-5 population, have received at least one dose, the CDC said.

Meanwhile, analysis of “data from the first several weeks following availability of the vaccine in this age group indicate high variability across states,” the AAP said in its weekly vaccination report. In the District of Columbia, 20.7% of all children under age 5 have received an initial dose as of July 27, as have 15.5% of those in Vermont and 12.5% in Massachusetts. No other state was above 10%, but Mississippi, at 0.7%, was the only one below 1%.

The older children, obviously, have a head start, so their numbers are much higher. At the state level, Vermont has the highest initial dose rate, 69%, for those aged 5-11 years, while Alabama, Mississippi, and Wyoming, at 17%, are looking up at everyone else in the country. Among children aged 12-17 years, D.C. is the highest with 100% vaccination – Massachusetts and Rhode Island are at 98% – and Wyoming is the lowest with 40%, the AAP said.

[email protected]

New pediatric COVID-19 cases increased for the third straight week as a substantial number of children under age 5 years started to receive their second doses of the vaccine.

Despite the 3-week trend, however, there are some positive signs. The new-case count for the latest reporting week (July 22-28) was over 95,000, but the 3.9% increase over the previous week’s 92,000 cases is much smaller than that week’s (July 15-21) corresponding jump of almost 22% over the July 8-14 total (75,000), according to the American Academy of Pediatrics and the Children’s Hospital Association.

On the not-so-positive side is the trend in admissions among children aged 0-17 years, which continue to climb steadily and have nearly equaled the highest rate seen during the Delta surge in 2021. The rate on July 29 was 0.46 admissions per 100,000 population, and the highest rate over the course of the Delta surge was 0.47 per 100,000, but the all-time high from the Omicron surge – 1.25 per 100,000 in mid-January – is still a long way off, based on data from the Centers for Disease Control and Prevention.

A similar situation is occurring with emergency department visits, but there is differentiation by age group. Among those aged 0-11 years, visits with diagnosed COVID made up 6.5% of all their ED visits on July 25, which was well above the high (4.0%) during the Delta surge, the CDC said.

That is not the case, however, for the older children, for whom rates are rising more slowly. Those aged 12-15 have reached 3.4% so far this summer, as have the 16- to 17-years-olds, versus Delta highs last year of around 7%, the CDC said on its COVID Data Tracker. As with admissions, though, current rates are well below the all-time Omicron high points, the CDC data show.
 

Joining the ranks of the fully vaccinated

Over the last 2 weeks, the first children to receive the COVID vaccine after its approval for those under age 5 years have been coming back for their second doses. Almost 50,000, about 0.3% of all those in that age group, had done so by July 27. Just over 662,000, about 3.4% of the total under-5 population, have received at least one dose, the CDC said.

Meanwhile, analysis of “data from the first several weeks following availability of the vaccine in this age group indicate high variability across states,” the AAP said in its weekly vaccination report. In the District of Columbia, 20.7% of all children under age 5 have received an initial dose as of July 27, as have 15.5% of those in Vermont and 12.5% in Massachusetts. No other state was above 10%, but Mississippi, at 0.7%, was the only one below 1%.

The older children, obviously, have a head start, so their numbers are much higher. At the state level, Vermont has the highest initial dose rate, 69%, for those aged 5-11 years, while Alabama, Mississippi, and Wyoming, at 17%, are looking up at everyone else in the country. Among children aged 12-17 years, D.C. is the highest with 100% vaccination – Massachusetts and Rhode Island are at 98% – and Wyoming is the lowest with 40%, the AAP said.

[email protected]

There was no significant increase in the post-COVID pandemic monthly rate of incident diabetes in children and youth in Ontario, compared with the pre-pandemic rate, in new research.

This contrasts with findings from a U.S. study and a German study, but this is “not the final word” about this possible association, lead author Rayzel Shulman, MD, admits, since the study may have been underpowered.

The population-based, cross-sectional study was published recently as a research letter in JAMA Open.

The researchers found a nonsignificant increase in the monthly rate of new diabetes during the first 18 months of the COVID-19 pandemic, compared with the 3 prior years (relative risk 1.09, 95% confidence interval).
 

New study contrasts with previous reports

This differs from a Morbidity and Mortality Weekly Report from the U.S. Centers for Disease Control and Prevention, in which COVID-19 infection was associated with a significant increase in new onset of diabetes in children during March 2020 through June 2021, “although some experts have criticized the study methods and conclusion validity,” Dr. Shulman and colleagues write.

Another study, from Germany, reported a significant 1.15-fold increase in type 1 diabetes in children during the pandemic, they note.

The current study may have been underpowered and too small to show a significant association between COVID-19 and new diabetes, the researchers acknowledge. 

And the 1.30 upper limit of the confidence interval shows that it “cannot rule out a possible 1.3-fold increase” in relative risk of a diagnosis of diabetes related to COVID, Dr. Shulman explained to this news organization. 

It will be important to see how the rates have changed since September 2021 (the end of the current study), added Dr. Shulman, an adjunct scientist at the Institute for Clinical Evaluative Sciences (ICES) and a physician and scientist at the Hospital for Sick Children, Toronto.

The current study did find a decreased (delayed) rate of diagnosis of new diabetes during the first months of the pandemic when there were lockdowns, followed by a “catch-up” increase in rates later on, as has been reported earlier.

“Our study is definitely not the final word on this,” Dr. Shulman summarized in a statement from ICES. “However, our findings call into question whether a direct association between COVID-19 and new-onset diabetes in children exists.”
 

COVID-diabetes link?

The researchers analyzed health administrative data from January 2017 to September 2021.

They identified 2,700,178 children and youth in Ontario who were under age 18 in 2021, who had a mean age of 9.2, and about half were girls.

Between November 2020 and April 2021, an estimated 3.3% of children in Ontario had a SARS-COV-2 infection.

New diagnoses of diabetes in this age group are mostly type 1 diabetes, based on previous studies.

The rate of incident diabetes was 15%-32% lower during the first 3 months of the pandemic, March-May 2020 (1.67-2.34 cases per 100,000), compared with the pre-pandemic monthly rate during 2017, 2018, and 2019 (2.54-2.59 cases per 100,000).

The rate of incident diabetes was 33%-50% higher during February to July 2021 (3.48-4.18 cases per 100,000), compared with the pre-pandemic rate.

The pre-pandemic and pandemic monthly rates of incident diabetes were similar during the other months.

The group concludes: “The lack of both an observable increase in overall diabetes incidence among children during the 18-month pandemic restrictions [in this Ontario study] and a plausible biological mechanism call into question an association between COVID-19 and new-onset diabetes.”

More research is needed. “Given the variability in monthly [relative risks], additional population-based, longer-term data are needed to examine the direct and indirect effects of COVID-19 and diabetes risk among children,” the authors write.

This study was supported by ICES (which is funded by the Ontario Ministry of Health) and by a grant from the Canadian Institutes of Health Research. Dr. Shulman reported receiving fees from Dexcom outside the submitted work, and she and three other authors reported receiving grants from the Canadian Institutes of Health Research outside the submitted work.

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

There was no significant increase in the post-COVID pandemic monthly rate of incident diabetes in children and youth in Ontario, compared with the pre-pandemic rate, in new research.

This contrasts with findings from a U.S. study and a German study, but this is “not the final word” about this possible association, lead author Rayzel Shulman, MD, admits, since the study may have been underpowered.

The population-based, cross-sectional study was published recently as a research letter in JAMA Open.

The researchers found a nonsignificant increase in the monthly rate of new diabetes during the first 18 months of the COVID-19 pandemic, compared with the 3 prior years (relative risk 1.09, 95% confidence interval).
 

New study contrasts with previous reports

This differs from a Morbidity and Mortality Weekly Report from the U.S. Centers for Disease Control and Prevention, in which COVID-19 infection was associated with a significant increase in new onset of diabetes in children during March 2020 through June 2021, “although some experts have criticized the study methods and conclusion validity,” Dr. Shulman and colleagues write.

Another study, from Germany, reported a significant 1.15-fold increase in type 1 diabetes in children during the pandemic, they note.

The current study may have been underpowered and too small to show a significant association between COVID-19 and new diabetes, the researchers acknowledge. 

And the 1.30 upper limit of the confidence interval shows that it “cannot rule out a possible 1.3-fold increase” in relative risk of a diagnosis of diabetes related to COVID, Dr. Shulman explained to this news organization. 

It will be important to see how the rates have changed since September 2021 (the end of the current study), added Dr. Shulman, an adjunct scientist at the Institute for Clinical Evaluative Sciences (ICES) and a physician and scientist at the Hospital for Sick Children, Toronto.

The current study did find a decreased (delayed) rate of diagnosis of new diabetes during the first months of the pandemic when there were lockdowns, followed by a “catch-up” increase in rates later on, as has been reported earlier.

“Our study is definitely not the final word on this,” Dr. Shulman summarized in a statement from ICES. “However, our findings call into question whether a direct association between COVID-19 and new-onset diabetes in children exists.”
 

COVID-diabetes link?

The researchers analyzed health administrative data from January 2017 to September 2021.

They identified 2,700,178 children and youth in Ontario who were under age 18 in 2021, who had a mean age of 9.2, and about half were girls.

Between November 2020 and April 2021, an estimated 3.3% of children in Ontario had a SARS-COV-2 infection.

New diagnoses of diabetes in this age group are mostly type 1 diabetes, based on previous studies.

The rate of incident diabetes was 15%-32% lower during the first 3 months of the pandemic, March-May 2020 (1.67-2.34 cases per 100,000), compared with the pre-pandemic monthly rate during 2017, 2018, and 2019 (2.54-2.59 cases per 100,000).

The rate of incident diabetes was 33%-50% higher during February to July 2021 (3.48-4.18 cases per 100,000), compared with the pre-pandemic rate.

The pre-pandemic and pandemic monthly rates of incident diabetes were similar during the other months.

The group concludes: “The lack of both an observable increase in overall diabetes incidence among children during the 18-month pandemic restrictions [in this Ontario study] and a plausible biological mechanism call into question an association between COVID-19 and new-onset diabetes.”

More research is needed. “Given the variability in monthly [relative risks], additional population-based, longer-term data are needed to examine the direct and indirect effects of COVID-19 and diabetes risk among children,” the authors write.

This study was supported by ICES (which is funded by the Ontario Ministry of Health) and by a grant from the Canadian Institutes of Health Research. Dr. Shulman reported receiving fees from Dexcom outside the submitted work, and she and three other authors reported receiving grants from the Canadian Institutes of Health Research outside the submitted work.

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

There was no significant increase in the post-COVID pandemic monthly rate of incident diabetes in children and youth in Ontario, compared with the pre-pandemic rate, in new research.

This contrasts with findings from a U.S. study and a German study, but this is “not the final word” about this possible association, lead author Rayzel Shulman, MD, admits, since the study may have been underpowered.

The population-based, cross-sectional study was published recently as a research letter in JAMA Open.

The researchers found a nonsignificant increase in the monthly rate of new diabetes during the first 18 months of the COVID-19 pandemic, compared with the 3 prior years (relative risk 1.09, 95% confidence interval).
 

New study contrasts with previous reports

This differs from a Morbidity and Mortality Weekly Report from the U.S. Centers for Disease Control and Prevention, in which COVID-19 infection was associated with a significant increase in new onset of diabetes in children during March 2020 through June 2021, “although some experts have criticized the study methods and conclusion validity,” Dr. Shulman and colleagues write.

Another study, from Germany, reported a significant 1.15-fold increase in type 1 diabetes in children during the pandemic, they note.

The current study may have been underpowered and too small to show a significant association between COVID-19 and new diabetes, the researchers acknowledge. 

And the 1.30 upper limit of the confidence interval shows that it “cannot rule out a possible 1.3-fold increase” in relative risk of a diagnosis of diabetes related to COVID, Dr. Shulman explained to this news organization. 

It will be important to see how the rates have changed since September 2021 (the end of the current study), added Dr. Shulman, an adjunct scientist at the Institute for Clinical Evaluative Sciences (ICES) and a physician and scientist at the Hospital for Sick Children, Toronto.

The current study did find a decreased (delayed) rate of diagnosis of new diabetes during the first months of the pandemic when there were lockdowns, followed by a “catch-up” increase in rates later on, as has been reported earlier.

“Our study is definitely not the final word on this,” Dr. Shulman summarized in a statement from ICES. “However, our findings call into question whether a direct association between COVID-19 and new-onset diabetes in children exists.”
 

COVID-diabetes link?

The researchers analyzed health administrative data from January 2017 to September 2021.

They identified 2,700,178 children and youth in Ontario who were under age 18 in 2021, who had a mean age of 9.2, and about half were girls.

Between November 2020 and April 2021, an estimated 3.3% of children in Ontario had a SARS-COV-2 infection.

New diagnoses of diabetes in this age group are mostly type 1 diabetes, based on previous studies.

The rate of incident diabetes was 15%-32% lower during the first 3 months of the pandemic, March-May 2020 (1.67-2.34 cases per 100,000), compared with the pre-pandemic monthly rate during 2017, 2018, and 2019 (2.54-2.59 cases per 100,000).

The rate of incident diabetes was 33%-50% higher during February to July 2021 (3.48-4.18 cases per 100,000), compared with the pre-pandemic rate.

The pre-pandemic and pandemic monthly rates of incident diabetes were similar during the other months.

The group concludes: “The lack of both an observable increase in overall diabetes incidence among children during the 18-month pandemic restrictions [in this Ontario study] and a plausible biological mechanism call into question an association between COVID-19 and new-onset diabetes.”

More research is needed. “Given the variability in monthly [relative risks], additional population-based, longer-term data are needed to examine the direct and indirect effects of COVID-19 and diabetes risk among children,” the authors write.

This study was supported by ICES (which is funded by the Ontario Ministry of Health) and by a grant from the Canadian Institutes of Health Research. Dr. Shulman reported receiving fees from Dexcom outside the submitted work, and she and three other authors reported receiving grants from the Canadian Institutes of Health Research outside the submitted work.

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

Dr. George Sakoulas is an infectious diseases clinician at Sharp Memorial Hospital in San Diego and professor of pediatrics at the University of California, San Diego School of Medicine. He was the lead investigator in a study published in the May/June 2022 issue of JCOM that found that, when allocated to the appropriate patient type, intravenous immunoglobulin can reduce hospital costs for COVID-19 care. ¹ He joined JCOM’s Editor-in-Chief, Dr. Ebrahim Barkoudah, to discuss the study’s background and highlight its main findings.

The following has been edited for length and clarity.

Dr. Barkoudah Dr. Sakoulas is an investigator and a clinician, bridging both worlds to bring the best evidence to our patients. We’re discussing his new article regarding intravenous immunoglobulin in treating nonventilated COVID-19 patients with moderate-to-severe hypoxia. Dr. Sakoulas, could you please share with our readers the clinical question your study addressed and what your work around COVID-19 management means for clinical practice?

Dr. Sakoulas Thank you. I’m an infectious disease physician. I’ve been treating patients with viral acute respiratory distress syndrome for almost 20 years as an ID doctor. Most of these cases are due to influenza or other viruses. And from time to time, anecdotally and supported by some literature, we’ve been using IVIG, or intravenous immunoglobulin, in some of these cases. And again, I can report anecdotal success with that over the years.

So when COVID emerged in March of 2020, we deployed IVIG in a couple of patients early who were heading downhill. Remember, in March of 2020, we didn’t have the knowledge of steroids helping, patients being ventilated very promptly, and we saw some patients who made a turnaround after treatment with IVIG. We were able to get some support from an industry sponsor and perform and publish a pilot study, enrolling patients early in the pandemic. That study actually showed benefits, which then led the sponsor to fund a phase 3 multicenter clinical trial. Unfortunately, a couple of things happened. First, the trial was designed with the knowledge we had in April of 2020, and again, this is before steroids, before we incorporated proning patients in the ICU, or started ventilating people early. So there were some management changes and evolutions and improvements that happened. And second, the trial was enrolling a very broad repertoire of patients. There were no age limitations, and the trial, ultimately a phase 3 multicenter trial, failed to meet its endpoint.

There were some trends for benefit in younger patients, and as the trial was ongoing, we continued to evolve our knowledge, and we really honed it down to seeing a benefit of using IVIG in patients with COVID with specific criteria in mind. They had to be relatively younger patients, under 65, and not have any major comorbidities. In other words, they weren’t dialysis patients or end-stage disease patients, heart failure patients, cancer or malignancy patients. So, you know, we’re looking at the patients under 65 with obesity, diabetes, and hypertension, who are rapidly declining, going from room air to BiPAP or high-flow oxygen in a short amount of time. And we learned that when using IVIG early, we actually saw patients improve and turn around.

What this article in JCOM highlighted was, number one, incorporating that outcome or that patient type and then looking at the cost of hospitalization of patients who received IVIG versus those that did not. There were 2 groups that were studied. One was the group of patients in that original pilot trial that I discussed who were randomized to receive 1 or the other prospectively; it was an unblinded randomized study. And the second group was a matched case-control study where we had patients treated with IVIG matched by age and comorbidity status and level of hypoxia to patients that did not receive IVIG. We saw a financial benefit in shortening or reducing hospitalizations, really coming down to getting rid of that 20% tail of patients that wound up going to the ICU, getting intubated, and using a high amount of hospital resources that would ramp up the cost of hospitalization. We saw great mitigation of that with IVIG, and even with a small subset of patients, we were able to show a benefit.

Dr. Barkoudah Any thoughts on where we can implement the new findings from your article in our practice at the moment, knowing we now have practice guidelines and protocols to treat COVID-19? There was a tangible benefit in treating the patients the way you approached it in your important work. Could you share with us what would be implementable at the moment?

Dr. Sakoulas I think, fortunately, with the increasing host immunity in the population and decreased virulence of the virus, perhaps we won’t see as many patients of the type that were in these trials going forward, but I suspect we will perhaps in the unvaccinated patients that remain. I believe one-third of the United States is not vaccinated. So there is certainly a vulnerable group of people out there. Potentially, an unvaccinated patient who winds up getting very sick, the patient who is relatively young—what I’m looking at is the 30- to 65-year-old obese, hypertensive, or diabetic patient who comes in and, despite the steroids and the antivirals, rapidly deteriorates into requiring high-flow oxygen. I think implementing IVIG in that patient type would be helpful. I don’t think it’s going to be as helpful in patients who are very elderly, because I think the mechanism of the disease is different in an 80-year-old versus a 50-year-old patient. So again, hopefully, it will not amount to a lot of patients, but I still suspect hospitals are going to see, perhaps in the fall, when they’re expecting a greater number of cases, a trickling of patients that do meet the criteria that I described.

Dr. Barkoudah JCOM’s audience are the QI implementers and hospital leadership. And what caught my eye in your article is your perspective on the pharmacoeconomics of treating COVID-19, and I really appreciate your looking at the cost aspect. Would you talk about the economics of inpatient care, the total care that we provide now that we’re in the age of tocilizumab, and the current state of multiple layers of therapy?

Dr. Sakoulas The reason to look at the economics of it is because IVIG—which is actually not a drug, it’s a blood product—is very expensive. So, we received a considerable amount of administrative pushback implementing this treatment at the beginning outside of the clinical trial setting because it hadn’t been studied on a large scale and because the cost was so high, even though, as a clinician at the bedside, I was seeing a benefit in patients. This study came out of my trying to demonstrate to the folks that are keeping the economics of medicine in mind that, in fact, investing several thousand dollars of treatment in IVIG will save you cost of care, the cost of an ICU bed, the cost of a ventilator, and the cost even of ECMO, which is hugely expensive.

If you look at the numbers in the study, for two-thirds or three-quarters of the patients, your cost of care is actually greater than the controls because you’re giving them IVIG, and it’s increasing the cost of their care, even though three-quarters of the patients are going to do just as well without it. It’s that 20% to 25% of patients that really are going to benefit from it, where you’re reducing your cost of care so much, and you’re getting rid of that very, very expensive 20%, that there’s a cost savings across the board per patient. So, it’s hard to understand when you say you’re losing money on three-quarters of the patients, you’re only saving money on a quarter of the patients, but that cost of saving on that small subset is so substantial it’s really impacting all numbers.

Also, abandoning the outlier principle is sort of an underlying theme in how we think of things. We tend to ignore outliers, not consider them, but I think we really have to pay attention to the more extreme cases because those patients are the ones that drive not just the financial cost of care. Remember, if you’re down to 1 ventilator and you can cut down the use of scarce ICU resources, the cost is sort of even beyond the cost of money. It’s the cost of resources that may become scarce in some settings. So, I think it speaks to that as well.

A lot of the drugs that we use, for example, tocilizumab, were able to be studied in thousands of patients. If you look at the absolute numbers, the benefit of tocilizumab from a magnitude standpoint—low to mid twenties to high twenties—you know, reducing mortality from 29% to 24%. I mean, just take a step back and think about that. Even though it’s statistically significant, try telling a patient, “Well, I’m going to give you this treatment that’s going to reduce mortality from 29% to 24%.” You know, that doesn’t really change anything from a clinical significance standpoint. But they have a P value less than .05, which is our standard, and they were able to do a study with thousands of patients. We didn’t have that luxury with IVIG. No one studied thousands of patients, only retrospectively, and those retrospective studies don’t get the attention because they’re considered biased with all their limitations. But I think one of the difficulties we have here is the balance between statistical and clinical significance. For example, in our pilot study, our ventilation rate was 58% with the non-IVIG patients versus 14% for IVIG patients. So you might say, magnitude-wise, that’s a big number, but the statistical significance of it is borderline because of small numbers.

Anyway, that’s a challenge that we have as clinicians trying to incorporate what’s published—the balancing of statistics, absolute numbers, and practicalities of delivering care. And I think this study highlights some of the nuances that go into that incorporation and those clinical decisions.

Dr. Barkoudah Would you mind sharing with our audience how we can make the connection between the medical outcomes and pharmacoeconomics findings from your article and link it to the bedside and treatment of our patients?

Dr. Sakoulas One of the points this article brings out is the importance of bringing together not just level 1A data, but also small studies with data such as this, where the magnitude of the effect is pretty big but you lose the statistics because of the small numbers. And then also the patients’ aspects of things. I think, as a bedside clinician, you appreciate things, the nuances, much sooner than what percolates out from a level 1A study. Case in point, in the sponsored phase 3 study that we did, and in some other studies that were prospectively done as well, these studies of IVIG simply had an enrollment of patients that was very broad, and not every patient benefits from the same therapy. A great example of this is the sepsis trials with Xigris and those types of agents that failed. You know, there are clinicians to this day who believe that there is a subset of patients that benefit from agents like this. The IVIG story falls a little bit into that category. It comes down to trying to identify the subset of patients that might benefit. And I think we’ve outlined this subset pretty well in our study: the younger, obese diabetic or hypertensive patient who’s rapidly declining.

It really brings together the need to not necessarily toss out these smaller studies, but kind of summarize everything together, and clinicians who are bedside, who are more in tune with the nuances of individual decisions at the individual patient level, might better appreciate these kinds of data. But I think we all have to put it together. IVIG does not make treatment guidelines at national levels and so forth. It’s not even listed in many of them. But there are patients out there who, if you ask them specifically how they felt, including a friend of mine who received the medication, there’s no question from their end, how they felt about this treatment option. Now, some people will get it and will not benefit. We just have to be really tuned into the fact that the same drug does not have the same result for every patient. And just to consider this in the high-risk patients that we talked about in our study.

Dr. Barkoudah While we were prepping for this interview, you made an analogy regarding clinical evidence along the lines of, “Do we need randomized clinical trials to do a parachute-type of experiment,” and we chatted about clinical wisdom. Would you mind sharing with our readers your thoughts on that?

Dr. Sakoulas Sometimes, we try a treatment and it’s very obvious for that particular patient that it helped them. Then you study the treatment in a large trial setting and it doesn’t work. For us bedside clinicians, there are some interventions sometimes that do appear as beneficial as a parachute would be, but yet, there has never been a randomized clinical trial proving that parachutes work. Again, a part of the challenge we have is patients are so different, their immunology is different, the pathogen infecting them is different, the time they present is different. Some present early, some present late. There are just so many moving parts to treating an infection that only a subset of people are going to benefit. And sometimes as clinicians, we’re so nuanced, that we identify a specific subset of patients where we know we can help them. And it’s so obvious for us, like a parachute would be, but to people who are looking at the world from 30,000 feet, they don’t necessarily grasp that because, when you look at all comers, it doesn’t show a benefit.

So the problem is that now those treatments that might help a subset of patients are being denied, and the subset of patients that are going to benefit never get the treatment. Now we have to balance that with a lot of stuff that went on during the pandemic with, you know, ivermectin, hydroxychloroquine, and people pushing those things. Someone asked me once what I thought about hydroxychloroquine, and I said, “Well, somebody in the lab probably showed that it was beneficial, analogous to lighting tissue paper on fire on a plate and taking a cup of water and putting the fire out. Well, now, if you take that cup of water to the Caldor fire that’s burning in California on thousands of acres, you’re not going to be able to put the fire out with that cup of water.” So while it might work in the lab, it’s truly not going to work in a clinical setting. We have to balance individualizing care for patients with some information people are pushing out there that may not be necessarily translatable to the clinical setting.

I think there’s nothing better than being at the bedside, though, and being able to implement something and seeing what works. And really, experience goes a long way in being able to individually treat a patient optimally.

Dr. Barkoudah Thank you for everything you do at the bedside and your work on improving the treatment we have and how we can leverage knowledge to treat our patients. Thank you very much for your time and your scholarly contribution. We appreciate it and I hope the work will continue. We will keep working on treating COVID-19 patients with the best knowledge we have.

Q&A participants: George Sakoulas, MD, Sharp Rees-Stealy Medical Group, La Jolla, CA, and University of California San Diego School of Medicine, San Diego, CA; and Ebrahim Barkoudah, MD, MPH, Department of Medicine, Brigham and Women’s Hospital, Boston, MA.

Disclosures: None reported.

Dr. George Sakoulas is an infectious diseases clinician at Sharp Memorial Hospital in San Diego and professor of pediatrics at the University of California, San Diego School of Medicine. He was the lead investigator in a study published in the May/June 2022 issue of JCOM that found that, when allocated to the appropriate patient type, intravenous immunoglobulin can reduce hospital costs for COVID-19 care. ¹ He joined JCOM’s Editor-in-Chief, Dr. Ebrahim Barkoudah, to discuss the study’s background and highlight its main findings.

The following has been edited for length and clarity.

Dr. Barkoudah Dr. Sakoulas is an investigator and a clinician, bridging both worlds to bring the best evidence to our patients. We’re discussing his new article regarding intravenous immunoglobulin in treating nonventilated COVID-19 patients with moderate-to-severe hypoxia. Dr. Sakoulas, could you please share with our readers the clinical question your study addressed and what your work around COVID-19 management means for clinical practice?

Dr. Sakoulas Thank you. I’m an infectious disease physician. I’ve been treating patients with viral acute respiratory distress syndrome for almost 20 years as an ID doctor. Most of these cases are due to influenza or other viruses. And from time to time, anecdotally and supported by some literature, we’ve been using IVIG, or intravenous immunoglobulin, in some of these cases. And again, I can report anecdotal success with that over the years.

So when COVID emerged in March of 2020, we deployed IVIG in a couple of patients early who were heading downhill. Remember, in March of 2020, we didn’t have the knowledge of steroids helping, patients being ventilated very promptly, and we saw some patients who made a turnaround after treatment with IVIG. We were able to get some support from an industry sponsor and perform and publish a pilot study, enrolling patients early in the pandemic. That study actually showed benefits, which then led the sponsor to fund a phase 3 multicenter clinical trial. Unfortunately, a couple of things happened. First, the trial was designed with the knowledge we had in April of 2020, and again, this is before steroids, before we incorporated proning patients in the ICU, or started ventilating people early. So there were some management changes and evolutions and improvements that happened. And second, the trial was enrolling a very broad repertoire of patients. There were no age limitations, and the trial, ultimately a phase 3 multicenter trial, failed to meet its endpoint.

There were some trends for benefit in younger patients, and as the trial was ongoing, we continued to evolve our knowledge, and we really honed it down to seeing a benefit of using IVIG in patients with COVID with specific criteria in mind. They had to be relatively younger patients, under 65, and not have any major comorbidities. In other words, they weren’t dialysis patients or end-stage disease patients, heart failure patients, cancer or malignancy patients. So, you know, we’re looking at the patients under 65 with obesity, diabetes, and hypertension, who are rapidly declining, going from room air to BiPAP or high-flow oxygen in a short amount of time. And we learned that when using IVIG early, we actually saw patients improve and turn around.

What this article in JCOM highlighted was, number one, incorporating that outcome or that patient type and then looking at the cost of hospitalization of patients who received IVIG versus those that did not. There were 2 groups that were studied. One was the group of patients in that original pilot trial that I discussed who were randomized to receive 1 or the other prospectively; it was an unblinded randomized study. And the second group was a matched case-control study where we had patients treated with IVIG matched by age and comorbidity status and level of hypoxia to patients that did not receive IVIG. We saw a financial benefit in shortening or reducing hospitalizations, really coming down to getting rid of that 20% tail of patients that wound up going to the ICU, getting intubated, and using a high amount of hospital resources that would ramp up the cost of hospitalization. We saw great mitigation of that with IVIG, and even with a small subset of patients, we were able to show a benefit.

Dr. Barkoudah Any thoughts on where we can implement the new findings from your article in our practice at the moment, knowing we now have practice guidelines and protocols to treat COVID-19? There was a tangible benefit in treating the patients the way you approached it in your important work. Could you share with us what would be implementable at the moment?

Dr. Sakoulas I think, fortunately, with the increasing host immunity in the population and decreased virulence of the virus, perhaps we won’t see as many patients of the type that were in these trials going forward, but I suspect we will perhaps in the unvaccinated patients that remain. I believe one-third of the United States is not vaccinated. So there is certainly a vulnerable group of people out there. Potentially, an unvaccinated patient who winds up getting very sick, the patient who is relatively young—what I’m looking at is the 30- to 65-year-old obese, hypertensive, or diabetic patient who comes in and, despite the steroids and the antivirals, rapidly deteriorates into requiring high-flow oxygen. I think implementing IVIG in that patient type would be helpful. I don’t think it’s going to be as helpful in patients who are very elderly, because I think the mechanism of the disease is different in an 80-year-old versus a 50-year-old patient. So again, hopefully, it will not amount to a lot of patients, but I still suspect hospitals are going to see, perhaps in the fall, when they’re expecting a greater number of cases, a trickling of patients that do meet the criteria that I described.

Dr. Barkoudah JCOM’s audience are the QI implementers and hospital leadership. And what caught my eye in your article is your perspective on the pharmacoeconomics of treating COVID-19, and I really appreciate your looking at the cost aspect. Would you talk about the economics of inpatient care, the total care that we provide now that we’re in the age of tocilizumab, and the current state of multiple layers of therapy?

Dr. Sakoulas The reason to look at the economics of it is because IVIG—which is actually not a drug, it’s a blood product—is very expensive. So, we received a considerable amount of administrative pushback implementing this treatment at the beginning outside of the clinical trial setting because it hadn’t been studied on a large scale and because the cost was so high, even though, as a clinician at the bedside, I was seeing a benefit in patients. This study came out of my trying to demonstrate to the folks that are keeping the economics of medicine in mind that, in fact, investing several thousand dollars of treatment in IVIG will save you cost of care, the cost of an ICU bed, the cost of a ventilator, and the cost even of ECMO, which is hugely expensive.

If you look at the numbers in the study, for two-thirds or three-quarters of the patients, your cost of care is actually greater than the controls because you’re giving them IVIG, and it’s increasing the cost of their care, even though three-quarters of the patients are going to do just as well without it. It’s that 20% to 25% of patients that really are going to benefit from it, where you’re reducing your cost of care so much, and you’re getting rid of that very, very expensive 20%, that there’s a cost savings across the board per patient. So, it’s hard to understand when you say you’re losing money on three-quarters of the patients, you’re only saving money on a quarter of the patients, but that cost of saving on that small subset is so substantial it’s really impacting all numbers.

Also, abandoning the outlier principle is sort of an underlying theme in how we think of things. We tend to ignore outliers, not consider them, but I think we really have to pay attention to the more extreme cases because those patients are the ones that drive not just the financial cost of care. Remember, if you’re down to 1 ventilator and you can cut down the use of scarce ICU resources, the cost is sort of even beyond the cost of money. It’s the cost of resources that may become scarce in some settings. So, I think it speaks to that as well.

A lot of the drugs that we use, for example, tocilizumab, were able to be studied in thousands of patients. If you look at the absolute numbers, the benefit of tocilizumab from a magnitude standpoint—low to mid twenties to high twenties—you know, reducing mortality from 29% to 24%. I mean, just take a step back and think about that. Even though it’s statistically significant, try telling a patient, “Well, I’m going to give you this treatment that’s going to reduce mortality from 29% to 24%.” You know, that doesn’t really change anything from a clinical significance standpoint. But they have a P value less than .05, which is our standard, and they were able to do a study with thousands of patients. We didn’t have that luxury with IVIG. No one studied thousands of patients, only retrospectively, and those retrospective studies don’t get the attention because they’re considered biased with all their limitations. But I think one of the difficulties we have here is the balance between statistical and clinical significance. For example, in our pilot study, our ventilation rate was 58% with the non-IVIG patients versus 14% for IVIG patients. So you might say, magnitude-wise, that’s a big number, but the statistical significance of it is borderline because of small numbers.

Anyway, that’s a challenge that we have as clinicians trying to incorporate what’s published—the balancing of statistics, absolute numbers, and practicalities of delivering care. And I think this study highlights some of the nuances that go into that incorporation and those clinical decisions.

Dr. Barkoudah Would you mind sharing with our audience how we can make the connection between the medical outcomes and pharmacoeconomics findings from your article and link it to the bedside and treatment of our patients?

Dr. Sakoulas One of the points this article brings out is the importance of bringing together not just level 1A data, but also small studies with data such as this, where the magnitude of the effect is pretty big but you lose the statistics because of the small numbers. And then also the patients’ aspects of things. I think, as a bedside clinician, you appreciate things, the nuances, much sooner than what percolates out from a level 1A study. Case in point, in the sponsored phase 3 study that we did, and in some other studies that were prospectively done as well, these studies of IVIG simply had an enrollment of patients that was very broad, and not every patient benefits from the same therapy. A great example of this is the sepsis trials with Xigris and those types of agents that failed. You know, there are clinicians to this day who believe that there is a subset of patients that benefit from agents like this. The IVIG story falls a little bit into that category. It comes down to trying to identify the subset of patients that might benefit. And I think we’ve outlined this subset pretty well in our study: the younger, obese diabetic or hypertensive patient who’s rapidly declining.

It really brings together the need to not necessarily toss out these smaller studies, but kind of summarize everything together, and clinicians who are bedside, who are more in tune with the nuances of individual decisions at the individual patient level, might better appreciate these kinds of data. But I think we all have to put it together. IVIG does not make treatment guidelines at national levels and so forth. It’s not even listed in many of them. But there are patients out there who, if you ask them specifically how they felt, including a friend of mine who received the medication, there’s no question from their end, how they felt about this treatment option. Now, some people will get it and will not benefit. We just have to be really tuned into the fact that the same drug does not have the same result for every patient. And just to consider this in the high-risk patients that we talked about in our study.

Dr. Barkoudah While we were prepping for this interview, you made an analogy regarding clinical evidence along the lines of, “Do we need randomized clinical trials to do a parachute-type of experiment,” and we chatted about clinical wisdom. Would you mind sharing with our readers your thoughts on that?

Dr. Sakoulas Sometimes, we try a treatment and it’s very obvious for that particular patient that it helped them. Then you study the treatment in a large trial setting and it doesn’t work. For us bedside clinicians, there are some interventions sometimes that do appear as beneficial as a parachute would be, but yet, there has never been a randomized clinical trial proving that parachutes work. Again, a part of the challenge we have is patients are so different, their immunology is different, the pathogen infecting them is different, the time they present is different. Some present early, some present late. There are just so many moving parts to treating an infection that only a subset of people are going to benefit. And sometimes as clinicians, we’re so nuanced, that we identify a specific subset of patients where we know we can help them. And it’s so obvious for us, like a parachute would be, but to people who are looking at the world from 30,000 feet, they don’t necessarily grasp that because, when you look at all comers, it doesn’t show a benefit.

So the problem is that now those treatments that might help a subset of patients are being denied, and the subset of patients that are going to benefit never get the treatment. Now we have to balance that with a lot of stuff that went on during the pandemic with, you know, ivermectin, hydroxychloroquine, and people pushing those things. Someone asked me once what I thought about hydroxychloroquine, and I said, “Well, somebody in the lab probably showed that it was beneficial, analogous to lighting tissue paper on fire on a plate and taking a cup of water and putting the fire out. Well, now, if you take that cup of water to the Caldor fire that’s burning in California on thousands of acres, you’re not going to be able to put the fire out with that cup of water.” So while it might work in the lab, it’s truly not going to work in a clinical setting. We have to balance individualizing care for patients with some information people are pushing out there that may not be necessarily translatable to the clinical setting.

I think there’s nothing better than being at the bedside, though, and being able to implement something and seeing what works. And really, experience goes a long way in being able to individually treat a patient optimally.

Dr. Barkoudah Thank you for everything you do at the bedside and your work on improving the treatment we have and how we can leverage knowledge to treat our patients. Thank you very much for your time and your scholarly contribution. We appreciate it and I hope the work will continue. We will keep working on treating COVID-19 patients with the best knowledge we have.

Q&A participants: George Sakoulas, MD, Sharp Rees-Stealy Medical Group, La Jolla, CA, and University of California San Diego School of Medicine, San Diego, CA; and Ebrahim Barkoudah, MD, MPH, Department of Medicine, Brigham and Women’s Hospital, Boston, MA.

Disclosures: None reported.

Dr. George Sakoulas is an infectious diseases clinician at Sharp Memorial Hospital in San Diego and professor of pediatrics at the University of California, San Diego School of Medicine. He was the lead investigator in a study published in the May/June 2022 issue of JCOM that found that, when allocated to the appropriate patient type, intravenous immunoglobulin can reduce hospital costs for COVID-19 care. ¹ He joined JCOM’s Editor-in-Chief, Dr. Ebrahim Barkoudah, to discuss the study’s background and highlight its main findings.

The following has been edited for length and clarity.

Dr. Barkoudah Dr. Sakoulas is an investigator and a clinician, bridging both worlds to bring the best evidence to our patients. We’re discussing his new article regarding intravenous immunoglobulin in treating nonventilated COVID-19 patients with moderate-to-severe hypoxia. Dr. Sakoulas, could you please share with our readers the clinical question your study addressed and what your work around COVID-19 management means for clinical practice?

Dr. Sakoulas Thank you. I’m an infectious disease physician. I’ve been treating patients with viral acute respiratory distress syndrome for almost 20 years as an ID doctor. Most of these cases are due to influenza or other viruses. And from time to time, anecdotally and supported by some literature, we’ve been using IVIG, or intravenous immunoglobulin, in some of these cases. And again, I can report anecdotal success with that over the years.

So when COVID emerged in March of 2020, we deployed IVIG in a couple of patients early who were heading downhill. Remember, in March of 2020, we didn’t have the knowledge of steroids helping, patients being ventilated very promptly, and we saw some patients who made a turnaround after treatment with IVIG. We were able to get some support from an industry sponsor and perform and publish a pilot study, enrolling patients early in the pandemic. That study actually showed benefits, which then led the sponsor to fund a phase 3 multicenter clinical trial. Unfortunately, a couple of things happened. First, the trial was designed with the knowledge we had in April of 2020, and again, this is before steroids, before we incorporated proning patients in the ICU, or started ventilating people early. So there were some management changes and evolutions and improvements that happened. And second, the trial was enrolling a very broad repertoire of patients. There were no age limitations, and the trial, ultimately a phase 3 multicenter trial, failed to meet its endpoint.

There were some trends for benefit in younger patients, and as the trial was ongoing, we continued to evolve our knowledge, and we really honed it down to seeing a benefit of using IVIG in patients with COVID with specific criteria in mind. They had to be relatively younger patients, under 65, and not have any major comorbidities. In other words, they weren’t dialysis patients or end-stage disease patients, heart failure patients, cancer or malignancy patients. So, you know, we’re looking at the patients under 65 with obesity, diabetes, and hypertension, who are rapidly declining, going from room air to BiPAP or high-flow oxygen in a short amount of time. And we learned that when using IVIG early, we actually saw patients improve and turn around.

What this article in JCOM highlighted was, number one, incorporating that outcome or that patient type and then looking at the cost of hospitalization of patients who received IVIG versus those that did not. There were 2 groups that were studied. One was the group of patients in that original pilot trial that I discussed who were randomized to receive 1 or the other prospectively; it was an unblinded randomized study. And the second group was a matched case-control study where we had patients treated with IVIG matched by age and comorbidity status and level of hypoxia to patients that did not receive IVIG. We saw a financial benefit in shortening or reducing hospitalizations, really coming down to getting rid of that 20% tail of patients that wound up going to the ICU, getting intubated, and using a high amount of hospital resources that would ramp up the cost of hospitalization. We saw great mitigation of that with IVIG, and even with a small subset of patients, we were able to show a benefit.

Dr. Barkoudah Any thoughts on where we can implement the new findings from your article in our practice at the moment, knowing we now have practice guidelines and protocols to treat COVID-19? There was a tangible benefit in treating the patients the way you approached it in your important work. Could you share with us what would be implementable at the moment?

Dr. Sakoulas I think, fortunately, with the increasing host immunity in the population and decreased virulence of the virus, perhaps we won’t see as many patients of the type that were in these trials going forward, but I suspect we will perhaps in the unvaccinated patients that remain. I believe one-third of the United States is not vaccinated. So there is certainly a vulnerable group of people out there. Potentially, an unvaccinated patient who winds up getting very sick, the patient who is relatively young—what I’m looking at is the 30- to 65-year-old obese, hypertensive, or diabetic patient who comes in and, despite the steroids and the antivirals, rapidly deteriorates into requiring high-flow oxygen. I think implementing IVIG in that patient type would be helpful. I don’t think it’s going to be as helpful in patients who are very elderly, because I think the mechanism of the disease is different in an 80-year-old versus a 50-year-old patient. So again, hopefully, it will not amount to a lot of patients, but I still suspect hospitals are going to see, perhaps in the fall, when they’re expecting a greater number of cases, a trickling of patients that do meet the criteria that I described.

Dr. Barkoudah JCOM’s audience are the QI implementers and hospital leadership. And what caught my eye in your article is your perspective on the pharmacoeconomics of treating COVID-19, and I really appreciate your looking at the cost aspect. Would you talk about the economics of inpatient care, the total care that we provide now that we’re in the age of tocilizumab, and the current state of multiple layers of therapy?

Dr. Sakoulas The reason to look at the economics of it is because IVIG—which is actually not a drug, it’s a blood product—is very expensive. So, we received a considerable amount of administrative pushback implementing this treatment at the beginning outside of the clinical trial setting because it hadn’t been studied on a large scale and because the cost was so high, even though, as a clinician at the bedside, I was seeing a benefit in patients. This study came out of my trying to demonstrate to the folks that are keeping the economics of medicine in mind that, in fact, investing several thousand dollars of treatment in IVIG will save you cost of care, the cost of an ICU bed, the cost of a ventilator, and the cost even of ECMO, which is hugely expensive.

If you look at the numbers in the study, for two-thirds or three-quarters of the patients, your cost of care is actually greater than the controls because you’re giving them IVIG, and it’s increasing the cost of their care, even though three-quarters of the patients are going to do just as well without it. It’s that 20% to 25% of patients that really are going to benefit from it, where you’re reducing your cost of care so much, and you’re getting rid of that very, very expensive 20%, that there’s a cost savings across the board per patient. So, it’s hard to understand when you say you’re losing money on three-quarters of the patients, you’re only saving money on a quarter of the patients, but that cost of saving on that small subset is so substantial it’s really impacting all numbers.

Also, abandoning the outlier principle is sort of an underlying theme in how we think of things. We tend to ignore outliers, not consider them, but I think we really have to pay attention to the more extreme cases because those patients are the ones that drive not just the financial cost of care. Remember, if you’re down to 1 ventilator and you can cut down the use of scarce ICU resources, the cost is sort of even beyond the cost of money. It’s the cost of resources that may become scarce in some settings. So, I think it speaks to that as well.

A lot of the drugs that we use, for example, tocilizumab, were able to be studied in thousands of patients. If you look at the absolute numbers, the benefit of tocilizumab from a magnitude standpoint—low to mid twenties to high twenties—you know, reducing mortality from 29% to 24%. I mean, just take a step back and think about that. Even though it’s statistically significant, try telling a patient, “Well, I’m going to give you this treatment that’s going to reduce mortality from 29% to 24%.” You know, that doesn’t really change anything from a clinical significance standpoint. But they have a P value less than .05, which is our standard, and they were able to do a study with thousands of patients. We didn’t have that luxury with IVIG. No one studied thousands of patients, only retrospectively, and those retrospective studies don’t get the attention because they’re considered biased with all their limitations. But I think one of the difficulties we have here is the balance between statistical and clinical significance. For example, in our pilot study, our ventilation rate was 58% with the non-IVIG patients versus 14% for IVIG patients. So you might say, magnitude-wise, that’s a big number, but the statistical significance of it is borderline because of small numbers.

Anyway, that’s a challenge that we have as clinicians trying to incorporate what’s published—the balancing of statistics, absolute numbers, and practicalities of delivering care. And I think this study highlights some of the nuances that go into that incorporation and those clinical decisions.

Dr. Barkoudah Would you mind sharing with our audience how we can make the connection between the medical outcomes and pharmacoeconomics findings from your article and link it to the bedside and treatment of our patients?

Dr. Sakoulas One of the points this article brings out is the importance of bringing together not just level 1A data, but also small studies with data such as this, where the magnitude of the effect is pretty big but you lose the statistics because of the small numbers. And then also the patients’ aspects of things. I think, as a bedside clinician, you appreciate things, the nuances, much sooner than what percolates out from a level 1A study. Case in point, in the sponsored phase 3 study that we did, and in some other studies that were prospectively done as well, these studies of IVIG simply had an enrollment of patients that was very broad, and not every patient benefits from the same therapy. A great example of this is the sepsis trials with Xigris and those types of agents that failed. You know, there are clinicians to this day who believe that there is a subset of patients that benefit from agents like this. The IVIG story falls a little bit into that category. It comes down to trying to identify the subset of patients that might benefit. And I think we’ve outlined this subset pretty well in our study: the younger, obese diabetic or hypertensive patient who’s rapidly declining.

It really brings together the need to not necessarily toss out these smaller studies, but kind of summarize everything together, and clinicians who are bedside, who are more in tune with the nuances of individual decisions at the individual patient level, might better appreciate these kinds of data. But I think we all have to put it together. IVIG does not make treatment guidelines at national levels and so forth. It’s not even listed in many of them. But there are patients out there who, if you ask them specifically how they felt, including a friend of mine who received the medication, there’s no question from their end, how they felt about this treatment option. Now, some people will get it and will not benefit. We just have to be really tuned into the fact that the same drug does not have the same result for every patient. And just to consider this in the high-risk patients that we talked about in our study.

Dr. Barkoudah While we were prepping for this interview, you made an analogy regarding clinical evidence along the lines of, “Do we need randomized clinical trials to do a parachute-type of experiment,” and we chatted about clinical wisdom. Would you mind sharing with our readers your thoughts on that?

Dr. Sakoulas Sometimes, we try a treatment and it’s very obvious for that particular patient that it helped them. Then you study the treatment in a large trial setting and it doesn’t work. For us bedside clinicians, there are some interventions sometimes that do appear as beneficial as a parachute would be, but yet, there has never been a randomized clinical trial proving that parachutes work. Again, a part of the challenge we have is patients are so different, their immunology is different, the pathogen infecting them is different, the time they present is different. Some present early, some present late. There are just so many moving parts to treating an infection that only a subset of people are going to benefit. And sometimes as clinicians, we’re so nuanced, that we identify a specific subset of patients where we know we can help them. And it’s so obvious for us, like a parachute would be, but to people who are looking at the world from 30,000 feet, they don’t necessarily grasp that because, when you look at all comers, it doesn’t show a benefit.

So the problem is that now those treatments that might help a subset of patients are being denied, and the subset of patients that are going to benefit never get the treatment. Now we have to balance that with a lot of stuff that went on during the pandemic with, you know, ivermectin, hydroxychloroquine, and people pushing those things. Someone asked me once what I thought about hydroxychloroquine, and I said, “Well, somebody in the lab probably showed that it was beneficial, analogous to lighting tissue paper on fire on a plate and taking a cup of water and putting the fire out. Well, now, if you take that cup of water to the Caldor fire that’s burning in California on thousands of acres, you’re not going to be able to put the fire out with that cup of water.” So while it might work in the lab, it’s truly not going to work in a clinical setting. We have to balance individualizing care for patients with some information people are pushing out there that may not be necessarily translatable to the clinical setting.

I think there’s nothing better than being at the bedside, though, and being able to implement something and seeing what works. And really, experience goes a long way in being able to individually treat a patient optimally.

Dr. Barkoudah Thank you for everything you do at the bedside and your work on improving the treatment we have and how we can leverage knowledge to treat our patients. Thank you very much for your time and your scholarly contribution. We appreciate it and I hope the work will continue. We will keep working on treating COVID-19 patients with the best knowledge we have.

Q&A participants: George Sakoulas, MD, Sharp Rees-Stealy Medical Group, La Jolla, CA, and University of California San Diego School of Medicine, San Diego, CA; and Ebrahim Barkoudah, MD, MPH, Department of Medicine, Brigham and Women’s Hospital, Boston, MA.

Disclosures: None reported.

From the University of Chicago Medical Center, Chicago, IL.

Abstract

Background: Epistaxis is a common chief complaint addressed by otolaryngologists. A review of the literature showed that there is a deficit in epistaxis education within the nursing community. Conversations with our nursing colleagues confirmed this unmet demand.

Objective: This quality improvement project aimed to increase general epistaxis knowledge, perceived comfort level managing nosebleeds, and perceived ability to stop nosebleeds among our nursing staff.

Methods: Data were collected through a survey administered before and after our intervention. The survey tested general epistaxis knowledge and assessed comfort and confidence in stopping epistaxis. Our intervention was an educational session covering pertinent epistaxis etiology and management. Quality improvement principles were used to optimize delivery of the intervention.

Results: A total of 51 nurses participated in the project. After participating in the in-service educational session, nurses answered significantly more epistaxis general knowledge questions correctly (mean [SD] difference, 2.07 [1.10] questions; 95% CI, 1.74-2.39; P < .001). There was no statistically significant difference in additional correct questions when stratified by clinical experience or clinical setting (P = .128 and P = 0.446, respectively). Nurses also reported feeling significantly more comfortable and significantly more confident in managing nosebleeds after the in-service (P = .007 and P < 0.001, respectively); 74.46% of nurses had an improvement in comfort level in managing epistaxis and 43.90% of nurses had an improvement in confidence in stopping epistaxis. After we moved the educational session from mid-shift to shift change, the nursing staff reported more satisfaction while maintaining similar improvements in knowledge and confidence.

Conclusion: We were able to significantly increase epistaxis knowledge, improve comfort levels managing epistaxis, and improve confidence in successful epistaxis management. Nurses of varying clinical experience and different clinical settings benefitted equally from our intervention.

Keywords: nosebleed; in-service; quality improvement.

Epistaxis, or nosebleed, is estimated to be the chief complaint in 1 in 200 emergency department visits in the United States.¹ Additionally, it represents up to one-third of otolaryngology-related emergency room admissions.² There is no existing literature, to our best knowledge, specifically investigating the incidence of epistaxis after a patient is admitted. Anecdotally, inpatients who develop epistaxis account for an appreciable number of consults to otolaryngology (ENT). Epistaxis is a cross-disciplinary issue, occurring in a range of clinical settings. For example, patients with epistaxis can present to the emergency department or to an outpatient primary care clinic before being referred to ENT. Additionally, inpatients on many different services can develop spontaneous epistaxis due to a variety of environmental and iatrogenic factors, such as dry air, use of nasal cannula, and initiation of anticoagulation. Based on the experience of our ENT providers and discussions with our nursing colleagues, we concluded that there was an interest in epistaxis management training among our nursing workforce.

The presence of unmet demand for epistaxis education among our nursing colleagues was supported by our literature review. A study performed in England surveyed emergency department nurses on first aid measures for management of epistaxis, including ideal head positioning, location of pressure application, and duration of pressure application.³ Overall, only 12% to 14% of the nursing staff answered all 3 questions correctly.³ Additionally, 73% to 78% of the nursing staff felt that their training in epistaxis management was inadequate, and 88% desired further training in epistaxis management.³ If generalized, this study confirms the demand for further epistaxis education among nurses.

In-services have previously been shown to be effective educational tools within the nursing community. A study in Ethiopia that evaluated pain management knowledge and attitudes before and after an in-service found a significant improvement in mean rank score of nurses’ knowledge and attitudes regarding pain management after they participated in the in-service.⁴ Scores on the knowledge survey improved from 41.4% before the intervention to 63.0% post intervention.⁴ A study in Connecticut evaluated nurses’ confidence in discussing suicidal ideation with patients and knowledge surrounding suicide precautions.⁵ After participating in an in-service, nurses were significantly more confident in discussing suicidal ideation with patients; application of appropriate suicide precautions also increased after the in-service.⁵

Our aim was for nurses to have an improvement in overall epistaxis knowledge, perceived comfort level managing nosebleeds, and perceived ability to stop nosebleeds after attending our in-service. Additionally, an overarching priority was to provide high-quality epistaxis education based on the literature and best practice guidelines.

Methods

Setting

This study was carried out at an 811-bed quaternary care center located in Chicago, Illinois. In fiscal year 2021, there were 91 643 emergency department visits and 33 805 hospital admissions. At our flagship hospital, 2658 patients were diagnosed with epistaxis during fiscal year 2021. The emergency department saw 533 patients with epistaxis, with 342 requiring admission and 191 being discharged. Separately, 566 inpatients received a diagnosis of epistaxis during their admission. The remainder of the patients with epistaxis were seen on an outpatient basis.

Data Collection

Data were collected from nurses on 5 different inpatient units. An email with information about the in-service was sent to the nurse managers of the inpatient units. These 5 units were included because the nurse managers responded to the email and facilitated delivery of the in-service. Data collection took place from August to December 2020.

Intervention

A quality improvement team composed of a resident physician champion, nurse educators, and nurse managers was formed. The physician champion was a senior otolaryngology resident who was responsible for designing and administering the pre-test, in-service, and post test. The nurse educators and nurse managers helped coordinate times for the in-service and promoted the in-service for their staff.

Our intervention was an educational in-service, a technique that is commonly used at our institution for nurse education. In-services typically involve delivering a lecture on a clinically relevant topic to a group of nurses on a unit. In developing the in-service, a top priority was to present high-quality evidence-based material. There is an abundance of information in the literature surrounding epistaxis management. The clinical practice guideline published by the American Academy of Otolaryngology lists nasal compression, application of vasoconstrictors, nasal packing, and nasal cautery as first-line treatments for the management of epistaxis.⁶ Nasal packing and nasal cautery tend to be perceived as interventions that require a certain level of expertise and specialized supplies. As such, these interventions are not often performed by floor nurses. In contrast, nasal compression and application of vasoconstrictors require only a few easily accessible supplies, and the risks are relatively minimal. When performing nasal compression, the clinical practice guidelines recommend firm, sustained compression to the lower third of the nose for 5 minutes or longer.⁶ Topical vasoconstrictors are generally underutilized in epistaxis management. In a study looking at a random sample of all US emergency department visits from 1992 to 2001, only 18% of visits used an epistaxis-related medication.² Oxymetazoline hydrochloride is a topical vasoconstrictor that is commonly used as a nasal decongestant. However, its vasoconstrictor properties also make it a useful tool for controlling epistaxis. In a study looking at emergency department visits at the University of Texas Health Science Center, 65% of patients had resolution of nosebleed with application of oxymetazoline hydrochloride as the only intervention, with another 18% experiencing resolution of nosebleed with a combination of oxymetazoline hydrochloride and silver nitrate cautery.⁷ Based on review of the literature, nasal compression and application of vasoconstrictors seemed to be low-resource interventions with minimal morbidity. Therefore, management centered around nasal compression and use of topical vasoconstrictors seemed appropriate for our nursing staff.

The in-service included information about the etiology and management of epistaxis. Particular emphasis was placed on addressing and debunking common misconceptions about nosebleed management. With regards to management, our presentation focused on the use of topical vasoconstrictors and firm pressure to the lower third of the nose for at least 5 minutes. Nasal packing and nasal cautery were presented as procedures that ENT would perform. After the in-service, questions from the nurses were answered as time permitted.

Testing and Outcomes

A pre-test was administered before each in-service. The pre-test components comprised a knowledge survey and a descriptive survey. The general epistaxis knowledge questions on the pre-test included the location of blood vessels most commonly responsible for nosebleeds, the ideal positioning of a patient during a nosebleed, the appropriate location to hold pressure during a nosebleed, and the appropriate duration to hold pressure during a nosebleed. The descriptive survey portion asked nurses to rate whether they felt “very comfortable,” “comfortable,” “uncomfortable,” or “very uncomfortable” managing nosebleeds. It also asked whether nurses thought they would be able to “always,” “usually,” “rarely,” or “never” stop nosebleeds on the floor. We collected demographic information, including gender identity, years of clinical experience, and primary clinical environment.

The post test asked the same questions as the pre-test and was administered immediately after the in-service in order to assess its impact. We also established an ongoing dialogue with our nursing colleagues to obtain feedback on the sessions.

Primary outcomes of interest were the difference in general epistaxis knowledge questions answered correctly between the pre-test and the post test; the difference in comfort level in managing epistaxis before and after the in-service; and the difference in confidence to stop nosebleeds before and after the in-service. A secondary outcome was determining the audience for the in-service. Specifically, we wanted to determine whether there were different outcomes based on clinical setting or years of clinical experience. If nurses in a certain clinical environment or beyond a certain experience level did not show significant improvement from pre-test to post test, we would not target them for the in-service. Another secondary outcome was determining optimal timing for delivery of the in-service. We wanted to determine if there was a nursing preference for delivering the in-service at mid-shift vs shift change.

Analysis

Statistical calculations were performed using Stata 15 (StataCorp LLC). A P value < .05 was considered to be statistically significant. Where applicable, 95% confidence intervals (CI) were calculated. T-test was used to determine whether there was a statistically significant difference between pre-test and post-test epistaxis knowledge question scores. T-test was also used to determine whether there was a statistically significant difference in test scores between nurses receiving the in-service at mid-shift vs shift change. Pearson chi-squared tests were used to determine if there was a statistically significant difference between pre-test and post-test perceptions of epistaxis management, and to investigate outcomes between different subsets of nurses.

SQUIRE 2.0 guidelines were utilized to provide a framework for this project and to structure the manuscript.⁸ This study met criteria for exemption from institutional review board approval.

Results

Fifty-one nurses took part in this project (Table). The majority of participants identified as female (88.24%), and just over half worked on medical floors (52.94%), with most of the remainder working in intensive care (25.49%) and surgical (15.69%) settings. There was a wide range of clinical experience, with 1.96% reporting 0 to 1 years of experience, 29.41% reporting 2 to 5 years, 23.53% reporting 5 to 10 years, 25.49% reporting 10 to 20 years, and 17.65% reporting more than 20 years.

There were unanswered questions on both the pre-test and post test. There was no consistently unanswered question. Omitted answers on the epistaxis knowledge questions were recorded as an “incorrect” answer. Omitted answers on the perception questions were considered null values and not considered in final analysis.

Primary Measures

General epistaxis knowledge (Figure, part A) improved from the pre-test, where out of 4 questions, the mean (SD) score was 1.74 (1.02) correct questions, to the post-test, where out of 4 questions, the mean score was 3.80 (0.40) correct questions. After participating in the in-service, nurses answered significantly more questions about epistaxis general knowledge correctly (mean difference, 2.07 [1.10]; 95% CI, 1.74-2.39; P < .001), and 80.43% of them got a perfect score on the epistaxis knowledge questions.

The second primary measure was the difference in comfort level in managing nosebleed. After participating in the in-service, nurses felt significantly more comfortable in managing nosebleeds (Figure, part B; P = .007), with 74.46% of nurses having an improved comfort level managing nosebleeds. Before the in-service, 12.76% of nurses felt “very comfortable” in managing nosebleeds vs more than three-quarters (76.59%) after the in-service. Of those who answered that they felt “comfortable” managing nosebleeds on the pre-test, 82.35% improved to feeling “very comfortable” in managing nosebleeds. Before the in-service, 14.89% of nurses felt “uncomfortable” or “very uncomfortable” in managing nosebleeds, and this decreased to 0 post intervention. After the in-service, 100.00% of nurses felt “comfortable” or “very comfortable” in managing nosebleeds.

After receiving the in-service, nurses felt significantly more confident in stopping nosebleeds (Figure, part C; P < .001), with 43.90% of them having an improvement in confidence in stopping epistaxis. Before the in-service, 7.31% of nurses felt that they would “always” be able to stop a nose-bleed, and this increased to 41.46% after the in-service. Of those who answered that they felt that they would “usually” be able to stop a nosebleed on the pre-test, 36.67% changed their answer to state that they would “always” be able to stop a nosebleed on the post test. Before the in-service, 19.51% of nurses felt that they would “rarely” or “never” be able to stop a nosebleed, and this decreased to 2.44% after the in-service.

Secondary Measures

All of the nurses who participated either “strongly agreed” or “agreed” that they learned something new from the in-service. However, to determine whether there was a population who would benefit most from the in-service, we stratified the data by years of clinical experience. There was no statistically significant difference in whether nurses with varying clinical experience learned something new (P = .148): 100% of nurses with 0-1 years of experience, 80.00% of nurses with 2-5 years of experience, 100% of nurses with 5-10 years of experience, 69.23% of nurses with 10-20 years of experience, and 100% of nurses with >20 years of experience “strongly agreed” that they learned something new from this in-service. There was no statistically significant difference on the post test compared to the pre-test in additional correct questions when stratified by clinical experience (P = .128). Second, when we stratified by clinical setting, we did not find a statistically significant difference in whether nurses in different clinical settings learned something new (P = .929): 88.89% of nurses in the medical setting, 87.50% of nurses in the surgical setting, and 84.62% of nurses in the intensive care setting “strongly agreed” that they learned something new from this presentation. On investigating additional questions correct on the post test compared to the pre-test, there was no statistically significant difference in additional correct questions when stratified by clinical setting (P = .446).

Optimal timing of the in-service was another important outcome. Initially, the in-service was administered at mid-shift, with 9 nurses participating at mid-shift, but our nursing colleagues gave unanimous feedback that this was a suboptimal time for delivery of an in-service. We changed the timing of the in-service to shift change; 42 nurses received the in-service at shift-change. There was no statistically significant difference in scores on the epistaxis knowledge questions between these two groups (P = .123). This indicated to us that changing the timing of the delivery resulted in similarly improved outcomes while having the added benefit of being preferred by our nursing colleagues.

Discussion

In undertaking this project, our primary aims were to improve epistaxis knowledge and perceived management in our nursing staff. Among our nursing staff, we were able to significantly increase epistaxis knowledge, improve comfort levels managing epistaxis, and improve confidence in successful epistaxis management. We also found that nurses of varying clinical experience and different clinical settings benefited equally from our intervention. Using quality improvement principles, we optimized our delivery. Our in-service focused on educating nurses to use epistaxis management techniques that were resource-efficient and low risk.

After participating in the in-service, nurses answered significantly more questions about epistaxis general knowledge correctly (Figure, part A; mean difference, 2.07 questions [1.10]; 95% CI, 1.74-2.39; P < .001), felt significantly more comfortable in managing nosebleeds (Figure, part B; P = .007), and felt significantly more confident in stopping nosebleeds (Figure, part C; P < .001). Based on these results, we successfully achieved our primary aims.

Our secondary aim was to determine the audience that would benefit the most from the in-service. All of the nurses who participated either “strongly agreed” or “agreed” that they learned something new from the in-service. There was no statistically significant difference in whether nurses of varying clinical experience learned something new (P = .148) or in additional correct questions when stratified by clinical experience (P =.128). Also, there was no statistically significant difference in whether nurses in different clinical settings learned something new (P = .929) or in additional correct questions when stratified by clinical setting (P = .446). These results indicated to us that all participants learned something new and that there was no specific target audience, but rather that all participants benefitted from our session.

Our nursing colleagues gave us feedback that the timing of the in-service during mid-shift was not ideal. It was difficult to gather nurses mid-shift due to pressing patient-care duties. Nurses also found it difficult to give their full attention at this time. Nurses, nurse educators, and nurse managers suggested that we conduct the in-service at shift change in order to capture a larger population and take advantage of time relatively free of clinical duties. Giving the in-service at a time with relatively fewer clinical responsibilities allowed for a more robust question-and-answer session. It also allowed our nursing colleagues to pay full attention to the in-service. There was no statistically significant difference in epistaxis general knowledge questions answered correctly; this indicates that the quality of the education session did not vary greatly. However, our nursing colleagues strongly preferred the in-service at shift change. By making this modification to our intervention, we were able to optimize our intervention.

The previously mentioned study in England reported that only 12% to 14% of their nursing staff got a perfect score on epistaxis knowledge questions. Prior to our study, there was no literature investigating the impact of an in-service on epistaxis knowledge. After our intervention, 80.43% of our nurses got a perfect score on the epistaxis knowledge questions. We believe that this is a fair comparison because our post-test questions were identical to the survey questions used in the previously mentioned study in England, with the addition of one question.³ Further, the findings of our study are consistent with other studies regarding the positive effect of in-service education on knowledge and attitudes surrounding clinical topics. Similar to the study in Ethiopia investigating nurses’ knowledge surrounding pain management, our study noted a significant improvement in nurses’ knowledge after participating in the in-service.⁴ Also, when comparing our study to the study performed in Connecticut investigating nurses’ confidence surrounding suicide precautions, we found a similar significant improvement in confidence in management after participating in the in-service.⁵

Given our reliance on a survey as a tool to collect information, our study was subject to nonresponse bias. For each main outcome question, there was a handful of nonresponders. While this likely indicated either overlooking a question or deferring to answer due to clinical inexperience or nonapplicable clinical role, it is possible that this may have represented a respondent who did not benefit from the in-service. Another source of possible bias is sampling bias. Attempts were made to capture a wide range of nurses at the in-service. However, if a nurse was not interested in the topic material, whether due to abundant clinical experience or disinterest, it is possible that they may not have attended. Additionally, the cohort was selected purely based on responses from nursing managers to the initial email. It is possible that nonresponding units may have benefitted differently from this in-service.

There were several limitations within our analysis. We did not collect data assessing the long-term retention of epistaxis knowledge and management techniques. It is possible that epistaxis knowledge, comfort in managing nosebleeds, and perceived confidence in stopping nosebleeds decreased back to baseline several months after the in-service. Ideally, we would have been able to collect this data to assess retention of the in-service information. Unfortunately, a significant number of nurses who initially participated in the project became lost to follow-up, making such data collection impossible. Additionally, there was no assessment of actual ability to stop nosebleeds before vs after this in-service. Perceived management of epistaxis vs actual management of epistaxis are 2 vastly different things. However, this data would have been difficult to collect, and it likely would not have been in the best interest of patients, especially before the in-service was administered. As an improvement to this project, we could have assessed how many nosebleeds nurses had seen and successfully stopped after the in-service. As previously mentioned, this was not possible due to losing a significant number of nurses to follow-up. Finally, we did not collect objective data on preference for administration of in-service at mid-shift vs shift change. We relied on subjective data from conversations with our colleagues. By collecting objective data, we could have supported this change to our intervention with data.

The primary challenge to sustainability for this intervention is nursing turnover. With each wave of departing nurses and new nursing hires, the difficulty of ensuring a consistent knowledge base and management standards within our nursing workforce became clearer. After optimizing our intervention, our solution was to provide a hospital-wide in-service, which was recorded and uploaded to an institution-wide in-service library. In this way, a nurse with the desire to learn about epistaxis management could access the material at any point in time. Another solution would have been to appoint champions for epistaxis management within each major department to deliver the epistaxis in-service to new hires and new rotators within the department. However, given the turnover witnessed in our study cohort, this may not be sustainable long term.

Conclusion

Epistaxis is a chief complaint that can present in many different clinical settings and situations. Therefore, the ability to stop epistaxis in a timely and effective fashion is valuable. Our study demonstrated that in-services can improve epistaxis knowledge and improve perceived epistaxis management. Ideally, this intervention will lead to improved patient care. Given that epistaxis is a ubiquitous issue, this study may benefit other institutions who want to improve care for patients with epistaxis.

Next steps for this intervention include utilizing in-services for epistaxis education at other institutions and collecting long-term data within our own institution. Collecting long-term data would allow us to assess the retention of epistaxis knowledge from our in-service.

Acknowledgments: The author thanks the nurse managers, nurse educators, and staff nurses involved in this project, as well as Dr. Louis Portugal for providing mentorship throughout this process and Dr. Dara Adams for assisting with statistical analysis.

Corresponding author: Avery Nelson, MD, University of Chicago Medical Center, 5841 S Maryland Ave, MC 1035, Chicago, IL 60637; [email protected]

Disclosures: None reported.

From the University of Chicago Medical Center, Chicago, IL.

Abstract

Background: Epistaxis is a common chief complaint addressed by otolaryngologists. A review of the literature showed that there is a deficit in epistaxis education within the nursing community. Conversations with our nursing colleagues confirmed this unmet demand.

Objective: This quality improvement project aimed to increase general epistaxis knowledge, perceived comfort level managing nosebleeds, and perceived ability to stop nosebleeds among our nursing staff.

Methods: Data were collected through a survey administered before and after our intervention. The survey tested general epistaxis knowledge and assessed comfort and confidence in stopping epistaxis. Our intervention was an educational session covering pertinent epistaxis etiology and management. Quality improvement principles were used to optimize delivery of the intervention.

Results: A total of 51 nurses participated in the project. After participating in the in-service educational session, nurses answered significantly more epistaxis general knowledge questions correctly (mean [SD] difference, 2.07 [1.10] questions; 95% CI, 1.74-2.39; P < .001). There was no statistically significant difference in additional correct questions when stratified by clinical experience or clinical setting (P = .128 and P = 0.446, respectively). Nurses also reported feeling significantly more comfortable and significantly more confident in managing nosebleeds after the in-service (P = .007 and P < 0.001, respectively); 74.46% of nurses had an improvement in comfort level in managing epistaxis and 43.90% of nurses had an improvement in confidence in stopping epistaxis. After we moved the educational session from mid-shift to shift change, the nursing staff reported more satisfaction while maintaining similar improvements in knowledge and confidence.

Conclusion: We were able to significantly increase epistaxis knowledge, improve comfort levels managing epistaxis, and improve confidence in successful epistaxis management. Nurses of varying clinical experience and different clinical settings benefitted equally from our intervention.

Keywords: nosebleed; in-service; quality improvement.

Epistaxis, or nosebleed, is estimated to be the chief complaint in 1 in 200 emergency department visits in the United States.¹ Additionally, it represents up to one-third of otolaryngology-related emergency room admissions.² There is no existing literature, to our best knowledge, specifically investigating the incidence of epistaxis after a patient is admitted. Anecdotally, inpatients who develop epistaxis account for an appreciable number of consults to otolaryngology (ENT). Epistaxis is a cross-disciplinary issue, occurring in a range of clinical settings. For example, patients with epistaxis can present to the emergency department or to an outpatient primary care clinic before being referred to ENT. Additionally, inpatients on many different services can develop spontaneous epistaxis due to a variety of environmental and iatrogenic factors, such as dry air, use of nasal cannula, and initiation of anticoagulation. Based on the experience of our ENT providers and discussions with our nursing colleagues, we concluded that there was an interest in epistaxis management training among our nursing workforce.

The presence of unmet demand for epistaxis education among our nursing colleagues was supported by our literature review. A study performed in England surveyed emergency department nurses on first aid measures for management of epistaxis, including ideal head positioning, location of pressure application, and duration of pressure application.³ Overall, only 12% to 14% of the nursing staff answered all 3 questions correctly.³ Additionally, 73% to 78% of the nursing staff felt that their training in epistaxis management was inadequate, and 88% desired further training in epistaxis management.³ If generalized, this study confirms the demand for further epistaxis education among nurses.

In-services have previously been shown to be effective educational tools within the nursing community. A study in Ethiopia that evaluated pain management knowledge and attitudes before and after an in-service found a significant improvement in mean rank score of nurses’ knowledge and attitudes regarding pain management after they participated in the in-service.⁴ Scores on the knowledge survey improved from 41.4% before the intervention to 63.0% post intervention.⁴ A study in Connecticut evaluated nurses’ confidence in discussing suicidal ideation with patients and knowledge surrounding suicide precautions.⁵ After participating in an in-service, nurses were significantly more confident in discussing suicidal ideation with patients; application of appropriate suicide precautions also increased after the in-service.⁵

Our aim was for nurses to have an improvement in overall epistaxis knowledge, perceived comfort level managing nosebleeds, and perceived ability to stop nosebleeds after attending our in-service. Additionally, an overarching priority was to provide high-quality epistaxis education based on the literature and best practice guidelines.

Methods

Setting

This study was carried out at an 811-bed quaternary care center located in Chicago, Illinois. In fiscal year 2021, there were 91 643 emergency department visits and 33 805 hospital admissions. At our flagship hospital, 2658 patients were diagnosed with epistaxis during fiscal year 2021. The emergency department saw 533 patients with epistaxis, with 342 requiring admission and 191 being discharged. Separately, 566 inpatients received a diagnosis of epistaxis during their admission. The remainder of the patients with epistaxis were seen on an outpatient basis.

Data Collection

Data were collected from nurses on 5 different inpatient units. An email with information about the in-service was sent to the nurse managers of the inpatient units. These 5 units were included because the nurse managers responded to the email and facilitated delivery of the in-service. Data collection took place from August to December 2020.

Intervention

A quality improvement team composed of a resident physician champion, nurse educators, and nurse managers was formed. The physician champion was a senior otolaryngology resident who was responsible for designing and administering the pre-test, in-service, and post test. The nurse educators and nurse managers helped coordinate times for the in-service and promoted the in-service for their staff.

Our intervention was an educational in-service, a technique that is commonly used at our institution for nurse education. In-services typically involve delivering a lecture on a clinically relevant topic to a group of nurses on a unit. In developing the in-service, a top priority was to present high-quality evidence-based material. There is an abundance of information in the literature surrounding epistaxis management. The clinical practice guideline published by the American Academy of Otolaryngology lists nasal compression, application of vasoconstrictors, nasal packing, and nasal cautery as first-line treatments for the management of epistaxis.⁶ Nasal packing and nasal cautery tend to be perceived as interventions that require a certain level of expertise and specialized supplies. As such, these interventions are not often performed by floor nurses. In contrast, nasal compression and application of vasoconstrictors require only a few easily accessible supplies, and the risks are relatively minimal. When performing nasal compression, the clinical practice guidelines recommend firm, sustained compression to the lower third of the nose for 5 minutes or longer.⁶ Topical vasoconstrictors are generally underutilized in epistaxis management. In a study looking at a random sample of all US emergency department visits from 1992 to 2001, only 18% of visits used an epistaxis-related medication.² Oxymetazoline hydrochloride is a topical vasoconstrictor that is commonly used as a nasal decongestant. However, its vasoconstrictor properties also make it a useful tool for controlling epistaxis. In a study looking at emergency department visits at the University of Texas Health Science Center, 65% of patients had resolution of nosebleed with application of oxymetazoline hydrochloride as the only intervention, with another 18% experiencing resolution of nosebleed with a combination of oxymetazoline hydrochloride and silver nitrate cautery.⁷ Based on review of the literature, nasal compression and application of vasoconstrictors seemed to be low-resource interventions with minimal morbidity. Therefore, management centered around nasal compression and use of topical vasoconstrictors seemed appropriate for our nursing staff.

The in-service included information about the etiology and management of epistaxis. Particular emphasis was placed on addressing and debunking common misconceptions about nosebleed management. With regards to management, our presentation focused on the use of topical vasoconstrictors and firm pressure to the lower third of the nose for at least 5 minutes. Nasal packing and nasal cautery were presented as procedures that ENT would perform. After the in-service, questions from the nurses were answered as time permitted.

Testing and Outcomes

A pre-test was administered before each in-service. The pre-test components comprised a knowledge survey and a descriptive survey. The general epistaxis knowledge questions on the pre-test included the location of blood vessels most commonly responsible for nosebleeds, the ideal positioning of a patient during a nosebleed, the appropriate location to hold pressure during a nosebleed, and the appropriate duration to hold pressure during a nosebleed. The descriptive survey portion asked nurses to rate whether they felt “very comfortable,” “comfortable,” “uncomfortable,” or “very uncomfortable” managing nosebleeds. It also asked whether nurses thought they would be able to “always,” “usually,” “rarely,” or “never” stop nosebleeds on the floor. We collected demographic information, including gender identity, years of clinical experience, and primary clinical environment.

The post test asked the same questions as the pre-test and was administered immediately after the in-service in order to assess its impact. We also established an ongoing dialogue with our nursing colleagues to obtain feedback on the sessions.

Primary outcomes of interest were the difference in general epistaxis knowledge questions answered correctly between the pre-test and the post test; the difference in comfort level in managing epistaxis before and after the in-service; and the difference in confidence to stop nosebleeds before and after the in-service. A secondary outcome was determining the audience for the in-service. Specifically, we wanted to determine whether there were different outcomes based on clinical setting or years of clinical experience. If nurses in a certain clinical environment or beyond a certain experience level did not show significant improvement from pre-test to post test, we would not target them for the in-service. Another secondary outcome was determining optimal timing for delivery of the in-service. We wanted to determine if there was a nursing preference for delivering the in-service at mid-shift vs shift change.

Analysis

Statistical calculations were performed using Stata 15 (StataCorp LLC). A P value < .05 was considered to be statistically significant. Where applicable, 95% confidence intervals (CI) were calculated. T-test was used to determine whether there was a statistically significant difference between pre-test and post-test epistaxis knowledge question scores. T-test was also used to determine whether there was a statistically significant difference in test scores between nurses receiving the in-service at mid-shift vs shift change. Pearson chi-squared tests were used to determine if there was a statistically significant difference between pre-test and post-test perceptions of epistaxis management, and to investigate outcomes between different subsets of nurses.

SQUIRE 2.0 guidelines were utilized to provide a framework for this project and to structure the manuscript.⁸ This study met criteria for exemption from institutional review board approval.

Results

Fifty-one nurses took part in this project (Table). The majority of participants identified as female (88.24%), and just over half worked on medical floors (52.94%), with most of the remainder working in intensive care (25.49%) and surgical (15.69%) settings. There was a wide range of clinical experience, with 1.96% reporting 0 to 1 years of experience, 29.41% reporting 2 to 5 years, 23.53% reporting 5 to 10 years, 25.49% reporting 10 to 20 years, and 17.65% reporting more than 20 years.

There were unanswered questions on both the pre-test and post test. There was no consistently unanswered question. Omitted answers on the epistaxis knowledge questions were recorded as an “incorrect” answer. Omitted answers on the perception questions were considered null values and not considered in final analysis.

Primary Measures

General epistaxis knowledge (Figure, part A) improved from the pre-test, where out of 4 questions, the mean (SD) score was 1.74 (1.02) correct questions, to the post-test, where out of 4 questions, the mean score was 3.80 (0.40) correct questions. After participating in the in-service, nurses answered significantly more questions about epistaxis general knowledge correctly (mean difference, 2.07 [1.10]; 95% CI, 1.74-2.39; P < .001), and 80.43% of them got a perfect score on the epistaxis knowledge questions.

The second primary measure was the difference in comfort level in managing nosebleed. After participating in the in-service, nurses felt significantly more comfortable in managing nosebleeds (Figure, part B; P = .007), with 74.46% of nurses having an improved comfort level managing nosebleeds. Before the in-service, 12.76% of nurses felt “very comfortable” in managing nosebleeds vs more than three-quarters (76.59%) after the in-service. Of those who answered that they felt “comfortable” managing nosebleeds on the pre-test, 82.35% improved to feeling “very comfortable” in managing nosebleeds. Before the in-service, 14.89% of nurses felt “uncomfortable” or “very uncomfortable” in managing nosebleeds, and this decreased to 0 post intervention. After the in-service, 100.00% of nurses felt “comfortable” or “very comfortable” in managing nosebleeds.

After receiving the in-service, nurses felt significantly more confident in stopping nosebleeds (Figure, part C; P < .001), with 43.90% of them having an improvement in confidence in stopping epistaxis. Before the in-service, 7.31% of nurses felt that they would “always” be able to stop a nose-bleed, and this increased to 41.46% after the in-service. Of those who answered that they felt that they would “usually” be able to stop a nosebleed on the pre-test, 36.67% changed their answer to state that they would “always” be able to stop a nosebleed on the post test. Before the in-service, 19.51% of nurses felt that they would “rarely” or “never” be able to stop a nosebleed, and this decreased to 2.44% after the in-service.

Secondary Measures

All of the nurses who participated either “strongly agreed” or “agreed” that they learned something new from the in-service. However, to determine whether there was a population who would benefit most from the in-service, we stratified the data by years of clinical experience. There was no statistically significant difference in whether nurses with varying clinical experience learned something new (P = .148): 100% of nurses with 0-1 years of experience, 80.00% of nurses with 2-5 years of experience, 100% of nurses with 5-10 years of experience, 69.23% of nurses with 10-20 years of experience, and 100% of nurses with >20 years of experience “strongly agreed” that they learned something new from this in-service. There was no statistically significant difference on the post test compared to the pre-test in additional correct questions when stratified by clinical experience (P = .128). Second, when we stratified by clinical setting, we did not find a statistically significant difference in whether nurses in different clinical settings learned something new (P = .929): 88.89% of nurses in the medical setting, 87.50% of nurses in the surgical setting, and 84.62% of nurses in the intensive care setting “strongly agreed” that they learned something new from this presentation. On investigating additional questions correct on the post test compared to the pre-test, there was no statistically significant difference in additional correct questions when stratified by clinical setting (P = .446).

Optimal timing of the in-service was another important outcome. Initially, the in-service was administered at mid-shift, with 9 nurses participating at mid-shift, but our nursing colleagues gave unanimous feedback that this was a suboptimal time for delivery of an in-service. We changed the timing of the in-service to shift change; 42 nurses received the in-service at shift-change. There was no statistically significant difference in scores on the epistaxis knowledge questions between these two groups (P = .123). This indicated to us that changing the timing of the delivery resulted in similarly improved outcomes while having the added benefit of being preferred by our nursing colleagues.

Discussion

In undertaking this project, our primary aims were to improve epistaxis knowledge and perceived management in our nursing staff. Among our nursing staff, we were able to significantly increase epistaxis knowledge, improve comfort levels managing epistaxis, and improve confidence in successful epistaxis management. We also found that nurses of varying clinical experience and different clinical settings benefited equally from our intervention. Using quality improvement principles, we optimized our delivery. Our in-service focused on educating nurses to use epistaxis management techniques that were resource-efficient and low risk.

After participating in the in-service, nurses answered significantly more questions about epistaxis general knowledge correctly (Figure, part A; mean difference, 2.07 questions [1.10]; 95% CI, 1.74-2.39; P < .001), felt significantly more comfortable in managing nosebleeds (Figure, part B; P = .007), and felt significantly more confident in stopping nosebleeds (Figure, part C; P < .001). Based on these results, we successfully achieved our primary aims.

Our secondary aim was to determine the audience that would benefit the most from the in-service. All of the nurses who participated either “strongly agreed” or “agreed” that they learned something new from the in-service. There was no statistically significant difference in whether nurses of varying clinical experience learned something new (P = .148) or in additional correct questions when stratified by clinical experience (P =.128). Also, there was no statistically significant difference in whether nurses in different clinical settings learned something new (P = .929) or in additional correct questions when stratified by clinical setting (P = .446). These results indicated to us that all participants learned something new and that there was no specific target audience, but rather that all participants benefitted from our session.

Our nursing colleagues gave us feedback that the timing of the in-service during mid-shift was not ideal. It was difficult to gather nurses mid-shift due to pressing patient-care duties. Nurses also found it difficult to give their full attention at this time. Nurses, nurse educators, and nurse managers suggested that we conduct the in-service at shift change in order to capture a larger population and take advantage of time relatively free of clinical duties. Giving the in-service at a time with relatively fewer clinical responsibilities allowed for a more robust question-and-answer session. It also allowed our nursing colleagues to pay full attention to the in-service. There was no statistically significant difference in epistaxis general knowledge questions answered correctly; this indicates that the quality of the education session did not vary greatly. However, our nursing colleagues strongly preferred the in-service at shift change. By making this modification to our intervention, we were able to optimize our intervention.

The previously mentioned study in England reported that only 12% to 14% of their nursing staff got a perfect score on epistaxis knowledge questions. Prior to our study, there was no literature investigating the impact of an in-service on epistaxis knowledge. After our intervention, 80.43% of our nurses got a perfect score on the epistaxis knowledge questions. We believe that this is a fair comparison because our post-test questions were identical to the survey questions used in the previously mentioned study in England, with the addition of one question.³ Further, the findings of our study are consistent with other studies regarding the positive effect of in-service education on knowledge and attitudes surrounding clinical topics. Similar to the study in Ethiopia investigating nurses’ knowledge surrounding pain management, our study noted a significant improvement in nurses’ knowledge after participating in the in-service.⁴ Also, when comparing our study to the study performed in Connecticut investigating nurses’ confidence surrounding suicide precautions, we found a similar significant improvement in confidence in management after participating in the in-service.⁵

Given our reliance on a survey as a tool to collect information, our study was subject to nonresponse bias. For each main outcome question, there was a handful of nonresponders. While this likely indicated either overlooking a question or deferring to answer due to clinical inexperience or nonapplicable clinical role, it is possible that this may have represented a respondent who did not benefit from the in-service. Another source of possible bias is sampling bias. Attempts were made to capture a wide range of nurses at the in-service. However, if a nurse was not interested in the topic material, whether due to abundant clinical experience or disinterest, it is possible that they may not have attended. Additionally, the cohort was selected purely based on responses from nursing managers to the initial email. It is possible that nonresponding units may have benefitted differently from this in-service.

There were several limitations within our analysis. We did not collect data assessing the long-term retention of epistaxis knowledge and management techniques. It is possible that epistaxis knowledge, comfort in managing nosebleeds, and perceived confidence in stopping nosebleeds decreased back to baseline several months after the in-service. Ideally, we would have been able to collect this data to assess retention of the in-service information. Unfortunately, a significant number of nurses who initially participated in the project became lost to follow-up, making such data collection impossible. Additionally, there was no assessment of actual ability to stop nosebleeds before vs after this in-service. Perceived management of epistaxis vs actual management of epistaxis are 2 vastly different things. However, this data would have been difficult to collect, and it likely would not have been in the best interest of patients, especially before the in-service was administered. As an improvement to this project, we could have assessed how many nosebleeds nurses had seen and successfully stopped after the in-service. As previously mentioned, this was not possible due to losing a significant number of nurses to follow-up. Finally, we did not collect objective data on preference for administration of in-service at mid-shift vs shift change. We relied on subjective data from conversations with our colleagues. By collecting objective data, we could have supported this change to our intervention with data.

The primary challenge to sustainability for this intervention is nursing turnover. With each wave of departing nurses and new nursing hires, the difficulty of ensuring a consistent knowledge base and management standards within our nursing workforce became clearer. After optimizing our intervention, our solution was to provide a hospital-wide in-service, which was recorded and uploaded to an institution-wide in-service library. In this way, a nurse with the desire to learn about epistaxis management could access the material at any point in time. Another solution would have been to appoint champions for epistaxis management within each major department to deliver the epistaxis in-service to new hires and new rotators within the department. However, given the turnover witnessed in our study cohort, this may not be sustainable long term.

Conclusion

Epistaxis is a chief complaint that can present in many different clinical settings and situations. Therefore, the ability to stop epistaxis in a timely and effective fashion is valuable. Our study demonstrated that in-services can improve epistaxis knowledge and improve perceived epistaxis management. Ideally, this intervention will lead to improved patient care. Given that epistaxis is a ubiquitous issue, this study may benefit other institutions who want to improve care for patients with epistaxis.

Next steps for this intervention include utilizing in-services for epistaxis education at other institutions and collecting long-term data within our own institution. Collecting long-term data would allow us to assess the retention of epistaxis knowledge from our in-service.

Acknowledgments: The author thanks the nurse managers, nurse educators, and staff nurses involved in this project, as well as Dr. Louis Portugal for providing mentorship throughout this process and Dr. Dara Adams for assisting with statistical analysis.

Corresponding author: Avery Nelson, MD, University of Chicago Medical Center, 5841 S Maryland Ave, MC 1035, Chicago, IL 60637; [email protected]

Disclosures: None reported.

From the University of Chicago Medical Center, Chicago, IL.

Abstract

Background: Epistaxis is a common chief complaint addressed by otolaryngologists. A review of the literature showed that there is a deficit in epistaxis education within the nursing community. Conversations with our nursing colleagues confirmed this unmet demand.

Objective: This quality improvement project aimed to increase general epistaxis knowledge, perceived comfort level managing nosebleeds, and perceived ability to stop nosebleeds among our nursing staff.

Methods: Data were collected through a survey administered before and after our intervention. The survey tested general epistaxis knowledge and assessed comfort and confidence in stopping epistaxis. Our intervention was an educational session covering pertinent epistaxis etiology and management. Quality improvement principles were used to optimize delivery of the intervention.

Results: A total of 51 nurses participated in the project. After participating in the in-service educational session, nurses answered significantly more epistaxis general knowledge questions correctly (mean [SD] difference, 2.07 [1.10] questions; 95% CI, 1.74-2.39; P < .001). There was no statistically significant difference in additional correct questions when stratified by clinical experience or clinical setting (P = .128 and P = 0.446, respectively). Nurses also reported feeling significantly more comfortable and significantly more confident in managing nosebleeds after the in-service (P = .007 and P < 0.001, respectively); 74.46% of nurses had an improvement in comfort level in managing epistaxis and 43.90% of nurses had an improvement in confidence in stopping epistaxis. After we moved the educational session from mid-shift to shift change, the nursing staff reported more satisfaction while maintaining similar improvements in knowledge and confidence.

Conclusion: We were able to significantly increase epistaxis knowledge, improve comfort levels managing epistaxis, and improve confidence in successful epistaxis management. Nurses of varying clinical experience and different clinical settings benefitted equally from our intervention.

Keywords: nosebleed; in-service; quality improvement.

Epistaxis, or nosebleed, is estimated to be the chief complaint in 1 in 200 emergency department visits in the United States.¹ Additionally, it represents up to one-third of otolaryngology-related emergency room admissions.² There is no existing literature, to our best knowledge, specifically investigating the incidence of epistaxis after a patient is admitted. Anecdotally, inpatients who develop epistaxis account for an appreciable number of consults to otolaryngology (ENT). Epistaxis is a cross-disciplinary issue, occurring in a range of clinical settings. For example, patients with epistaxis can present to the emergency department or to an outpatient primary care clinic before being referred to ENT. Additionally, inpatients on many different services can develop spontaneous epistaxis due to a variety of environmental and iatrogenic factors, such as dry air, use of nasal cannula, and initiation of anticoagulation. Based on the experience of our ENT providers and discussions with our nursing colleagues, we concluded that there was an interest in epistaxis management training among our nursing workforce.

The presence of unmet demand for epistaxis education among our nursing colleagues was supported by our literature review. A study performed in England surveyed emergency department nurses on first aid measures for management of epistaxis, including ideal head positioning, location of pressure application, and duration of pressure application.³ Overall, only 12% to 14% of the nursing staff answered all 3 questions correctly.³ Additionally, 73% to 78% of the nursing staff felt that their training in epistaxis management was inadequate, and 88% desired further training in epistaxis management.³ If generalized, this study confirms the demand for further epistaxis education among nurses.

In-services have previously been shown to be effective educational tools within the nursing community. A study in Ethiopia that evaluated pain management knowledge and attitudes before and after an in-service found a significant improvement in mean rank score of nurses’ knowledge and attitudes regarding pain management after they participated in the in-service.⁴ Scores on the knowledge survey improved from 41.4% before the intervention to 63.0% post intervention.⁴ A study in Connecticut evaluated nurses’ confidence in discussing suicidal ideation with patients and knowledge surrounding suicide precautions.⁵ After participating in an in-service, nurses were significantly more confident in discussing suicidal ideation with patients; application of appropriate suicide precautions also increased after the in-service.⁵

Our aim was for nurses to have an improvement in overall epistaxis knowledge, perceived comfort level managing nosebleeds, and perceived ability to stop nosebleeds after attending our in-service. Additionally, an overarching priority was to provide high-quality epistaxis education based on the literature and best practice guidelines.

Methods

Setting

This study was carried out at an 811-bed quaternary care center located in Chicago, Illinois. In fiscal year 2021, there were 91 643 emergency department visits and 33 805 hospital admissions. At our flagship hospital, 2658 patients were diagnosed with epistaxis during fiscal year 2021. The emergency department saw 533 patients with epistaxis, with 342 requiring admission and 191 being discharged. Separately, 566 inpatients received a diagnosis of epistaxis during their admission. The remainder of the patients with epistaxis were seen on an outpatient basis.

Data Collection

Data were collected from nurses on 5 different inpatient units. An email with information about the in-service was sent to the nurse managers of the inpatient units. These 5 units were included because the nurse managers responded to the email and facilitated delivery of the in-service. Data collection took place from August to December 2020.

Intervention

A quality improvement team composed of a resident physician champion, nurse educators, and nurse managers was formed. The physician champion was a senior otolaryngology resident who was responsible for designing and administering the pre-test, in-service, and post test. The nurse educators and nurse managers helped coordinate times for the in-service and promoted the in-service for their staff.

Our intervention was an educational in-service, a technique that is commonly used at our institution for nurse education. In-services typically involve delivering a lecture on a clinically relevant topic to a group of nurses on a unit. In developing the in-service, a top priority was to present high-quality evidence-based material. There is an abundance of information in the literature surrounding epistaxis management. The clinical practice guideline published by the American Academy of Otolaryngology lists nasal compression, application of vasoconstrictors, nasal packing, and nasal cautery as first-line treatments for the management of epistaxis.⁶ Nasal packing and nasal cautery tend to be perceived as interventions that require a certain level of expertise and specialized supplies. As such, these interventions are not often performed by floor nurses. In contrast, nasal compression and application of vasoconstrictors require only a few easily accessible supplies, and the risks are relatively minimal. When performing nasal compression, the clinical practice guidelines recommend firm, sustained compression to the lower third of the nose for 5 minutes or longer.⁶ Topical vasoconstrictors are generally underutilized in epistaxis management. In a study looking at a random sample of all US emergency department visits from 1992 to 2001, only 18% of visits used an epistaxis-related medication.² Oxymetazoline hydrochloride is a topical vasoconstrictor that is commonly used as a nasal decongestant. However, its vasoconstrictor properties also make it a useful tool for controlling epistaxis. In a study looking at emergency department visits at the University of Texas Health Science Center, 65% of patients had resolution of nosebleed with application of oxymetazoline hydrochloride as the only intervention, with another 18% experiencing resolution of nosebleed with a combination of oxymetazoline hydrochloride and silver nitrate cautery.⁷ Based on review of the literature, nasal compression and application of vasoconstrictors seemed to be low-resource interventions with minimal morbidity. Therefore, management centered around nasal compression and use of topical vasoconstrictors seemed appropriate for our nursing staff.

The in-service included information about the etiology and management of epistaxis. Particular emphasis was placed on addressing and debunking common misconceptions about nosebleed management. With regards to management, our presentation focused on the use of topical vasoconstrictors and firm pressure to the lower third of the nose for at least 5 minutes. Nasal packing and nasal cautery were presented as procedures that ENT would perform. After the in-service, questions from the nurses were answered as time permitted.

Testing and Outcomes

A pre-test was administered before each in-service. The pre-test components comprised a knowledge survey and a descriptive survey. The general epistaxis knowledge questions on the pre-test included the location of blood vessels most commonly responsible for nosebleeds, the ideal positioning of a patient during a nosebleed, the appropriate location to hold pressure during a nosebleed, and the appropriate duration to hold pressure during a nosebleed. The descriptive survey portion asked nurses to rate whether they felt “very comfortable,” “comfortable,” “uncomfortable,” or “very uncomfortable” managing nosebleeds. It also asked whether nurses thought they would be able to “always,” “usually,” “rarely,” or “never” stop nosebleeds on the floor. We collected demographic information, including gender identity, years of clinical experience, and primary clinical environment.

The post test asked the same questions as the pre-test and was administered immediately after the in-service in order to assess its impact. We also established an ongoing dialogue with our nursing colleagues to obtain feedback on the sessions.

Primary outcomes of interest were the difference in general epistaxis knowledge questions answered correctly between the pre-test and the post test; the difference in comfort level in managing epistaxis before and after the in-service; and the difference in confidence to stop nosebleeds before and after the in-service. A secondary outcome was determining the audience for the in-service. Specifically, we wanted to determine whether there were different outcomes based on clinical setting or years of clinical experience. If nurses in a certain clinical environment or beyond a certain experience level did not show significant improvement from pre-test to post test, we would not target them for the in-service. Another secondary outcome was determining optimal timing for delivery of the in-service. We wanted to determine if there was a nursing preference for delivering the in-service at mid-shift vs shift change.

Analysis

Statistical calculations were performed using Stata 15 (StataCorp LLC). A P value < .05 was considered to be statistically significant. Where applicable, 95% confidence intervals (CI) were calculated. T-test was used to determine whether there was a statistically significant difference between pre-test and post-test epistaxis knowledge question scores. T-test was also used to determine whether there was a statistically significant difference in test scores between nurses receiving the in-service at mid-shift vs shift change. Pearson chi-squared tests were used to determine if there was a statistically significant difference between pre-test and post-test perceptions of epistaxis management, and to investigate outcomes between different subsets of nurses.

SQUIRE 2.0 guidelines were utilized to provide a framework for this project and to structure the manuscript.⁸ This study met criteria for exemption from institutional review board approval.

Results

Fifty-one nurses took part in this project (Table). The majority of participants identified as female (88.24%), and just over half worked on medical floors (52.94%), with most of the remainder working in intensive care (25.49%) and surgical (15.69%) settings. There was a wide range of clinical experience, with 1.96% reporting 0 to 1 years of experience, 29.41% reporting 2 to 5 years, 23.53% reporting 5 to 10 years, 25.49% reporting 10 to 20 years, and 17.65% reporting more than 20 years.

There were unanswered questions on both the pre-test and post test. There was no consistently unanswered question. Omitted answers on the epistaxis knowledge questions were recorded as an “incorrect” answer. Omitted answers on the perception questions were considered null values and not considered in final analysis.

Primary Measures

General epistaxis knowledge (Figure, part A) improved from the pre-test, where out of 4 questions, the mean (SD) score was 1.74 (1.02) correct questions, to the post-test, where out of 4 questions, the mean score was 3.80 (0.40) correct questions. After participating in the in-service, nurses answered significantly more questions about epistaxis general knowledge correctly (mean difference, 2.07 [1.10]; 95% CI, 1.74-2.39; P < .001), and 80.43% of them got a perfect score on the epistaxis knowledge questions.

The second primary measure was the difference in comfort level in managing nosebleed. After participating in the in-service, nurses felt significantly more comfortable in managing nosebleeds (Figure, part B; P = .007), with 74.46% of nurses having an improved comfort level managing nosebleeds. Before the in-service, 12.76% of nurses felt “very comfortable” in managing nosebleeds vs more than three-quarters (76.59%) after the in-service. Of those who answered that they felt “comfortable” managing nosebleeds on the pre-test, 82.35% improved to feeling “very comfortable” in managing nosebleeds. Before the in-service, 14.89% of nurses felt “uncomfortable” or “very uncomfortable” in managing nosebleeds, and this decreased to 0 post intervention. After the in-service, 100.00% of nurses felt “comfortable” or “very comfortable” in managing nosebleeds.

After receiving the in-service, nurses felt significantly more confident in stopping nosebleeds (Figure, part C; P < .001), with 43.90% of them having an improvement in confidence in stopping epistaxis. Before the in-service, 7.31% of nurses felt that they would “always” be able to stop a nose-bleed, and this increased to 41.46% after the in-service. Of those who answered that they felt that they would “usually” be able to stop a nosebleed on the pre-test, 36.67% changed their answer to state that they would “always” be able to stop a nosebleed on the post test. Before the in-service, 19.51% of nurses felt that they would “rarely” or “never” be able to stop a nosebleed, and this decreased to 2.44% after the in-service.

Secondary Measures

All of the nurses who participated either “strongly agreed” or “agreed” that they learned something new from the in-service. However, to determine whether there was a population who would benefit most from the in-service, we stratified the data by years of clinical experience. There was no statistically significant difference in whether nurses with varying clinical experience learned something new (P = .148): 100% of nurses with 0-1 years of experience, 80.00% of nurses with 2-5 years of experience, 100% of nurses with 5-10 years of experience, 69.23% of nurses with 10-20 years of experience, and 100% of nurses with >20 years of experience “strongly agreed” that they learned something new from this in-service. There was no statistically significant difference on the post test compared to the pre-test in additional correct questions when stratified by clinical experience (P = .128). Second, when we stratified by clinical setting, we did not find a statistically significant difference in whether nurses in different clinical settings learned something new (P = .929): 88.89% of nurses in the medical setting, 87.50% of nurses in the surgical setting, and 84.62% of nurses in the intensive care setting “strongly agreed” that they learned something new from this presentation. On investigating additional questions correct on the post test compared to the pre-test, there was no statistically significant difference in additional correct questions when stratified by clinical setting (P = .446).

Optimal timing of the in-service was another important outcome. Initially, the in-service was administered at mid-shift, with 9 nurses participating at mid-shift, but our nursing colleagues gave unanimous feedback that this was a suboptimal time for delivery of an in-service. We changed the timing of the in-service to shift change; 42 nurses received the in-service at shift-change. There was no statistically significant difference in scores on the epistaxis knowledge questions between these two groups (P = .123). This indicated to us that changing the timing of the delivery resulted in similarly improved outcomes while having the added benefit of being preferred by our nursing colleagues.

Discussion

In undertaking this project, our primary aims were to improve epistaxis knowledge and perceived management in our nursing staff. Among our nursing staff, we were able to significantly increase epistaxis knowledge, improve comfort levels managing epistaxis, and improve confidence in successful epistaxis management. We also found that nurses of varying clinical experience and different clinical settings benefited equally from our intervention. Using quality improvement principles, we optimized our delivery. Our in-service focused on educating nurses to use epistaxis management techniques that were resource-efficient and low risk.

After participating in the in-service, nurses answered significantly more questions about epistaxis general knowledge correctly (Figure, part A; mean difference, 2.07 questions [1.10]; 95% CI, 1.74-2.39; P < .001), felt significantly more comfortable in managing nosebleeds (Figure, part B; P = .007), and felt significantly more confident in stopping nosebleeds (Figure, part C; P < .001). Based on these results, we successfully achieved our primary aims.

Our secondary aim was to determine the audience that would benefit the most from the in-service. All of the nurses who participated either “strongly agreed” or “agreed” that they learned something new from the in-service. There was no statistically significant difference in whether nurses of varying clinical experience learned something new (P = .148) or in additional correct questions when stratified by clinical experience (P =.128). Also, there was no statistically significant difference in whether nurses in different clinical settings learned something new (P = .929) or in additional correct questions when stratified by clinical setting (P = .446). These results indicated to us that all participants learned something new and that there was no specific target audience, but rather that all participants benefitted from our session.

Our nursing colleagues gave us feedback that the timing of the in-service during mid-shift was not ideal. It was difficult to gather nurses mid-shift due to pressing patient-care duties. Nurses also found it difficult to give their full attention at this time. Nurses, nurse educators, and nurse managers suggested that we conduct the in-service at shift change in order to capture a larger population and take advantage of time relatively free of clinical duties. Giving the in-service at a time with relatively fewer clinical responsibilities allowed for a more robust question-and-answer session. It also allowed our nursing colleagues to pay full attention to the in-service. There was no statistically significant difference in epistaxis general knowledge questions answered correctly; this indicates that the quality of the education session did not vary greatly. However, our nursing colleagues strongly preferred the in-service at shift change. By making this modification to our intervention, we were able to optimize our intervention.

The previously mentioned study in England reported that only 12% to 14% of their nursing staff got a perfect score on epistaxis knowledge questions. Prior to our study, there was no literature investigating the impact of an in-service on epistaxis knowledge. After our intervention, 80.43% of our nurses got a perfect score on the epistaxis knowledge questions. We believe that this is a fair comparison because our post-test questions were identical to the survey questions used in the previously mentioned study in England, with the addition of one question.³ Further, the findings of our study are consistent with other studies regarding the positive effect of in-service education on knowledge and attitudes surrounding clinical topics. Similar to the study in Ethiopia investigating nurses’ knowledge surrounding pain management, our study noted a significant improvement in nurses’ knowledge after participating in the in-service.⁴ Also, when comparing our study to the study performed in Connecticut investigating nurses’ confidence surrounding suicide precautions, we found a similar significant improvement in confidence in management after participating in the in-service.⁵

Given our reliance on a survey as a tool to collect information, our study was subject to nonresponse bias. For each main outcome question, there was a handful of nonresponders. While this likely indicated either overlooking a question or deferring to answer due to clinical inexperience or nonapplicable clinical role, it is possible that this may have represented a respondent who did not benefit from the in-service. Another source of possible bias is sampling bias. Attempts were made to capture a wide range of nurses at the in-service. However, if a nurse was not interested in the topic material, whether due to abundant clinical experience or disinterest, it is possible that they may not have attended. Additionally, the cohort was selected purely based on responses from nursing managers to the initial email. It is possible that nonresponding units may have benefitted differently from this in-service.

There were several limitations within our analysis. We did not collect data assessing the long-term retention of epistaxis knowledge and management techniques. It is possible that epistaxis knowledge, comfort in managing nosebleeds, and perceived confidence in stopping nosebleeds decreased back to baseline several months after the in-service. Ideally, we would have been able to collect this data to assess retention of the in-service information. Unfortunately, a significant number of nurses who initially participated in the project became lost to follow-up, making such data collection impossible. Additionally, there was no assessment of actual ability to stop nosebleeds before vs after this in-service. Perceived management of epistaxis vs actual management of epistaxis are 2 vastly different things. However, this data would have been difficult to collect, and it likely would not have been in the best interest of patients, especially before the in-service was administered. As an improvement to this project, we could have assessed how many nosebleeds nurses had seen and successfully stopped after the in-service. As previously mentioned, this was not possible due to losing a significant number of nurses to follow-up. Finally, we did not collect objective data on preference for administration of in-service at mid-shift vs shift change. We relied on subjective data from conversations with our colleagues. By collecting objective data, we could have supported this change to our intervention with data.

The primary challenge to sustainability for this intervention is nursing turnover. With each wave of departing nurses and new nursing hires, the difficulty of ensuring a consistent knowledge base and management standards within our nursing workforce became clearer. After optimizing our intervention, our solution was to provide a hospital-wide in-service, which was recorded and uploaded to an institution-wide in-service library. In this way, a nurse with the desire to learn about epistaxis management could access the material at any point in time. Another solution would have been to appoint champions for epistaxis management within each major department to deliver the epistaxis in-service to new hires and new rotators within the department. However, given the turnover witnessed in our study cohort, this may not be sustainable long term.

Conclusion

Epistaxis is a chief complaint that can present in many different clinical settings and situations. Therefore, the ability to stop epistaxis in a timely and effective fashion is valuable. Our study demonstrated that in-services can improve epistaxis knowledge and improve perceived epistaxis management. Ideally, this intervention will lead to improved patient care. Given that epistaxis is a ubiquitous issue, this study may benefit other institutions who want to improve care for patients with epistaxis.

Next steps for this intervention include utilizing in-services for epistaxis education at other institutions and collecting long-term data within our own institution. Collecting long-term data would allow us to assess the retention of epistaxis knowledge from our in-service.

Acknowledgments: The author thanks the nurse managers, nurse educators, and staff nurses involved in this project, as well as Dr. Louis Portugal for providing mentorship throughout this process and Dr. Dara Adams for assisting with statistical analysis.

Corresponding author: Avery Nelson, MD, University of Chicago Medical Center, 5841 S Maryland Ave, MC 1035, Chicago, IL 60637; [email protected]

Disclosures: None reported.

Authors' Response

We agree with the valid comments made by Dr. Kerguelen and will respond to each set of questions in order.

Regarding the first set of questions on how we knew that our CMI was low and our patient acuity was under- represented, the University of Miami Health System is a designated cancer center with a Prospective Payment System exempt model (PPS exempt), and is one of 11 hospitals in the United States excluded for payment under the Inpatient Prospective Payment System. We know, therefore, that we care for a very complex patient population. Additionally, we benchmark ourselves against other academic medical centers (AMCs) with similarly complex patients and had noted that our patients appeared “less complex.” Specifically, our baseline CMI was 1.77 in early 2018 compared with an overall higher CMI for the AMC cohort; also, the total number of diagnoses we captured was lower than that in other AMCs. These 2 facts together alerted us that we likely had coding and clinical documentation improvement (CDI) opportunities. We recognized that our complexity was not being captured both because the clinical information was not documented in a manner readily translatable to ICD-10 codes and codes were missed when the documentation did exist. To remedy these problems, we implemented multiple immediate “fixes,” which included revamping our CDI efforts, re-education, and enhancements to our electronic health record for providers, CDIs, and coders. Since publication of our article, our CMI has continued to increase month over month, up to 2.57 most recently in May 2022, as we have continued to focus on several additional initiatives to impact both better documentation and coding.

The second set of questions asked whether the perceived low CMI was causing problems with payers and about the risk of artificially increasing the CMI through overdiagnosis as well as audit mechanisms to avoid this, and changes in expected mortality and observed mortality. To our knowledge, the lower CMI did not cause any problems with payers, but this is something we are currently tracking. Coding and documentation are constantly audited both internally (by our quality department) and externally (using Inter-Rater Reliability audits and validation), with no noted trend or targeted opportunities. We only include comorbidities that are current, actively monitored/managed, and pertinent to the care of our patients. We have not noted a change in denials, which gives us confidence we are not now overdiagnosing.

Our observed mortality has also increased. We, like all institutions, experienced the confounding factor of the COVID-19 pandemic, which coincided with the higher observed mortality over the course of the past 2 years. While the observed mortality (indicating sicker patients assuming no worsening of care processes) may partly explain our increased coding complexity, our decreasing mortality index (observed:expected mortality) suggests that our efforts to improve documentation and coding likely reflect improved capture of missed complexity (Figure).

We understand the concerns raised by Dr. Kerguelen about potential mis(over)coding. As part of this quality initiative, therefore, we plan long-term evaluations of our processes and metrics to better determine and guide our understanding of the impact of what we have already implemented and future interventions. In fact, we are in the process of analyzing additional interventions and hope to share results from these evaluations soon.

Marie Anne Sosa, MD
Tanira Ferreira, MD
Hayley Gershengorn, MD
Melissa Soto
Estin Kelly
Ameena Shrestha
Julianne Burgos
Sandeep Devabhaktuni
Dipen Parekh, MD
Maritza Suarez, MD
University of Miami Hospital and Clinics, Miami, FL
[email protected]

Disclosures: None reported.

Authors' Response

We agree with the valid comments made by Dr. Kerguelen and will respond to each set of questions in order.

Regarding the first set of questions on how we knew that our CMI was low and our patient acuity was under- represented, the University of Miami Health System is a designated cancer center with a Prospective Payment System exempt model (PPS exempt), and is one of 11 hospitals in the United States excluded for payment under the Inpatient Prospective Payment System. We know, therefore, that we care for a very complex patient population. Additionally, we benchmark ourselves against other academic medical centers (AMCs) with similarly complex patients and had noted that our patients appeared “less complex.” Specifically, our baseline CMI was 1.77 in early 2018 compared with an overall higher CMI for the AMC cohort; also, the total number of diagnoses we captured was lower than that in other AMCs. These 2 facts together alerted us that we likely had coding and clinical documentation improvement (CDI) opportunities. We recognized that our complexity was not being captured both because the clinical information was not documented in a manner readily translatable to ICD-10 codes and codes were missed when the documentation did exist. To remedy these problems, we implemented multiple immediate “fixes,” which included revamping our CDI efforts, re-education, and enhancements to our electronic health record for providers, CDIs, and coders. Since publication of our article, our CMI has continued to increase month over month, up to 2.57 most recently in May 2022, as we have continued to focus on several additional initiatives to impact both better documentation and coding.

The second set of questions asked whether the perceived low CMI was causing problems with payers and about the risk of artificially increasing the CMI through overdiagnosis as well as audit mechanisms to avoid this, and changes in expected mortality and observed mortality. To our knowledge, the lower CMI did not cause any problems with payers, but this is something we are currently tracking. Coding and documentation are constantly audited both internally (by our quality department) and externally (using Inter-Rater Reliability audits and validation), with no noted trend or targeted opportunities. We only include comorbidities that are current, actively monitored/managed, and pertinent to the care of our patients. We have not noted a change in denials, which gives us confidence we are not now overdiagnosing.

Our observed mortality has also increased. We, like all institutions, experienced the confounding factor of the COVID-19 pandemic, which coincided with the higher observed mortality over the course of the past 2 years. While the observed mortality (indicating sicker patients assuming no worsening of care processes) may partly explain our increased coding complexity, our decreasing mortality index (observed:expected mortality) suggests that our efforts to improve documentation and coding likely reflect improved capture of missed complexity (Figure).

We understand the concerns raised by Dr. Kerguelen about potential mis(over)coding. As part of this quality initiative, therefore, we plan long-term evaluations of our processes and metrics to better determine and guide our understanding of the impact of what we have already implemented and future interventions. In fact, we are in the process of analyzing additional interventions and hope to share results from these evaluations soon.

Marie Anne Sosa, MD
Tanira Ferreira, MD
Hayley Gershengorn, MD
Melissa Soto
Estin Kelly
Ameena Shrestha
Julianne Burgos
Sandeep Devabhaktuni
Dipen Parekh, MD
Maritza Suarez, MD
University of Miami Hospital and Clinics, Miami, FL
[email protected]

Disclosures: None reported.

Authors' Response

We agree with the valid comments made by Dr. Kerguelen and will respond to each set of questions in order.

Regarding the first set of questions on how we knew that our CMI was low and our patient acuity was under- represented, the University of Miami Health System is a designated cancer center with a Prospective Payment System exempt model (PPS exempt), and is one of 11 hospitals in the United States excluded for payment under the Inpatient Prospective Payment System. We know, therefore, that we care for a very complex patient population. Additionally, we benchmark ourselves against other academic medical centers (AMCs) with similarly complex patients and had noted that our patients appeared “less complex.” Specifically, our baseline CMI was 1.77 in early 2018 compared with an overall higher CMI for the AMC cohort; also, the total number of diagnoses we captured was lower than that in other AMCs. These 2 facts together alerted us that we likely had coding and clinical documentation improvement (CDI) opportunities. We recognized that our complexity was not being captured both because the clinical information was not documented in a manner readily translatable to ICD-10 codes and codes were missed when the documentation did exist. To remedy these problems, we implemented multiple immediate “fixes,” which included revamping our CDI efforts, re-education, and enhancements to our electronic health record for providers, CDIs, and coders. Since publication of our article, our CMI has continued to increase month over month, up to 2.57 most recently in May 2022, as we have continued to focus on several additional initiatives to impact both better documentation and coding.

The second set of questions asked whether the perceived low CMI was causing problems with payers and about the risk of artificially increasing the CMI through overdiagnosis as well as audit mechanisms to avoid this, and changes in expected mortality and observed mortality. To our knowledge, the lower CMI did not cause any problems with payers, but this is something we are currently tracking. Coding and documentation are constantly audited both internally (by our quality department) and externally (using Inter-Rater Reliability audits and validation), with no noted trend or targeted opportunities. We only include comorbidities that are current, actively monitored/managed, and pertinent to the care of our patients. We have not noted a change in denials, which gives us confidence we are not now overdiagnosing.

Our observed mortality has also increased. We, like all institutions, experienced the confounding factor of the COVID-19 pandemic, which coincided with the higher observed mortality over the course of the past 2 years. While the observed mortality (indicating sicker patients assuming no worsening of care processes) may partly explain our increased coding complexity, our decreasing mortality index (observed:expected mortality) suggests that our efforts to improve documentation and coding likely reflect improved capture of missed complexity (Figure).

We understand the concerns raised by Dr. Kerguelen about potential mis(over)coding. As part of this quality initiative, therefore, we plan long-term evaluations of our processes and metrics to better determine and guide our understanding of the impact of what we have already implemented and future interventions. In fact, we are in the process of analyzing additional interventions and hope to share results from these evaluations soon.

Marie Anne Sosa, MD
Tanira Ferreira, MD
Hayley Gershengorn, MD
Melissa Soto
Estin Kelly
Ameena Shrestha
Julianne Burgos
Sandeep Devabhaktuni
Dipen Parekh, MD
Maritza Suarez, MD
University of Miami Hospital and Clinics, Miami, FL
[email protected]

Disclosures: None reported.