The Epstein-Barr virus (EBV) is our constant companion, infecting an estimated 90%-95% of adults. Many of us are first infected as children, when the germ may trigger cold and flu symptoms. EBV also causes mononucleosis, or kissing disease, a glandular fever that has afflicted generations of amorous young people.

Post infection, EBV settles in for the long haul and remains in the body until death. It’s thought to be largely innocuous, but EBV is now implicated as a cause of several types of cancer — including lymphoma and nasopharyngeal tumors – and multiple sclerosis (MS). In 2022, a landmark study in Science suggested that previous EBV infection is the primary cause of MS.

While there aren’t many implications for current treatment, greater insight into the origin story of MS may eventually help neurologists better diagnose and treat patients, experts said. The goal is to uncover clues that “can help us understand MS a little bit better and reveal insights that could lead to new disease-modifying therapy,” Bruce Bebo, PhD, executive vice president of research with the National MS Society, said in an interview.
 

EBV Boosts MS Risk 32-Fold

EBV was first linked to MS back in 1981. For the 2022 study, researchers at the Harvard T.H. Chan School of Public Health and Harvard Medical School, Boston, analyzed blood serum from 10 million active-duty members of the US military. They focused on 801 recruits with MS and matched them with more than 1500 controls. All but one of those with MS had been infected with EBV; infection appeared to boost the risk for MS 32-fold (95% CI, 4.3-245.3; P < .001).

Neurologist and associate professor Michael Levy, MD, PhD, of Harvard Medical School and Massachusetts General Hospital, said in an interview that the findings are “groundbreaking” and confirm that EBV is “likely the primary cause of MS.”

According to Dr. Levy, there are two main theories about why EBV causes MS. The first hypothesis, known as the “molecular mimicry” theory, suggests that “EBV is a trigger of MS, possibly when the immune system mistakes a viral protein for a myelin protein and then attacks myelin,” Dr. Levy said. In MS, the immune system attacks the protective myelin sheath and the axons it insulates.

“After that point, the virus is not necessary to maintain the disease state and eradicating the virus likely won’t have much effect since the immune response is already triggered,” he said.

The second theory is that “EBV is a driver of MS where there is an ongoing, lifelong immunological response to EBV that continuously causes damage in the central nervous system [CNS]. In theory, if we could eradicate the virus, the destructive immune response could also resolve. Thus, an EBV antiviral treatment could potentially treat and maybe cure MS,” Dr. Levy explained, noting that “removing the pathogenic antigen may be a more effective strategy than removing the immune response.”

However, “we don’t yet know which hypothesis is correct,” he said. But “there is preliminary evidence in favor of each one.”
 

‘Additional Fuses Must Be Ignited’

It’s also unclear why most people infected with EBV do not develop MS. It appears that “additional fuses must be ignited,” for MS to take hold, according to a commentary accompanying the landmark 2022 study.

“As far as clinical implications, knowing whether a patient has a medical or family history of mononucleosis may be a small clue, a small piece of evidence, to help with diagnosis,” Dr. Bebo said.

He agreed with Dr. Levy that an antiviral could be a promising approach “If the problem in MS is a dysfunctional immune response to EBV.”

Natalia Drosu, MD, PhD, a postdoctoral fellow at Harvard-MIT Biomedical Engineering Center, said that a clinical trial of a non-immunosuppressive antiviral targeting EBV in patients with MS would be a crucial step toward better understanding the MS-EBV connection. “If we learn that antivirals are effective in MS, we should develop non-immunosuppressive therapies for patients with MS as soon as possible,” she said.

Stanford University’s Lawrence Steinman, MD, professor of neurology and neurological sciences, pediatrics, and genetics, who coauthored the commentary on the original Science paper, agreed that it’s worth investigating whether antiviral therapies targeting EBV will benefit patients who already have MS. But he cautioned against clinicians experimenting on their own outside of a research study. “You’d want to use the right antiviral and a properly designed trial,” he said.
 

Antivirals May Place a Crucial Role in MS Control

While there are no approved therapies for EBV, several MS disease-modifying therapies have anti-EBV effects, Dr. Levy said, citing anti-CD20 therapy as a clear example. It depletes B cells from the circulation, and it depletes EBV because the virus lives in the B-cell compartment. “Some MS treatments may be inadvertent EBV antivirals,” he said.

Researchers are also thinking about how they might exploit the MS-EBV link to prevent MS from developing in the first place, but there are uncertainties on that front too.

Conceivably, there may be some way to intervene in patients to treat EBV and prevent MS, such as a unique treatment for infectious mononucleosis (IM), Dr. Levy said.

Researchers are especially intrigued by signs that the timing of infection may play a role, with people infected with EBV via IM after early childhood at especially a high risk of developing MS. A 2022 German study calculated that people who developed IM were almost twice as likely as those who didn’t to develop MS within 10 years, although the risks in both groups were very small. Subgroup analysis revealed the strongest association between IM and MS was in the group infected between age 14 and 20 years (hazard ratio, 3.52; 95% CI, 1.00-12.37). They also saw a stronger association in men than in women.

The authors of a 2023 review in Clinical & Translational Immunology wrote that “further understanding of IM may be critical in solving the mystery” of EBV’s role in MS.

Dr. Levy said this line of questioning is important. “In theory, if we can tell who is prone to develop MS or whose immune system might be reacting to EBV to cause MS, we can intervene early to prevent neurological manifestations.”

However, “remember that while most of the world gets EBV infections, only 1 in 1000 will get MS. So, it might not be feasible to test everyone before neurological manifestations occur,” he said.
 

More Questions to Answer About EBV and MS

Researchers hope to answer several questions moving forward. For one, why is EBV uniquely connected to MS? “You would think that if there were cross-reactivity to myelin, there are many viruses that could cause MS. But the association seems to be very restricted to EBV,” Dr. Levy said. “It is probably due to the fact that EBV is one of the only human viruses that can infect B cells, which play important roles in controlling immune responses.”

The molecular mimicry theory also opens up a potential treatment pathway.

A 2022 study reported “high-affinity molecular mimicry between the EBV transcription factor EBV nuclear antigen 1 (EBNA1) and the central nervous system protein glial cell adhesion molecule (GlialCAM)”. Antibodies against EBNA1 and GlialCAM are prevalent in patients with MS. In a mouse model of MS, the researchers showed that EBNA1 immunization exacerbates disease. The authors wrote that “Our results provide a mechanistic link for the association between MS and EBV and could guide the development of new MS therapies.”
 

Could an EBV Vaccine Be the Answer?

On the prevention front, perhaps the most obvious question is whether an EBV vaccine could eliminate MS for good?

Dr. Bebo, from the National MS Society, said it will be important to determine which kind of vaccine is best. Is it one that neutralizes infection with EBV? Or is it enough to simply prevent clinical manifestations?

Both types of vaccines are in development, and at least two clinical trials are now in the works. The National Institute of Allergy and Infectious Diseases is sponsoring a phase 1 study of an adjuvanted EBV gp350-Ferritin nanoparticle vaccine. Forty subjects aged 18-29 years will take part: 20 with EBV and 20 who are not infected. The study is expected to end in 2025.

There is also a phase 1 placebo-controlled study in progress testing an EBV vaccine based on mRNA-1189 in 422 subjects aged 12-30 years. This trial is also due to end in 2025.

“This is very exciting, but it may take a decade or two to determine whether a vaccine is effective at preventing MS,” Dr. Levy said.

Dr. Levy, Dr. Steinman, Dr. Drosu, and Dr. Bebo had no disclosures.
 

A version of this article appeared on Medscape.com.

The Epstein-Barr virus (EBV) is our constant companion, infecting an estimated 90%-95% of adults. Many of us are first infected as children, when the germ may trigger cold and flu symptoms. EBV also causes mononucleosis, or kissing disease, a glandular fever that has afflicted generations of amorous young people.

Post infection, EBV settles in for the long haul and remains in the body until death. It’s thought to be largely innocuous, but EBV is now implicated as a cause of several types of cancer — including lymphoma and nasopharyngeal tumors – and multiple sclerosis (MS). In 2022, a landmark study in Science suggested that previous EBV infection is the primary cause of MS.

While there aren’t many implications for current treatment, greater insight into the origin story of MS may eventually help neurologists better diagnose and treat patients, experts said. The goal is to uncover clues that “can help us understand MS a little bit better and reveal insights that could lead to new disease-modifying therapy,” Bruce Bebo, PhD, executive vice president of research with the National MS Society, said in an interview.
 

EBV Boosts MS Risk 32-Fold

EBV was first linked to MS back in 1981. For the 2022 study, researchers at the Harvard T.H. Chan School of Public Health and Harvard Medical School, Boston, analyzed blood serum from 10 million active-duty members of the US military. They focused on 801 recruits with MS and matched them with more than 1500 controls. All but one of those with MS had been infected with EBV; infection appeared to boost the risk for MS 32-fold (95% CI, 4.3-245.3; P < .001).

Neurologist and associate professor Michael Levy, MD, PhD, of Harvard Medical School and Massachusetts General Hospital, said in an interview that the findings are “groundbreaking” and confirm that EBV is “likely the primary cause of MS.”

According to Dr. Levy, there are two main theories about why EBV causes MS. The first hypothesis, known as the “molecular mimicry” theory, suggests that “EBV is a trigger of MS, possibly when the immune system mistakes a viral protein for a myelin protein and then attacks myelin,” Dr. Levy said. In MS, the immune system attacks the protective myelin sheath and the axons it insulates.

“After that point, the virus is not necessary to maintain the disease state and eradicating the virus likely won’t have much effect since the immune response is already triggered,” he said.

The second theory is that “EBV is a driver of MS where there is an ongoing, lifelong immunological response to EBV that continuously causes damage in the central nervous system [CNS]. In theory, if we could eradicate the virus, the destructive immune response could also resolve. Thus, an EBV antiviral treatment could potentially treat and maybe cure MS,” Dr. Levy explained, noting that “removing the pathogenic antigen may be a more effective strategy than removing the immune response.”

However, “we don’t yet know which hypothesis is correct,” he said. But “there is preliminary evidence in favor of each one.”
 

‘Additional Fuses Must Be Ignited’

It’s also unclear why most people infected with EBV do not develop MS. It appears that “additional fuses must be ignited,” for MS to take hold, according to a commentary accompanying the landmark 2022 study.

“As far as clinical implications, knowing whether a patient has a medical or family history of mononucleosis may be a small clue, a small piece of evidence, to help with diagnosis,” Dr. Bebo said.

He agreed with Dr. Levy that an antiviral could be a promising approach “If the problem in MS is a dysfunctional immune response to EBV.”

Natalia Drosu, MD, PhD, a postdoctoral fellow at Harvard-MIT Biomedical Engineering Center, said that a clinical trial of a non-immunosuppressive antiviral targeting EBV in patients with MS would be a crucial step toward better understanding the MS-EBV connection. “If we learn that antivirals are effective in MS, we should develop non-immunosuppressive therapies for patients with MS as soon as possible,” she said.

Stanford University’s Lawrence Steinman, MD, professor of neurology and neurological sciences, pediatrics, and genetics, who coauthored the commentary on the original Science paper, agreed that it’s worth investigating whether antiviral therapies targeting EBV will benefit patients who already have MS. But he cautioned against clinicians experimenting on their own outside of a research study. “You’d want to use the right antiviral and a properly designed trial,” he said.
 

Antivirals May Place a Crucial Role in MS Control

While there are no approved therapies for EBV, several MS disease-modifying therapies have anti-EBV effects, Dr. Levy said, citing anti-CD20 therapy as a clear example. It depletes B cells from the circulation, and it depletes EBV because the virus lives in the B-cell compartment. “Some MS treatments may be inadvertent EBV antivirals,” he said.

Researchers are also thinking about how they might exploit the MS-EBV link to prevent MS from developing in the first place, but there are uncertainties on that front too.

Conceivably, there may be some way to intervene in patients to treat EBV and prevent MS, such as a unique treatment for infectious mononucleosis (IM), Dr. Levy said.

Researchers are especially intrigued by signs that the timing of infection may play a role, with people infected with EBV via IM after early childhood at especially a high risk of developing MS. A 2022 German study calculated that people who developed IM were almost twice as likely as those who didn’t to develop MS within 10 years, although the risks in both groups were very small. Subgroup analysis revealed the strongest association between IM and MS was in the group infected between age 14 and 20 years (hazard ratio, 3.52; 95% CI, 1.00-12.37). They also saw a stronger association in men than in women.

The authors of a 2023 review in Clinical & Translational Immunology wrote that “further understanding of IM may be critical in solving the mystery” of EBV’s role in MS.

Dr. Levy said this line of questioning is important. “In theory, if we can tell who is prone to develop MS or whose immune system might be reacting to EBV to cause MS, we can intervene early to prevent neurological manifestations.”

However, “remember that while most of the world gets EBV infections, only 1 in 1000 will get MS. So, it might not be feasible to test everyone before neurological manifestations occur,” he said.
 

More Questions to Answer About EBV and MS

Researchers hope to answer several questions moving forward. For one, why is EBV uniquely connected to MS? “You would think that if there were cross-reactivity to myelin, there are many viruses that could cause MS. But the association seems to be very restricted to EBV,” Dr. Levy said. “It is probably due to the fact that EBV is one of the only human viruses that can infect B cells, which play important roles in controlling immune responses.”

The molecular mimicry theory also opens up a potential treatment pathway.

A 2022 study reported “high-affinity molecular mimicry between the EBV transcription factor EBV nuclear antigen 1 (EBNA1) and the central nervous system protein glial cell adhesion molecule (GlialCAM)”. Antibodies against EBNA1 and GlialCAM are prevalent in patients with MS. In a mouse model of MS, the researchers showed that EBNA1 immunization exacerbates disease. The authors wrote that “Our results provide a mechanistic link for the association between MS and EBV and could guide the development of new MS therapies.”
 

Could an EBV Vaccine Be the Answer?

On the prevention front, perhaps the most obvious question is whether an EBV vaccine could eliminate MS for good?

Dr. Bebo, from the National MS Society, said it will be important to determine which kind of vaccine is best. Is it one that neutralizes infection with EBV? Or is it enough to simply prevent clinical manifestations?

Both types of vaccines are in development, and at least two clinical trials are now in the works. The National Institute of Allergy and Infectious Diseases is sponsoring a phase 1 study of an adjuvanted EBV gp350-Ferritin nanoparticle vaccine. Forty subjects aged 18-29 years will take part: 20 with EBV and 20 who are not infected. The study is expected to end in 2025.

There is also a phase 1 placebo-controlled study in progress testing an EBV vaccine based on mRNA-1189 in 422 subjects aged 12-30 years. This trial is also due to end in 2025.

“This is very exciting, but it may take a decade or two to determine whether a vaccine is effective at preventing MS,” Dr. Levy said.

Dr. Levy, Dr. Steinman, Dr. Drosu, and Dr. Bebo had no disclosures.
 

A version of this article appeared on Medscape.com.

The Epstein-Barr virus (EBV) is our constant companion, infecting an estimated 90%-95% of adults. Many of us are first infected as children, when the germ may trigger cold and flu symptoms. EBV also causes mononucleosis, or kissing disease, a glandular fever that has afflicted generations of amorous young people.

Post infection, EBV settles in for the long haul and remains in the body until death. It’s thought to be largely innocuous, but EBV is now implicated as a cause of several types of cancer — including lymphoma and nasopharyngeal tumors – and multiple sclerosis (MS). In 2022, a landmark study in Science suggested that previous EBV infection is the primary cause of MS.

While there aren’t many implications for current treatment, greater insight into the origin story of MS may eventually help neurologists better diagnose and treat patients, experts said. The goal is to uncover clues that “can help us understand MS a little bit better and reveal insights that could lead to new disease-modifying therapy,” Bruce Bebo, PhD, executive vice president of research with the National MS Society, said in an interview.
 

EBV Boosts MS Risk 32-Fold

EBV was first linked to MS back in 1981. For the 2022 study, researchers at the Harvard T.H. Chan School of Public Health and Harvard Medical School, Boston, analyzed blood serum from 10 million active-duty members of the US military. They focused on 801 recruits with MS and matched them with more than 1500 controls. All but one of those with MS had been infected with EBV; infection appeared to boost the risk for MS 32-fold (95% CI, 4.3-245.3; P < .001).

Neurologist and associate professor Michael Levy, MD, PhD, of Harvard Medical School and Massachusetts General Hospital, said in an interview that the findings are “groundbreaking” and confirm that EBV is “likely the primary cause of MS.”

According to Dr. Levy, there are two main theories about why EBV causes MS. The first hypothesis, known as the “molecular mimicry” theory, suggests that “EBV is a trigger of MS, possibly when the immune system mistakes a viral protein for a myelin protein and then attacks myelin,” Dr. Levy said. In MS, the immune system attacks the protective myelin sheath and the axons it insulates.

“After that point, the virus is not necessary to maintain the disease state and eradicating the virus likely won’t have much effect since the immune response is already triggered,” he said.

The second theory is that “EBV is a driver of MS where there is an ongoing, lifelong immunological response to EBV that continuously causes damage in the central nervous system [CNS]. In theory, if we could eradicate the virus, the destructive immune response could also resolve. Thus, an EBV antiviral treatment could potentially treat and maybe cure MS,” Dr. Levy explained, noting that “removing the pathogenic antigen may be a more effective strategy than removing the immune response.”

However, “we don’t yet know which hypothesis is correct,” he said. But “there is preliminary evidence in favor of each one.”
 

‘Additional Fuses Must Be Ignited’

It’s also unclear why most people infected with EBV do not develop MS. It appears that “additional fuses must be ignited,” for MS to take hold, according to a commentary accompanying the landmark 2022 study.

“As far as clinical implications, knowing whether a patient has a medical or family history of mononucleosis may be a small clue, a small piece of evidence, to help with diagnosis,” Dr. Bebo said.

He agreed with Dr. Levy that an antiviral could be a promising approach “If the problem in MS is a dysfunctional immune response to EBV.”

Natalia Drosu, MD, PhD, a postdoctoral fellow at Harvard-MIT Biomedical Engineering Center, said that a clinical trial of a non-immunosuppressive antiviral targeting EBV in patients with MS would be a crucial step toward better understanding the MS-EBV connection. “If we learn that antivirals are effective in MS, we should develop non-immunosuppressive therapies for patients with MS as soon as possible,” she said.

Stanford University’s Lawrence Steinman, MD, professor of neurology and neurological sciences, pediatrics, and genetics, who coauthored the commentary on the original Science paper, agreed that it’s worth investigating whether antiviral therapies targeting EBV will benefit patients who already have MS. But he cautioned against clinicians experimenting on their own outside of a research study. “You’d want to use the right antiviral and a properly designed trial,” he said.
 

Antivirals May Place a Crucial Role in MS Control

While there are no approved therapies for EBV, several MS disease-modifying therapies have anti-EBV effects, Dr. Levy said, citing anti-CD20 therapy as a clear example. It depletes B cells from the circulation, and it depletes EBV because the virus lives in the B-cell compartment. “Some MS treatments may be inadvertent EBV antivirals,” he said.

Researchers are also thinking about how they might exploit the MS-EBV link to prevent MS from developing in the first place, but there are uncertainties on that front too.

Conceivably, there may be some way to intervene in patients to treat EBV and prevent MS, such as a unique treatment for infectious mononucleosis (IM), Dr. Levy said.

Researchers are especially intrigued by signs that the timing of infection may play a role, with people infected with EBV via IM after early childhood at especially a high risk of developing MS. A 2022 German study calculated that people who developed IM were almost twice as likely as those who didn’t to develop MS within 10 years, although the risks in both groups were very small. Subgroup analysis revealed the strongest association between IM and MS was in the group infected between age 14 and 20 years (hazard ratio, 3.52; 95% CI, 1.00-12.37). They also saw a stronger association in men than in women.

The authors of a 2023 review in Clinical & Translational Immunology wrote that “further understanding of IM may be critical in solving the mystery” of EBV’s role in MS.

Dr. Levy said this line of questioning is important. “In theory, if we can tell who is prone to develop MS or whose immune system might be reacting to EBV to cause MS, we can intervene early to prevent neurological manifestations.”

However, “remember that while most of the world gets EBV infections, only 1 in 1000 will get MS. So, it might not be feasible to test everyone before neurological manifestations occur,” he said.
 

More Questions to Answer About EBV and MS

Researchers hope to answer several questions moving forward. For one, why is EBV uniquely connected to MS? “You would think that if there were cross-reactivity to myelin, there are many viruses that could cause MS. But the association seems to be very restricted to EBV,” Dr. Levy said. “It is probably due to the fact that EBV is one of the only human viruses that can infect B cells, which play important roles in controlling immune responses.”

The molecular mimicry theory also opens up a potential treatment pathway.

A 2022 study reported “high-affinity molecular mimicry between the EBV transcription factor EBV nuclear antigen 1 (EBNA1) and the central nervous system protein glial cell adhesion molecule (GlialCAM)”. Antibodies against EBNA1 and GlialCAM are prevalent in patients with MS. In a mouse model of MS, the researchers showed that EBNA1 immunization exacerbates disease. The authors wrote that “Our results provide a mechanistic link for the association between MS and EBV and could guide the development of new MS therapies.”
 

Could an EBV Vaccine Be the Answer?

On the prevention front, perhaps the most obvious question is whether an EBV vaccine could eliminate MS for good?

Dr. Bebo, from the National MS Society, said it will be important to determine which kind of vaccine is best. Is it one that neutralizes infection with EBV? Or is it enough to simply prevent clinical manifestations?

Both types of vaccines are in development, and at least two clinical trials are now in the works. The National Institute of Allergy and Infectious Diseases is sponsoring a phase 1 study of an adjuvanted EBV gp350-Ferritin nanoparticle vaccine. Forty subjects aged 18-29 years will take part: 20 with EBV and 20 who are not infected. The study is expected to end in 2025.

There is also a phase 1 placebo-controlled study in progress testing an EBV vaccine based on mRNA-1189 in 422 subjects aged 12-30 years. This trial is also due to end in 2025.

“This is very exciting, but it may take a decade or two to determine whether a vaccine is effective at preventing MS,” Dr. Levy said.

Dr. Levy, Dr. Steinman, Dr. Drosu, and Dr. Bebo had no disclosures.
 

A version of this article appeared on Medscape.com.

At first glance, hematologists may not seem like they’d be likely to get urgent calls from the emergency department at 3 a.m. After all, they typically work during normal business hours. However, severe medical crises in blood-cancer patients can occur, and drowsy hematologists may find themselves providing guidance to emergency physicians about how to deal with rapidly deteriorating patients.

When a patient with a blood-cancer crisis comes in, “I can recognize what’s going on, and I can initiate treatment. But if you do have a true hematologic emergency, then you need a hematologist to be able to contribute to your care,” Molly Estes, MD, an emergency physician with California’s Loma Linda University, said in an interview.

In situations such as a patient with an extraordinarily high white blood count, “you’ll be calling your hematologist for treatment recommendations and calling your nephrologist for assistance managing electrolyte disorders,” Megan Boysen-Osborn, MD, an emergency physician with the University of California at Irvine, said in an interview.

Here’s a look at three emergency hematologic conditions that lead to late-night phone calls:
 

Leukocytosis

Blood cancers can cause white blood cell counts to skyrocket, a condition known as leukocytosis, but a high count is not necessarily an emergency. The key is to figure out whether the high count is normal for the patient — perhaps due to the disease or the medical treatment — or a sign of an internal medical crisis, Dr. Estes said.

“Let’s say you stubbed your toe in the night, and I happened to get blood work on you and incidentally notice that your white blood cells are high. But they’re the same high level that they always are,” Dr. Estes said. “That’s a completely different scenario than if I’m seeing you for fever, vomiting, and stomach pain.”

Indeed, there’s no cut-off that differentiates a dangerously high white blood count from one that’s acceptable, Mikkael A. Sekeres, MD, MS, chief of hematology at Sylvester Comprehensive Cancer Center at the University of Miami Health System, said in an interview.

“In the past, I’ve taken care of a couple of patients who had chronic lymphocytic leukemia and white blood cell counts that were 200,000 or 300,000 [white blood cells per microliter] and worked out in the gym every day,” he said. “It didn’t negatively affect them. On the flip side, I have also taken care of patients with acute myeloid leukemia with a white blood cell count of 50,000. That landed them in the intensive care unit.”

Dr. Estes said that her first impulse in cases of high white blood cell count is to give IV fluids to dilute the blood and prevent the cells from turning blood into sludge via hyperviscosity syndrome. Dr. Sekeres said this makes sense, since the condition can lead to blockages in vessels and cause heart attacks and strokes.

There are other options, depending on the severity of the case. Hydroxyurea can be administered to lower white blood cell counts along with allopurinol to protect the kidneys, Dr. Sekeres said. In some situations, he said, “we’ll consider initiating chemotherapy immediately to reduce the level of the white blood cells. Or we will consider placing a patient on dialysis to take off some of those white blood cells.”
 

Tumor lysis syndrome

While it’s rare, tumor lysis syndrome can occur when tumors release their content into blood stream. According to Dr. Sekeres, this can happen when “cancers that grow so quickly that they can start to outgrow their own blood supply and start dying before we even treat patients. When this happens, it causes electrolyte disarray.”

It’s crucial to understand the potential for patients to quickly get worse, he said. He advises clinicians to aggressively check lab values for electrolyte abnormalities and aggressively administer IV fluids and electrolyte replacement when needed. “It’s also important to let the intensive care unit know that they may need to be activated,” he said. Fortunately, he noted, patients can often be stabilized.
 

Differentiation syndrome

According to the Cleveland Clinic, medications used to treat acute myeloid leukemia and acute promyelocytic leukemia cause cancer cells to differentiate from immature states to mature normal states. But the process can go awry when fluid leaks out of blood vessels in a condition called differentiation syndrome. This can cause multiple problems, Dr. Sekeres said.

A 2020 report noted the potential for “acute end-organ damage with peripheral edema, hypotension, acute renal failure, and interstitial pulmonary infiltrates.”

In these cases, aggressive supportive management is key, Dr. Sekeres said. If a patient is having difficulty breathing, for example, they’ll need electrolyte management and perhaps support via a respirator, he said.

“Most people with acute promyelocytic leukemia can fully recover from differentiation syndrome with prompt, effective treatment,” the Cleveland Clinic notes. It adds that the disease is “highly curable.”

In all of these emergent crises, Dr. Sekeres said, it’s important for hematologists understand that “patients can get very sick very quickly,” and it’s important to intervene early and often.

Dr. Sekeres serves on advisory boards for BMS and Curium Pharma. Dr. Estes and Dr. Boysen-Osborn have no disclosures.

At first glance, hematologists may not seem like they’d be likely to get urgent calls from the emergency department at 3 a.m. After all, they typically work during normal business hours. However, severe medical crises in blood-cancer patients can occur, and drowsy hematologists may find themselves providing guidance to emergency physicians about how to deal with rapidly deteriorating patients.

When a patient with a blood-cancer crisis comes in, “I can recognize what’s going on, and I can initiate treatment. But if you do have a true hematologic emergency, then you need a hematologist to be able to contribute to your care,” Molly Estes, MD, an emergency physician with California’s Loma Linda University, said in an interview.

In situations such as a patient with an extraordinarily high white blood count, “you’ll be calling your hematologist for treatment recommendations and calling your nephrologist for assistance managing electrolyte disorders,” Megan Boysen-Osborn, MD, an emergency physician with the University of California at Irvine, said in an interview.

Here’s a look at three emergency hematologic conditions that lead to late-night phone calls:
 

Leukocytosis

Blood cancers can cause white blood cell counts to skyrocket, a condition known as leukocytosis, but a high count is not necessarily an emergency. The key is to figure out whether the high count is normal for the patient — perhaps due to the disease or the medical treatment — or a sign of an internal medical crisis, Dr. Estes said.

“Let’s say you stubbed your toe in the night, and I happened to get blood work on you and incidentally notice that your white blood cells are high. But they’re the same high level that they always are,” Dr. Estes said. “That’s a completely different scenario than if I’m seeing you for fever, vomiting, and stomach pain.”

Indeed, there’s no cut-off that differentiates a dangerously high white blood count from one that’s acceptable, Mikkael A. Sekeres, MD, MS, chief of hematology at Sylvester Comprehensive Cancer Center at the University of Miami Health System, said in an interview.

“In the past, I’ve taken care of a couple of patients who had chronic lymphocytic leukemia and white blood cell counts that were 200,000 or 300,000 [white blood cells per microliter] and worked out in the gym every day,” he said. “It didn’t negatively affect them. On the flip side, I have also taken care of patients with acute myeloid leukemia with a white blood cell count of 50,000. That landed them in the intensive care unit.”

Dr. Estes said that her first impulse in cases of high white blood cell count is to give IV fluids to dilute the blood and prevent the cells from turning blood into sludge via hyperviscosity syndrome. Dr. Sekeres said this makes sense, since the condition can lead to blockages in vessels and cause heart attacks and strokes.

There are other options, depending on the severity of the case. Hydroxyurea can be administered to lower white blood cell counts along with allopurinol to protect the kidneys, Dr. Sekeres said. In some situations, he said, “we’ll consider initiating chemotherapy immediately to reduce the level of the white blood cells. Or we will consider placing a patient on dialysis to take off some of those white blood cells.”
 

Tumor lysis syndrome

While it’s rare, tumor lysis syndrome can occur when tumors release their content into blood stream. According to Dr. Sekeres, this can happen when “cancers that grow so quickly that they can start to outgrow their own blood supply and start dying before we even treat patients. When this happens, it causes electrolyte disarray.”

It’s crucial to understand the potential for patients to quickly get worse, he said. He advises clinicians to aggressively check lab values for electrolyte abnormalities and aggressively administer IV fluids and electrolyte replacement when needed. “It’s also important to let the intensive care unit know that they may need to be activated,” he said. Fortunately, he noted, patients can often be stabilized.
 

Differentiation syndrome

According to the Cleveland Clinic, medications used to treat acute myeloid leukemia and acute promyelocytic leukemia cause cancer cells to differentiate from immature states to mature normal states. But the process can go awry when fluid leaks out of blood vessels in a condition called differentiation syndrome. This can cause multiple problems, Dr. Sekeres said.

A 2020 report noted the potential for “acute end-organ damage with peripheral edema, hypotension, acute renal failure, and interstitial pulmonary infiltrates.”

In these cases, aggressive supportive management is key, Dr. Sekeres said. If a patient is having difficulty breathing, for example, they’ll need electrolyte management and perhaps support via a respirator, he said.

“Most people with acute promyelocytic leukemia can fully recover from differentiation syndrome with prompt, effective treatment,” the Cleveland Clinic notes. It adds that the disease is “highly curable.”

In all of these emergent crises, Dr. Sekeres said, it’s important for hematologists understand that “patients can get very sick very quickly,” and it’s important to intervene early and often.

Dr. Sekeres serves on advisory boards for BMS and Curium Pharma. Dr. Estes and Dr. Boysen-Osborn have no disclosures.

At first glance, hematologists may not seem like they’d be likely to get urgent calls from the emergency department at 3 a.m. After all, they typically work during normal business hours. However, severe medical crises in blood-cancer patients can occur, and drowsy hematologists may find themselves providing guidance to emergency physicians about how to deal with rapidly deteriorating patients.

When a patient with a blood-cancer crisis comes in, “I can recognize what’s going on, and I can initiate treatment. But if you do have a true hematologic emergency, then you need a hematologist to be able to contribute to your care,” Molly Estes, MD, an emergency physician with California’s Loma Linda University, said in an interview.

In situations such as a patient with an extraordinarily high white blood count, “you’ll be calling your hematologist for treatment recommendations and calling your nephrologist for assistance managing electrolyte disorders,” Megan Boysen-Osborn, MD, an emergency physician with the University of California at Irvine, said in an interview.

Here’s a look at three emergency hematologic conditions that lead to late-night phone calls:
 

Leukocytosis

Blood cancers can cause white blood cell counts to skyrocket, a condition known as leukocytosis, but a high count is not necessarily an emergency. The key is to figure out whether the high count is normal for the patient — perhaps due to the disease or the medical treatment — or a sign of an internal medical crisis, Dr. Estes said.

“Let’s say you stubbed your toe in the night, and I happened to get blood work on you and incidentally notice that your white blood cells are high. But they’re the same high level that they always are,” Dr. Estes said. “That’s a completely different scenario than if I’m seeing you for fever, vomiting, and stomach pain.”

Indeed, there’s no cut-off that differentiates a dangerously high white blood count from one that’s acceptable, Mikkael A. Sekeres, MD, MS, chief of hematology at Sylvester Comprehensive Cancer Center at the University of Miami Health System, said in an interview.

“In the past, I’ve taken care of a couple of patients who had chronic lymphocytic leukemia and white blood cell counts that were 200,000 or 300,000 [white blood cells per microliter] and worked out in the gym every day,” he said. “It didn’t negatively affect them. On the flip side, I have also taken care of patients with acute myeloid leukemia with a white blood cell count of 50,000. That landed them in the intensive care unit.”

Dr. Estes said that her first impulse in cases of high white blood cell count is to give IV fluids to dilute the blood and prevent the cells from turning blood into sludge via hyperviscosity syndrome. Dr. Sekeres said this makes sense, since the condition can lead to blockages in vessels and cause heart attacks and strokes.

There are other options, depending on the severity of the case. Hydroxyurea can be administered to lower white blood cell counts along with allopurinol to protect the kidneys, Dr. Sekeres said. In some situations, he said, “we’ll consider initiating chemotherapy immediately to reduce the level of the white blood cells. Or we will consider placing a patient on dialysis to take off some of those white blood cells.”
 

Tumor lysis syndrome

While it’s rare, tumor lysis syndrome can occur when tumors release their content into blood stream. According to Dr. Sekeres, this can happen when “cancers that grow so quickly that they can start to outgrow their own blood supply and start dying before we even treat patients. When this happens, it causes electrolyte disarray.”

It’s crucial to understand the potential for patients to quickly get worse, he said. He advises clinicians to aggressively check lab values for electrolyte abnormalities and aggressively administer IV fluids and electrolyte replacement when needed. “It’s also important to let the intensive care unit know that they may need to be activated,” he said. Fortunately, he noted, patients can often be stabilized.
 

Differentiation syndrome

According to the Cleveland Clinic, medications used to treat acute myeloid leukemia and acute promyelocytic leukemia cause cancer cells to differentiate from immature states to mature normal states. But the process can go awry when fluid leaks out of blood vessels in a condition called differentiation syndrome. This can cause multiple problems, Dr. Sekeres said.

A 2020 report noted the potential for “acute end-organ damage with peripheral edema, hypotension, acute renal failure, and interstitial pulmonary infiltrates.”

In these cases, aggressive supportive management is key, Dr. Sekeres said. If a patient is having difficulty breathing, for example, they’ll need electrolyte management and perhaps support via a respirator, he said.

“Most people with acute promyelocytic leukemia can fully recover from differentiation syndrome with prompt, effective treatment,” the Cleveland Clinic notes. It adds that the disease is “highly curable.”

In all of these emergent crises, Dr. Sekeres said, it’s important for hematologists understand that “patients can get very sick very quickly,” and it’s important to intervene early and often.

Dr. Sekeres serves on advisory boards for BMS and Curium Pharma. Dr. Estes and Dr. Boysen-Osborn have no disclosures.

This transcript has been edited for clarity.

I think we’re all aware that Alabama has put itself and the rest of the country into a moral bind when it comes to abortion and the status of human embryos. Back on February 16, 2024, the Alabama Supreme Court rendered a decision in a case called LePage v. Center for Reproductive Medicine, in which the court said that cryopreserved embryos in frozen nitrogen were legally equivalent to children.

They basically said they’re granted the same rights, meaning you certainly can’t destroy them. You certainly could not be in a situation where somebody said, “I’m going to not use them,” because once you create them, you seem to have some duty to make sure they end up in an environment where they can become full-fledged adults.

This decision that embryos in frozen nitrogen — but literally embryos anywhere — are the equivalent of full-bore children put Alabama in a terrible situation if you were a person or a couple seeking in vitro fertilization (IVF).

IVF requires the creation of many eggs. Women have to undergo drug treatment so that they superovulate. It’s too expensive to just go one egg at a time, egg procurement costs too much, and a cycle of IVF could cost as much as $15,000. There are some people who don’t make many eggs, so you want to get as many as you can.

When you get them, you freeze them, as happened in this Alabama case. By the way, what triggered the court case was that somebody in the lab dropped the tray with embryos in it, and they were basically accused not just of a mistake but of murder.

It’s pretty serious when you see this decision and you realize that if you make a multitude of embryos and then you had a child after two tries, but you have six more, you can’t destroy them. What are you going to do with them? Will they be under the governance of the utility company? What’s going to happen?

Many women in Alabama were outraged by the court’s opinion because they want to do IVF. In fact, politically, proponents of thinking that life begins at conception — or fetal personhood as it’s called, and the view that human embryos are children from the minute of conception — were stuck. It’s hard to argue that IVF is not pro-life. It’s hard to argue that people who desperately want to have children should find it difficult to use the technique.

The state has tried to pass a law that exempts IVF clinics from liability if they’re trying to use human embryos to make babies. I do not think this will stand. The court decision is fundamentally wrong, in part because human embryos are not children. They are potential children. They are possible children, but outside of implantation in the environment of a woman’s uterus, they’ll never become anything.

In fact, the court decision is a version of what used to be called preformationism, which sees a tiny baby inside a human embryo. That’s not true. We know today that you’ve got sets of genes that need messages from the mom in order to begin the process of division and development. It isn’t just expanding a tiny, miniature baby into a full-bore baby, as the court in Alabama seems to think.

Dr. Caplan, director, division of medical ethics, New York University Langone Medical Center, New York, has served as a director, officer, partner, employee, adviser, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). He is a contributing author and adviser for Medscape.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I think we’re all aware that Alabama has put itself and the rest of the country into a moral bind when it comes to abortion and the status of human embryos. Back on February 16, 2024, the Alabama Supreme Court rendered a decision in a case called LePage v. Center for Reproductive Medicine, in which the court said that cryopreserved embryos in frozen nitrogen were legally equivalent to children.

They basically said they’re granted the same rights, meaning you certainly can’t destroy them. You certainly could not be in a situation where somebody said, “I’m going to not use them,” because once you create them, you seem to have some duty to make sure they end up in an environment where they can become full-fledged adults.

This decision that embryos in frozen nitrogen — but literally embryos anywhere — are the equivalent of full-bore children put Alabama in a terrible situation if you were a person or a couple seeking in vitro fertilization (IVF).

IVF requires the creation of many eggs. Women have to undergo drug treatment so that they superovulate. It’s too expensive to just go one egg at a time, egg procurement costs too much, and a cycle of IVF could cost as much as $15,000. There are some people who don’t make many eggs, so you want to get as many as you can.

When you get them, you freeze them, as happened in this Alabama case. By the way, what triggered the court case was that somebody in the lab dropped the tray with embryos in it, and they were basically accused not just of a mistake but of murder.

It’s pretty serious when you see this decision and you realize that if you make a multitude of embryos and then you had a child after two tries, but you have six more, you can’t destroy them. What are you going to do with them? Will they be under the governance of the utility company? What’s going to happen?

Many women in Alabama were outraged by the court’s opinion because they want to do IVF. In fact, politically, proponents of thinking that life begins at conception — or fetal personhood as it’s called, and the view that human embryos are children from the minute of conception — were stuck. It’s hard to argue that IVF is not pro-life. It’s hard to argue that people who desperately want to have children should find it difficult to use the technique.

The state has tried to pass a law that exempts IVF clinics from liability if they’re trying to use human embryos to make babies. I do not think this will stand. The court decision is fundamentally wrong, in part because human embryos are not children. They are potential children. They are possible children, but outside of implantation in the environment of a woman’s uterus, they’ll never become anything.

In fact, the court decision is a version of what used to be called preformationism, which sees a tiny baby inside a human embryo. That’s not true. We know today that you’ve got sets of genes that need messages from the mom in order to begin the process of division and development. It isn’t just expanding a tiny, miniature baby into a full-bore baby, as the court in Alabama seems to think.

Dr. Caplan, director, division of medical ethics, New York University Langone Medical Center, New York, has served as a director, officer, partner, employee, adviser, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). He is a contributing author and adviser for Medscape.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I think we’re all aware that Alabama has put itself and the rest of the country into a moral bind when it comes to abortion and the status of human embryos. Back on February 16, 2024, the Alabama Supreme Court rendered a decision in a case called LePage v. Center for Reproductive Medicine, in which the court said that cryopreserved embryos in frozen nitrogen were legally equivalent to children.

They basically said they’re granted the same rights, meaning you certainly can’t destroy them. You certainly could not be in a situation where somebody said, “I’m going to not use them,” because once you create them, you seem to have some duty to make sure they end up in an environment where they can become full-fledged adults.

This decision that embryos in frozen nitrogen — but literally embryos anywhere — are the equivalent of full-bore children put Alabama in a terrible situation if you were a person or a couple seeking in vitro fertilization (IVF).

IVF requires the creation of many eggs. Women have to undergo drug treatment so that they superovulate. It’s too expensive to just go one egg at a time, egg procurement costs too much, and a cycle of IVF could cost as much as $15,000. There are some people who don’t make many eggs, so you want to get as many as you can.

When you get them, you freeze them, as happened in this Alabama case. By the way, what triggered the court case was that somebody in the lab dropped the tray with embryos in it, and they were basically accused not just of a mistake but of murder.

It’s pretty serious when you see this decision and you realize that if you make a multitude of embryos and then you had a child after two tries, but you have six more, you can’t destroy them. What are you going to do with them? Will they be under the governance of the utility company? What’s going to happen?

Many women in Alabama were outraged by the court’s opinion because they want to do IVF. In fact, politically, proponents of thinking that life begins at conception — or fetal personhood as it’s called, and the view that human embryos are children from the minute of conception — were stuck. It’s hard to argue that IVF is not pro-life. It’s hard to argue that people who desperately want to have children should find it difficult to use the technique.

The state has tried to pass a law that exempts IVF clinics from liability if they’re trying to use human embryos to make babies. I do not think this will stand. The court decision is fundamentally wrong, in part because human embryos are not children. They are potential children. They are possible children, but outside of implantation in the environment of a woman’s uterus, they’ll never become anything.

In fact, the court decision is a version of what used to be called preformationism, which sees a tiny baby inside a human embryo. That’s not true. We know today that you’ve got sets of genes that need messages from the mom in order to begin the process of division and development. It isn’t just expanding a tiny, miniature baby into a full-bore baby, as the court in Alabama seems to think.

Dr. Caplan, director, division of medical ethics, New York University Langone Medical Center, New York, has served as a director, officer, partner, employee, adviser, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). He is a contributing author and adviser for Medscape.

A version of this article appeared on Medscape.com.

TOPLINE: 

The geriatric emergency medication safety recommendations (GEMS-Rx) is the first expert consensus-based list identifying high-risk medication classes that should not be prescribed to older patients visiting the emergency department (ED).

METHODOLOGY:

• Around half of the geriatric patients presenting to the ED get discharged with new prescriptions. Some of the newly prescribed drugs may not be appropriate for use in individuals aged ≥ 65 years, thereby increasing the risk for unfavorable adverse events.
• The American Geriatrics Society (AGS)  has already established guidelines to identify potentially inappropriate medications in older adults; however, the criteria are centered on chronic conditions and long-term medication use and are unsuitable for managing ED prescriptions.
• In this study, the GEMS-Rx high-risk prescription list was prepared with a panel of 10 ED physicians with expertise in geriatrics and quality measurement and a pharmacist with expertise in geriatric pharmacotherapy and emergency medicine.
• They reviewed over 30 medication classes from the 2019 AGS Beers Criteria that were deemed inappropriate for use in older patients. Despite their not being included in the Beers list, the use of short- and long-acting opioids was also discussed.
• After three rounds of review and discussion, the panelists ranked each class of medication on a 5-point Likert scale, with a score of 1 indicating the lowest and 5 indicating the greatest need for avoiding a drug in an ED prescription.

TAKEAWAY:

• The first round suggested that first-generation antihistamines, metoclopramide, short-acting opioids, antipsychotics, barbiturates, skeletal muscle relaxants, and benzodiazepines should be avoided, with mean Likert scores ranging from 3.7 to 4.6.
• Although nonbenzodiazepine and benzodiazepine receptor agonist hypnotics (“Z-drugs”) were not initially considered owing to their low frequency of prescription in ED settings, the panelists finally included “Z” drugs and sulfonylureas in the GEMS-Rx list after the second and third rounds.
• The final list of high-risk medications to be avoided in ED settings that were prioritized included benzodiazepines, skeletal muscle relaxants, barbiturates, first-generation antipsychotics, first-generation antihistamines, “Z” drugs, metoclopramide, and sulfonylureas.
• However, seizure disorders, benzodiazepine withdrawal, ethanol withdrawal, severe generalized anxiety disorder, end-of-life care, allergic reactions, and ED visits for prescription refilling were deemed exceptional cases in which these high-risk medications could be prescribed.

IN PRACTICE:

“By combining expert consensus and evidence-based criteria, this list can serve as a resource to guide prescribing decisions and mitigate potential risks associated with medications at this crucial care transition. The incorporation of this emergency medicine-specific geriatric prescription list in a national quality measure has the potential to improve patient safety and enhance the quality of care for the millions of older adults who seek care in EDs each year,” the authors said.

SOURCE:

This study was led by Rachel M. Skains, MD, MSPH, Department of Emergency Medicine, University of Alabama at Birmingham, and published online in Annals of Emergency Medicine.

LIMITATIONS:

The GEMS-Rx list was prepared by physicians and pharmacists and may not have fully captured data regarding individual patient preferences, comorbidities, or other contextual factors. During the meetings, the panelists’ identities were not concealed from one another, which may have affected the conversations owing to response and social desirability bias. Furthermore, this list may not be generalizable to other settings because it was produced and intended for usage in US EDs.

DISCLOSURES:

This work was supported by the American College of Emergency Physicians. Some of the authors, including the lead author, declared being supported by various funding agencies. Few authors also declared serving in leadership positions for several sources.

A version of this article appeared on Medscape.com.

TOPLINE: 

The geriatric emergency medication safety recommendations (GEMS-Rx) is the first expert consensus-based list identifying high-risk medication classes that should not be prescribed to older patients visiting the emergency department (ED).

METHODOLOGY:

• Around half of the geriatric patients presenting to the ED get discharged with new prescriptions. Some of the newly prescribed drugs may not be appropriate for use in individuals aged ≥ 65 years, thereby increasing the risk for unfavorable adverse events.
• The American Geriatrics Society (AGS)  has already established guidelines to identify potentially inappropriate medications in older adults; however, the criteria are centered on chronic conditions and long-term medication use and are unsuitable for managing ED prescriptions.
• In this study, the GEMS-Rx high-risk prescription list was prepared with a panel of 10 ED physicians with expertise in geriatrics and quality measurement and a pharmacist with expertise in geriatric pharmacotherapy and emergency medicine.
• They reviewed over 30 medication classes from the 2019 AGS Beers Criteria that were deemed inappropriate for use in older patients. Despite their not being included in the Beers list, the use of short- and long-acting opioids was also discussed.
• After three rounds of review and discussion, the panelists ranked each class of medication on a 5-point Likert scale, with a score of 1 indicating the lowest and 5 indicating the greatest need for avoiding a drug in an ED prescription.

TAKEAWAY:

• The first round suggested that first-generation antihistamines, metoclopramide, short-acting opioids, antipsychotics, barbiturates, skeletal muscle relaxants, and benzodiazepines should be avoided, with mean Likert scores ranging from 3.7 to 4.6.
• Although nonbenzodiazepine and benzodiazepine receptor agonist hypnotics (“Z-drugs”) were not initially considered owing to their low frequency of prescription in ED settings, the panelists finally included “Z” drugs and sulfonylureas in the GEMS-Rx list after the second and third rounds.
• The final list of high-risk medications to be avoided in ED settings that were prioritized included benzodiazepines, skeletal muscle relaxants, barbiturates, first-generation antipsychotics, first-generation antihistamines, “Z” drugs, metoclopramide, and sulfonylureas.
• However, seizure disorders, benzodiazepine withdrawal, ethanol withdrawal, severe generalized anxiety disorder, end-of-life care, allergic reactions, and ED visits for prescription refilling were deemed exceptional cases in which these high-risk medications could be prescribed.

IN PRACTICE:

“By combining expert consensus and evidence-based criteria, this list can serve as a resource to guide prescribing decisions and mitigate potential risks associated with medications at this crucial care transition. The incorporation of this emergency medicine-specific geriatric prescription list in a national quality measure has the potential to improve patient safety and enhance the quality of care for the millions of older adults who seek care in EDs each year,” the authors said.

SOURCE:

This study was led by Rachel M. Skains, MD, MSPH, Department of Emergency Medicine, University of Alabama at Birmingham, and published online in Annals of Emergency Medicine.

LIMITATIONS:

The GEMS-Rx list was prepared by physicians and pharmacists and may not have fully captured data regarding individual patient preferences, comorbidities, or other contextual factors. During the meetings, the panelists’ identities were not concealed from one another, which may have affected the conversations owing to response and social desirability bias. Furthermore, this list may not be generalizable to other settings because it was produced and intended for usage in US EDs.

DISCLOSURES:

This work was supported by the American College of Emergency Physicians. Some of the authors, including the lead author, declared being supported by various funding agencies. Few authors also declared serving in leadership positions for several sources.

A version of this article appeared on Medscape.com.

TOPLINE: 

The geriatric emergency medication safety recommendations (GEMS-Rx) is the first expert consensus-based list identifying high-risk medication classes that should not be prescribed to older patients visiting the emergency department (ED).

METHODOLOGY:

• Around half of the geriatric patients presenting to the ED get discharged with new prescriptions. Some of the newly prescribed drugs may not be appropriate for use in individuals aged ≥ 65 years, thereby increasing the risk for unfavorable adverse events.
• The American Geriatrics Society (AGS)  has already established guidelines to identify potentially inappropriate medications in older adults; however, the criteria are centered on chronic conditions and long-term medication use and are unsuitable for managing ED prescriptions.
• In this study, the GEMS-Rx high-risk prescription list was prepared with a panel of 10 ED physicians with expertise in geriatrics and quality measurement and a pharmacist with expertise in geriatric pharmacotherapy and emergency medicine.
• They reviewed over 30 medication classes from the 2019 AGS Beers Criteria that were deemed inappropriate for use in older patients. Despite their not being included in the Beers list, the use of short- and long-acting opioids was also discussed.
• After three rounds of review and discussion, the panelists ranked each class of medication on a 5-point Likert scale, with a score of 1 indicating the lowest and 5 indicating the greatest need for avoiding a drug in an ED prescription.

TAKEAWAY:

• The first round suggested that first-generation antihistamines, metoclopramide, short-acting opioids, antipsychotics, barbiturates, skeletal muscle relaxants, and benzodiazepines should be avoided, with mean Likert scores ranging from 3.7 to 4.6.
• Although nonbenzodiazepine and benzodiazepine receptor agonist hypnotics (“Z-drugs”) were not initially considered owing to their low frequency of prescription in ED settings, the panelists finally included “Z” drugs and sulfonylureas in the GEMS-Rx list after the second and third rounds.
• The final list of high-risk medications to be avoided in ED settings that were prioritized included benzodiazepines, skeletal muscle relaxants, barbiturates, first-generation antipsychotics, first-generation antihistamines, “Z” drugs, metoclopramide, and sulfonylureas.
• However, seizure disorders, benzodiazepine withdrawal, ethanol withdrawal, severe generalized anxiety disorder, end-of-life care, allergic reactions, and ED visits for prescription refilling were deemed exceptional cases in which these high-risk medications could be prescribed.

IN PRACTICE:

“By combining expert consensus and evidence-based criteria, this list can serve as a resource to guide prescribing decisions and mitigate potential risks associated with medications at this crucial care transition. The incorporation of this emergency medicine-specific geriatric prescription list in a national quality measure has the potential to improve patient safety and enhance the quality of care for the millions of older adults who seek care in EDs each year,” the authors said.

SOURCE:

This study was led by Rachel M. Skains, MD, MSPH, Department of Emergency Medicine, University of Alabama at Birmingham, and published online in Annals of Emergency Medicine.

LIMITATIONS:

The GEMS-Rx list was prepared by physicians and pharmacists and may not have fully captured data regarding individual patient preferences, comorbidities, or other contextual factors. During the meetings, the panelists’ identities were not concealed from one another, which may have affected the conversations owing to response and social desirability bias. Furthermore, this list may not be generalizable to other settings because it was produced and intended for usage in US EDs.

DISCLOSURES:

This work was supported by the American College of Emergency Physicians. Some of the authors, including the lead author, declared being supported by various funding agencies. Few authors also declared serving in leadership positions for several sources.

A version of this article appeared on Medscape.com.

CORRECTED April 7, 2024 // An earlier version of this article misstated the clinical factors of children with CNO that were significantly associated with the need for second-line treatment, as well as the scope of assessments of aspects of disease involvement and their relationship to total number of days on NSAID monotherapy and the odds of needing a second-line treatment.

Children with chronic nonbacterial osteomyelitis (CNO) who had symmetric bone lesions or multiple affected body regions were more likely to need second-line treatment than were patients without these features, according to findings presented at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance.

CNO is an auto-inflammatory condition that results in sterile inflammatory bone lesions and most commonly affects the long bones of people who are skeletally immature. After a first-line treatment of nonsteroidal anti-inflammatory drugs (NSAIDs), second-line treatments per CARRA guidelines typically include methotrexate or sulfasalazine, tumor necrosis factor (TNF)–alpha inhibitors, and bisphosphonates.

“Since it’s common for there to be long delays before diagnosis of CNO, it is important to start an effective treatment promptly,” Katherine D. Nowicki, MD, of Children’s Hospital Colorado, Aurora, told attendees. “While we have guidance on which treatments to use, it remains unclear which patients are most likely to respond to NSAIDs and which patients will require a second-line treatment.”
 

Findings Helpful for Counseling

Melissa S. Oliver, MD, MS, assistant professor of clinical pediatrics in rheumatology at Riley Children’s Health at Indiana University Health, Indianapolis, who was not involved in the research, said the findings of this study are helpful in “counseling families and patients at that initial visit and having a lower threshold to start a second-line agent if NSAID monotherapy is not working well.”

There are no clinical trials on patients with CNO, Dr. Oliver said, so very little data exist for guiding clinicians on the best therapy to use and how long to keep patients on therapy while minimizing risk for flare when coming off therapy.

A key clinical takeaway for clinicians is being able to tell patients with unifocal disease that they may not need to be on NSAIDs for a long period and can still do well, Dr. Oliver said. For patients with multifocal disease with symmetric bone lesions or multiple regions involved with CNO, “pediatric rheumatologists should have a lower threshold to start a second-line therapy for these patients,” she said.

Findings From Largest Single-Center Cohort in North America

Their topline findings revealed that patients with unifocal disease at diagnosis required 47% fewer total days of NSAID monotherapy treatment than those with multifocal disease at diagnosis, Dr. Nowicki told attendees. Having symmetric bone lesions increased the likelihood of needing a second-line therapy by 6.86 times compared with those without symmetric bone lesions, and for each additional region affected by CNO, the odds of needing a second-line therapy increased by a factor of 1.94, she said.

There were no significant differences in patient ages or sex or in mean interval from symptom onset to treatment onset across treatment groups. However, patients who received second-line treatment did have a significantly longer average time from symptom onset to diagnosis (324 days) than those who had a short course (119 days) or long course (270 days) of NSAIDs (P = .023). Mean follow-up was also significantly longer for patients with second-line treatment (3.8 years) or long-course NSAIDs (2.7 years) than for those with short-course NSAIDs (1.2 years; P < .001).

Mean erythrocyte sedimentation rate or C-reactive protein did not differ across treatment groups nor did presence of a CNO lesion on x-rays at presentation. But significantly more patients in the second-line group had a biopsy (94%) than in the long-course (74%) or short-course (69%) NSAID groups (P = .0025). They were also more likely to have one or more whole-body MRIs. Most of the patients on short-course (88%) and long-course (82%) NSAIDs did not undergo a whole-body MRI, whereas most patients (59%) on a second-line treatment underwent at least one and 24% underwent three or more MRIs (P < .001).

More patients on short-course NSAIDs had unifocal disease at diagnosis (72%) than those on long-course NSAIDs (47%) or a second-line treatment (41%; P = .015). Patients on a second-line treatment were also more likely to have symmetric involvement in the same bone (73% vs 16% short-course and 23% long-course NSAIDs) and to have more regions of the body affected (P < .001).

There were significant differences in mean days on NSAID monotherapy and number of NSAIDs trialed. Patients on a second-line treatment had a mean 441 days of NSAID monotherapy compared with 175 days for patients on short-course NSAIDs and 725 for patients on long-course NSAIDs (P < .001). Nearly all the short-course patients (94%) trialed a single NSAID, while more than half the long-course and second-line patients trialed two or more (P < .001).

None of the patients on short-course NSAIDs had complications. More patients on second-line treatments had vertebral height loss (20%) or amplified pain (14%) than long-course patients (13% and 5%, respectively; P = .02).

At the study’s end date, nearly all the patients on short-course NSAIDs were in remission (94%) compared with 71% of patients on long-course NSAIDs and only half of patients (51%) on the second-line treatment (P < .001). None of the patients on short-course NSAIDs had active disease compared with 11% of patients on long-course NSAIDs and 20% of patients on second-line treatments (P = .02).

This study included the largest single-center cohort of patients with CNO in North America, all treated at a multidisciplinary clinic with a protocolized treatment approach, but it remains limited by its retrospective nature and the missing data for 70 patients, Dr. Nowicki said. She noted that whole-body MRI was not systematically performed on all patients, so it was possible patients without a whole-body MRI had undetected asymptomatic lesions.

Despite these limitations, Dr. Oliver said retrospective studies like these can help pediatric rheumatologists get an idea of reasonable therapies to start, how long to keep patients on them, and when to escalate to the next step.

“I hope one day our CNO research will be able to tell us about which is the optimal second-line therapy for patients, such as bisphosphonates vs TNF inhibitors vs DMARDs [disease-modifying antirheumatic drugs],” Dr. Oliver said.

Dr. Nowicki and Dr. Oliver reported no disclosures. Information on study funding was not provided.

A version of this article appeared on Medscape.com .

CORRECTED April 7, 2024 // An earlier version of this article misstated the clinical factors of children with CNO that were significantly associated with the need for second-line treatment, as well as the scope of assessments of aspects of disease involvement and their relationship to total number of days on NSAID monotherapy and the odds of needing a second-line treatment.

Children with chronic nonbacterial osteomyelitis (CNO) who had symmetric bone lesions or multiple affected body regions were more likely to need second-line treatment than were patients without these features, according to findings presented at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance.

CNO is an auto-inflammatory condition that results in sterile inflammatory bone lesions and most commonly affects the long bones of people who are skeletally immature. After a first-line treatment of nonsteroidal anti-inflammatory drugs (NSAIDs), second-line treatments per CARRA guidelines typically include methotrexate or sulfasalazine, tumor necrosis factor (TNF)–alpha inhibitors, and bisphosphonates.

“Since it’s common for there to be long delays before diagnosis of CNO, it is important to start an effective treatment promptly,” Katherine D. Nowicki, MD, of Children’s Hospital Colorado, Aurora, told attendees. “While we have guidance on which treatments to use, it remains unclear which patients are most likely to respond to NSAIDs and which patients will require a second-line treatment.”
 

Findings Helpful for Counseling

Melissa S. Oliver, MD, MS, assistant professor of clinical pediatrics in rheumatology at Riley Children’s Health at Indiana University Health, Indianapolis, who was not involved in the research, said the findings of this study are helpful in “counseling families and patients at that initial visit and having a lower threshold to start a second-line agent if NSAID monotherapy is not working well.”

There are no clinical trials on patients with CNO, Dr. Oliver said, so very little data exist for guiding clinicians on the best therapy to use and how long to keep patients on therapy while minimizing risk for flare when coming off therapy.

A key clinical takeaway for clinicians is being able to tell patients with unifocal disease that they may not need to be on NSAIDs for a long period and can still do well, Dr. Oliver said. For patients with multifocal disease with symmetric bone lesions or multiple regions involved with CNO, “pediatric rheumatologists should have a lower threshold to start a second-line therapy for these patients,” she said.

Findings From Largest Single-Center Cohort in North America

Their topline findings revealed that patients with unifocal disease at diagnosis required 47% fewer total days of NSAID monotherapy treatment than those with multifocal disease at diagnosis, Dr. Nowicki told attendees. Having symmetric bone lesions increased the likelihood of needing a second-line therapy by 6.86 times compared with those without symmetric bone lesions, and for each additional region affected by CNO, the odds of needing a second-line therapy increased by a factor of 1.94, she said.

There were no significant differences in patient ages or sex or in mean interval from symptom onset to treatment onset across treatment groups. However, patients who received second-line treatment did have a significantly longer average time from symptom onset to diagnosis (324 days) than those who had a short course (119 days) or long course (270 days) of NSAIDs (P = .023). Mean follow-up was also significantly longer for patients with second-line treatment (3.8 years) or long-course NSAIDs (2.7 years) than for those with short-course NSAIDs (1.2 years; P < .001).

Mean erythrocyte sedimentation rate or C-reactive protein did not differ across treatment groups nor did presence of a CNO lesion on x-rays at presentation. But significantly more patients in the second-line group had a biopsy (94%) than in the long-course (74%) or short-course (69%) NSAID groups (P = .0025). They were also more likely to have one or more whole-body MRIs. Most of the patients on short-course (88%) and long-course (82%) NSAIDs did not undergo a whole-body MRI, whereas most patients (59%) on a second-line treatment underwent at least one and 24% underwent three or more MRIs (P < .001).

More patients on short-course NSAIDs had unifocal disease at diagnosis (72%) than those on long-course NSAIDs (47%) or a second-line treatment (41%; P = .015). Patients on a second-line treatment were also more likely to have symmetric involvement in the same bone (73% vs 16% short-course and 23% long-course NSAIDs) and to have more regions of the body affected (P < .001).

There were significant differences in mean days on NSAID monotherapy and number of NSAIDs trialed. Patients on a second-line treatment had a mean 441 days of NSAID monotherapy compared with 175 days for patients on short-course NSAIDs and 725 for patients on long-course NSAIDs (P < .001). Nearly all the short-course patients (94%) trialed a single NSAID, while more than half the long-course and second-line patients trialed two or more (P < .001).

None of the patients on short-course NSAIDs had complications. More patients on second-line treatments had vertebral height loss (20%) or amplified pain (14%) than long-course patients (13% and 5%, respectively; P = .02).

At the study’s end date, nearly all the patients on short-course NSAIDs were in remission (94%) compared with 71% of patients on long-course NSAIDs and only half of patients (51%) on the second-line treatment (P < .001). None of the patients on short-course NSAIDs had active disease compared with 11% of patients on long-course NSAIDs and 20% of patients on second-line treatments (P = .02).

This study included the largest single-center cohort of patients with CNO in North America, all treated at a multidisciplinary clinic with a protocolized treatment approach, but it remains limited by its retrospective nature and the missing data for 70 patients, Dr. Nowicki said. She noted that whole-body MRI was not systematically performed on all patients, so it was possible patients without a whole-body MRI had undetected asymptomatic lesions.

Despite these limitations, Dr. Oliver said retrospective studies like these can help pediatric rheumatologists get an idea of reasonable therapies to start, how long to keep patients on them, and when to escalate to the next step.

“I hope one day our CNO research will be able to tell us about which is the optimal second-line therapy for patients, such as bisphosphonates vs TNF inhibitors vs DMARDs [disease-modifying antirheumatic drugs],” Dr. Oliver said.

Dr. Nowicki and Dr. Oliver reported no disclosures. Information on study funding was not provided.

A version of this article appeared on Medscape.com .

CORRECTED April 7, 2024 // An earlier version of this article misstated the clinical factors of children with CNO that were significantly associated with the need for second-line treatment, as well as the scope of assessments of aspects of disease involvement and their relationship to total number of days on NSAID monotherapy and the odds of needing a second-line treatment.

Children with chronic nonbacterial osteomyelitis (CNO) who had symmetric bone lesions or multiple affected body regions were more likely to need second-line treatment than were patients without these features, according to findings presented at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance.

CNO is an auto-inflammatory condition that results in sterile inflammatory bone lesions and most commonly affects the long bones of people who are skeletally immature. After a first-line treatment of nonsteroidal anti-inflammatory drugs (NSAIDs), second-line treatments per CARRA guidelines typically include methotrexate or sulfasalazine, tumor necrosis factor (TNF)–alpha inhibitors, and bisphosphonates.

“Since it’s common for there to be long delays before diagnosis of CNO, it is important to start an effective treatment promptly,” Katherine D. Nowicki, MD, of Children’s Hospital Colorado, Aurora, told attendees. “While we have guidance on which treatments to use, it remains unclear which patients are most likely to respond to NSAIDs and which patients will require a second-line treatment.”
 

Findings Helpful for Counseling

Melissa S. Oliver, MD, MS, assistant professor of clinical pediatrics in rheumatology at Riley Children’s Health at Indiana University Health, Indianapolis, who was not involved in the research, said the findings of this study are helpful in “counseling families and patients at that initial visit and having a lower threshold to start a second-line agent if NSAID monotherapy is not working well.”

There are no clinical trials on patients with CNO, Dr. Oliver said, so very little data exist for guiding clinicians on the best therapy to use and how long to keep patients on therapy while minimizing risk for flare when coming off therapy.

A key clinical takeaway for clinicians is being able to tell patients with unifocal disease that they may not need to be on NSAIDs for a long period and can still do well, Dr. Oliver said. For patients with multifocal disease with symmetric bone lesions or multiple regions involved with CNO, “pediatric rheumatologists should have a lower threshold to start a second-line therapy for these patients,” she said.

Findings From Largest Single-Center Cohort in North America

Their topline findings revealed that patients with unifocal disease at diagnosis required 47% fewer total days of NSAID monotherapy treatment than those with multifocal disease at diagnosis, Dr. Nowicki told attendees. Having symmetric bone lesions increased the likelihood of needing a second-line therapy by 6.86 times compared with those without symmetric bone lesions, and for each additional region affected by CNO, the odds of needing a second-line therapy increased by a factor of 1.94, she said.

There were no significant differences in patient ages or sex or in mean interval from symptom onset to treatment onset across treatment groups. However, patients who received second-line treatment did have a significantly longer average time from symptom onset to diagnosis (324 days) than those who had a short course (119 days) or long course (270 days) of NSAIDs (P = .023). Mean follow-up was also significantly longer for patients with second-line treatment (3.8 years) or long-course NSAIDs (2.7 years) than for those with short-course NSAIDs (1.2 years; P < .001).

Mean erythrocyte sedimentation rate or C-reactive protein did not differ across treatment groups nor did presence of a CNO lesion on x-rays at presentation. But significantly more patients in the second-line group had a biopsy (94%) than in the long-course (74%) or short-course (69%) NSAID groups (P = .0025). They were also more likely to have one or more whole-body MRIs. Most of the patients on short-course (88%) and long-course (82%) NSAIDs did not undergo a whole-body MRI, whereas most patients (59%) on a second-line treatment underwent at least one and 24% underwent three or more MRIs (P < .001).

More patients on short-course NSAIDs had unifocal disease at diagnosis (72%) than those on long-course NSAIDs (47%) or a second-line treatment (41%; P = .015). Patients on a second-line treatment were also more likely to have symmetric involvement in the same bone (73% vs 16% short-course and 23% long-course NSAIDs) and to have more regions of the body affected (P < .001).

There were significant differences in mean days on NSAID monotherapy and number of NSAIDs trialed. Patients on a second-line treatment had a mean 441 days of NSAID monotherapy compared with 175 days for patients on short-course NSAIDs and 725 for patients on long-course NSAIDs (P < .001). Nearly all the short-course patients (94%) trialed a single NSAID, while more than half the long-course and second-line patients trialed two or more (P < .001).

None of the patients on short-course NSAIDs had complications. More patients on second-line treatments had vertebral height loss (20%) or amplified pain (14%) than long-course patients (13% and 5%, respectively; P = .02).

At the study’s end date, nearly all the patients on short-course NSAIDs were in remission (94%) compared with 71% of patients on long-course NSAIDs and only half of patients (51%) on the second-line treatment (P < .001). None of the patients on short-course NSAIDs had active disease compared with 11% of patients on long-course NSAIDs and 20% of patients on second-line treatments (P = .02).

This study included the largest single-center cohort of patients with CNO in North America, all treated at a multidisciplinary clinic with a protocolized treatment approach, but it remains limited by its retrospective nature and the missing data for 70 patients, Dr. Nowicki said. She noted that whole-body MRI was not systematically performed on all patients, so it was possible patients without a whole-body MRI had undetected asymptomatic lesions.

Despite these limitations, Dr. Oliver said retrospective studies like these can help pediatric rheumatologists get an idea of reasonable therapies to start, how long to keep patients on them, and when to escalate to the next step.

“I hope one day our CNO research will be able to tell us about which is the optimal second-line therapy for patients, such as bisphosphonates vs TNF inhibitors vs DMARDs [disease-modifying antirheumatic drugs],” Dr. Oliver said.

Dr. Nowicki and Dr. Oliver reported no disclosures. Information on study funding was not provided.

A version of this article appeared on Medscape.com .

TOPLINE:

The rates of screening for latent tuberculosis remain suboptimal among new users of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), with notable variations by medication type and demographic characteristics. 

METHODOLOGY:

• Professional society guidelines recommend screening for tuberculosis before starting treatment with most b/tsDMARDs.
• In an attempt to estimate the extent of latent tuberculosis screening, researchers combined claims and electronic health record datasets to evaluate 2853 new b/tsDMARD users (mean age, 73 years; 72% women; and 73% non-Hispanic White).
• The primary analysis focused on assessing the proportion of patients screened for latent tuberculosis in the year before starting a new b/tsDMARD.
• A sensitivity analysis evaluated the extent of screening within the 3 years preceding the initiation of a new b/tsDMARD.
• A total of 65.6% of patients received screening for latent tuberculosis in the year before initiating a new b/tsDMARD.
• Screening rates improved only slightly on expanding the window to 3 years, with 72.9% of patients receiving any tuberculosis screening.
• When stratified by drug type, over half of new users of Janus kinase inhibitors and nearly 90% of new users of interleukin-17 inhibitors had not received screening.
• Hispanic patients had lower odds of tuberculosis screening within 1 year than White patients (odds ratio [OR], 0.64; 95% CI, 0.46-0.90), as did those in the highest socioeconomic quartile, compared with the lowest (OR, 0.61; 95% CI, 0.40-0.94).

IN PRACTICE:

“Educational initiatives, team-based care delivery, task shifting, and technological interventions to address observed gaps in patient safety procedures are needed,” the authors wrote.

SOURCE:

The study was led by Eric T. Roberts, PhD, University of California, San Francisco, and published online in Arthritis Care & Research

LIMITATIONS:

The study lacked access to scanned documents or clinical notes, which may have resulted in the omission of a small number of tests that had no Medicare billing. Moreover, the study was restricted to a 3-year lookback period, potentially missing some remote screenings. The findings may have limited generalizability to younger patients or those not dually eligible for Medicare and Medicaid.

DISCLOSURES:

This study was funded by grants from the Agency for Healthcare Research and Quality and the National Institute for Arthritis and Musculoskeletal and Skin Diseases. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

The rates of screening for latent tuberculosis remain suboptimal among new users of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), with notable variations by medication type and demographic characteristics. 

METHODOLOGY:

• Professional society guidelines recommend screening for tuberculosis before starting treatment with most b/tsDMARDs.
• In an attempt to estimate the extent of latent tuberculosis screening, researchers combined claims and electronic health record datasets to evaluate 2853 new b/tsDMARD users (mean age, 73 years; 72% women; and 73% non-Hispanic White).
• The primary analysis focused on assessing the proportion of patients screened for latent tuberculosis in the year before starting a new b/tsDMARD.
• A sensitivity analysis evaluated the extent of screening within the 3 years preceding the initiation of a new b/tsDMARD.
• A total of 65.6% of patients received screening for latent tuberculosis in the year before initiating a new b/tsDMARD.
• Screening rates improved only slightly on expanding the window to 3 years, with 72.9% of patients receiving any tuberculosis screening.
• When stratified by drug type, over half of new users of Janus kinase inhibitors and nearly 90% of new users of interleukin-17 inhibitors had not received screening.
• Hispanic patients had lower odds of tuberculosis screening within 1 year than White patients (odds ratio [OR], 0.64; 95% CI, 0.46-0.90), as did those in the highest socioeconomic quartile, compared with the lowest (OR, 0.61; 95% CI, 0.40-0.94).

IN PRACTICE:

“Educational initiatives, team-based care delivery, task shifting, and technological interventions to address observed gaps in patient safety procedures are needed,” the authors wrote.

SOURCE:

The study was led by Eric T. Roberts, PhD, University of California, San Francisco, and published online in Arthritis Care & Research

LIMITATIONS:

The study lacked access to scanned documents or clinical notes, which may have resulted in the omission of a small number of tests that had no Medicare billing. Moreover, the study was restricted to a 3-year lookback period, potentially missing some remote screenings. The findings may have limited generalizability to younger patients or those not dually eligible for Medicare and Medicaid.

DISCLOSURES:

This study was funded by grants from the Agency for Healthcare Research and Quality and the National Institute for Arthritis and Musculoskeletal and Skin Diseases. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

The rates of screening for latent tuberculosis remain suboptimal among new users of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), with notable variations by medication type and demographic characteristics. 

METHODOLOGY:

• Professional society guidelines recommend screening for tuberculosis before starting treatment with most b/tsDMARDs.
• In an attempt to estimate the extent of latent tuberculosis screening, researchers combined claims and electronic health record datasets to evaluate 2853 new b/tsDMARD users (mean age, 73 years; 72% women; and 73% non-Hispanic White).
• The primary analysis focused on assessing the proportion of patients screened for latent tuberculosis in the year before starting a new b/tsDMARD.
• A sensitivity analysis evaluated the extent of screening within the 3 years preceding the initiation of a new b/tsDMARD.
• A total of 65.6% of patients received screening for latent tuberculosis in the year before initiating a new b/tsDMARD.
• Screening rates improved only slightly on expanding the window to 3 years, with 72.9% of patients receiving any tuberculosis screening.
• When stratified by drug type, over half of new users of Janus kinase inhibitors and nearly 90% of new users of interleukin-17 inhibitors had not received screening.
• Hispanic patients had lower odds of tuberculosis screening within 1 year than White patients (odds ratio [OR], 0.64; 95% CI, 0.46-0.90), as did those in the highest socioeconomic quartile, compared with the lowest (OR, 0.61; 95% CI, 0.40-0.94).

IN PRACTICE:

“Educational initiatives, team-based care delivery, task shifting, and technological interventions to address observed gaps in patient safety procedures are needed,” the authors wrote.

SOURCE:

The study was led by Eric T. Roberts, PhD, University of California, San Francisco, and published online in Arthritis Care & Research

LIMITATIONS:

The study lacked access to scanned documents or clinical notes, which may have resulted in the omission of a small number of tests that had no Medicare billing. Moreover, the study was restricted to a 3-year lookback period, potentially missing some remote screenings. The findings may have limited generalizability to younger patients or those not dually eligible for Medicare and Medicaid.

DISCLOSURES:

This study was funded by grants from the Agency for Healthcare Research and Quality and the National Institute for Arthritis and Musculoskeletal and Skin Diseases. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

What dietary recommendations are appropriate for gastroesophageal reflux disease (GERD)? While 85% of patients identify at least one food associated with reflux symptoms, misconceptions about diet in GERD are widespread. The issue was discussed during a dedicated session at the Francophone Days of Hepatology, Gastroenterology, and Digestive Oncology.

GERD occurs when the contents, especially acid, of the stomach back up into the esophagus, leading to symptoms or lesions of the esophageal mucosa.

In addition to proton pump inhibitors, several hygienic-dietary rules are integrated into the therapeutic management of GERD. Some, such as elevating the head of the bed and allowing a 2- to 3-hour gap between meals and bedtime, have proven effective.

Diet and obesity also play a role in the onset of GERD symptoms. Thus, hygienic-dietary rules are an integral part of current recommendations.

“Weight loss is effective in reducing reflux symptoms and should be recommended,” stated Frank Zerbib, MD, head of Hepatology, Gastroenterology, and Digestive Oncology at University Hospital of Bordeaux in France, during the presentation.

Furthermore, most patients with GERD identify foods that may trigger their symptoms, even if there is no evidence to support this in the literature. However, it has been shown that reducing the consumption of these foods is effective.
 

Caloric Intake and Lipid Content

Meal intake affects esophagogastric physiology in several ways: It reduces the tone of the lower esophageal sphincter (LES) and increases the number of transient LES relaxations (TLESRs), which are induced by distension and relaxation of the proximal stomach. These effects are mediated by vagal afferent stimulation and the stretching of the mechanoreceptors of the fundic wall. They are influenced by neuropeptide effects such as cholecystokinin (CCK), which is released in the presence of lipids in the duodenal lumen. Hence, the importance of caloric intake and lipid content, even though it is difficult to distinguish their respective effects.

A high-calorie meal slows gastric emptying, thus prolonging gastric distension, reducing LES tone, and promoting the onset of TLESRs. Several studies have emphasized that at equivalent caloric intake, lipid composition has no impact on LES tone and the number of TLESRs in healthy patients or those with GERD. However, with equivalent caloric intake, and thus equivalent acid exposure, the presence of lipids in the meal increases the perception of reflux. This “reflux hypersensitivity” effect induced by lipids is caused by the endogenous release of CCK and its action on vagal afferents. This effect also is observed in the perception of functional dyspepsia symptoms.

Several studies have established a correlation between saturated fat consumption and the presence of GERD symptoms.
 

The Role of Carbohydrates

While the protein component of a meal has little impact on esophagogastric physiology, carbohydrates produce effects on esophagogastric motility that are mediated by their fermentation products, especially short-chain fatty acids (SCFAs), which are synthesized in the colon. Colonic perfusion of these SCFAs leads to fundus relaxation, reduced LES tone, and increased TLESRs. Moreover, in patients with GERD, adding prebiotics (fructo-oligosaccharide) to the meal content increases the number of TLESRs, acid reflux, and symptoms by amplifying colonic fermentation and SCFA production.

Several studies have evaluated low-carbohydrate diets in GERD. A small study of eight patients with morbid obesity on a very low–carbohydrate diet observed benefits on symptoms and esophageal acid exposure in pH probe testing.

A randomized French study of 31 patients with refractory GERD found no significant difference between a low fermentable oligo-, di-, monosaccharides, and polyols diet and usual dietary advice.

A recent American study of 95 veterans found an improvement in pH in the group reducing simple sugars but symptomatic improvement in all groups reducing sugar consumption in general.

Therefore, based on all these data, according to Dr. Zerbib, “high-calorie meals, rich in fats or carbohydrates, promote the onset of reflux episodes and their perception. Diets low in fats and carbohydrates should be recommended.”
 

Questionable Studies

Certain foods can reduce LES pressure, such as coffee (excluding decaf), chocolate, and white wine. Moreover, white wine, beer, and chocolate have been associated with increased esophageal acid exposure. No significant effects on LES pressure or reflux have been observed with the consumption of citrus fruits or spicy foods. These conclusions, however, are based on older studies and subject to methodological criticisms.

Population studies on tea and coffee yield conflicting results. A recent study of 48,000 nurses without documented GERD found that consumption of tea, coffee, or sodas increased the risk for reflux symptoms by about 30% at least once per week, while water, milk, or fruit juice had no effect. Furthermore, the consumption of carbonated beverages also does not seem to increase the risk for GERD.

Regarding alcohol consumption as a risk factor for GERD, epidemiological data do not allow for a definitive conclusion. Most studies have not found a significant link, a finding confirmed by a recent meta-analysis of 24 publications.

Obesity contributes to GERD by promoting increased abdominal pressure and constraints on the esophagogastric junction. A high-resolution manometry study provided robust evidence for this mechanism. Generally, the relative risk for symptomatic GERD with obesity is 2-3 compared with normal body mass index (BMI), with a linear increase according to BMI.

Dr. Zerbib reported no relevant financial conflicts related to his presentation.

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

What dietary recommendations are appropriate for gastroesophageal reflux disease (GERD)? While 85% of patients identify at least one food associated with reflux symptoms, misconceptions about diet in GERD are widespread. The issue was discussed during a dedicated session at the Francophone Days of Hepatology, Gastroenterology, and Digestive Oncology.

GERD occurs when the contents, especially acid, of the stomach back up into the esophagus, leading to symptoms or lesions of the esophageal mucosa.

In addition to proton pump inhibitors, several hygienic-dietary rules are integrated into the therapeutic management of GERD. Some, such as elevating the head of the bed and allowing a 2- to 3-hour gap between meals and bedtime, have proven effective.

Diet and obesity also play a role in the onset of GERD symptoms. Thus, hygienic-dietary rules are an integral part of current recommendations.

“Weight loss is effective in reducing reflux symptoms and should be recommended,” stated Frank Zerbib, MD, head of Hepatology, Gastroenterology, and Digestive Oncology at University Hospital of Bordeaux in France, during the presentation.

Furthermore, most patients with GERD identify foods that may trigger their symptoms, even if there is no evidence to support this in the literature. However, it has been shown that reducing the consumption of these foods is effective.
 

Caloric Intake and Lipid Content

Meal intake affects esophagogastric physiology in several ways: It reduces the tone of the lower esophageal sphincter (LES) and increases the number of transient LES relaxations (TLESRs), which are induced by distension and relaxation of the proximal stomach. These effects are mediated by vagal afferent stimulation and the stretching of the mechanoreceptors of the fundic wall. They are influenced by neuropeptide effects such as cholecystokinin (CCK), which is released in the presence of lipids in the duodenal lumen. Hence, the importance of caloric intake and lipid content, even though it is difficult to distinguish their respective effects.

A high-calorie meal slows gastric emptying, thus prolonging gastric distension, reducing LES tone, and promoting the onset of TLESRs. Several studies have emphasized that at equivalent caloric intake, lipid composition has no impact on LES tone and the number of TLESRs in healthy patients or those with GERD. However, with equivalent caloric intake, and thus equivalent acid exposure, the presence of lipids in the meal increases the perception of reflux. This “reflux hypersensitivity” effect induced by lipids is caused by the endogenous release of CCK and its action on vagal afferents. This effect also is observed in the perception of functional dyspepsia symptoms.

Several studies have established a correlation between saturated fat consumption and the presence of GERD symptoms.
 

The Role of Carbohydrates

While the protein component of a meal has little impact on esophagogastric physiology, carbohydrates produce effects on esophagogastric motility that are mediated by their fermentation products, especially short-chain fatty acids (SCFAs), which are synthesized in the colon. Colonic perfusion of these SCFAs leads to fundus relaxation, reduced LES tone, and increased TLESRs. Moreover, in patients with GERD, adding prebiotics (fructo-oligosaccharide) to the meal content increases the number of TLESRs, acid reflux, and symptoms by amplifying colonic fermentation and SCFA production.

Several studies have evaluated low-carbohydrate diets in GERD. A small study of eight patients with morbid obesity on a very low–carbohydrate diet observed benefits on symptoms and esophageal acid exposure in pH probe testing.

A randomized French study of 31 patients with refractory GERD found no significant difference between a low fermentable oligo-, di-, monosaccharides, and polyols diet and usual dietary advice.

A recent American study of 95 veterans found an improvement in pH in the group reducing simple sugars but symptomatic improvement in all groups reducing sugar consumption in general.

Therefore, based on all these data, according to Dr. Zerbib, “high-calorie meals, rich in fats or carbohydrates, promote the onset of reflux episodes and their perception. Diets low in fats and carbohydrates should be recommended.”
 

Questionable Studies

Certain foods can reduce LES pressure, such as coffee (excluding decaf), chocolate, and white wine. Moreover, white wine, beer, and chocolate have been associated with increased esophageal acid exposure. No significant effects on LES pressure or reflux have been observed with the consumption of citrus fruits or spicy foods. These conclusions, however, are based on older studies and subject to methodological criticisms.

Population studies on tea and coffee yield conflicting results. A recent study of 48,000 nurses without documented GERD found that consumption of tea, coffee, or sodas increased the risk for reflux symptoms by about 30% at least once per week, while water, milk, or fruit juice had no effect. Furthermore, the consumption of carbonated beverages also does not seem to increase the risk for GERD.

Regarding alcohol consumption as a risk factor for GERD, epidemiological data do not allow for a definitive conclusion. Most studies have not found a significant link, a finding confirmed by a recent meta-analysis of 24 publications.

Obesity contributes to GERD by promoting increased abdominal pressure and constraints on the esophagogastric junction. A high-resolution manometry study provided robust evidence for this mechanism. Generally, the relative risk for symptomatic GERD with obesity is 2-3 compared with normal body mass index (BMI), with a linear increase according to BMI.

Dr. Zerbib reported no relevant financial conflicts related to his presentation.

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

What dietary recommendations are appropriate for gastroesophageal reflux disease (GERD)? While 85% of patients identify at least one food associated with reflux symptoms, misconceptions about diet in GERD are widespread. The issue was discussed during a dedicated session at the Francophone Days of Hepatology, Gastroenterology, and Digestive Oncology.

GERD occurs when the contents, especially acid, of the stomach back up into the esophagus, leading to symptoms or lesions of the esophageal mucosa.

In addition to proton pump inhibitors, several hygienic-dietary rules are integrated into the therapeutic management of GERD. Some, such as elevating the head of the bed and allowing a 2- to 3-hour gap between meals and bedtime, have proven effective.

Diet and obesity also play a role in the onset of GERD symptoms. Thus, hygienic-dietary rules are an integral part of current recommendations.

“Weight loss is effective in reducing reflux symptoms and should be recommended,” stated Frank Zerbib, MD, head of Hepatology, Gastroenterology, and Digestive Oncology at University Hospital of Bordeaux in France, during the presentation.

Furthermore, most patients with GERD identify foods that may trigger their symptoms, even if there is no evidence to support this in the literature. However, it has been shown that reducing the consumption of these foods is effective.
 

Caloric Intake and Lipid Content

Meal intake affects esophagogastric physiology in several ways: It reduces the tone of the lower esophageal sphincter (LES) and increases the number of transient LES relaxations (TLESRs), which are induced by distension and relaxation of the proximal stomach. These effects are mediated by vagal afferent stimulation and the stretching of the mechanoreceptors of the fundic wall. They are influenced by neuropeptide effects such as cholecystokinin (CCK), which is released in the presence of lipids in the duodenal lumen. Hence, the importance of caloric intake and lipid content, even though it is difficult to distinguish their respective effects.

A high-calorie meal slows gastric emptying, thus prolonging gastric distension, reducing LES tone, and promoting the onset of TLESRs. Several studies have emphasized that at equivalent caloric intake, lipid composition has no impact on LES tone and the number of TLESRs in healthy patients or those with GERD. However, with equivalent caloric intake, and thus equivalent acid exposure, the presence of lipids in the meal increases the perception of reflux. This “reflux hypersensitivity” effect induced by lipids is caused by the endogenous release of CCK and its action on vagal afferents. This effect also is observed in the perception of functional dyspepsia symptoms.

Several studies have established a correlation between saturated fat consumption and the presence of GERD symptoms.
 

The Role of Carbohydrates

While the protein component of a meal has little impact on esophagogastric physiology, carbohydrates produce effects on esophagogastric motility that are mediated by their fermentation products, especially short-chain fatty acids (SCFAs), which are synthesized in the colon. Colonic perfusion of these SCFAs leads to fundus relaxation, reduced LES tone, and increased TLESRs. Moreover, in patients with GERD, adding prebiotics (fructo-oligosaccharide) to the meal content increases the number of TLESRs, acid reflux, and symptoms by amplifying colonic fermentation and SCFA production.

Several studies have evaluated low-carbohydrate diets in GERD. A small study of eight patients with morbid obesity on a very low–carbohydrate diet observed benefits on symptoms and esophageal acid exposure in pH probe testing.

A randomized French study of 31 patients with refractory GERD found no significant difference between a low fermentable oligo-, di-, monosaccharides, and polyols diet and usual dietary advice.

A recent American study of 95 veterans found an improvement in pH in the group reducing simple sugars but symptomatic improvement in all groups reducing sugar consumption in general.

Therefore, based on all these data, according to Dr. Zerbib, “high-calorie meals, rich in fats or carbohydrates, promote the onset of reflux episodes and their perception. Diets low in fats and carbohydrates should be recommended.”
 

Questionable Studies

Certain foods can reduce LES pressure, such as coffee (excluding decaf), chocolate, and white wine. Moreover, white wine, beer, and chocolate have been associated with increased esophageal acid exposure. No significant effects on LES pressure or reflux have been observed with the consumption of citrus fruits or spicy foods. These conclusions, however, are based on older studies and subject to methodological criticisms.

Population studies on tea and coffee yield conflicting results. A recent study of 48,000 nurses without documented GERD found that consumption of tea, coffee, or sodas increased the risk for reflux symptoms by about 30% at least once per week, while water, milk, or fruit juice had no effect. Furthermore, the consumption of carbonated beverages also does not seem to increase the risk for GERD.

Regarding alcohol consumption as a risk factor for GERD, epidemiological data do not allow for a definitive conclusion. Most studies have not found a significant link, a finding confirmed by a recent meta-analysis of 24 publications.

Obesity contributes to GERD by promoting increased abdominal pressure and constraints on the esophagogastric junction. A high-resolution manometry study provided robust evidence for this mechanism. Generally, the relative risk for symptomatic GERD with obesity is 2-3 compared with normal body mass index (BMI), with a linear increase according to BMI.

Dr. Zerbib reported no relevant financial conflicts related to his presentation.

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

You can’t spell “ophthalmologist” without artificial intelligence (AI) — a fact that might have many eye specialists looking warily over their shoulders. But should they be concerned, or is it time to embrace the new technology?

Ophthalmologists, like most other medical specialists, might be looking warily over their shoulders as AI continues to evolve. But should they be concerned, or is it time to embrace the new technology?

Two recent studies have demonstrated the ability of AI to match ophthalmologists’ answers to patients’ questions about eye disease, and the technology is poised to assist ophthalmologists in managing patient workflow and overcome shortages in the ophthalmic workforce, attendees at the American Glaucoma Society meeting presented on March 2, 2024, in Huntington Beach, California, were told.

A study at the Icahn School of Medicine at Mount Sinai in New York City found chatbots matched the proficiency of fellowship-trained ophthalmologists in diagnostic accuracy and completeness in handling questions about eye disease and real patient cases. Another study found a similar result in handling 200 eye care questions from an online chat forum, Robert Chang, MD, co-author of the second study and a glaucoma specialist and associate professor of ophthalmology at Stanford University in Stanford, California, reported.

“Using prompt engineering of ChatGPT, replies to patient online forum questions are becoming so realistic that specialist physicians are having difficulty telling the difference between human- and machine-generated responses,” Dr. Chang said.

The study used questions patients submitted to an online medical forum that received responses from ophthalmologists, then presented those responses plus answers generated by ChatGPT to a panel of eight ophthalmologists and asked them to distinguish between the two. “The accuracy of judging whether you could tell if it was written by AI or a human was about 61%,” Dr. Chang reported. “So most of the time you could not tell the difference.”

The study reported that of 800 evaluations of chatbot-written answers, ophthalmologists rated 21% of them as human-written, while they marked 64.6% of human-written answers as AI-written. The study also found that the likelihood of chatbot answers containing incorrect or inappropriate material was comparable with human answers: Less than 1% for both.

Dr. Chang also referenced a similar, more recent study from the Icahn School of Medicine in which 15 clinicians reviewed answers to patient questions by fellowship-trained glaucoma and retina specialists and those generated by ChatGPT-4, the chatbot model released by OpenAI in the spring of 2023. The study used a statistical tool to evaluate the combined question-case mean rank for accuracy, which was 506.2 for ChatGPT and 403.4 for glaucoma specialists based on 831 question cases. The mean rank for completeness was 528.3 and 398.7, respectively, based on 828 question cases (P < .001).

“The specialists themselves didn’t rate their answers as good as they rated the chatbot answers,” Dr. Chang said. “So it’s really showing that what we can come up with generative AI so human-like that it’s difficult for us to tell the difference on accuracy and completeness.”
 

‘Getting Close’

However, he noted that chatbots still have some kinks to work out with factual errors, difficulty referencing reliable sources, and hallucinations — fabricated material that may not be accurate. “We’re not quite there yet, but it’s getting close,” Dr. Chang added.

Dr. Chang noted that his clinic at Stanford is testing an AI platform to perform virtual scribing of patient encounters in real time. “That can save a lot of time on documentation,” he said. “I think this is a direction moving forward to increase our productivity because as we know, we all have workforce problems whether it’s the doctors or having enough technicians.”

Chatbots also are being tested for scheduling and generating letters. “Because of the unique needs of each ophthalmologist, AI agents that augment the existing workforce on specific administrative tasks will be the most likely early use case rather than autonomous disease screening or clinical decision support tools, which will take longer to validate prospectively in specific cohorts,” he said.

“Any AI today still has a long way to go before it can ingest and verify all the data for independent decision-making and be validated for fairness and generalizability,” Dr. Chang added. “It is much easier to have ‘low-level thinking’, repetitive tasks be taken care of by algorithms first.”

Dr. Chang “made a convincing case for embracing currently feasible applications of AI, highlighting the potential benefits of leveraging LLMs such as ChatGPT to enhance clinical productivity,” said Thasarat Vajaranant, MD, MHA, director of the glaucoma service and of data sourcing and strategy for the AI Ophthalmology Center at Illinois Eye and Ear Infirmary and the University of Illinois Chicago.

“With the growing demands of an aging population and workforce shortages in ophthalmology, AI-driven solutions offer promise in various areas, including telemedicine triage, organizing clinical notes, assisting in assessments and treatment planning, and virtual scribing,” Dr. Vajaranant said. “Rather than fearing this technology, we should approach its integration with caution.”

Dr. Chang disclosed relationships with Alcon, Genentech/Roche, Itnalight, Verana Health, Sight Sciences, Ocular Therapeutix, Glaukos, Carl Zeiss Meditec, and Apple. Dr. Vajaranant had no relevant disclosures.

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

You can’t spell “ophthalmologist” without artificial intelligence (AI) — a fact that might have many eye specialists looking warily over their shoulders. But should they be concerned, or is it time to embrace the new technology?

Ophthalmologists, like most other medical specialists, might be looking warily over their shoulders as AI continues to evolve. But should they be concerned, or is it time to embrace the new technology?

Two recent studies have demonstrated the ability of AI to match ophthalmologists’ answers to patients’ questions about eye disease, and the technology is poised to assist ophthalmologists in managing patient workflow and overcome shortages in the ophthalmic workforce, attendees at the American Glaucoma Society meeting presented on March 2, 2024, in Huntington Beach, California, were told.

A study at the Icahn School of Medicine at Mount Sinai in New York City found chatbots matched the proficiency of fellowship-trained ophthalmologists in diagnostic accuracy and completeness in handling questions about eye disease and real patient cases. Another study found a similar result in handling 200 eye care questions from an online chat forum, Robert Chang, MD, co-author of the second study and a glaucoma specialist and associate professor of ophthalmology at Stanford University in Stanford, California, reported.

“Using prompt engineering of ChatGPT, replies to patient online forum questions are becoming so realistic that specialist physicians are having difficulty telling the difference between human- and machine-generated responses,” Dr. Chang said.

The study used questions patients submitted to an online medical forum that received responses from ophthalmologists, then presented those responses plus answers generated by ChatGPT to a panel of eight ophthalmologists and asked them to distinguish between the two. “The accuracy of judging whether you could tell if it was written by AI or a human was about 61%,” Dr. Chang reported. “So most of the time you could not tell the difference.”

The study reported that of 800 evaluations of chatbot-written answers, ophthalmologists rated 21% of them as human-written, while they marked 64.6% of human-written answers as AI-written. The study also found that the likelihood of chatbot answers containing incorrect or inappropriate material was comparable with human answers: Less than 1% for both.

Dr. Chang also referenced a similar, more recent study from the Icahn School of Medicine in which 15 clinicians reviewed answers to patient questions by fellowship-trained glaucoma and retina specialists and those generated by ChatGPT-4, the chatbot model released by OpenAI in the spring of 2023. The study used a statistical tool to evaluate the combined question-case mean rank for accuracy, which was 506.2 for ChatGPT and 403.4 for glaucoma specialists based on 831 question cases. The mean rank for completeness was 528.3 and 398.7, respectively, based on 828 question cases (P < .001).

“The specialists themselves didn’t rate their answers as good as they rated the chatbot answers,” Dr. Chang said. “So it’s really showing that what we can come up with generative AI so human-like that it’s difficult for us to tell the difference on accuracy and completeness.”
 

‘Getting Close’

However, he noted that chatbots still have some kinks to work out with factual errors, difficulty referencing reliable sources, and hallucinations — fabricated material that may not be accurate. “We’re not quite there yet, but it’s getting close,” Dr. Chang added.

Dr. Chang noted that his clinic at Stanford is testing an AI platform to perform virtual scribing of patient encounters in real time. “That can save a lot of time on documentation,” he said. “I think this is a direction moving forward to increase our productivity because as we know, we all have workforce problems whether it’s the doctors or having enough technicians.”

Chatbots also are being tested for scheduling and generating letters. “Because of the unique needs of each ophthalmologist, AI agents that augment the existing workforce on specific administrative tasks will be the most likely early use case rather than autonomous disease screening or clinical decision support tools, which will take longer to validate prospectively in specific cohorts,” he said.

“Any AI today still has a long way to go before it can ingest and verify all the data for independent decision-making and be validated for fairness and generalizability,” Dr. Chang added. “It is much easier to have ‘low-level thinking’, repetitive tasks be taken care of by algorithms first.”

Dr. Chang “made a convincing case for embracing currently feasible applications of AI, highlighting the potential benefits of leveraging LLMs such as ChatGPT to enhance clinical productivity,” said Thasarat Vajaranant, MD, MHA, director of the glaucoma service and of data sourcing and strategy for the AI Ophthalmology Center at Illinois Eye and Ear Infirmary and the University of Illinois Chicago.

“With the growing demands of an aging population and workforce shortages in ophthalmology, AI-driven solutions offer promise in various areas, including telemedicine triage, organizing clinical notes, assisting in assessments and treatment planning, and virtual scribing,” Dr. Vajaranant said. “Rather than fearing this technology, we should approach its integration with caution.”

Dr. Chang disclosed relationships with Alcon, Genentech/Roche, Itnalight, Verana Health, Sight Sciences, Ocular Therapeutix, Glaukos, Carl Zeiss Meditec, and Apple. Dr. Vajaranant had no relevant disclosures.

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

You can’t spell “ophthalmologist” without artificial intelligence (AI) — a fact that might have many eye specialists looking warily over their shoulders. But should they be concerned, or is it time to embrace the new technology?

Ophthalmologists, like most other medical specialists, might be looking warily over their shoulders as AI continues to evolve. But should they be concerned, or is it time to embrace the new technology?

Two recent studies have demonstrated the ability of AI to match ophthalmologists’ answers to patients’ questions about eye disease, and the technology is poised to assist ophthalmologists in managing patient workflow and overcome shortages in the ophthalmic workforce, attendees at the American Glaucoma Society meeting presented on March 2, 2024, in Huntington Beach, California, were told.

A study at the Icahn School of Medicine at Mount Sinai in New York City found chatbots matched the proficiency of fellowship-trained ophthalmologists in diagnostic accuracy and completeness in handling questions about eye disease and real patient cases. Another study found a similar result in handling 200 eye care questions from an online chat forum, Robert Chang, MD, co-author of the second study and a glaucoma specialist and associate professor of ophthalmology at Stanford University in Stanford, California, reported.

“Using prompt engineering of ChatGPT, replies to patient online forum questions are becoming so realistic that specialist physicians are having difficulty telling the difference between human- and machine-generated responses,” Dr. Chang said.

The study used questions patients submitted to an online medical forum that received responses from ophthalmologists, then presented those responses plus answers generated by ChatGPT to a panel of eight ophthalmologists and asked them to distinguish between the two. “The accuracy of judging whether you could tell if it was written by AI or a human was about 61%,” Dr. Chang reported. “So most of the time you could not tell the difference.”

The study reported that of 800 evaluations of chatbot-written answers, ophthalmologists rated 21% of them as human-written, while they marked 64.6% of human-written answers as AI-written. The study also found that the likelihood of chatbot answers containing incorrect or inappropriate material was comparable with human answers: Less than 1% for both.

Dr. Chang also referenced a similar, more recent study from the Icahn School of Medicine in which 15 clinicians reviewed answers to patient questions by fellowship-trained glaucoma and retina specialists and those generated by ChatGPT-4, the chatbot model released by OpenAI in the spring of 2023. The study used a statistical tool to evaluate the combined question-case mean rank for accuracy, which was 506.2 for ChatGPT and 403.4 for glaucoma specialists based on 831 question cases. The mean rank for completeness was 528.3 and 398.7, respectively, based on 828 question cases (P < .001).

“The specialists themselves didn’t rate their answers as good as they rated the chatbot answers,” Dr. Chang said. “So it’s really showing that what we can come up with generative AI so human-like that it’s difficult for us to tell the difference on accuracy and completeness.”
 

‘Getting Close’

However, he noted that chatbots still have some kinks to work out with factual errors, difficulty referencing reliable sources, and hallucinations — fabricated material that may not be accurate. “We’re not quite there yet, but it’s getting close,” Dr. Chang added.

Dr. Chang noted that his clinic at Stanford is testing an AI platform to perform virtual scribing of patient encounters in real time. “That can save a lot of time on documentation,” he said. “I think this is a direction moving forward to increase our productivity because as we know, we all have workforce problems whether it’s the doctors or having enough technicians.”

Chatbots also are being tested for scheduling and generating letters. “Because of the unique needs of each ophthalmologist, AI agents that augment the existing workforce on specific administrative tasks will be the most likely early use case rather than autonomous disease screening or clinical decision support tools, which will take longer to validate prospectively in specific cohorts,” he said.

“Any AI today still has a long way to go before it can ingest and verify all the data for independent decision-making and be validated for fairness and generalizability,” Dr. Chang added. “It is much easier to have ‘low-level thinking’, repetitive tasks be taken care of by algorithms first.”

Dr. Chang “made a convincing case for embracing currently feasible applications of AI, highlighting the potential benefits of leveraging LLMs such as ChatGPT to enhance clinical productivity,” said Thasarat Vajaranant, MD, MHA, director of the glaucoma service and of data sourcing and strategy for the AI Ophthalmology Center at Illinois Eye and Ear Infirmary and the University of Illinois Chicago.

“With the growing demands of an aging population and workforce shortages in ophthalmology, AI-driven solutions offer promise in various areas, including telemedicine triage, organizing clinical notes, assisting in assessments and treatment planning, and virtual scribing,” Dr. Vajaranant said. “Rather than fearing this technology, we should approach its integration with caution.”

Dr. Chang disclosed relationships with Alcon, Genentech/Roche, Itnalight, Verana Health, Sight Sciences, Ocular Therapeutix, Glaukos, Carl Zeiss Meditec, and Apple. Dr. Vajaranant had no relevant disclosures.

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

A review of the federal Open Payments database found that the pharmaceutical and medical device industry paid physicians $12.1 billion over nearly a decade.

Almost two thirds of eligible physicians — 826,313 doctors — received a payment from a drug or device maker from 2013 to 2022, according to a study published online in JAMA on March 28. Overall, the median payment was $48 per physician.

Orthopedists received the largest amount of payments in aggregate, $1.3 billion, followed by neurologists and psychiatrists at $1.2 billion and cardiologists at $1.29 billion.

Geriatric and nuclear medicine specialists and trauma and pediatric surgeons received the least amount of money in aggregate, and the mean amount paid to a pediatric surgeon in the top 0.1% was just $338,183 over the 9-year study period.

Excluding 2013 (the database was established in August that year), the total value of payments was highest in 2019 at $1.6 billion, up from $1.34 billion in 2014. It was lowest in 2020, the peak year of the COVID-19 pandemic, but dipped to $864 billion that year and rebounded to $1.28 billion in 2022, wrote the authors.

The Open Payments database, administered by the Centers for Medicare & Medicaid Services, requires drug and device makers and group purchasing organizations to report payments made to physicians, including for consulting services, speaking fees, food and beverages, travel and lodging, education, gifts, grants, and honoraria.

The database was created to shed light on these payments, which have been linked in multiple studies to more prescribing of a particular drug or more use of a particular device.

The JAMA review appeared to show that with the exception of the pandemic year, the relationships have more or less stayed the same since Open Payments began.

“There’s been no sea change, no massive shift in how these interactions are happening,” said Deborah C. Marshall, MD, assistant professor in the Department of Radiation Oncology at the Icahn School of Medicine at Mount Sinai in New York City, who has studied industry payments.

“There’s no suggestion that anything is really changing other than that’s there is transparency,” said Robert Steinbrook, MD, director of the Health Research Group at Public Citizen.

Still, Dr. Steinbrook told this news organization, “it’s better to know this than to not know this.”

The unchanging nature of industry-physician relationships “suggests that to reduce the volume and magnitude of payments, more would need to be done,” he said.

“Really, this should be banned. Doctors should not be allowed to get gifts from pharmaceutical companies,” said Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices.

“The interactions wouldn’t be happening unless there was a purpose for them,” said Dr. Marshall. The relationships are “built with intention,” Dr. Marshall told this news organization.
 

Top Earners Range From $195,000 to $4.8 Million

Payments to the median physician over the study period ranged from $0 to $2339, but the mean payment to top earners — those in the top 0.1% — ranged from $194,933 for hospitalists to $4.8 million for orthopedic specialists.

Overall, the median payment was $48 per physician.

But small dollar amounts should not be discounted — even if it’s just a $25-catered lunch — said Aaron Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center in New York City who has studied industry-physician relationships. “The influence is not just in the dollar value,” Dr. Mitchell told this news organization. “It’s about the time listening to and the time in personal contact with industry representatives that these dollars are a marker for,” he said.

“There’s no such thing as a free lunch,” agreed Dr. Marshall. It’s “pretty well established” that lower-value payments do have influence, which is why academic institutions have established policies that limit gifts and meals and other payments from industry, she said.

Dr. Fugh-Berman said, “the size of the gift doesn’t really matter,” adding that research she conducted had shown that “accepting a meal increased not only the expense of the prescriptions that Medicare physicians wrote but also the number of prescriptions.”
 

Payments Mostly for High-Dollar Products

The top 25 drugs and devices that were related to industry payments tended to be high-cost brand-name products.

The top drug was Janssen’s Xarelto, an anticoagulant first approved in 2011 that costs about $600 a month, according to GoodRx. The drug has had annual sales of $4-$6 billion.

Xarelto was followed by Eliquis, another anticoagulant; Humira, used for a variety of autoimmune conditions including plaque psoriasis, rheumatoid arthritis, Crohn’s disease, and ulcerative colitis; Invokana, Jardiance, and Farxiga, all for type 2 diabetes.

The top medical devices included the da Vinci Surgical System, Mako SmartRobotics, CoreValve Evolut, Natrelle Implants, and Impella, a heart pump that received a US Food and Drug Administration (FDA) warning that it was associated with a heightened risk for death.
 

Industry Influence May Lead to Higher Cost, Poor Quality Care

Multiple studies have shown that payments to physicians tend to lead to increased prescribing and, often, higher costs for Medicare, a health system, or patients.

“I’m sure there are still a lot of physicians out there who think they’re getting away with something, that they can take meals, or they can take consulting fees and not be influenced, but there’s overwhelming data showing that it always influences you,” said Dr. Fugh-Berman.

One study in 2020 that used the Open Payments database found that physicians increase prescribing of the drugs for which they receive payment in the months just after the payment. The authors also showed that physicians who are paid prescribe lower-quality drugs following the payment, “although the magnitude is small and unlikely to be clinically significant.”

Dr. Marshall said that more studies are needed to determine whether quality of care is being affected when a physician prescribes a drug after an industry payment.

For now, there seems to be little appetite among physicians to give up the payments, said Dr. Marshall and others.

Physicians in some specialties see the payments as “an implicit statement about their value,” said Dr. Marshall.

In oncology, having received a lot of payments “gets worn more as a badge of honor,” said Dr. Mitchell.

The clinicians believe that “by collaborating with industry we are providing scientific expertise to help develop the next generation of technology and cures,” Dr. Mitchell said, adding that they see the payments “as a mark of their impact.”

Among the JAMA study authors, Joseph S. Ross, MD, reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of the manuscript or its review. Dr. Ross also reported receiving grants from the FDA, Johnson and Johnson, the Medical Devices Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Steinbrook, Dr. Marshall, and Dr. Mitchell reported no relevant financial relationships. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.

A version of this article appeared on Medscape.com.

A review of the federal Open Payments database found that the pharmaceutical and medical device industry paid physicians $12.1 billion over nearly a decade.

Almost two thirds of eligible physicians — 826,313 doctors — received a payment from a drug or device maker from 2013 to 2022, according to a study published online in JAMA on March 28. Overall, the median payment was $48 per physician.

Orthopedists received the largest amount of payments in aggregate, $1.3 billion, followed by neurologists and psychiatrists at $1.2 billion and cardiologists at $1.29 billion.

Geriatric and nuclear medicine specialists and trauma and pediatric surgeons received the least amount of money in aggregate, and the mean amount paid to a pediatric surgeon in the top 0.1% was just $338,183 over the 9-year study period.

Excluding 2013 (the database was established in August that year), the total value of payments was highest in 2019 at $1.6 billion, up from $1.34 billion in 2014. It was lowest in 2020, the peak year of the COVID-19 pandemic, but dipped to $864 billion that year and rebounded to $1.28 billion in 2022, wrote the authors.

The Open Payments database, administered by the Centers for Medicare & Medicaid Services, requires drug and device makers and group purchasing organizations to report payments made to physicians, including for consulting services, speaking fees, food and beverages, travel and lodging, education, gifts, grants, and honoraria.

The database was created to shed light on these payments, which have been linked in multiple studies to more prescribing of a particular drug or more use of a particular device.

The JAMA review appeared to show that with the exception of the pandemic year, the relationships have more or less stayed the same since Open Payments began.

“There’s been no sea change, no massive shift in how these interactions are happening,” said Deborah C. Marshall, MD, assistant professor in the Department of Radiation Oncology at the Icahn School of Medicine at Mount Sinai in New York City, who has studied industry payments.

“There’s no suggestion that anything is really changing other than that’s there is transparency,” said Robert Steinbrook, MD, director of the Health Research Group at Public Citizen.

Still, Dr. Steinbrook told this news organization, “it’s better to know this than to not know this.”

The unchanging nature of industry-physician relationships “suggests that to reduce the volume and magnitude of payments, more would need to be done,” he said.

“Really, this should be banned. Doctors should not be allowed to get gifts from pharmaceutical companies,” said Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices.

“The interactions wouldn’t be happening unless there was a purpose for them,” said Dr. Marshall. The relationships are “built with intention,” Dr. Marshall told this news organization.
 

Top Earners Range From $195,000 to $4.8 Million

Payments to the median physician over the study period ranged from $0 to $2339, but the mean payment to top earners — those in the top 0.1% — ranged from $194,933 for hospitalists to $4.8 million for orthopedic specialists.

Overall, the median payment was $48 per physician.

But small dollar amounts should not be discounted — even if it’s just a $25-catered lunch — said Aaron Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center in New York City who has studied industry-physician relationships. “The influence is not just in the dollar value,” Dr. Mitchell told this news organization. “It’s about the time listening to and the time in personal contact with industry representatives that these dollars are a marker for,” he said.

“There’s no such thing as a free lunch,” agreed Dr. Marshall. It’s “pretty well established” that lower-value payments do have influence, which is why academic institutions have established policies that limit gifts and meals and other payments from industry, she said.

Dr. Fugh-Berman said, “the size of the gift doesn’t really matter,” adding that research she conducted had shown that “accepting a meal increased not only the expense of the prescriptions that Medicare physicians wrote but also the number of prescriptions.”
 

Payments Mostly for High-Dollar Products

The top 25 drugs and devices that were related to industry payments tended to be high-cost brand-name products.

The top drug was Janssen’s Xarelto, an anticoagulant first approved in 2011 that costs about $600 a month, according to GoodRx. The drug has had annual sales of $4-$6 billion.

Xarelto was followed by Eliquis, another anticoagulant; Humira, used for a variety of autoimmune conditions including plaque psoriasis, rheumatoid arthritis, Crohn’s disease, and ulcerative colitis; Invokana, Jardiance, and Farxiga, all for type 2 diabetes.

The top medical devices included the da Vinci Surgical System, Mako SmartRobotics, CoreValve Evolut, Natrelle Implants, and Impella, a heart pump that received a US Food and Drug Administration (FDA) warning that it was associated with a heightened risk for death.
 

Industry Influence May Lead to Higher Cost, Poor Quality Care

Multiple studies have shown that payments to physicians tend to lead to increased prescribing and, often, higher costs for Medicare, a health system, or patients.

“I’m sure there are still a lot of physicians out there who think they’re getting away with something, that they can take meals, or they can take consulting fees and not be influenced, but there’s overwhelming data showing that it always influences you,” said Dr. Fugh-Berman.

One study in 2020 that used the Open Payments database found that physicians increase prescribing of the drugs for which they receive payment in the months just after the payment. The authors also showed that physicians who are paid prescribe lower-quality drugs following the payment, “although the magnitude is small and unlikely to be clinically significant.”

Dr. Marshall said that more studies are needed to determine whether quality of care is being affected when a physician prescribes a drug after an industry payment.

For now, there seems to be little appetite among physicians to give up the payments, said Dr. Marshall and others.

Physicians in some specialties see the payments as “an implicit statement about their value,” said Dr. Marshall.

In oncology, having received a lot of payments “gets worn more as a badge of honor,” said Dr. Mitchell.

The clinicians believe that “by collaborating with industry we are providing scientific expertise to help develop the next generation of technology and cures,” Dr. Mitchell said, adding that they see the payments “as a mark of their impact.”

Among the JAMA study authors, Joseph S. Ross, MD, reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of the manuscript or its review. Dr. Ross also reported receiving grants from the FDA, Johnson and Johnson, the Medical Devices Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Steinbrook, Dr. Marshall, and Dr. Mitchell reported no relevant financial relationships. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.

A version of this article appeared on Medscape.com.

A review of the federal Open Payments database found that the pharmaceutical and medical device industry paid physicians $12.1 billion over nearly a decade.

Almost two thirds of eligible physicians — 826,313 doctors — received a payment from a drug or device maker from 2013 to 2022, according to a study published online in JAMA on March 28. Overall, the median payment was $48 per physician.

Orthopedists received the largest amount of payments in aggregate, $1.3 billion, followed by neurologists and psychiatrists at $1.2 billion and cardiologists at $1.29 billion.

Geriatric and nuclear medicine specialists and trauma and pediatric surgeons received the least amount of money in aggregate, and the mean amount paid to a pediatric surgeon in the top 0.1% was just $338,183 over the 9-year study period.

Excluding 2013 (the database was established in August that year), the total value of payments was highest in 2019 at $1.6 billion, up from $1.34 billion in 2014. It was lowest in 2020, the peak year of the COVID-19 pandemic, but dipped to $864 billion that year and rebounded to $1.28 billion in 2022, wrote the authors.

The Open Payments database, administered by the Centers for Medicare & Medicaid Services, requires drug and device makers and group purchasing organizations to report payments made to physicians, including for consulting services, speaking fees, food and beverages, travel and lodging, education, gifts, grants, and honoraria.

The database was created to shed light on these payments, which have been linked in multiple studies to more prescribing of a particular drug or more use of a particular device.

The JAMA review appeared to show that with the exception of the pandemic year, the relationships have more or less stayed the same since Open Payments began.

“There’s been no sea change, no massive shift in how these interactions are happening,” said Deborah C. Marshall, MD, assistant professor in the Department of Radiation Oncology at the Icahn School of Medicine at Mount Sinai in New York City, who has studied industry payments.

“There’s no suggestion that anything is really changing other than that’s there is transparency,” said Robert Steinbrook, MD, director of the Health Research Group at Public Citizen.

Still, Dr. Steinbrook told this news organization, “it’s better to know this than to not know this.”

The unchanging nature of industry-physician relationships “suggests that to reduce the volume and magnitude of payments, more would need to be done,” he said.

“Really, this should be banned. Doctors should not be allowed to get gifts from pharmaceutical companies,” said Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices.

“The interactions wouldn’t be happening unless there was a purpose for them,” said Dr. Marshall. The relationships are “built with intention,” Dr. Marshall told this news organization.
 

Top Earners Range From $195,000 to $4.8 Million

Payments to the median physician over the study period ranged from $0 to $2339, but the mean payment to top earners — those in the top 0.1% — ranged from $194,933 for hospitalists to $4.8 million for orthopedic specialists.

Overall, the median payment was $48 per physician.

But small dollar amounts should not be discounted — even if it’s just a $25-catered lunch — said Aaron Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center in New York City who has studied industry-physician relationships. “The influence is not just in the dollar value,” Dr. Mitchell told this news organization. “It’s about the time listening to and the time in personal contact with industry representatives that these dollars are a marker for,” he said.

“There’s no such thing as a free lunch,” agreed Dr. Marshall. It’s “pretty well established” that lower-value payments do have influence, which is why academic institutions have established policies that limit gifts and meals and other payments from industry, she said.

Dr. Fugh-Berman said, “the size of the gift doesn’t really matter,” adding that research she conducted had shown that “accepting a meal increased not only the expense of the prescriptions that Medicare physicians wrote but also the number of prescriptions.”
 

Payments Mostly for High-Dollar Products

The top 25 drugs and devices that were related to industry payments tended to be high-cost brand-name products.

The top drug was Janssen’s Xarelto, an anticoagulant first approved in 2011 that costs about $600 a month, according to GoodRx. The drug has had annual sales of $4-$6 billion.

Xarelto was followed by Eliquis, another anticoagulant; Humira, used for a variety of autoimmune conditions including plaque psoriasis, rheumatoid arthritis, Crohn’s disease, and ulcerative colitis; Invokana, Jardiance, and Farxiga, all for type 2 diabetes.

The top medical devices included the da Vinci Surgical System, Mako SmartRobotics, CoreValve Evolut, Natrelle Implants, and Impella, a heart pump that received a US Food and Drug Administration (FDA) warning that it was associated with a heightened risk for death.
 

Industry Influence May Lead to Higher Cost, Poor Quality Care

Multiple studies have shown that payments to physicians tend to lead to increased prescribing and, often, higher costs for Medicare, a health system, or patients.

“I’m sure there are still a lot of physicians out there who think they’re getting away with something, that they can take meals, or they can take consulting fees and not be influenced, but there’s overwhelming data showing that it always influences you,” said Dr. Fugh-Berman.

One study in 2020 that used the Open Payments database found that physicians increase prescribing of the drugs for which they receive payment in the months just after the payment. The authors also showed that physicians who are paid prescribe lower-quality drugs following the payment, “although the magnitude is small and unlikely to be clinically significant.”

Dr. Marshall said that more studies are needed to determine whether quality of care is being affected when a physician prescribes a drug after an industry payment.

For now, there seems to be little appetite among physicians to give up the payments, said Dr. Marshall and others.

Physicians in some specialties see the payments as “an implicit statement about their value,” said Dr. Marshall.

In oncology, having received a lot of payments “gets worn more as a badge of honor,” said Dr. Mitchell.

The clinicians believe that “by collaborating with industry we are providing scientific expertise to help develop the next generation of technology and cures,” Dr. Mitchell said, adding that they see the payments “as a mark of their impact.”

Among the JAMA study authors, Joseph S. Ross, MD, reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of the manuscript or its review. Dr. Ross also reported receiving grants from the FDA, Johnson and Johnson, the Medical Devices Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Steinbrook, Dr. Marshall, and Dr. Mitchell reported no relevant financial relationships. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I’m going to tell you about a chemical that might cause cancer — one I suspect you haven’t heard of before.

These types of stories usually end with a call for regulation — to ban said chemical or substance, or to regulate it — but in this case, that has already happened. This new carcinogen I’m telling you about is actually an old chemical. And it has not been manufactured or legally imported in the US since 2013.

So, why bother? Because in this case, the chemical — or, really, a group of chemicals called polybrominated diphenyl ethers (PBDEs) — are still around: in our soil, in our food, and in our blood.

PBDEs are a group of compounds that confer flame-retardant properties to plastics, and they were used extensively in the latter part of the 20th century in electronic enclosures, business equipment, and foam cushioning in upholstery.

But there was a problem. They don’t chemically bond to plastics; they are just sort of mixed in, which means they can leach out. They are hydrophobic, meaning they don’t get washed out of soil, and, when ingested or inhaled by humans, they dissolve in our fat stores, making it difficult for our normal excretory systems to excrete them.

PBDEs biomagnify. Small animals can take them up from contaminated soil or water, and those animals are eaten by larger animals, which accumulate higher concentrations of the chemicals. This bioaccumulation increases as you move up the food web until you get to an apex predator — like you and me.

This is true of lots of chemicals, of course. The concern arises when these chemicals are toxic. To date, the toxicity data for PBDEs were pretty limited. There were some animal studies where rats were exposed to extremely high doses and they developed liver lesions — but I am always very wary of extrapolating high-dose rat toxicity studies to humans. There was also some suggestion that the chemicals could be endocrine disruptors, affecting breast and thyroid tissue.

What about cancer? In 2016, the International Agency for Research on Cancer concluded there was “inadequate evidence in humans for the carcinogencity of” PBDEs.

In the same report, though, they suggested PBDEs are “probably carcinogenic to humans” based on mechanistic studies.

In other words, we can’t prove they’re cancerous — but come on, they probably are.

Finally, we have some evidence that really pushes us toward the carcinogenic conclusion, in the form of this study, appearing in JAMA Network Open. It’s a nice bit of epidemiology leveraging the population-based National Health and Nutrition Examination Survey (NHANES).

Researchers measured PBDE levels in blood samples from 1100 people enrolled in NHANES in 2003 and 2004 and linked them to death records collected over the next 20 years or so.

The first thing to note is that the researchers were able to measure PBDEs in the blood samples. They were in there. They were detectable. And they were variable. Dividing the 1100 participants into low, medium, and high PBDE tertiles, you can see a nearly 10-fold difference across the population.

Importantly, not many baseline variables correlated with PBDE levels. People in the highest group were a bit younger but had a fairly similar sex distribution, race, ethnicity, education, income, physical activity, smoking status, and body mass index.

This is not a randomized trial, of course — but at least based on these data, exposure levels do seem fairly random, which is what you would expect from an environmental toxin that percolates up through the food chain. They are often somewhat indiscriminate.

This similarity in baseline characteristics between people with low or high blood levels of PBDE also allows us to make some stronger inferences about the observed outcomes. Let’s take a look at them.

After adjustment for baseline factors, individuals in the highest PBDE group had a 43% higher rate of death from any cause over the follow-up period. This was not enough to achieve statistical significance, but it was close.

Dr. Wilson

Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I’m going to tell you about a chemical that might cause cancer — one I suspect you haven’t heard of before.

These types of stories usually end with a call for regulation — to ban said chemical or substance, or to regulate it — but in this case, that has already happened. This new carcinogen I’m telling you about is actually an old chemical. And it has not been manufactured or legally imported in the US since 2013.

So, why bother? Because in this case, the chemical — or, really, a group of chemicals called polybrominated diphenyl ethers (PBDEs) — are still around: in our soil, in our food, and in our blood.

PBDEs are a group of compounds that confer flame-retardant properties to plastics, and they were used extensively in the latter part of the 20th century in electronic enclosures, business equipment, and foam cushioning in upholstery.

But there was a problem. They don’t chemically bond to plastics; they are just sort of mixed in, which means they can leach out. They are hydrophobic, meaning they don’t get washed out of soil, and, when ingested or inhaled by humans, they dissolve in our fat stores, making it difficult for our normal excretory systems to excrete them.

PBDEs biomagnify. Small animals can take them up from contaminated soil or water, and those animals are eaten by larger animals, which accumulate higher concentrations of the chemicals. This bioaccumulation increases as you move up the food web until you get to an apex predator — like you and me.

This is true of lots of chemicals, of course. The concern arises when these chemicals are toxic. To date, the toxicity data for PBDEs were pretty limited. There were some animal studies where rats were exposed to extremely high doses and they developed liver lesions — but I am always very wary of extrapolating high-dose rat toxicity studies to humans. There was also some suggestion that the chemicals could be endocrine disruptors, affecting breast and thyroid tissue.

What about cancer? In 2016, the International Agency for Research on Cancer concluded there was “inadequate evidence in humans for the carcinogencity of” PBDEs.

In the same report, though, they suggested PBDEs are “probably carcinogenic to humans” based on mechanistic studies.

In other words, we can’t prove they’re cancerous — but come on, they probably are.

Finally, we have some evidence that really pushes us toward the carcinogenic conclusion, in the form of this study, appearing in JAMA Network Open. It’s a nice bit of epidemiology leveraging the population-based National Health and Nutrition Examination Survey (NHANES).

Researchers measured PBDE levels in blood samples from 1100 people enrolled in NHANES in 2003 and 2004 and linked them to death records collected over the next 20 years or so.

The first thing to note is that the researchers were able to measure PBDEs in the blood samples. They were in there. They were detectable. And they were variable. Dividing the 1100 participants into low, medium, and high PBDE tertiles, you can see a nearly 10-fold difference across the population.

Importantly, not many baseline variables correlated with PBDE levels. People in the highest group were a bit younger but had a fairly similar sex distribution, race, ethnicity, education, income, physical activity, smoking status, and body mass index.

This is not a randomized trial, of course — but at least based on these data, exposure levels do seem fairly random, which is what you would expect from an environmental toxin that percolates up through the food chain. They are often somewhat indiscriminate.

This similarity in baseline characteristics between people with low or high blood levels of PBDE also allows us to make some stronger inferences about the observed outcomes. Let’s take a look at them.

After adjustment for baseline factors, individuals in the highest PBDE group had a 43% higher rate of death from any cause over the follow-up period. This was not enough to achieve statistical significance, but it was close.

Dr. Wilson

Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I’m going to tell you about a chemical that might cause cancer — one I suspect you haven’t heard of before.

These types of stories usually end with a call for regulation — to ban said chemical or substance, or to regulate it — but in this case, that has already happened. This new carcinogen I’m telling you about is actually an old chemical. And it has not been manufactured or legally imported in the US since 2013.

So, why bother? Because in this case, the chemical — or, really, a group of chemicals called polybrominated diphenyl ethers (PBDEs) — are still around: in our soil, in our food, and in our blood.

PBDEs are a group of compounds that confer flame-retardant properties to plastics, and they were used extensively in the latter part of the 20th century in electronic enclosures, business equipment, and foam cushioning in upholstery.

But there was a problem. They don’t chemically bond to plastics; they are just sort of mixed in, which means they can leach out. They are hydrophobic, meaning they don’t get washed out of soil, and, when ingested or inhaled by humans, they dissolve in our fat stores, making it difficult for our normal excretory systems to excrete them.

PBDEs biomagnify. Small animals can take them up from contaminated soil or water, and those animals are eaten by larger animals, which accumulate higher concentrations of the chemicals. This bioaccumulation increases as you move up the food web until you get to an apex predator — like you and me.

This is true of lots of chemicals, of course. The concern arises when these chemicals are toxic. To date, the toxicity data for PBDEs were pretty limited. There were some animal studies where rats were exposed to extremely high doses and they developed liver lesions — but I am always very wary of extrapolating high-dose rat toxicity studies to humans. There was also some suggestion that the chemicals could be endocrine disruptors, affecting breast and thyroid tissue.

What about cancer? In 2016, the International Agency for Research on Cancer concluded there was “inadequate evidence in humans for the carcinogencity of” PBDEs.

In the same report, though, they suggested PBDEs are “probably carcinogenic to humans” based on mechanistic studies.

In other words, we can’t prove they’re cancerous — but come on, they probably are.

Finally, we have some evidence that really pushes us toward the carcinogenic conclusion, in the form of this study, appearing in JAMA Network Open. It’s a nice bit of epidemiology leveraging the population-based National Health and Nutrition Examination Survey (NHANES).

Researchers measured PBDE levels in blood samples from 1100 people enrolled in NHANES in 2003 and 2004 and linked them to death records collected over the next 20 years or so.

The first thing to note is that the researchers were able to measure PBDEs in the blood samples. They were in there. They were detectable. And they were variable. Dividing the 1100 participants into low, medium, and high PBDE tertiles, you can see a nearly 10-fold difference across the population.

Importantly, not many baseline variables correlated with PBDE levels. People in the highest group were a bit younger but had a fairly similar sex distribution, race, ethnicity, education, income, physical activity, smoking status, and body mass index.

This is not a randomized trial, of course — but at least based on these data, exposure levels do seem fairly random, which is what you would expect from an environmental toxin that percolates up through the food chain. They are often somewhat indiscriminate.

This similarity in baseline characteristics between people with low or high blood levels of PBDE also allows us to make some stronger inferences about the observed outcomes. Let’s take a look at them.

After adjustment for baseline factors, individuals in the highest PBDE group had a 43% higher rate of death from any cause over the follow-up period. This was not enough to achieve statistical significance, but it was close.

Dr. Wilson

Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.