Cardiology News

In preparation for a future international treaty aimed at reducing plastic pollution, the French Parliamentary Office for the Evaluation of Scientific and Technological Choices presented the conclusions of a public hearing on the impact of plastics on various aspects of human health.

Increased Global Plastic Production

Philippe Bolo, a member of the French Democratic Party and the rapporteur for the public mission on the health impacts of plastics, spoke about the latest round of treaty negotiations, held from November 25 to December 1 in South Korea, attended by leading French and global experts about the impact of plastics on human health.

The hearing highlighted a sharp increase in plastic production. “It has doubled in the last 20 years and is expected to exceed 500 million tons in 2024,” Bolo said. This is about 60 kg per person. According to projections from the Organization for Economic Co-operation and Development, on its current trajectory, plastic production will reach 750 million tons by 2040 and surpass 1 billion tons before 2050, he said.

 

Minimal Plastic Waste Recycling

Around one third (32%) of plastics are used for packaging. “Therefore, most plastic production is still intended for single-use purposes,” he said. Plastic waste follows a similar growth trajectory, with volumes expected to rise from 360 million tons in 2020 to 617 million tons by 2040 unless action is taken. Very little of this waste is recycled, even in the most countries that are most advanced in terms of collection, sorting, and processing.

In France, for example, in 2018, only 0.6 million tons of the 3.6 million tons of plastic waste produced was truly recycled. This is less than one fifth (17%). Globally, less than 10% of plastic waste is recycled. In 2020, plastic waste that ended up in the environment represented 81 million tons, or 22% of the total. “Beyond waste, this leads to pollution by microplastics and nanoplastics, resulting from their fragmentation. All environments are affected: Seas, rivers, soils, air, and even living organisms,” Bolo said.

 

Methodological Challenges

However, measuring the impact of plastics on health faces methodological difficulties due to the wide variety of composition, size, and shape of plastics. Nevertheless, the French Standardization Association (Association Française de Normalisation) has conducted work to establish a characterization standard for microplastics in water, which serves as an international reference.

“It is also very difficult to know what we are ingesting,” Bolo said. “A study conducted in 2019 estimated that the average human absorbs 5 grams of plastics per week, the equivalent of a credit card.» Since then, other studies have revised this estimate downward, but no consensus has been reached.

A recent study across 109 countries, both industrialized and developing, found significant exposure, estimated at 500 mg/d, particularly in Southeast Asian countries, where it was due mainly to seafood consumption.

A study concluded that plastic water bottles contain 240,000 particles per liter, 90% of which are nanoplastics. These nanoparticles can pass through the intestinal barrier to enter the bloodstream and reach several organs including the heart, brain, and placenta, as well as the fetus.

 

Changes to the Microbiome

Microplastics also accumulate in organs. Thus, the amount of plastic in the lungs increases with age, suggesting that particles may persist in the body without being eliminated. The health consequences of this are still poorly understood, but exposure to plastics appears to cause changes in the composition of the intestinal microbiota. Pathobionts (commensal bacteria with harmful potential) have been found in both adults and children, which could contribute to dysbiosis of the gut microbiome. Furthermore, a decrease in butyrate, a short-chain fatty acid beneficial to health, has been observed in children’s intestines.

Inhaled nanoplastics may disrupt the mucociliary clearance mechanisms of the respiratory system. The toxicity of inhaled plastic particles was demonstrated as early as the 1970s among workers in the flocking industry. Some developed lung function impairments, shortness of breath, inflammation, fibrosis, and even lung cancer. Similar symptoms have been observed in workers in the textile and polyvinyl chloride industries.

A study published recently in The New England Journal of Medicine measured the amount of microplastics collected from carotid plaque of more than 300 patients who had undergone carotid endarterectomy for asymptomatic carotid artery disease. It found a 4.53 times higher risk for the primary endpoint, a composite of myocardial infarction, stroke, and all-cause mortality, among individuals with microplastics and nanoplastics in plaque compared with those without.

 

Health Affects High

The danger of plastics is also directly linked to the chemical substances they contain. A general scientific review looked at the health impacts of three chemicals used almost exclusively in plastics: Polybromodiphenyl ethers (PBDEs), used as flame retardants in textiles or electronics; bisphenol A (BPA), used in the lining of cans and bottles; and phthalates, particularly diethylhexyl phthalate (DEHP), used to make plastics more flexible.

The review highlighted strong epidemiological evidence linking fetal exposure to PBDEs during pregnancy to low birth weight and later exposure to delayed or impaired cognitive development in children and even a loss of IQ. Statistically significant evidence of disruption of thyroid function in adults was also found.

BPA is linked to genital malformations in female newborns exposed to BPA in utero, type 2 diabetes in adults, insulin resistance, and polycystic ovary syndrome in women. BPA exposure also increases the risk for obesity and hypertension in both children and adults, as well as the risk for cardiovascular disease in adults.

Finally, the review established links between exposure to DEHP and miscarriages, genital malformations in male newborns, delayed or impaired cognitive development in children, loss of IQ, delayed psychomotor development, early puberty in young girls, and endometriosis in young women. DEHP exposure also has multiple effects on cardiometabolic health, including insulin resistance, obesity, and elevated blood pressure.

The economic costs associated with the health impacts of these three substances have been estimated at $675 billion in the United States.

Bolo said that the solution to this plastic pollution is necessarily international. “We need an ambitious and legally binding treaty to reduce plastic production,” he said. “The damage is already done; we need to act to protect human health,” he concluded. The parliamentary office has made nine recommendations to the treaty negotiators.

This story was translated from Medscape’s 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 appeared on Medscape.com.

In preparation for a future international treaty aimed at reducing plastic pollution, the French Parliamentary Office for the Evaluation of Scientific and Technological Choices presented the conclusions of a public hearing on the impact of plastics on various aspects of human health.

Increased Global Plastic Production

Philippe Bolo, a member of the French Democratic Party and the rapporteur for the public mission on the health impacts of plastics, spoke about the latest round of treaty negotiations, held from November 25 to December 1 in South Korea, attended by leading French and global experts about the impact of plastics on human health.

The hearing highlighted a sharp increase in plastic production. “It has doubled in the last 20 years and is expected to exceed 500 million tons in 2024,” Bolo said. This is about 60 kg per person. According to projections from the Organization for Economic Co-operation and Development, on its current trajectory, plastic production will reach 750 million tons by 2040 and surpass 1 billion tons before 2050, he said.

 

Minimal Plastic Waste Recycling

Around one third (32%) of plastics are used for packaging. “Therefore, most plastic production is still intended for single-use purposes,” he said. Plastic waste follows a similar growth trajectory, with volumes expected to rise from 360 million tons in 2020 to 617 million tons by 2040 unless action is taken. Very little of this waste is recycled, even in the most countries that are most advanced in terms of collection, sorting, and processing.

In France, for example, in 2018, only 0.6 million tons of the 3.6 million tons of plastic waste produced was truly recycled. This is less than one fifth (17%). Globally, less than 10% of plastic waste is recycled. In 2020, plastic waste that ended up in the environment represented 81 million tons, or 22% of the total. “Beyond waste, this leads to pollution by microplastics and nanoplastics, resulting from their fragmentation. All environments are affected: Seas, rivers, soils, air, and even living organisms,” Bolo said.

 

Methodological Challenges

However, measuring the impact of plastics on health faces methodological difficulties due to the wide variety of composition, size, and shape of plastics. Nevertheless, the French Standardization Association (Association Française de Normalisation) has conducted work to establish a characterization standard for microplastics in water, which serves as an international reference.

“It is also very difficult to know what we are ingesting,” Bolo said. “A study conducted in 2019 estimated that the average human absorbs 5 grams of plastics per week, the equivalent of a credit card.» Since then, other studies have revised this estimate downward, but no consensus has been reached.

A recent study across 109 countries, both industrialized and developing, found significant exposure, estimated at 500 mg/d, particularly in Southeast Asian countries, where it was due mainly to seafood consumption.

A study concluded that plastic water bottles contain 240,000 particles per liter, 90% of which are nanoplastics. These nanoparticles can pass through the intestinal barrier to enter the bloodstream and reach several organs including the heart, brain, and placenta, as well as the fetus.

 

Changes to the Microbiome

Microplastics also accumulate in organs. Thus, the amount of plastic in the lungs increases with age, suggesting that particles may persist in the body without being eliminated. The health consequences of this are still poorly understood, but exposure to plastics appears to cause changes in the composition of the intestinal microbiota. Pathobionts (commensal bacteria with harmful potential) have been found in both adults and children, which could contribute to dysbiosis of the gut microbiome. Furthermore, a decrease in butyrate, a short-chain fatty acid beneficial to health, has been observed in children’s intestines.

Inhaled nanoplastics may disrupt the mucociliary clearance mechanisms of the respiratory system. The toxicity of inhaled plastic particles was demonstrated as early as the 1970s among workers in the flocking industry. Some developed lung function impairments, shortness of breath, inflammation, fibrosis, and even lung cancer. Similar symptoms have been observed in workers in the textile and polyvinyl chloride industries.

A study published recently in The New England Journal of Medicine measured the amount of microplastics collected from carotid plaque of more than 300 patients who had undergone carotid endarterectomy for asymptomatic carotid artery disease. It found a 4.53 times higher risk for the primary endpoint, a composite of myocardial infarction, stroke, and all-cause mortality, among individuals with microplastics and nanoplastics in plaque compared with those without.

 

Health Affects High

The danger of plastics is also directly linked to the chemical substances they contain. A general scientific review looked at the health impacts of three chemicals used almost exclusively in plastics: Polybromodiphenyl ethers (PBDEs), used as flame retardants in textiles or electronics; bisphenol A (BPA), used in the lining of cans and bottles; and phthalates, particularly diethylhexyl phthalate (DEHP), used to make plastics more flexible.

The review highlighted strong epidemiological evidence linking fetal exposure to PBDEs during pregnancy to low birth weight and later exposure to delayed or impaired cognitive development in children and even a loss of IQ. Statistically significant evidence of disruption of thyroid function in adults was also found.

BPA is linked to genital malformations in female newborns exposed to BPA in utero, type 2 diabetes in adults, insulin resistance, and polycystic ovary syndrome in women. BPA exposure also increases the risk for obesity and hypertension in both children and adults, as well as the risk for cardiovascular disease in adults.

Finally, the review established links between exposure to DEHP and miscarriages, genital malformations in male newborns, delayed or impaired cognitive development in children, loss of IQ, delayed psychomotor development, early puberty in young girls, and endometriosis in young women. DEHP exposure also has multiple effects on cardiometabolic health, including insulin resistance, obesity, and elevated blood pressure.

The economic costs associated with the health impacts of these three substances have been estimated at $675 billion in the United States.

Bolo said that the solution to this plastic pollution is necessarily international. “We need an ambitious and legally binding treaty to reduce plastic production,” he said. “The damage is already done; we need to act to protect human health,” he concluded. The parliamentary office has made nine recommendations to the treaty negotiators.

This story was translated from Medscape’s 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 appeared on Medscape.com.

In preparation for a future international treaty aimed at reducing plastic pollution, the French Parliamentary Office for the Evaluation of Scientific and Technological Choices presented the conclusions of a public hearing on the impact of plastics on various aspects of human health.

Increased Global Plastic Production

Philippe Bolo, a member of the French Democratic Party and the rapporteur for the public mission on the health impacts of plastics, spoke about the latest round of treaty negotiations, held from November 25 to December 1 in South Korea, attended by leading French and global experts about the impact of plastics on human health.

The hearing highlighted a sharp increase in plastic production. “It has doubled in the last 20 years and is expected to exceed 500 million tons in 2024,” Bolo said. This is about 60 kg per person. According to projections from the Organization for Economic Co-operation and Development, on its current trajectory, plastic production will reach 750 million tons by 2040 and surpass 1 billion tons before 2050, he said.

 

Minimal Plastic Waste Recycling

Around one third (32%) of plastics are used for packaging. “Therefore, most plastic production is still intended for single-use purposes,” he said. Plastic waste follows a similar growth trajectory, with volumes expected to rise from 360 million tons in 2020 to 617 million tons by 2040 unless action is taken. Very little of this waste is recycled, even in the most countries that are most advanced in terms of collection, sorting, and processing.

In France, for example, in 2018, only 0.6 million tons of the 3.6 million tons of plastic waste produced was truly recycled. This is less than one fifth (17%). Globally, less than 10% of plastic waste is recycled. In 2020, plastic waste that ended up in the environment represented 81 million tons, or 22% of the total. “Beyond waste, this leads to pollution by microplastics and nanoplastics, resulting from their fragmentation. All environments are affected: Seas, rivers, soils, air, and even living organisms,” Bolo said.

 

Methodological Challenges

However, measuring the impact of plastics on health faces methodological difficulties due to the wide variety of composition, size, and shape of plastics. Nevertheless, the French Standardization Association (Association Française de Normalisation) has conducted work to establish a characterization standard for microplastics in water, which serves as an international reference.

“It is also very difficult to know what we are ingesting,” Bolo said. “A study conducted in 2019 estimated that the average human absorbs 5 grams of plastics per week, the equivalent of a credit card.» Since then, other studies have revised this estimate downward, but no consensus has been reached.

A recent study across 109 countries, both industrialized and developing, found significant exposure, estimated at 500 mg/d, particularly in Southeast Asian countries, where it was due mainly to seafood consumption.

A study concluded that plastic water bottles contain 240,000 particles per liter, 90% of which are nanoplastics. These nanoparticles can pass through the intestinal barrier to enter the bloodstream and reach several organs including the heart, brain, and placenta, as well as the fetus.

 

Changes to the Microbiome

Microplastics also accumulate in organs. Thus, the amount of plastic in the lungs increases with age, suggesting that particles may persist in the body without being eliminated. The health consequences of this are still poorly understood, but exposure to plastics appears to cause changes in the composition of the intestinal microbiota. Pathobionts (commensal bacteria with harmful potential) have been found in both adults and children, which could contribute to dysbiosis of the gut microbiome. Furthermore, a decrease in butyrate, a short-chain fatty acid beneficial to health, has been observed in children’s intestines.

Inhaled nanoplastics may disrupt the mucociliary clearance mechanisms of the respiratory system. The toxicity of inhaled plastic particles was demonstrated as early as the 1970s among workers in the flocking industry. Some developed lung function impairments, shortness of breath, inflammation, fibrosis, and even lung cancer. Similar symptoms have been observed in workers in the textile and polyvinyl chloride industries.

A study published recently in The New England Journal of Medicine measured the amount of microplastics collected from carotid plaque of more than 300 patients who had undergone carotid endarterectomy for asymptomatic carotid artery disease. It found a 4.53 times higher risk for the primary endpoint, a composite of myocardial infarction, stroke, and all-cause mortality, among individuals with microplastics and nanoplastics in plaque compared with those without.

 

Health Affects High

The danger of plastics is also directly linked to the chemical substances they contain. A general scientific review looked at the health impacts of three chemicals used almost exclusively in plastics: Polybromodiphenyl ethers (PBDEs), used as flame retardants in textiles or electronics; bisphenol A (BPA), used in the lining of cans and bottles; and phthalates, particularly diethylhexyl phthalate (DEHP), used to make plastics more flexible.

The review highlighted strong epidemiological evidence linking fetal exposure to PBDEs during pregnancy to low birth weight and later exposure to delayed or impaired cognitive development in children and even a loss of IQ. Statistically significant evidence of disruption of thyroid function in adults was also found.

BPA is linked to genital malformations in female newborns exposed to BPA in utero, type 2 diabetes in adults, insulin resistance, and polycystic ovary syndrome in women. BPA exposure also increases the risk for obesity and hypertension in both children and adults, as well as the risk for cardiovascular disease in adults.

Finally, the review established links between exposure to DEHP and miscarriages, genital malformations in male newborns, delayed or impaired cognitive development in children, loss of IQ, delayed psychomotor development, early puberty in young girls, and endometriosis in young women. DEHP exposure also has multiple effects on cardiometabolic health, including insulin resistance, obesity, and elevated blood pressure.

The economic costs associated with the health impacts of these three substances have been estimated at $675 billion in the United States.

Bolo said that the solution to this plastic pollution is necessarily international. “We need an ambitious and legally binding treaty to reduce plastic production,” he said. “The damage is already done; we need to act to protect human health,” he concluded. The parliamentary office has made nine recommendations to the treaty negotiators.

This story was translated from Medscape’s 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 appeared on Medscape.com.

LOS ANGELES — Angiotensin receptor blockers are more effective than other antihypertensive medications in reducing the risk for post-stroke epilepsy (PSE), new research showed.

Investigators found angiotensin receptor blockers are better at cutting the PSE risk in individuals with high blood pressure than angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers, and beta-blockers.

The results suggested angiotensin receptor blockers could be a frontline strategy to proactively forestall development of epilepsy in patients with a history of stroke and hypertension, said the study’s co-lead investigator Giacomo Evangelista, MD, PhD, a resident in neurology at the Epilepsy Center at “G. d’Annunzio” University of Chieti-Pescara, Italy.

The findings were presented at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

Stroke and Seizures Tightly Linked

Stroke is the most common cause of seizures in patients older than 60 years. About 6%-8% of new epilepsy diagnoses in older adult patients are associated with a brain ischemic event.

Hypertension is among the most common risk factors for both epilepsy and stroke. The European Society of Cardiology recommends ACE inhibitors and angiotensin receptor blockers be considered first-line hypertension treatments.

Angiotensin receptor blockers seem to provide a protective effect in terms of seizures in the general population, but their possible preventive role in PSE has not been clear.

The retrospective, observational study included 528 patients (mean age, 71.4 years; 57.19% men) with hypertension and ischemic stroke without a history of epilepsy.

Researchers divided patients into those who developed PSE during the 2-year follow-up and those who didn’t. The main outcome was incidence of PSE associated with angiotensin receptor blocker therapy compared with other antihypertensive drug classes (ACE inhibitors, calcium channel blockers, and beta blockers).

Of the total, 7.2% of patients developed PSE. The study found patients treated with an angiotensin receptor blockers had a lower risk for PSE (P = .009). PSE incidence was higher among patients receiving calcium channel blockers (P = .019) and beta blockers (P = .008), but ACE inhibitors did not appear to affect PSE risk.

Further analysis showed that patients taking a beta blocker were 120% more likely to develop PSE, and those taking a calcium channel blocker were 110% more likely to develop PSE than those taking an angiotensin receptor blocker. The corresponding comparison was 65% for those taking an ACE inhibitor.

 

Potential Mechanisms

Angiotensin receptor blockers block the angiotensin II type 1 receptor, which may lead to numerous neuroprotective benefits such as improved blood flow to the brain and less neuroinflammation. The blockage may also reduce epilepsy severity and seizure frequency.

ACE inhibitors work in the same system as angiotensin receptor blockers but don’t bind directly to the angiotensin receptor. Experts believe these drugs may lead to inflammation that raises the risk for PSE.

Calcium channel blockers and beta blockers may increase the likelihood of seizures by inducing excessive excitability in the brain, which can trigger seizures.

Other research presented at the meeting found that angiotensin receptor blockers reduce the risk for epilepsy in patients with hypertension even in the absence of stroke.

Using data from an US national administrative database, the retrospective cohort study included 2,261,964 eligible adult beneficiaries diagnosed with hypertension and dispensed at least one angiotensin receptor blocker, ACE inhibitor, beta blocker, or calcium channel blocker from 2010 to 2017.

The study found angiotensin receptor blockers were associated with lower epilepsy incidence than ACE inhibitors (hazard ratio [HR], 0.75; 95% CI, 0.58-0.96), beta blockers (HR, 0.70; 95% CI, 0.54-0.90), and calcium channel blockers (HR, 0.80; 95% CI, 0.61-1.04).

The effect was most robust for the angiotensin receptor blocker losartan and among patients with no preexisting stroke or cardiovascular conditions.

Researchers ran the analysis excluding stroke and the association was still there, said lead study author Kimford Meador, MD, professor of neurology and neurological sciences, Stanford University, Palo Alto, California. “People with hypertension who use angiotensin receptor blockers — even if they don’t have a stroke — are less likely to develop epilepsy than if they use other major anti-hypertensives.”

 

Exciting and Suggestive

These new studies are “exciting” and “very suggestive,” said Meador. “We don’t have any true antiepileptic drugs; we have antiseizure medications. If we could reduce the incidence of epilepsy, that would be a very big thing.”

But the research to date hasn’t been “definitive” and is subject to bias, he said. “What we really need is a large randomized controlled trial to see if this is real because any observational study in humans has the potential for confounding from unmeasured variables.”

If such a study does show the effect is real, “that would change clinical practice,” said Meador.

As angiotensin receptor blockers have anti-inflammatory effects, researchers are now investigating whether this class of drugs might be useful in other diseases linked to inflammation such as multiple sclerosis, said Meador.

Commenting on the research, Alain Zingraff Looti, MD, assistant professor of neurology and public health sciences, Penn State College of Medicine, Hershey, Pennsylvania, said this new research is “important” although still at a “very preliminary stage.”

As the studies so far have all been observational, “they showed an association, but that doesn’t mean causality,” said Looti. These studies just looked at known potential confounders, “and there may be some unknown confounders that could explain the association,” he added.

But he acknowledged the results make sense from a biological standpoint. He noted that infusing angiotensin receptor blockers into rats causes a “cascade reaction” leading to reduced inflammation in the brain and then to less epilepsy. “Inflammation plays a major role in several models of epilepsy,” he added.

While these new results are important, Looti, too, would like to see a randomized controlled trial to confirm the findings.

Looti and Meador reported no relevant financial disclosures.

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

LOS ANGELES — Angiotensin receptor blockers are more effective than other antihypertensive medications in reducing the risk for post-stroke epilepsy (PSE), new research showed.

Investigators found angiotensin receptor blockers are better at cutting the PSE risk in individuals with high blood pressure than angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers, and beta-blockers.

The results suggested angiotensin receptor blockers could be a frontline strategy to proactively forestall development of epilepsy in patients with a history of stroke and hypertension, said the study’s co-lead investigator Giacomo Evangelista, MD, PhD, a resident in neurology at the Epilepsy Center at “G. d’Annunzio” University of Chieti-Pescara, Italy.

The findings were presented at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

Stroke and Seizures Tightly Linked

Stroke is the most common cause of seizures in patients older than 60 years. About 6%-8% of new epilepsy diagnoses in older adult patients are associated with a brain ischemic event.

Hypertension is among the most common risk factors for both epilepsy and stroke. The European Society of Cardiology recommends ACE inhibitors and angiotensin receptor blockers be considered first-line hypertension treatments.

Angiotensin receptor blockers seem to provide a protective effect in terms of seizures in the general population, but their possible preventive role in PSE has not been clear.

The retrospective, observational study included 528 patients (mean age, 71.4 years; 57.19% men) with hypertension and ischemic stroke without a history of epilepsy.

Researchers divided patients into those who developed PSE during the 2-year follow-up and those who didn’t. The main outcome was incidence of PSE associated with angiotensin receptor blocker therapy compared with other antihypertensive drug classes (ACE inhibitors, calcium channel blockers, and beta blockers).

Of the total, 7.2% of patients developed PSE. The study found patients treated with an angiotensin receptor blockers had a lower risk for PSE (P = .009). PSE incidence was higher among patients receiving calcium channel blockers (P = .019) and beta blockers (P = .008), but ACE inhibitors did not appear to affect PSE risk.

Further analysis showed that patients taking a beta blocker were 120% more likely to develop PSE, and those taking a calcium channel blocker were 110% more likely to develop PSE than those taking an angiotensin receptor blocker. The corresponding comparison was 65% for those taking an ACE inhibitor.

 

Potential Mechanisms

Angiotensin receptor blockers block the angiotensin II type 1 receptor, which may lead to numerous neuroprotective benefits such as improved blood flow to the brain and less neuroinflammation. The blockage may also reduce epilepsy severity and seizure frequency.

ACE inhibitors work in the same system as angiotensin receptor blockers but don’t bind directly to the angiotensin receptor. Experts believe these drugs may lead to inflammation that raises the risk for PSE.

Calcium channel blockers and beta blockers may increase the likelihood of seizures by inducing excessive excitability in the brain, which can trigger seizures.

Other research presented at the meeting found that angiotensin receptor blockers reduce the risk for epilepsy in patients with hypertension even in the absence of stroke.

Using data from an US national administrative database, the retrospective cohort study included 2,261,964 eligible adult beneficiaries diagnosed with hypertension and dispensed at least one angiotensin receptor blocker, ACE inhibitor, beta blocker, or calcium channel blocker from 2010 to 2017.

The study found angiotensin receptor blockers were associated with lower epilepsy incidence than ACE inhibitors (hazard ratio [HR], 0.75; 95% CI, 0.58-0.96), beta blockers (HR, 0.70; 95% CI, 0.54-0.90), and calcium channel blockers (HR, 0.80; 95% CI, 0.61-1.04).

The effect was most robust for the angiotensin receptor blocker losartan and among patients with no preexisting stroke or cardiovascular conditions.

Researchers ran the analysis excluding stroke and the association was still there, said lead study author Kimford Meador, MD, professor of neurology and neurological sciences, Stanford University, Palo Alto, California. “People with hypertension who use angiotensin receptor blockers — even if they don’t have a stroke — are less likely to develop epilepsy than if they use other major anti-hypertensives.”

 

Exciting and Suggestive

These new studies are “exciting” and “very suggestive,” said Meador. “We don’t have any true antiepileptic drugs; we have antiseizure medications. If we could reduce the incidence of epilepsy, that would be a very big thing.”

But the research to date hasn’t been “definitive” and is subject to bias, he said. “What we really need is a large randomized controlled trial to see if this is real because any observational study in humans has the potential for confounding from unmeasured variables.”

If such a study does show the effect is real, “that would change clinical practice,” said Meador.

As angiotensin receptor blockers have anti-inflammatory effects, researchers are now investigating whether this class of drugs might be useful in other diseases linked to inflammation such as multiple sclerosis, said Meador.

Commenting on the research, Alain Zingraff Looti, MD, assistant professor of neurology and public health sciences, Penn State College of Medicine, Hershey, Pennsylvania, said this new research is “important” although still at a “very preliminary stage.”

As the studies so far have all been observational, “they showed an association, but that doesn’t mean causality,” said Looti. These studies just looked at known potential confounders, “and there may be some unknown confounders that could explain the association,” he added.

But he acknowledged the results make sense from a biological standpoint. He noted that infusing angiotensin receptor blockers into rats causes a “cascade reaction” leading to reduced inflammation in the brain and then to less epilepsy. “Inflammation plays a major role in several models of epilepsy,” he added.

While these new results are important, Looti, too, would like to see a randomized controlled trial to confirm the findings.

Looti and Meador reported no relevant financial disclosures.

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

LOS ANGELES — Angiotensin receptor blockers are more effective than other antihypertensive medications in reducing the risk for post-stroke epilepsy (PSE), new research showed.

Investigators found angiotensin receptor blockers are better at cutting the PSE risk in individuals with high blood pressure than angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers, and beta-blockers.

The results suggested angiotensin receptor blockers could be a frontline strategy to proactively forestall development of epilepsy in patients with a history of stroke and hypertension, said the study’s co-lead investigator Giacomo Evangelista, MD, PhD, a resident in neurology at the Epilepsy Center at “G. d’Annunzio” University of Chieti-Pescara, Italy.

The findings were presented at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

 

Stroke and Seizures Tightly Linked

Stroke is the most common cause of seizures in patients older than 60 years. About 6%-8% of new epilepsy diagnoses in older adult patients are associated with a brain ischemic event.

Hypertension is among the most common risk factors for both epilepsy and stroke. The European Society of Cardiology recommends ACE inhibitors and angiotensin receptor blockers be considered first-line hypertension treatments.

Angiotensin receptor blockers seem to provide a protective effect in terms of seizures in the general population, but their possible preventive role in PSE has not been clear.

The retrospective, observational study included 528 patients (mean age, 71.4 years; 57.19% men) with hypertension and ischemic stroke without a history of epilepsy.

Researchers divided patients into those who developed PSE during the 2-year follow-up and those who didn’t. The main outcome was incidence of PSE associated with angiotensin receptor blocker therapy compared with other antihypertensive drug classes (ACE inhibitors, calcium channel blockers, and beta blockers).

Of the total, 7.2% of patients developed PSE. The study found patients treated with an angiotensin receptor blockers had a lower risk for PSE (P = .009). PSE incidence was higher among patients receiving calcium channel blockers (P = .019) and beta blockers (P = .008), but ACE inhibitors did not appear to affect PSE risk.

Further analysis showed that patients taking a beta blocker were 120% more likely to develop PSE, and those taking a calcium channel blocker were 110% more likely to develop PSE than those taking an angiotensin receptor blocker. The corresponding comparison was 65% for those taking an ACE inhibitor.

 

Potential Mechanisms

Angiotensin receptor blockers block the angiotensin II type 1 receptor, which may lead to numerous neuroprotective benefits such as improved blood flow to the brain and less neuroinflammation. The blockage may also reduce epilepsy severity and seizure frequency.

ACE inhibitors work in the same system as angiotensin receptor blockers but don’t bind directly to the angiotensin receptor. Experts believe these drugs may lead to inflammation that raises the risk for PSE.

Calcium channel blockers and beta blockers may increase the likelihood of seizures by inducing excessive excitability in the brain, which can trigger seizures.

Other research presented at the meeting found that angiotensin receptor blockers reduce the risk for epilepsy in patients with hypertension even in the absence of stroke.

Using data from an US national administrative database, the retrospective cohort study included 2,261,964 eligible adult beneficiaries diagnosed with hypertension and dispensed at least one angiotensin receptor blocker, ACE inhibitor, beta blocker, or calcium channel blocker from 2010 to 2017.

The study found angiotensin receptor blockers were associated with lower epilepsy incidence than ACE inhibitors (hazard ratio [HR], 0.75; 95% CI, 0.58-0.96), beta blockers (HR, 0.70; 95% CI, 0.54-0.90), and calcium channel blockers (HR, 0.80; 95% CI, 0.61-1.04).

The effect was most robust for the angiotensin receptor blocker losartan and among patients with no preexisting stroke or cardiovascular conditions.

Researchers ran the analysis excluding stroke and the association was still there, said lead study author Kimford Meador, MD, professor of neurology and neurological sciences, Stanford University, Palo Alto, California. “People with hypertension who use angiotensin receptor blockers — even if they don’t have a stroke — are less likely to develop epilepsy than if they use other major anti-hypertensives.”

 

Exciting and Suggestive

These new studies are “exciting” and “very suggestive,” said Meador. “We don’t have any true antiepileptic drugs; we have antiseizure medications. If we could reduce the incidence of epilepsy, that would be a very big thing.”

But the research to date hasn’t been “definitive” and is subject to bias, he said. “What we really need is a large randomized controlled trial to see if this is real because any observational study in humans has the potential for confounding from unmeasured variables.”

If such a study does show the effect is real, “that would change clinical practice,” said Meador.

As angiotensin receptor blockers have anti-inflammatory effects, researchers are now investigating whether this class of drugs might be useful in other diseases linked to inflammation such as multiple sclerosis, said Meador.

Commenting on the research, Alain Zingraff Looti, MD, assistant professor of neurology and public health sciences, Penn State College of Medicine, Hershey, Pennsylvania, said this new research is “important” although still at a “very preliminary stage.”

As the studies so far have all been observational, “they showed an association, but that doesn’t mean causality,” said Looti. These studies just looked at known potential confounders, “and there may be some unknown confounders that could explain the association,” he added.

But he acknowledged the results make sense from a biological standpoint. He noted that infusing angiotensin receptor blockers into rats causes a “cascade reaction” leading to reduced inflammation in the brain and then to less epilepsy. “Inflammation plays a major role in several models of epilepsy,” he added.

While these new results are important, Looti, too, would like to see a randomized controlled trial to confirm the findings.

Looti and Meador reported no relevant financial disclosures.

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

Long COVID can have an enormous impact on people’s ability to work, particularly if they do not have workplace accommodations and support. Although some patients experience symptoms so severe that they cannot work under any conditions, medical providers and employers can help ensure many patients with long COVID can stay in the workforce.

Long COVID is an infection-associated chronic condition that occurs after SARS-CoV-2 infection and is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems. By the end of 2023, at least 400 million people worldwide were estimated to have long COVID.

As members of the Patient-Led Research Collaborative, an international group of more than 60 researchers and health advocates living with long COVID and other infection-associated chronic conditions, we have published one of the first research studies of people with long COVID and their desire to work, the specific needs they have, and what doctors and employers can do to create a path for returning to the workforce. 

In our recent paper, we document the barriers and facilitators that individuals living with long COVID experience when attempting to return to work. Our recommendations are based on these findings and include recommendations for both medical providers and employers. 

If you are a medical provider:

• Ensure you adequately document your patients’ COVID cases, any long COVID diagnoses, and the functional impairment that long COVID causes. Remember that you can diagnose a patient with long COVID on the basis of their symptoms, and clinical guidelines do not require a record of a positive COVID-19 test, which many patients lack owing to testing barriers.
• Keep up to date on research on long COVID and related infection-associated chronic conditions — for example, through the Project ECHO Long COVID and Fatiguing Illness Recovery Program — and learn about pacing and other treatment options.

If you are an employer: 

• Utilize a return-to-work model in which any worker with suspected or confirmed COVID discusses support they may need with their employer when they return to work, with additional check-in dates scheduled to reevaluate supports as needed. Planning for this collaborative and iterative evaluation of return-to-work supports for all workers with COVID-19 is important because it may not be immediately clear to a worker whether they have developed long COVID or are generally recuperating from the illness.
• Do not require medical documentation of a SARS-CoV-2 infection or a Long COVID diagnosis to access accommodations — this is owing to disparities in accessing documentation.
• Tailor job responsibilities, provide remote options, allow flexible hours, and provide longer-range deadlines to account for symptoms for people with long COVID and other infection-associated chronic conditions.
• Provide accommodations to any caregivers of people with long COVID in your workplace.
• If requiring in-person work, make the workplace as safe as possible through ventilation and masking requirements, which will help ensure fewer of your workers develop long COVID, and those already with infection-associated chronic conditions will not get worse.

Our findings and recommendations are specific to long COVID, but they can and should apply to other disabilities. Given that our study’s sample was predominately White and working in jobs that did not require substantial physical labor, additional recommendations may be needed for other populations and workers who have labor-intensive jobs.

 

510 Study Participants

Long COVID is characterized as a relapsing-remitting illness, often described as episodic, in which an individual’s symptoms may fluctuate. Symptoms can become more or less severe depending on tasks, exertion, and social support in addition to physiologic processes and medical intervention. In our paper, we illustrate how the long COVID return-to-work experience and individuals’ symptoms can be shaped by workplace, home, and medical environments. 

We randomly selected 510 participants from a global survey of people living with long COVID and systematically analyzed their open-ended responses using established qualitative analysis methods. In this study, we specifically analyzed what patients wrote about their return-to-work experiences, considering how work experiences and relapsing and remitting long COVID symptoms intersected with personal lives and medical care. 

Most of the study participants identified as White, were 30-60 years old (ie, in their key earning years), and had at least a baccalaureate degree. Participants lived in the United States (38%), United Kingdom (25%), continental Europe (8%), Canada (4%), or other countries (25%). Most participants worked in professions that did not require substantial physical labor, and individuals in those fields may experience even greater return-to-work barriers than are reported in this study.

 

Key Findings

Through our qualitative analysis, we identified four primary return-to-work themes: 

1. People living with long COVID have a strong desire and financial need to return to work. 

The participants in our study described how they had experienced financial hardship because they could not successfully return to work and may have incurred new expenses with long COVID. They also often wrote how they wanted to return to work because their jobs provided meaning and structure for their lives. Some people in this study shared how they had tried to return to their jobs but relapsed. As a result, they considered leaving the workforce.

2. Workers’ long COVID symptoms intersect with organization of work and home life.

Most of the people in our study were employed in positions that did not require substantial physical labor. Even so, workers described how their long COVID symptoms were exacerbated by some job tasks. Computer screen time; reading dense material or writing (including emails); and conversations and meetings, regardless of whether they were in-person or via phone or video conferencing, could trigger or make symptoms worse. Workers who needed to stand for long periods of time, such as teachers and healthcare workers, and workers who needed to do lifting as part of their jobs described how these requirements were too taxing and could lead to relapses.

Because of the relapsing and remitting nature of many long COVID symptoms, people reported how it could be difficult to predict how job tasks, long hours, or pressing deadlines may exacerbate symptoms, which would require them to take time off work. For these participants, “pushing through” symptoms only made the symptoms worse. However, people in the study who were allowed to work from home reported how pacing, elevating their legs, and conserving energy (especially by not commuting) was key to doing their jobs well.

Some people in the study described how they were only able to return to work because they had substantial support from family or partners at home. These individuals shared how the people they lived with did most of the cooking, cleaning, and other household tasks so that the person living with long COVID could conserve their energy for work. This reorganization of home life notably shifted household tasks and caregiving to other people in the household, but without this shift, the individual’s long COVID symptoms may be too severe to work.

3. People with long COVID experience disbelief and stigma at work and healthcare settings.

Some people in our study described how their colleagues, supervisors, and human resource managers insinuated that they were fabricating or exaggerating their symptoms. This made it hard for workers to communicate what support they needed and could limit access to necessary work accommodations.

Many people in our study also described how medical providers did not believe that they had long COVID despite experiencing debilitating symptoms, often because they did not have a positive COVID-19 test to prove they had had an acute infection. Many people with long COVID may not have a positive COVID-19 test because:

• They could not access a test because testing access was limited at the start of the COVID-19 pandemic, there are transportation and cost barriers to tests, many health insurance providers no longer cover tests; and there are fewer public testing sites since the World Health Organization declared an end to the public health emergency;
• There is a high probability of false-negative results for viral and antibody tests (especially during the first wave of the pandemic and for individuals with limited immune response); and
• People can develop long COVID after asymptomatic acute infection.

Although healthcare providers can provide a long COVID diagnosis without a positive COVID-19 test on the basis of a patient’s presentation of symptoms and clinical history, many people in our study said that their providers would not provide this diagnosis, which restricted access to worker’s compensation, paid time off, and job accommodations.

Many people in the study also reported that their medical providers misdiagnosed them with a mental health disorder, such as anxiety, instead of long COVID. Although some people with long COVID may experience poor mental health as a natural consequence of dealing with a debilitating medical condition or may have neuropsychiatric symptoms as part of their long COVID, long COVID is not caused by an underlying psychiatric illness.

4. Support of medical providers is key to successful return to work for people living with long COVID.

Some people in our study described how they were able to get workplace accommodations or access workers’ compensation or sick leave because their medical providers recognized they had long COVID and provided them with this documentation. Some of these participants did not have a positive COVID-19 test, but their medical providers were able to diagnose them with long COVID on the basis of symptom presentation and clinical history. This documentation was critical for helping workers remain financially stable and able to return to work.

 

Conclusion

While we continue to search for treatment and cures for long COVID and work to provide a robust social safety net, it is crucial to address the stigma, inaccessibility, and lack of support often experienced by patients in their workplaces. Disabled people have long faced these issues; long COVID may be an opportunity to revolutionize the workplace to ensure an inclusive and accessible environment that can improve the lives of all workers.

For more on how to best be inclusive of employees with long COVID, read Harvard Business Review’s “Long Covid at Work: A Manager’s Guide” and visit the Job Accommodation Network webpage dedicated to long COVID.

Additional discussion about our study and applying the findings to improve work and medical care can be found by listening to the Healthy Work podcast episode titled “Supporting Long COVID at Work.” 

 

Elisabeth Stelson, Gina Assaf, and Lisa McCorkell are members of the Patient-Led Research Collaborative, an international group of more than 60 researchers. Dr Stelson, Postdoctoral Research Fellow, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, has disclosed no relevant financial relationships. Gina Assaf is Research Lead, Patient-Led Research Collaborative, Washington, DC. Lisa McCorkell is a long COVID patient; Cofounder, Team Lead, Researcher, Patient-Led Research Collaborative, Washington, DC.

A version of this article appeared on Medscape.com.

Long COVID can have an enormous impact on people’s ability to work, particularly if they do not have workplace accommodations and support. Although some patients experience symptoms so severe that they cannot work under any conditions, medical providers and employers can help ensure many patients with long COVID can stay in the workforce.

Long COVID is an infection-associated chronic condition that occurs after SARS-CoV-2 infection and is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems. By the end of 2023, at least 400 million people worldwide were estimated to have long COVID.

As members of the Patient-Led Research Collaborative, an international group of more than 60 researchers and health advocates living with long COVID and other infection-associated chronic conditions, we have published one of the first research studies of people with long COVID and their desire to work, the specific needs they have, and what doctors and employers can do to create a path for returning to the workforce. 

In our recent paper, we document the barriers and facilitators that individuals living with long COVID experience when attempting to return to work. Our recommendations are based on these findings and include recommendations for both medical providers and employers. 

If you are a medical provider:

• Ensure you adequately document your patients’ COVID cases, any long COVID diagnoses, and the functional impairment that long COVID causes. Remember that you can diagnose a patient with long COVID on the basis of their symptoms, and clinical guidelines do not require a record of a positive COVID-19 test, which many patients lack owing to testing barriers.
• Keep up to date on research on long COVID and related infection-associated chronic conditions — for example, through the Project ECHO Long COVID and Fatiguing Illness Recovery Program — and learn about pacing and other treatment options.

If you are an employer: 

• Utilize a return-to-work model in which any worker with suspected or confirmed COVID discusses support they may need with their employer when they return to work, with additional check-in dates scheduled to reevaluate supports as needed. Planning for this collaborative and iterative evaluation of return-to-work supports for all workers with COVID-19 is important because it may not be immediately clear to a worker whether they have developed long COVID or are generally recuperating from the illness.
• Do not require medical documentation of a SARS-CoV-2 infection or a Long COVID diagnosis to access accommodations — this is owing to disparities in accessing documentation.
• Tailor job responsibilities, provide remote options, allow flexible hours, and provide longer-range deadlines to account for symptoms for people with long COVID and other infection-associated chronic conditions.
• Provide accommodations to any caregivers of people with long COVID in your workplace.
• If requiring in-person work, make the workplace as safe as possible through ventilation and masking requirements, which will help ensure fewer of your workers develop long COVID, and those already with infection-associated chronic conditions will not get worse.

Our findings and recommendations are specific to long COVID, but they can and should apply to other disabilities. Given that our study’s sample was predominately White and working in jobs that did not require substantial physical labor, additional recommendations may be needed for other populations and workers who have labor-intensive jobs.

 

510 Study Participants

Long COVID is characterized as a relapsing-remitting illness, often described as episodic, in which an individual’s symptoms may fluctuate. Symptoms can become more or less severe depending on tasks, exertion, and social support in addition to physiologic processes and medical intervention. In our paper, we illustrate how the long COVID return-to-work experience and individuals’ symptoms can be shaped by workplace, home, and medical environments. 

We randomly selected 510 participants from a global survey of people living with long COVID and systematically analyzed their open-ended responses using established qualitative analysis methods. In this study, we specifically analyzed what patients wrote about their return-to-work experiences, considering how work experiences and relapsing and remitting long COVID symptoms intersected with personal lives and medical care. 

Most of the study participants identified as White, were 30-60 years old (ie, in their key earning years), and had at least a baccalaureate degree. Participants lived in the United States (38%), United Kingdom (25%), continental Europe (8%), Canada (4%), or other countries (25%). Most participants worked in professions that did not require substantial physical labor, and individuals in those fields may experience even greater return-to-work barriers than are reported in this study.

 

Key Findings

Through our qualitative analysis, we identified four primary return-to-work themes: 

1. People living with long COVID have a strong desire and financial need to return to work. 

The participants in our study described how they had experienced financial hardship because they could not successfully return to work and may have incurred new expenses with long COVID. They also often wrote how they wanted to return to work because their jobs provided meaning and structure for their lives. Some people in this study shared how they had tried to return to their jobs but relapsed. As a result, they considered leaving the workforce.

2. Workers’ long COVID symptoms intersect with organization of work and home life.

Most of the people in our study were employed in positions that did not require substantial physical labor. Even so, workers described how their long COVID symptoms were exacerbated by some job tasks. Computer screen time; reading dense material or writing (including emails); and conversations and meetings, regardless of whether they were in-person or via phone or video conferencing, could trigger or make symptoms worse. Workers who needed to stand for long periods of time, such as teachers and healthcare workers, and workers who needed to do lifting as part of their jobs described how these requirements were too taxing and could lead to relapses.

Because of the relapsing and remitting nature of many long COVID symptoms, people reported how it could be difficult to predict how job tasks, long hours, or pressing deadlines may exacerbate symptoms, which would require them to take time off work. For these participants, “pushing through” symptoms only made the symptoms worse. However, people in the study who were allowed to work from home reported how pacing, elevating their legs, and conserving energy (especially by not commuting) was key to doing their jobs well.

Some people in the study described how they were only able to return to work because they had substantial support from family or partners at home. These individuals shared how the people they lived with did most of the cooking, cleaning, and other household tasks so that the person living with long COVID could conserve their energy for work. This reorganization of home life notably shifted household tasks and caregiving to other people in the household, but without this shift, the individual’s long COVID symptoms may be too severe to work.

3. People with long COVID experience disbelief and stigma at work and healthcare settings.

Some people in our study described how their colleagues, supervisors, and human resource managers insinuated that they were fabricating or exaggerating their symptoms. This made it hard for workers to communicate what support they needed and could limit access to necessary work accommodations.

Many people in our study also described how medical providers did not believe that they had long COVID despite experiencing debilitating symptoms, often because they did not have a positive COVID-19 test to prove they had had an acute infection. Many people with long COVID may not have a positive COVID-19 test because:

• They could not access a test because testing access was limited at the start of the COVID-19 pandemic, there are transportation and cost barriers to tests, many health insurance providers no longer cover tests; and there are fewer public testing sites since the World Health Organization declared an end to the public health emergency;
• There is a high probability of false-negative results for viral and antibody tests (especially during the first wave of the pandemic and for individuals with limited immune response); and
• People can develop long COVID after asymptomatic acute infection.

Although healthcare providers can provide a long COVID diagnosis without a positive COVID-19 test on the basis of a patient’s presentation of symptoms and clinical history, many people in our study said that their providers would not provide this diagnosis, which restricted access to worker’s compensation, paid time off, and job accommodations.

Many people in the study also reported that their medical providers misdiagnosed them with a mental health disorder, such as anxiety, instead of long COVID. Although some people with long COVID may experience poor mental health as a natural consequence of dealing with a debilitating medical condition or may have neuropsychiatric symptoms as part of their long COVID, long COVID is not caused by an underlying psychiatric illness.

4. Support of medical providers is key to successful return to work for people living with long COVID.

Some people in our study described how they were able to get workplace accommodations or access workers’ compensation or sick leave because their medical providers recognized they had long COVID and provided them with this documentation. Some of these participants did not have a positive COVID-19 test, but their medical providers were able to diagnose them with long COVID on the basis of symptom presentation and clinical history. This documentation was critical for helping workers remain financially stable and able to return to work.

 

Conclusion

While we continue to search for treatment and cures for long COVID and work to provide a robust social safety net, it is crucial to address the stigma, inaccessibility, and lack of support often experienced by patients in their workplaces. Disabled people have long faced these issues; long COVID may be an opportunity to revolutionize the workplace to ensure an inclusive and accessible environment that can improve the lives of all workers.

For more on how to best be inclusive of employees with long COVID, read Harvard Business Review’s “Long Covid at Work: A Manager’s Guide” and visit the Job Accommodation Network webpage dedicated to long COVID.

Additional discussion about our study and applying the findings to improve work and medical care can be found by listening to the Healthy Work podcast episode titled “Supporting Long COVID at Work.” 

 

Elisabeth Stelson, Gina Assaf, and Lisa McCorkell are members of the Patient-Led Research Collaborative, an international group of more than 60 researchers. Dr Stelson, Postdoctoral Research Fellow, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, has disclosed no relevant financial relationships. Gina Assaf is Research Lead, Patient-Led Research Collaborative, Washington, DC. Lisa McCorkell is a long COVID patient; Cofounder, Team Lead, Researcher, Patient-Led Research Collaborative, Washington, DC.

A version of this article appeared on Medscape.com.

Long COVID can have an enormous impact on people’s ability to work, particularly if they do not have workplace accommodations and support. Although some patients experience symptoms so severe that they cannot work under any conditions, medical providers and employers can help ensure many patients with long COVID can stay in the workforce.

Long COVID is an infection-associated chronic condition that occurs after SARS-CoV-2 infection and is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems. By the end of 2023, at least 400 million people worldwide were estimated to have long COVID.

As members of the Patient-Led Research Collaborative, an international group of more than 60 researchers and health advocates living with long COVID and other infection-associated chronic conditions, we have published one of the first research studies of people with long COVID and their desire to work, the specific needs they have, and what doctors and employers can do to create a path for returning to the workforce. 

In our recent paper, we document the barriers and facilitators that individuals living with long COVID experience when attempting to return to work. Our recommendations are based on these findings and include recommendations for both medical providers and employers. 

If you are a medical provider:

• Ensure you adequately document your patients’ COVID cases, any long COVID diagnoses, and the functional impairment that long COVID causes. Remember that you can diagnose a patient with long COVID on the basis of their symptoms, and clinical guidelines do not require a record of a positive COVID-19 test, which many patients lack owing to testing barriers.
• Keep up to date on research on long COVID and related infection-associated chronic conditions — for example, through the Project ECHO Long COVID and Fatiguing Illness Recovery Program — and learn about pacing and other treatment options.

If you are an employer: 

• Utilize a return-to-work model in which any worker with suspected or confirmed COVID discusses support they may need with their employer when they return to work, with additional check-in dates scheduled to reevaluate supports as needed. Planning for this collaborative and iterative evaluation of return-to-work supports for all workers with COVID-19 is important because it may not be immediately clear to a worker whether they have developed long COVID or are generally recuperating from the illness.
• Do not require medical documentation of a SARS-CoV-2 infection or a Long COVID diagnosis to access accommodations — this is owing to disparities in accessing documentation.
• Tailor job responsibilities, provide remote options, allow flexible hours, and provide longer-range deadlines to account for symptoms for people with long COVID and other infection-associated chronic conditions.
• Provide accommodations to any caregivers of people with long COVID in your workplace.
• If requiring in-person work, make the workplace as safe as possible through ventilation and masking requirements, which will help ensure fewer of your workers develop long COVID, and those already with infection-associated chronic conditions will not get worse.

Our findings and recommendations are specific to long COVID, but they can and should apply to other disabilities. Given that our study’s sample was predominately White and working in jobs that did not require substantial physical labor, additional recommendations may be needed for other populations and workers who have labor-intensive jobs.

 

510 Study Participants

Long COVID is characterized as a relapsing-remitting illness, often described as episodic, in which an individual’s symptoms may fluctuate. Symptoms can become more or less severe depending on tasks, exertion, and social support in addition to physiologic processes and medical intervention. In our paper, we illustrate how the long COVID return-to-work experience and individuals’ symptoms can be shaped by workplace, home, and medical environments. 

We randomly selected 510 participants from a global survey of people living with long COVID and systematically analyzed their open-ended responses using established qualitative analysis methods. In this study, we specifically analyzed what patients wrote about their return-to-work experiences, considering how work experiences and relapsing and remitting long COVID symptoms intersected with personal lives and medical care. 

Most of the study participants identified as White, were 30-60 years old (ie, in their key earning years), and had at least a baccalaureate degree. Participants lived in the United States (38%), United Kingdom (25%), continental Europe (8%), Canada (4%), or other countries (25%). Most participants worked in professions that did not require substantial physical labor, and individuals in those fields may experience even greater return-to-work barriers than are reported in this study.

 

Key Findings

Through our qualitative analysis, we identified four primary return-to-work themes: 

1. People living with long COVID have a strong desire and financial need to return to work. 

The participants in our study described how they had experienced financial hardship because they could not successfully return to work and may have incurred new expenses with long COVID. They also often wrote how they wanted to return to work because their jobs provided meaning and structure for their lives. Some people in this study shared how they had tried to return to their jobs but relapsed. As a result, they considered leaving the workforce.

2. Workers’ long COVID symptoms intersect with organization of work and home life.

Most of the people in our study were employed in positions that did not require substantial physical labor. Even so, workers described how their long COVID symptoms were exacerbated by some job tasks. Computer screen time; reading dense material or writing (including emails); and conversations and meetings, regardless of whether they were in-person or via phone or video conferencing, could trigger or make symptoms worse. Workers who needed to stand for long periods of time, such as teachers and healthcare workers, and workers who needed to do lifting as part of their jobs described how these requirements were too taxing and could lead to relapses.

Because of the relapsing and remitting nature of many long COVID symptoms, people reported how it could be difficult to predict how job tasks, long hours, or pressing deadlines may exacerbate symptoms, which would require them to take time off work. For these participants, “pushing through” symptoms only made the symptoms worse. However, people in the study who were allowed to work from home reported how pacing, elevating their legs, and conserving energy (especially by not commuting) was key to doing their jobs well.

Some people in the study described how they were only able to return to work because they had substantial support from family or partners at home. These individuals shared how the people they lived with did most of the cooking, cleaning, and other household tasks so that the person living with long COVID could conserve their energy for work. This reorganization of home life notably shifted household tasks and caregiving to other people in the household, but without this shift, the individual’s long COVID symptoms may be too severe to work.

3. People with long COVID experience disbelief and stigma at work and healthcare settings.

Some people in our study described how their colleagues, supervisors, and human resource managers insinuated that they were fabricating or exaggerating their symptoms. This made it hard for workers to communicate what support they needed and could limit access to necessary work accommodations.

Many people in our study also described how medical providers did not believe that they had long COVID despite experiencing debilitating symptoms, often because they did not have a positive COVID-19 test to prove they had had an acute infection. Many people with long COVID may not have a positive COVID-19 test because:

• They could not access a test because testing access was limited at the start of the COVID-19 pandemic, there are transportation and cost barriers to tests, many health insurance providers no longer cover tests; and there are fewer public testing sites since the World Health Organization declared an end to the public health emergency;
• There is a high probability of false-negative results for viral and antibody tests (especially during the first wave of the pandemic and for individuals with limited immune response); and
• People can develop long COVID after asymptomatic acute infection.

Although healthcare providers can provide a long COVID diagnosis without a positive COVID-19 test on the basis of a patient’s presentation of symptoms and clinical history, many people in our study said that their providers would not provide this diagnosis, which restricted access to worker’s compensation, paid time off, and job accommodations.

Many people in the study also reported that their medical providers misdiagnosed them with a mental health disorder, such as anxiety, instead of long COVID. Although some people with long COVID may experience poor mental health as a natural consequence of dealing with a debilitating medical condition or may have neuropsychiatric symptoms as part of their long COVID, long COVID is not caused by an underlying psychiatric illness.

4. Support of medical providers is key to successful return to work for people living with long COVID.

Some people in our study described how they were able to get workplace accommodations or access workers’ compensation or sick leave because their medical providers recognized they had long COVID and provided them with this documentation. Some of these participants did not have a positive COVID-19 test, but their medical providers were able to diagnose them with long COVID on the basis of symptom presentation and clinical history. This documentation was critical for helping workers remain financially stable and able to return to work.

 

Conclusion

While we continue to search for treatment and cures for long COVID and work to provide a robust social safety net, it is crucial to address the stigma, inaccessibility, and lack of support often experienced by patients in their workplaces. Disabled people have long faced these issues; long COVID may be an opportunity to revolutionize the workplace to ensure an inclusive and accessible environment that can improve the lives of all workers.

For more on how to best be inclusive of employees with long COVID, read Harvard Business Review’s “Long Covid at Work: A Manager’s Guide” and visit the Job Accommodation Network webpage dedicated to long COVID.

Additional discussion about our study and applying the findings to improve work and medical care can be found by listening to the Healthy Work podcast episode titled “Supporting Long COVID at Work.” 

 

Elisabeth Stelson, Gina Assaf, and Lisa McCorkell are members of the Patient-Led Research Collaborative, an international group of more than 60 researchers. Dr Stelson, Postdoctoral Research Fellow, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, has disclosed no relevant financial relationships. Gina Assaf is Research Lead, Patient-Led Research Collaborative, Washington, DC. Lisa McCorkell is a long COVID patient; Cofounder, Team Lead, Researcher, Patient-Led Research Collaborative, Washington, DC.

A version of this article appeared on Medscape.com.

An electronic nudge explaining the cardiovascular benefits of the influenza vaccine increased vaccination rates, particularly among people who had previously had a heart attack, showed the NUDGE FLU series of clinical trials.

Influenza has the potential to be a dangerous infection on its own, but it increases the risk for cardiovascular events among people with a history of heart attack, said the study’s lead author, Ankeet Bhatt, MD, a cardiologist at Kaiser Permanente San Francisco Medical Center, San Francisco.

“Yearly influenza vaccines help prevent influenza infection and, in patients with a heart attack, are potentially cardioprotective,” he said during his presentation at the American Heart Association (AHA) Scientific Sessions 2024 in Chicago. The NUDGE FLU results were simultaneously published online in JAMA Cardiology.

In Denmark, where the trials were conducted, about 80% of older adults get flu shots, but only about 40% of younger adults with chronic diseases do, Bhatt reported. In the United States, about 45% of adults and 55% of children received at least one dose of the flu vaccine in the 2023/24 flu season, according to the US Centers for Disease Control and Prevention (CDC).

 

The NUDGE FLU Trials

Bhatt and his colleagues conducted three related clinical trials during the 2022/23 and 2023/24 flu seasons: NUDGE-FLU and NUDGE-FLU-2 targeted older adults, whereas NUDGE-FLU-CHRONIC targeted younger adults with chronic diseases. Nearly 2 million people were involved in the three trials.

Participants were randomized to receive one of a series of different behavioral-science-informed letters, delivered through a government-run electronic communication system, or no reminder.

People who received any of the nudges had higher rates of vaccination; among heart attack survivors, there was a 1.8% improvement and among adults without a history of heart attack, there was a 1.3% improvement. But a nudge that explained the potential cardiovascular benefits of flu shots was even more effective, leading to a 3.9% increase among people with a history of heart attack and a 2% increase among those with no heart attack history.

“A simple sentence resulted in a durable improvement in the vaccination rate,” said Bhatt.

The effect was even greater among those who had not been vaccinated in the previous flu season. Among heart attack survivors, nearly 14% more people got the vaccine compared with just 1.5% more survivors who were previously vaccinated. And it was most effective among younger adults who had experienced a recent heart attack, resulting in a 26% increase.

“The impact was larger in patients with a history of acute myocardial infarction, in those who were vaccine-hesitant, and in younger people” — all groups with the most to gain from vaccination in terms of cardiovascular protection — Bhatt reported.

About 25% of people in the United States are unsure about whether to get a flu shot, said Orly Vardeny, PharmD, professor of medicine at the University of Minnesota Medical School in Minneapolis, who was not involved in the study. The fact that previously unvaccinated people were convinced by the nudges is reassuring. “That’s the group where this intervention is most likely to move the needle,” she said.

Around half of all people hospitalized for flu in the United States have cardiovascular disease, CDC data showed, so “even a small increase in the number of patients who get vaccinated has substantial public health benefits,” Vardeny said.

The NUDGE FLU series showed that nudges like this should be employed as a simple tool to improve vaccination rates, but the system would be much more difficult to implement in the United States, Bhatt said.

Denmark has a national health service and a preexisting government electronic communication system, whereas the US system is privately run and more fractured. It would be possible to make it work, he pointed out, but would take some effort.

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

An electronic nudge explaining the cardiovascular benefits of the influenza vaccine increased vaccination rates, particularly among people who had previously had a heart attack, showed the NUDGE FLU series of clinical trials.

Influenza has the potential to be a dangerous infection on its own, but it increases the risk for cardiovascular events among people with a history of heart attack, said the study’s lead author, Ankeet Bhatt, MD, a cardiologist at Kaiser Permanente San Francisco Medical Center, San Francisco.

“Yearly influenza vaccines help prevent influenza infection and, in patients with a heart attack, are potentially cardioprotective,” he said during his presentation at the American Heart Association (AHA) Scientific Sessions 2024 in Chicago. The NUDGE FLU results were simultaneously published online in JAMA Cardiology.

In Denmark, where the trials were conducted, about 80% of older adults get flu shots, but only about 40% of younger adults with chronic diseases do, Bhatt reported. In the United States, about 45% of adults and 55% of children received at least one dose of the flu vaccine in the 2023/24 flu season, according to the US Centers for Disease Control and Prevention (CDC).

 

The NUDGE FLU Trials

Bhatt and his colleagues conducted three related clinical trials during the 2022/23 and 2023/24 flu seasons: NUDGE-FLU and NUDGE-FLU-2 targeted older adults, whereas NUDGE-FLU-CHRONIC targeted younger adults with chronic diseases. Nearly 2 million people were involved in the three trials.

Participants were randomized to receive one of a series of different behavioral-science-informed letters, delivered through a government-run electronic communication system, or no reminder.

People who received any of the nudges had higher rates of vaccination; among heart attack survivors, there was a 1.8% improvement and among adults without a history of heart attack, there was a 1.3% improvement. But a nudge that explained the potential cardiovascular benefits of flu shots was even more effective, leading to a 3.9% increase among people with a history of heart attack and a 2% increase among those with no heart attack history.

“A simple sentence resulted in a durable improvement in the vaccination rate,” said Bhatt.

The effect was even greater among those who had not been vaccinated in the previous flu season. Among heart attack survivors, nearly 14% more people got the vaccine compared with just 1.5% more survivors who were previously vaccinated. And it was most effective among younger adults who had experienced a recent heart attack, resulting in a 26% increase.

“The impact was larger in patients with a history of acute myocardial infarction, in those who were vaccine-hesitant, and in younger people” — all groups with the most to gain from vaccination in terms of cardiovascular protection — Bhatt reported.

About 25% of people in the United States are unsure about whether to get a flu shot, said Orly Vardeny, PharmD, professor of medicine at the University of Minnesota Medical School in Minneapolis, who was not involved in the study. The fact that previously unvaccinated people were convinced by the nudges is reassuring. “That’s the group where this intervention is most likely to move the needle,” she said.

Around half of all people hospitalized for flu in the United States have cardiovascular disease, CDC data showed, so “even a small increase in the number of patients who get vaccinated has substantial public health benefits,” Vardeny said.

The NUDGE FLU series showed that nudges like this should be employed as a simple tool to improve vaccination rates, but the system would be much more difficult to implement in the United States, Bhatt said.

Denmark has a national health service and a preexisting government electronic communication system, whereas the US system is privately run and more fractured. It would be possible to make it work, he pointed out, but would take some effort.

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

An electronic nudge explaining the cardiovascular benefits of the influenza vaccine increased vaccination rates, particularly among people who had previously had a heart attack, showed the NUDGE FLU series of clinical trials.

Influenza has the potential to be a dangerous infection on its own, but it increases the risk for cardiovascular events among people with a history of heart attack, said the study’s lead author, Ankeet Bhatt, MD, a cardiologist at Kaiser Permanente San Francisco Medical Center, San Francisco.

“Yearly influenza vaccines help prevent influenza infection and, in patients with a heart attack, are potentially cardioprotective,” he said during his presentation at the American Heart Association (AHA) Scientific Sessions 2024 in Chicago. The NUDGE FLU results were simultaneously published online in JAMA Cardiology.

In Denmark, where the trials were conducted, about 80% of older adults get flu shots, but only about 40% of younger adults with chronic diseases do, Bhatt reported. In the United States, about 45% of adults and 55% of children received at least one dose of the flu vaccine in the 2023/24 flu season, according to the US Centers for Disease Control and Prevention (CDC).

 

The NUDGE FLU Trials

Bhatt and his colleagues conducted three related clinical trials during the 2022/23 and 2023/24 flu seasons: NUDGE-FLU and NUDGE-FLU-2 targeted older adults, whereas NUDGE-FLU-CHRONIC targeted younger adults with chronic diseases. Nearly 2 million people were involved in the three trials.

Participants were randomized to receive one of a series of different behavioral-science-informed letters, delivered through a government-run electronic communication system, or no reminder.

People who received any of the nudges had higher rates of vaccination; among heart attack survivors, there was a 1.8% improvement and among adults without a history of heart attack, there was a 1.3% improvement. But a nudge that explained the potential cardiovascular benefits of flu shots was even more effective, leading to a 3.9% increase among people with a history of heart attack and a 2% increase among those with no heart attack history.

“A simple sentence resulted in a durable improvement in the vaccination rate,” said Bhatt.

The effect was even greater among those who had not been vaccinated in the previous flu season. Among heart attack survivors, nearly 14% more people got the vaccine compared with just 1.5% more survivors who were previously vaccinated. And it was most effective among younger adults who had experienced a recent heart attack, resulting in a 26% increase.

“The impact was larger in patients with a history of acute myocardial infarction, in those who were vaccine-hesitant, and in younger people” — all groups with the most to gain from vaccination in terms of cardiovascular protection — Bhatt reported.

About 25% of people in the United States are unsure about whether to get a flu shot, said Orly Vardeny, PharmD, professor of medicine at the University of Minnesota Medical School in Minneapolis, who was not involved in the study. The fact that previously unvaccinated people were convinced by the nudges is reassuring. “That’s the group where this intervention is most likely to move the needle,” she said.

Around half of all people hospitalized for flu in the United States have cardiovascular disease, CDC data showed, so “even a small increase in the number of patients who get vaccinated has substantial public health benefits,” Vardeny said.

The NUDGE FLU series showed that nudges like this should be employed as a simple tool to improve vaccination rates, but the system would be much more difficult to implement in the United States, Bhatt said.

Denmark has a national health service and a preexisting government electronic communication system, whereas the US system is privately run and more fractured. It would be possible to make it work, he pointed out, but would take some effort.

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

Vaccines recommended by the Advisory Committee on Immunization Practices (ACIP) offer important protection against severe illness for pregnant people and their babies.¹ However, vaccination coverage estimates among pregnant people remain suboptimal.^2-5 Additionally, some measures indicate that vaccine hesitancy among pregnant people is increasing; for example, 17.5% of surveyed pregnant women reported being very hesitant about influenza vaccination during pregnancy in 2019-2020, compared with 24.7% in 2022-2023.⁶As fall and winter virus season continues, consider opportunities for you and your staff to help communicate the importance of prenatal vaccination to pregnant patients in your care. Explore updated provider toolkits and prenatal vaccination patient education resources, including fact sheets, social media assets, posters, and short videos on respiratory syncytial virus (RSV), Tdap, COVID-19, influenza, and hepatitis B.

In an interview, CDC’s Haben Debessai, MD, an adjunct instructor in obstetrics and gynecology at Emory School of Medicine, Atlanta, Georgia, contextualizes the data to help healthcare professionals communicate effectively with their pregnant patients. 

 

What can practitioners communicate to patients about why it is important to get vaccinated during their pregnancy?

When communicating with their patients, practitioners can consider opportunities to discuss how vaccines work during pregnancy, emphasizing that prenatal vaccinations are beneficial for both the pregnant person and the fetus. It can be helpful to educate patients on how a pregnant person’s immune system can develop antibodies that will then pass to the fetus during the pregnancy and confer protection during the infant’s early months of life — when they are highly susceptible to illnesses that can be severe, such as RSV-associated lower respiratory tract infections. It can also be useful to discuss pregnancy’s impact on the immune system, which contributes to pregnant people being at higher risk for severe illness from infections like COVID-19 and flu, if contracted. The outcomes of severe illness can be dire for both the pregnant person and their pregnancy, which is why vaccination is the best mitigation option. It can also be beneficial to share with patients that some vaccines, like RSV and Tdap, are specifically for neonatal benefit, which could help patients understand why some vaccines are recommended at a specific gestational age and in each pregnancy or subsequent pregnancies. 

What is known about pregnant populations that experience disparities in vaccination coverage? 

While vaccination coverage among pregnant people is suboptimal, coverage estimates are often lowest among Black pregnant people, some of whom report experiencing mistreatment and discrimination during pregnancy and delivery.⁷ It is important to recognize that there are many intersecting factors that may impact vaccination coverage. Systemic and structural factors may prohibit some patient populations from accessing vaccinations (eg, transportation barriers, difficulty accessing adequate healthcare for those on government assistance, language barriers). To be responsive to the intersectional lived realities of each of these communities, the medical and public health community continually strives to increase trustworthiness, which can lead to increased uptake of vaccinations in these populations. 

What vaccines are available and recommended for pregnant people?

Four vaccines are routinely recommended during pregnancy: Tdap, COVID-19, influenza (seasonal), and RSV (seasonal). CDC recommends getting a Tdap vaccine between the 27th and 36th week of each pregnancy, preferably during the earlier part of this time period. CDC recommends that everyone 6 months or older in the United States, including pregnant people, stay up to date on COVID-19 vaccines. A COVID-19 vaccine can be given during any trimester of pregnancy. CDC recommends an annual flu vaccine during each flu season (fall/winter) for everyone 6 months or older in the United States, including pregnant people. A flu vaccine can be given during any trimester of pregnancy. For individuals who will be between 32 and 36 weeks pregnant during September through January, CDC recommends getting an RSV vaccine. RSV season and timing of vaccination may vary depending on geography. If a pregnant patient does not get the RSV vaccine during their pregnancy, CDC recommends that their baby receive an RSV monoclonal antibody (nirsevimab) to provide additional protection during the infant’s first RSV season, if they are younger than 8 months. At this time, pregnant people who received an RSV vaccine during a previous pregnancy (last year) are not recommended to receive another RSV vaccine during pregnancy. The current recommendation is for babies born during subsequent pregnancies to receive nirsevimab. Some pregnant people may also need other vaccines, such as hepatitis B. 

How can practitioners approach conversations about vaccination during pregnancy amid increasing vaccine hesitancy?

Many pregnant people who do get vaccinated describe their provider’s recommendation as an important motivator toward vaccination.^8-11 Communications research suggests that practitioners can further increase trustworthiness by openly discussing potential side effects of prenatal vaccinations and providing patients with a rationale for why each vaccine is recommended. Practitioners can also utilize opportunities to communicate that the risk for severe illness from whooping cough, COVID-19, flu, and RSV in pregnancy and among neonates in the first few months of life is often higher than the risk for an adverse reaction from receiving ACIP-recommended vaccines. Finally, practitioners can consider sharing tested and refined patient education resources at least one appointment prior to the recommended administration of each vaccine, providing individuals with time to process the information they need to facilitate their vaccine decision-making process.

Some patients may be more comfortable with older, well-known prenatal vaccinations but have skepticism about newer vaccines like COVID-19 and RSV. How can practitioners respond to these concerns?

As pregnant people navigate the challenges of making health decisions that could impact their developing baby, practitioners can build trust through empathetically responding to safety concerns and questions, particularly with respect to newly authorized vaccines. Vaccine confidence may be strengthened by communicating to patients that all recommended vaccinations, including those that have been newly authorized, have been rigorously tested prior to being recommended for pregnant people. Additionally, in my clinical practice, I see that patients are often more comfortable accepting vaccines when the benefit for the baby is clearly communicated. I have been pleasantly surprised that most patients I have counseled on the new maternal RSV vaccine have been receptive, making statements like, “If this will help protect my baby from getting sick, then yes, I will get it.”

As you and your staff care for pregnant patients during fall and winter virus season, remember that a provider recommendation remains one of the strongest known predictors of vaccination uptake.¹² As a trusted source of information about prenatal vaccination, consider further incorporating patient education resources to help communicate how prenatal vaccination helps pregnant people share important protection against severe illnesses with their babies. 

Haben Debessai, MD, is a Gilstrap Fellow at the CDC Foundation. Debessai also serves as an Emory Obstetrics/Gynecology Adjunct Instructor at Grady Health System in Atlanta, Georgia. She disclosed no relevant conflicts of interest.

References

1. ACOG Committee Opinion No. 741: Maternal Immunization. Obstet Gynecol. 2018;131:e214-e217. doi:10.1097/AOG.0000000000002662

2. Centers for Disease Control and Prevention. Flu, Tdap, and COVID-19 vaccination coverage among pregnant women – United States, April 2024. 2024 Sep 23. 3. Centers for Disease Control and Prevention. Respiratory syncytial virus (rsv) vaccination coverage, pregnant persons. 2024 Nov 19. 4. Centers for Disease Control and Prevention. COVID-19 vaccination coverage, pregnant persons. 2024 Nov 19. 5. Centers for Disease Control and Prevention. Influenza vaccination coverage, pregnant persons. 2024 Nov 19.6. Razzaghi H et al. IMMWR Morb Mortal Wkly Rep. 2023;72:1065-1071. Published 2023 Sep 29. doi: 10.15585/mmwr.mm7239a4

7. Mohamoud YA et al. MMWR Morb Mortal Wkly Rep 2023;72:961-967. doi: https://dx.doi.org/10.15585/mmwr.mm7235e1.

8. Kiefer MK et al. Am J Obstet Gynecol MFM. 2022;4:100603. doi: 10.1016/j.ajogmf.2022.100603

9. Spires B et al. Obstet Gynecol Clin North Am. 2023;50:401-419. doi: 10.1016/j.ogc.2023.02.013

10. Wales DP et al. Public Health. 2020;179:38-44. doi: 10.1016/j.puhe.2019.10.001

11. Zimmerman M et al. J Natl Med Assoc. 2023;115:362-376. doi:10.1016/j.jnma.2023.04.003

12. Castillo E et al. Best Pract Res Clin Obstet Gynaecol. 2021;76:83-95. doi:10.1016/j.bpobgyn.2021.03.008

Vaccines recommended by the Advisory Committee on Immunization Practices (ACIP) offer important protection against severe illness for pregnant people and their babies.¹ However, vaccination coverage estimates among pregnant people remain suboptimal.^2-5 Additionally, some measures indicate that vaccine hesitancy among pregnant people is increasing; for example, 17.5% of surveyed pregnant women reported being very hesitant about influenza vaccination during pregnancy in 2019-2020, compared with 24.7% in 2022-2023.⁶As fall and winter virus season continues, consider opportunities for you and your staff to help communicate the importance of prenatal vaccination to pregnant patients in your care. Explore updated provider toolkits and prenatal vaccination patient education resources, including fact sheets, social media assets, posters, and short videos on respiratory syncytial virus (RSV), Tdap, COVID-19, influenza, and hepatitis B.

In an interview, CDC’s Haben Debessai, MD, an adjunct instructor in obstetrics and gynecology at Emory School of Medicine, Atlanta, Georgia, contextualizes the data to help healthcare professionals communicate effectively with their pregnant patients. 

 

What can practitioners communicate to patients about why it is important to get vaccinated during their pregnancy?

When communicating with their patients, practitioners can consider opportunities to discuss how vaccines work during pregnancy, emphasizing that prenatal vaccinations are beneficial for both the pregnant person and the fetus. It can be helpful to educate patients on how a pregnant person’s immune system can develop antibodies that will then pass to the fetus during the pregnancy and confer protection during the infant’s early months of life — when they are highly susceptible to illnesses that can be severe, such as RSV-associated lower respiratory tract infections. It can also be useful to discuss pregnancy’s impact on the immune system, which contributes to pregnant people being at higher risk for severe illness from infections like COVID-19 and flu, if contracted. The outcomes of severe illness can be dire for both the pregnant person and their pregnancy, which is why vaccination is the best mitigation option. It can also be beneficial to share with patients that some vaccines, like RSV and Tdap, are specifically for neonatal benefit, which could help patients understand why some vaccines are recommended at a specific gestational age and in each pregnancy or subsequent pregnancies. 

What is known about pregnant populations that experience disparities in vaccination coverage? 

While vaccination coverage among pregnant people is suboptimal, coverage estimates are often lowest among Black pregnant people, some of whom report experiencing mistreatment and discrimination during pregnancy and delivery.⁷ It is important to recognize that there are many intersecting factors that may impact vaccination coverage. Systemic and structural factors may prohibit some patient populations from accessing vaccinations (eg, transportation barriers, difficulty accessing adequate healthcare for those on government assistance, language barriers). To be responsive to the intersectional lived realities of each of these communities, the medical and public health community continually strives to increase trustworthiness, which can lead to increased uptake of vaccinations in these populations. 

What vaccines are available and recommended for pregnant people?

Four vaccines are routinely recommended during pregnancy: Tdap, COVID-19, influenza (seasonal), and RSV (seasonal). CDC recommends getting a Tdap vaccine between the 27th and 36th week of each pregnancy, preferably during the earlier part of this time period. CDC recommends that everyone 6 months or older in the United States, including pregnant people, stay up to date on COVID-19 vaccines. A COVID-19 vaccine can be given during any trimester of pregnancy. CDC recommends an annual flu vaccine during each flu season (fall/winter) for everyone 6 months or older in the United States, including pregnant people. A flu vaccine can be given during any trimester of pregnancy. For individuals who will be between 32 and 36 weeks pregnant during September through January, CDC recommends getting an RSV vaccine. RSV season and timing of vaccination may vary depending on geography. If a pregnant patient does not get the RSV vaccine during their pregnancy, CDC recommends that their baby receive an RSV monoclonal antibody (nirsevimab) to provide additional protection during the infant’s first RSV season, if they are younger than 8 months. At this time, pregnant people who received an RSV vaccine during a previous pregnancy (last year) are not recommended to receive another RSV vaccine during pregnancy. The current recommendation is for babies born during subsequent pregnancies to receive nirsevimab. Some pregnant people may also need other vaccines, such as hepatitis B. 

How can practitioners approach conversations about vaccination during pregnancy amid increasing vaccine hesitancy?

Many pregnant people who do get vaccinated describe their provider’s recommendation as an important motivator toward vaccination.^8-11 Communications research suggests that practitioners can further increase trustworthiness by openly discussing potential side effects of prenatal vaccinations and providing patients with a rationale for why each vaccine is recommended. Practitioners can also utilize opportunities to communicate that the risk for severe illness from whooping cough, COVID-19, flu, and RSV in pregnancy and among neonates in the first few months of life is often higher than the risk for an adverse reaction from receiving ACIP-recommended vaccines. Finally, practitioners can consider sharing tested and refined patient education resources at least one appointment prior to the recommended administration of each vaccine, providing individuals with time to process the information they need to facilitate their vaccine decision-making process.

Some patients may be more comfortable with older, well-known prenatal vaccinations but have skepticism about newer vaccines like COVID-19 and RSV. How can practitioners respond to these concerns?

As pregnant people navigate the challenges of making health decisions that could impact their developing baby, practitioners can build trust through empathetically responding to safety concerns and questions, particularly with respect to newly authorized vaccines. Vaccine confidence may be strengthened by communicating to patients that all recommended vaccinations, including those that have been newly authorized, have been rigorously tested prior to being recommended for pregnant people. Additionally, in my clinical practice, I see that patients are often more comfortable accepting vaccines when the benefit for the baby is clearly communicated. I have been pleasantly surprised that most patients I have counseled on the new maternal RSV vaccine have been receptive, making statements like, “If this will help protect my baby from getting sick, then yes, I will get it.”

As you and your staff care for pregnant patients during fall and winter virus season, remember that a provider recommendation remains one of the strongest known predictors of vaccination uptake.¹² As a trusted source of information about prenatal vaccination, consider further incorporating patient education resources to help communicate how prenatal vaccination helps pregnant people share important protection against severe illnesses with their babies. 

Haben Debessai, MD, is a Gilstrap Fellow at the CDC Foundation. Debessai also serves as an Emory Obstetrics/Gynecology Adjunct Instructor at Grady Health System in Atlanta, Georgia. She disclosed no relevant conflicts of interest.

References

1. ACOG Committee Opinion No. 741: Maternal Immunization. Obstet Gynecol. 2018;131:e214-e217. doi:10.1097/AOG.0000000000002662

2. Centers for Disease Control and Prevention. Flu, Tdap, and COVID-19 vaccination coverage among pregnant women – United States, April 2024. 2024 Sep 23. 3. Centers for Disease Control and Prevention. Respiratory syncytial virus (rsv) vaccination coverage, pregnant persons. 2024 Nov 19. 4. Centers for Disease Control and Prevention. COVID-19 vaccination coverage, pregnant persons. 2024 Nov 19. 5. Centers for Disease Control and Prevention. Influenza vaccination coverage, pregnant persons. 2024 Nov 19.6. Razzaghi H et al. IMMWR Morb Mortal Wkly Rep. 2023;72:1065-1071. Published 2023 Sep 29. doi: 10.15585/mmwr.mm7239a4

7. Mohamoud YA et al. MMWR Morb Mortal Wkly Rep 2023;72:961-967. doi: https://dx.doi.org/10.15585/mmwr.mm7235e1.

8. Kiefer MK et al. Am J Obstet Gynecol MFM. 2022;4:100603. doi: 10.1016/j.ajogmf.2022.100603

9. Spires B et al. Obstet Gynecol Clin North Am. 2023;50:401-419. doi: 10.1016/j.ogc.2023.02.013

10. Wales DP et al. Public Health. 2020;179:38-44. doi: 10.1016/j.puhe.2019.10.001

11. Zimmerman M et al. J Natl Med Assoc. 2023;115:362-376. doi:10.1016/j.jnma.2023.04.003

12. Castillo E et al. Best Pract Res Clin Obstet Gynaecol. 2021;76:83-95. doi:10.1016/j.bpobgyn.2021.03.008

Vaccines recommended by the Advisory Committee on Immunization Practices (ACIP) offer important protection against severe illness for pregnant people and their babies.¹ However, vaccination coverage estimates among pregnant people remain suboptimal.^2-5 Additionally, some measures indicate that vaccine hesitancy among pregnant people is increasing; for example, 17.5% of surveyed pregnant women reported being very hesitant about influenza vaccination during pregnancy in 2019-2020, compared with 24.7% in 2022-2023.⁶As fall and winter virus season continues, consider opportunities for you and your staff to help communicate the importance of prenatal vaccination to pregnant patients in your care. Explore updated provider toolkits and prenatal vaccination patient education resources, including fact sheets, social media assets, posters, and short videos on respiratory syncytial virus (RSV), Tdap, COVID-19, influenza, and hepatitis B.

In an interview, CDC’s Haben Debessai, MD, an adjunct instructor in obstetrics and gynecology at Emory School of Medicine, Atlanta, Georgia, contextualizes the data to help healthcare professionals communicate effectively with their pregnant patients. 

 

What can practitioners communicate to patients about why it is important to get vaccinated during their pregnancy?

When communicating with their patients, practitioners can consider opportunities to discuss how vaccines work during pregnancy, emphasizing that prenatal vaccinations are beneficial for both the pregnant person and the fetus. It can be helpful to educate patients on how a pregnant person’s immune system can develop antibodies that will then pass to the fetus during the pregnancy and confer protection during the infant’s early months of life — when they are highly susceptible to illnesses that can be severe, such as RSV-associated lower respiratory tract infections. It can also be useful to discuss pregnancy’s impact on the immune system, which contributes to pregnant people being at higher risk for severe illness from infections like COVID-19 and flu, if contracted. The outcomes of severe illness can be dire for both the pregnant person and their pregnancy, which is why vaccination is the best mitigation option. It can also be beneficial to share with patients that some vaccines, like RSV and Tdap, are specifically for neonatal benefit, which could help patients understand why some vaccines are recommended at a specific gestational age and in each pregnancy or subsequent pregnancies. 

What is known about pregnant populations that experience disparities in vaccination coverage? 

While vaccination coverage among pregnant people is suboptimal, coverage estimates are often lowest among Black pregnant people, some of whom report experiencing mistreatment and discrimination during pregnancy and delivery.⁷ It is important to recognize that there are many intersecting factors that may impact vaccination coverage. Systemic and structural factors may prohibit some patient populations from accessing vaccinations (eg, transportation barriers, difficulty accessing adequate healthcare for those on government assistance, language barriers). To be responsive to the intersectional lived realities of each of these communities, the medical and public health community continually strives to increase trustworthiness, which can lead to increased uptake of vaccinations in these populations. 

What vaccines are available and recommended for pregnant people?

Four vaccines are routinely recommended during pregnancy: Tdap, COVID-19, influenza (seasonal), and RSV (seasonal). CDC recommends getting a Tdap vaccine between the 27th and 36th week of each pregnancy, preferably during the earlier part of this time period. CDC recommends that everyone 6 months or older in the United States, including pregnant people, stay up to date on COVID-19 vaccines. A COVID-19 vaccine can be given during any trimester of pregnancy. CDC recommends an annual flu vaccine during each flu season (fall/winter) for everyone 6 months or older in the United States, including pregnant people. A flu vaccine can be given during any trimester of pregnancy. For individuals who will be between 32 and 36 weeks pregnant during September through January, CDC recommends getting an RSV vaccine. RSV season and timing of vaccination may vary depending on geography. If a pregnant patient does not get the RSV vaccine during their pregnancy, CDC recommends that their baby receive an RSV monoclonal antibody (nirsevimab) to provide additional protection during the infant’s first RSV season, if they are younger than 8 months. At this time, pregnant people who received an RSV vaccine during a previous pregnancy (last year) are not recommended to receive another RSV vaccine during pregnancy. The current recommendation is for babies born during subsequent pregnancies to receive nirsevimab. Some pregnant people may also need other vaccines, such as hepatitis B. 

How can practitioners approach conversations about vaccination during pregnancy amid increasing vaccine hesitancy?

Many pregnant people who do get vaccinated describe their provider’s recommendation as an important motivator toward vaccination.^8-11 Communications research suggests that practitioners can further increase trustworthiness by openly discussing potential side effects of prenatal vaccinations and providing patients with a rationale for why each vaccine is recommended. Practitioners can also utilize opportunities to communicate that the risk for severe illness from whooping cough, COVID-19, flu, and RSV in pregnancy and among neonates in the first few months of life is often higher than the risk for an adverse reaction from receiving ACIP-recommended vaccines. Finally, practitioners can consider sharing tested and refined patient education resources at least one appointment prior to the recommended administration of each vaccine, providing individuals with time to process the information they need to facilitate their vaccine decision-making process.

Some patients may be more comfortable with older, well-known prenatal vaccinations but have skepticism about newer vaccines like COVID-19 and RSV. How can practitioners respond to these concerns?

As pregnant people navigate the challenges of making health decisions that could impact their developing baby, practitioners can build trust through empathetically responding to safety concerns and questions, particularly with respect to newly authorized vaccines. Vaccine confidence may be strengthened by communicating to patients that all recommended vaccinations, including those that have been newly authorized, have been rigorously tested prior to being recommended for pregnant people. Additionally, in my clinical practice, I see that patients are often more comfortable accepting vaccines when the benefit for the baby is clearly communicated. I have been pleasantly surprised that most patients I have counseled on the new maternal RSV vaccine have been receptive, making statements like, “If this will help protect my baby from getting sick, then yes, I will get it.”

As you and your staff care for pregnant patients during fall and winter virus season, remember that a provider recommendation remains one of the strongest known predictors of vaccination uptake.¹² As a trusted source of information about prenatal vaccination, consider further incorporating patient education resources to help communicate how prenatal vaccination helps pregnant people share important protection against severe illnesses with their babies. 

Haben Debessai, MD, is a Gilstrap Fellow at the CDC Foundation. Debessai also serves as an Emory Obstetrics/Gynecology Adjunct Instructor at Grady Health System in Atlanta, Georgia. She disclosed no relevant conflicts of interest.

References

1. ACOG Committee Opinion No. 741: Maternal Immunization. Obstet Gynecol. 2018;131:e214-e217. doi:10.1097/AOG.0000000000002662

2. Centers for Disease Control and Prevention. Flu, Tdap, and COVID-19 vaccination coverage among pregnant women – United States, April 2024. 2024 Sep 23. 3. Centers for Disease Control and Prevention. Respiratory syncytial virus (rsv) vaccination coverage, pregnant persons. 2024 Nov 19. 4. Centers for Disease Control and Prevention. COVID-19 vaccination coverage, pregnant persons. 2024 Nov 19. 5. Centers for Disease Control and Prevention. Influenza vaccination coverage, pregnant persons. 2024 Nov 19.6. Razzaghi H et al. IMMWR Morb Mortal Wkly Rep. 2023;72:1065-1071. Published 2023 Sep 29. doi: 10.15585/mmwr.mm7239a4

7. Mohamoud YA et al. MMWR Morb Mortal Wkly Rep 2023;72:961-967. doi: https://dx.doi.org/10.15585/mmwr.mm7235e1.

8. Kiefer MK et al. Am J Obstet Gynecol MFM. 2022;4:100603. doi: 10.1016/j.ajogmf.2022.100603

9. Spires B et al. Obstet Gynecol Clin North Am. 2023;50:401-419. doi: 10.1016/j.ogc.2023.02.013

10. Wales DP et al. Public Health. 2020;179:38-44. doi: 10.1016/j.puhe.2019.10.001

11. Zimmerman M et al. J Natl Med Assoc. 2023;115:362-376. doi:10.1016/j.jnma.2023.04.003

12. Castillo E et al. Best Pract Res Clin Obstet Gynaecol. 2021;76:83-95. doi:10.1016/j.bpobgyn.2021.03.008

The heart’s “mini-brain” is independent and highly localized, according to researchers at the Karolinska Institutet in Stockholm, Sweden. The findings could lead to new research into arrhythmia, dementia, and Parkinson’s disease.

Although controlled by the brain, the heart has a separate, smaller intracardiac nervous system (IcNS) embedded within the superficial layers of the heart wall. Nicknamed the mini-brain by researchers decades ago, the IcNS was assumed to be a simple structure capable only of relaying simple information from the brain to the heart.

The neurons in the mini-brain, however, have been under-researched, said Konstantinos Ampatzis, principal researcher and assistant professor of neuroscience at the Karolinska Institutet. “Cardiologists know that neurons exist but never study them because their first concern is the cardiac muscle cells, or cardiomyocytes, that are responsible for the heartbeat,” he explained. “Neuroscientists understand and decode neurons but don’t know about neurons in the heart.”

Ampatzis’s team mapped the exact composition, organization, and function of neurons in the IcNS using zebrafish as an animal model. “The heart of the zebrafish is closer to that of humans than the mouse heart is,” he explained. “The heart rate of a zebrafish is exactly the same.”

Several techniques were used to characterize these neurons. Electrophysiology determined their function, and researchers at Columbia University in New York City helped identify their molecular signatures using single-cell RNA sequencing. Ampatzis and his team also analyzed neurotransmitters that the neurons release to communicate with each other. Researchers in Sweden and New York worked on this project in their spare time because they had no additional funding.

Ampatzis expected to see ganglions or relay neurons capable only of receiving or sending information. “But we found a very diverse set of neurons in a small network,” he said. Their findings included sympathetic, parasympathetic, and sensory neurons with apparent neurochemical and functional diversity. Most surprising was a subset of pacemaker neurons. “You cannot have a network that produces a rhythm without these neurons, and we didn’t expect exactly that, to be honest,” he said.

Pacemaker neurons are usually associated with so-called central pattern generator networks within the central nervous system. These independent, highly localized neuronal networks generate and control complex rhythmic behaviors such as respiration, mastication, urination, and ejaculation. “Most importantly, we found that this neuronal network works in an isolated heart, without brain information, and can change the rhythm of the heart and the regularity by itself,” said Ampatzis.

Further studies confirmed that neurons do not produce the rhythm, which is controlled by the cardiomyocytes. The neurons’ main function is to regulate the speed of the heartbeat. In other words, this smaller localized network acts as a kind of insurance system to safeguard the brain’s control of the heartbeat. “From an evolutionary perspective, I think that the system is like this because the heartbeat defines life,” Ampatzis added.

With the neurons of the heart mapped, medical researchers now have a toolbox of molecular markers, neurotransmitters, and other information on how such neurons function. These findings could become the basis of new research. It might be possible to investigate heart arrhythmia by modulating pacemaker neurons, Ampatzis suggested. “You could even repurpose or find specific drugs that can interfere with this local network of the heart,” he said, adding that this might be a less invasive option than is possible today.

Arrhythmia affects millions of people, said Oliver Guttmann, MD, a consultant cardiologist at The Wellington Hospital and honorary associate professor of cardiology at University College London, both in London, England. Beta-blockers remain the drug of choice for arrhythmia, but other options can be invasive. “We do ablations to try and burn or freeze certain areas of the heart to get rid of a rhythm because often this comes from hyperactive cells somewhere,” he said. Pacemakers and defibrillators are also needed to modulate dangerous rhythms. Innovation is focusing on making interventions far less invasive than they are today by creating smaller and smaller pacemakers, for example.

Moving from zebrafish to more complex mammalian systems will be the next big step, said David Paterson, DPhil, head of the Department of Physiology, Anatomy, and Genetics and honorary director of Burdon Sanderson Cardiac Science Centre at the University of Oxford in England. “If you can find the molecular road map of dysregulation, then that could be a potential target for a gene therapy or cell therapy or for neuromodulation therapy,” he explained. Interest in this field, which is sometimes called bioelectronic medicine, is mounting. “It’s like pharmaceutics, but there’s no drug. You’re tapping into the wiring of the nervous system,” he added.

More radical research pathways might look at ways to tackle neurodegenerative disorders from dementia to Parkinson’s disease. “If neurons die in the brain, then they die in the heart and can affect the rhythm of the heart,” said Ampatzis. But zebrafish neurons are now known to produce substances that induce a proliferation of stem cells in bones, skin, and even the nervous system. “We think those neurons of the heart could perhaps contribute to the regeneration of the heart,” he said.

Ampatzis, Guttmann, and Paterson reported having no relevant financial relationships.

A version of this article appeared on Medscape.com.

The heart’s “mini-brain” is independent and highly localized, according to researchers at the Karolinska Institutet in Stockholm, Sweden. The findings could lead to new research into arrhythmia, dementia, and Parkinson’s disease.

Although controlled by the brain, the heart has a separate, smaller intracardiac nervous system (IcNS) embedded within the superficial layers of the heart wall. Nicknamed the mini-brain by researchers decades ago, the IcNS was assumed to be a simple structure capable only of relaying simple information from the brain to the heart.

The neurons in the mini-brain, however, have been under-researched, said Konstantinos Ampatzis, principal researcher and assistant professor of neuroscience at the Karolinska Institutet. “Cardiologists know that neurons exist but never study them because their first concern is the cardiac muscle cells, or cardiomyocytes, that are responsible for the heartbeat,” he explained. “Neuroscientists understand and decode neurons but don’t know about neurons in the heart.”

Ampatzis’s team mapped the exact composition, organization, and function of neurons in the IcNS using zebrafish as an animal model. “The heart of the zebrafish is closer to that of humans than the mouse heart is,” he explained. “The heart rate of a zebrafish is exactly the same.”

Several techniques were used to characterize these neurons. Electrophysiology determined their function, and researchers at Columbia University in New York City helped identify their molecular signatures using single-cell RNA sequencing. Ampatzis and his team also analyzed neurotransmitters that the neurons release to communicate with each other. Researchers in Sweden and New York worked on this project in their spare time because they had no additional funding.

Ampatzis expected to see ganglions or relay neurons capable only of receiving or sending information. “But we found a very diverse set of neurons in a small network,” he said. Their findings included sympathetic, parasympathetic, and sensory neurons with apparent neurochemical and functional diversity. Most surprising was a subset of pacemaker neurons. “You cannot have a network that produces a rhythm without these neurons, and we didn’t expect exactly that, to be honest,” he said.

Pacemaker neurons are usually associated with so-called central pattern generator networks within the central nervous system. These independent, highly localized neuronal networks generate and control complex rhythmic behaviors such as respiration, mastication, urination, and ejaculation. “Most importantly, we found that this neuronal network works in an isolated heart, without brain information, and can change the rhythm of the heart and the regularity by itself,” said Ampatzis.

Further studies confirmed that neurons do not produce the rhythm, which is controlled by the cardiomyocytes. The neurons’ main function is to regulate the speed of the heartbeat. In other words, this smaller localized network acts as a kind of insurance system to safeguard the brain’s control of the heartbeat. “From an evolutionary perspective, I think that the system is like this because the heartbeat defines life,” Ampatzis added.

With the neurons of the heart mapped, medical researchers now have a toolbox of molecular markers, neurotransmitters, and other information on how such neurons function. These findings could become the basis of new research. It might be possible to investigate heart arrhythmia by modulating pacemaker neurons, Ampatzis suggested. “You could even repurpose or find specific drugs that can interfere with this local network of the heart,” he said, adding that this might be a less invasive option than is possible today.

Arrhythmia affects millions of people, said Oliver Guttmann, MD, a consultant cardiologist at The Wellington Hospital and honorary associate professor of cardiology at University College London, both in London, England. Beta-blockers remain the drug of choice for arrhythmia, but other options can be invasive. “We do ablations to try and burn or freeze certain areas of the heart to get rid of a rhythm because often this comes from hyperactive cells somewhere,” he said. Pacemakers and defibrillators are also needed to modulate dangerous rhythms. Innovation is focusing on making interventions far less invasive than they are today by creating smaller and smaller pacemakers, for example.

Moving from zebrafish to more complex mammalian systems will be the next big step, said David Paterson, DPhil, head of the Department of Physiology, Anatomy, and Genetics and honorary director of Burdon Sanderson Cardiac Science Centre at the University of Oxford in England. “If you can find the molecular road map of dysregulation, then that could be a potential target for a gene therapy or cell therapy or for neuromodulation therapy,” he explained. Interest in this field, which is sometimes called bioelectronic medicine, is mounting. “It’s like pharmaceutics, but there’s no drug. You’re tapping into the wiring of the nervous system,” he added.

More radical research pathways might look at ways to tackle neurodegenerative disorders from dementia to Parkinson’s disease. “If neurons die in the brain, then they die in the heart and can affect the rhythm of the heart,” said Ampatzis. But zebrafish neurons are now known to produce substances that induce a proliferation of stem cells in bones, skin, and even the nervous system. “We think those neurons of the heart could perhaps contribute to the regeneration of the heart,” he said.

Ampatzis, Guttmann, and Paterson reported having no relevant financial relationships.

A version of this article appeared on Medscape.com.

The heart’s “mini-brain” is independent and highly localized, according to researchers at the Karolinska Institutet in Stockholm, Sweden. The findings could lead to new research into arrhythmia, dementia, and Parkinson’s disease.

Although controlled by the brain, the heart has a separate, smaller intracardiac nervous system (IcNS) embedded within the superficial layers of the heart wall. Nicknamed the mini-brain by researchers decades ago, the IcNS was assumed to be a simple structure capable only of relaying simple information from the brain to the heart.

The neurons in the mini-brain, however, have been under-researched, said Konstantinos Ampatzis, principal researcher and assistant professor of neuroscience at the Karolinska Institutet. “Cardiologists know that neurons exist but never study them because their first concern is the cardiac muscle cells, or cardiomyocytes, that are responsible for the heartbeat,” he explained. “Neuroscientists understand and decode neurons but don’t know about neurons in the heart.”

Ampatzis’s team mapped the exact composition, organization, and function of neurons in the IcNS using zebrafish as an animal model. “The heart of the zebrafish is closer to that of humans than the mouse heart is,” he explained. “The heart rate of a zebrafish is exactly the same.”

Several techniques were used to characterize these neurons. Electrophysiology determined their function, and researchers at Columbia University in New York City helped identify their molecular signatures using single-cell RNA sequencing. Ampatzis and his team also analyzed neurotransmitters that the neurons release to communicate with each other. Researchers in Sweden and New York worked on this project in their spare time because they had no additional funding.

Ampatzis expected to see ganglions or relay neurons capable only of receiving or sending information. “But we found a very diverse set of neurons in a small network,” he said. Their findings included sympathetic, parasympathetic, and sensory neurons with apparent neurochemical and functional diversity. Most surprising was a subset of pacemaker neurons. “You cannot have a network that produces a rhythm without these neurons, and we didn’t expect exactly that, to be honest,” he said.

Pacemaker neurons are usually associated with so-called central pattern generator networks within the central nervous system. These independent, highly localized neuronal networks generate and control complex rhythmic behaviors such as respiration, mastication, urination, and ejaculation. “Most importantly, we found that this neuronal network works in an isolated heart, without brain information, and can change the rhythm of the heart and the regularity by itself,” said Ampatzis.

Further studies confirmed that neurons do not produce the rhythm, which is controlled by the cardiomyocytes. The neurons’ main function is to regulate the speed of the heartbeat. In other words, this smaller localized network acts as a kind of insurance system to safeguard the brain’s control of the heartbeat. “From an evolutionary perspective, I think that the system is like this because the heartbeat defines life,” Ampatzis added.

With the neurons of the heart mapped, medical researchers now have a toolbox of molecular markers, neurotransmitters, and other information on how such neurons function. These findings could become the basis of new research. It might be possible to investigate heart arrhythmia by modulating pacemaker neurons, Ampatzis suggested. “You could even repurpose or find specific drugs that can interfere with this local network of the heart,” he said, adding that this might be a less invasive option than is possible today.

Arrhythmia affects millions of people, said Oliver Guttmann, MD, a consultant cardiologist at The Wellington Hospital and honorary associate professor of cardiology at University College London, both in London, England. Beta-blockers remain the drug of choice for arrhythmia, but other options can be invasive. “We do ablations to try and burn or freeze certain areas of the heart to get rid of a rhythm because often this comes from hyperactive cells somewhere,” he said. Pacemakers and defibrillators are also needed to modulate dangerous rhythms. Innovation is focusing on making interventions far less invasive than they are today by creating smaller and smaller pacemakers, for example.

Moving from zebrafish to more complex mammalian systems will be the next big step, said David Paterson, DPhil, head of the Department of Physiology, Anatomy, and Genetics and honorary director of Burdon Sanderson Cardiac Science Centre at the University of Oxford in England. “If you can find the molecular road map of dysregulation, then that could be a potential target for a gene therapy or cell therapy or for neuromodulation therapy,” he explained. Interest in this field, which is sometimes called bioelectronic medicine, is mounting. “It’s like pharmaceutics, but there’s no drug. You’re tapping into the wiring of the nervous system,” he added.

More radical research pathways might look at ways to tackle neurodegenerative disorders from dementia to Parkinson’s disease. “If neurons die in the brain, then they die in the heart and can affect the rhythm of the heart,” said Ampatzis. But zebrafish neurons are now known to produce substances that induce a proliferation of stem cells in bones, skin, and even the nervous system. “We think those neurons of the heart could perhaps contribute to the regeneration of the heart,” he said.

Ampatzis, Guttmann, and Paterson reported having no relevant financial relationships.

A version of this article appeared on Medscape.com.

New questions about the landmark trial that launched the antiplatelet drug ticagrelor worldwide are being raised after an investigation uncovered more information about how the PLATO study was conducted.

Peter Doshi, PhD, senior editor at The BMJ, obtained primary records for the trial and unpublished data through a Freedom of Information Act request, and has detailed inconsistencies and omissions in data reporting from the 2009 trial originally published in The New England Journal of Medicine (NEJM). The new investigation into the Platelet Inhibition and Patient Outcomes (PLATO) trial is published in The BMJ.

The findings come as generic versions of ticagrelor (Brilinta) are expected to become available soon in the United States. Ticagrelor is the only P2Y12 inhibitor still under patent, and in 2022, the United States spent more than $750 million on it, according to the report.

PLATO, sponsored by ticagrelor manufacturer AstraZeneca, included more than 18,000 patients in 43 countries. Investigators reported that ticagrelor reduced deaths from vascular causes, heart attack, or stroke compared with clopidogrel (Plavix). However, in a subgroup analysis, among US patients, there were more deaths in the ticagrelor group, and AstraZeneca failed its first bid for approval from the US Food and Drug Administration (FDA).

 

Failed First Bid for FDA Approval

AstraZeneca resubmitted its application, which was met with objections by some FDA staff members, including medical officer Thomas Marciniak, who called the resubmission “the worst in my experience regarding completeness of the submissions and the sponsor responding completely and accurately to requests,” Doshi reports.

Despite the objections, the FDA in 2011 approved ticagrelor for acute coronary syndrome, kicking off intense controversy over the trial, as several other studies have failed to replicate PLATO’s positive results.

Doubts have grown about its apparent advantage over cheaper, off-patent P2Y12 inhibitors such as clopidogrel and prasugrel.

“Critics said it was noteworthy that ticagrelor failed in the US,” Doshi writes, “the only high enrolling country where sites were not monitored by the sponsor itself.” Doshi’s report points out that critics of the trial “highlight that AstraZeneca itself carried out the data monitoring for PLATO except for sites that were monitored by third party contract research organizations. In the four countries exclusively monitored by non-sponsor personnel—Georgia, Israel, Russia, and the US—ticagrelor fared worse.”

Victor Serebruany, MD, from Johns Hopkins University, said he was initially impressed by the trial results but became skeptical after noticing inconsistencies and anomalies in the data. He filed a complaint with the US District Court in the District of Columbia, suggesting that the cardiovascular events in the study “may have been manipulated.”

 

US Department of Justice Investigation

The US Department of Justice (DOJ) opened an investigation in 2013 and closed it in 2014 with no further action. Serebruany continues to publish critiques of the trial 15 years later but told The BMJ he has little hope that the questions will be resolved unless the DOJ re-engages with an investigation.

Doshi also points out discrepancies in the data reported. In the 2009 paper, published as an intent-to-treat analysis, investigators said there were 905 total deaths from any cause among all randomized patients. “An internal company report states, however, that 983 patients had died at this point. While 33 deaths occurred after the follow-up period, the NEJM tally still leaves out 45 deaths ‘discovered after withdrawal of consent,’” he reports.

The NEJM responded to Doshi that while it didn’t dispute the error in the number of deaths, it was uncertain about publishing a correction, citing new — not yet published — guidelines from the International Committee of Medical Journal Editors. NEJM Editor-in-Chief Eric Rubin told The BMJ that “for older manuscripts, correction is not necessarily appropriate unless there would be an effect on clinical practice.”

Doshi’s investigation includes an interview with Eric Bates, MD, professor of internal medicine at the University of Michigan in Ann Arbor, and a co-author of the US guidelines that recommend ticagrelor, who said he was “increasingly disturbed by how trial after trial came out as being not dramatically positive in any way.” Bates is now calling for a review of ticagrelor’s recommendation in guidelines, according to the report.

AstraZeneca declined to be interviewed for the BMJ investigation, according to Doshi, and a spokesperson from the company told the journal by email that they have “nothing to add,” directing editors to its 2014 public statement after the DOJ’s investigation into PLATO. The BMJ said PLATO trial co-chairs Robert A. Harrington, MD, and Lars Wallentin, MD, did not respond to The BMJ’s requests for comment.

 

Will the Guidelines Be Changed Now?

“I know and have worked with Drs Wallentin and Harrington,” Bates told Medscape Medical News, “and find them to be honest, intelligent clinical scientists with the highest ethical standards who manage conflicts of interest as well as can be done in the clinical research arena, where industry support is required to develop new knowledge,” he said.

“If there is a concern that AstraZeneca was manipulating the dataset and FDA submission, that is an important issue,” Bates said. “The US paradox and the failure of any other antiplatelet trial to find a comparative mortality advantage are two unexplained issues with PLATO that provide good fodder for conspiracy theories. I agree with the NEJM that this trial is 15 years old and may not be worth readjudicating in the current treatment era.”

Other calls for revisiting guidelines have come after disappointing postlicensure studies have repeatedly demonstrated that ticagrelor has “similar efficacy to clopidogrel but with increased bleeding and [dyspnea],” Doshi reports.

“My concern is the marketing spin by AstraZeneca and the promotion of ticagrelor by six to eight ‘thought leaders’ consistently funded by AstraZeneca over the past 10 years,” said Bates. “They have flooded the literature with supportive subset and post hoc analyses, review articles, and ‘meta-analyses’ flawed by selection and intellectual bias, and public interviews that consistently discount the findings of the many subsequent randomized controlled trials that have not supported the superiority of ticagrelor over clopidogrel or prasugrel.”

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

New questions about the landmark trial that launched the antiplatelet drug ticagrelor worldwide are being raised after an investigation uncovered more information about how the PLATO study was conducted.

Peter Doshi, PhD, senior editor at The BMJ, obtained primary records for the trial and unpublished data through a Freedom of Information Act request, and has detailed inconsistencies and omissions in data reporting from the 2009 trial originally published in The New England Journal of Medicine (NEJM). The new investigation into the Platelet Inhibition and Patient Outcomes (PLATO) trial is published in The BMJ.

The findings come as generic versions of ticagrelor (Brilinta) are expected to become available soon in the United States. Ticagrelor is the only P2Y12 inhibitor still under patent, and in 2022, the United States spent more than $750 million on it, according to the report.

PLATO, sponsored by ticagrelor manufacturer AstraZeneca, included more than 18,000 patients in 43 countries. Investigators reported that ticagrelor reduced deaths from vascular causes, heart attack, or stroke compared with clopidogrel (Plavix). However, in a subgroup analysis, among US patients, there were more deaths in the ticagrelor group, and AstraZeneca failed its first bid for approval from the US Food and Drug Administration (FDA).

 

Failed First Bid for FDA Approval

AstraZeneca resubmitted its application, which was met with objections by some FDA staff members, including medical officer Thomas Marciniak, who called the resubmission “the worst in my experience regarding completeness of the submissions and the sponsor responding completely and accurately to requests,” Doshi reports.

Despite the objections, the FDA in 2011 approved ticagrelor for acute coronary syndrome, kicking off intense controversy over the trial, as several other studies have failed to replicate PLATO’s positive results.

Doubts have grown about its apparent advantage over cheaper, off-patent P2Y12 inhibitors such as clopidogrel and prasugrel.

“Critics said it was noteworthy that ticagrelor failed in the US,” Doshi writes, “the only high enrolling country where sites were not monitored by the sponsor itself.” Doshi’s report points out that critics of the trial “highlight that AstraZeneca itself carried out the data monitoring for PLATO except for sites that were monitored by third party contract research organizations. In the four countries exclusively monitored by non-sponsor personnel—Georgia, Israel, Russia, and the US—ticagrelor fared worse.”

Victor Serebruany, MD, from Johns Hopkins University, said he was initially impressed by the trial results but became skeptical after noticing inconsistencies and anomalies in the data. He filed a complaint with the US District Court in the District of Columbia, suggesting that the cardiovascular events in the study “may have been manipulated.”

 

US Department of Justice Investigation

The US Department of Justice (DOJ) opened an investigation in 2013 and closed it in 2014 with no further action. Serebruany continues to publish critiques of the trial 15 years later but told The BMJ he has little hope that the questions will be resolved unless the DOJ re-engages with an investigation.

Doshi also points out discrepancies in the data reported. In the 2009 paper, published as an intent-to-treat analysis, investigators said there were 905 total deaths from any cause among all randomized patients. “An internal company report states, however, that 983 patients had died at this point. While 33 deaths occurred after the follow-up period, the NEJM tally still leaves out 45 deaths ‘discovered after withdrawal of consent,’” he reports.

The NEJM responded to Doshi that while it didn’t dispute the error in the number of deaths, it was uncertain about publishing a correction, citing new — not yet published — guidelines from the International Committee of Medical Journal Editors. NEJM Editor-in-Chief Eric Rubin told The BMJ that “for older manuscripts, correction is not necessarily appropriate unless there would be an effect on clinical practice.”

Doshi’s investigation includes an interview with Eric Bates, MD, professor of internal medicine at the University of Michigan in Ann Arbor, and a co-author of the US guidelines that recommend ticagrelor, who said he was “increasingly disturbed by how trial after trial came out as being not dramatically positive in any way.” Bates is now calling for a review of ticagrelor’s recommendation in guidelines, according to the report.

AstraZeneca declined to be interviewed for the BMJ investigation, according to Doshi, and a spokesperson from the company told the journal by email that they have “nothing to add,” directing editors to its 2014 public statement after the DOJ’s investigation into PLATO. The BMJ said PLATO trial co-chairs Robert A. Harrington, MD, and Lars Wallentin, MD, did not respond to The BMJ’s requests for comment.

 

Will the Guidelines Be Changed Now?

“I know and have worked with Drs Wallentin and Harrington,” Bates told Medscape Medical News, “and find them to be honest, intelligent clinical scientists with the highest ethical standards who manage conflicts of interest as well as can be done in the clinical research arena, where industry support is required to develop new knowledge,” he said.

“If there is a concern that AstraZeneca was manipulating the dataset and FDA submission, that is an important issue,” Bates said. “The US paradox and the failure of any other antiplatelet trial to find a comparative mortality advantage are two unexplained issues with PLATO that provide good fodder for conspiracy theories. I agree with the NEJM that this trial is 15 years old and may not be worth readjudicating in the current treatment era.”

Other calls for revisiting guidelines have come after disappointing postlicensure studies have repeatedly demonstrated that ticagrelor has “similar efficacy to clopidogrel but with increased bleeding and [dyspnea],” Doshi reports.

“My concern is the marketing spin by AstraZeneca and the promotion of ticagrelor by six to eight ‘thought leaders’ consistently funded by AstraZeneca over the past 10 years,” said Bates. “They have flooded the literature with supportive subset and post hoc analyses, review articles, and ‘meta-analyses’ flawed by selection and intellectual bias, and public interviews that consistently discount the findings of the many subsequent randomized controlled trials that have not supported the superiority of ticagrelor over clopidogrel or prasugrel.”

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

New questions about the landmark trial that launched the antiplatelet drug ticagrelor worldwide are being raised after an investigation uncovered more information about how the PLATO study was conducted.

Peter Doshi, PhD, senior editor at The BMJ, obtained primary records for the trial and unpublished data through a Freedom of Information Act request, and has detailed inconsistencies and omissions in data reporting from the 2009 trial originally published in The New England Journal of Medicine (NEJM). The new investigation into the Platelet Inhibition and Patient Outcomes (PLATO) trial is published in The BMJ.

The findings come as generic versions of ticagrelor (Brilinta) are expected to become available soon in the United States. Ticagrelor is the only P2Y12 inhibitor still under patent, and in 2022, the United States spent more than $750 million on it, according to the report.

PLATO, sponsored by ticagrelor manufacturer AstraZeneca, included more than 18,000 patients in 43 countries. Investigators reported that ticagrelor reduced deaths from vascular causes, heart attack, or stroke compared with clopidogrel (Plavix). However, in a subgroup analysis, among US patients, there were more deaths in the ticagrelor group, and AstraZeneca failed its first bid for approval from the US Food and Drug Administration (FDA).

 

Failed First Bid for FDA Approval

AstraZeneca resubmitted its application, which was met with objections by some FDA staff members, including medical officer Thomas Marciniak, who called the resubmission “the worst in my experience regarding completeness of the submissions and the sponsor responding completely and accurately to requests,” Doshi reports.

Despite the objections, the FDA in 2011 approved ticagrelor for acute coronary syndrome, kicking off intense controversy over the trial, as several other studies have failed to replicate PLATO’s positive results.

Doubts have grown about its apparent advantage over cheaper, off-patent P2Y12 inhibitors such as clopidogrel and prasugrel.

“Critics said it was noteworthy that ticagrelor failed in the US,” Doshi writes, “the only high enrolling country where sites were not monitored by the sponsor itself.” Doshi’s report points out that critics of the trial “highlight that AstraZeneca itself carried out the data monitoring for PLATO except for sites that were monitored by third party contract research organizations. In the four countries exclusively monitored by non-sponsor personnel—Georgia, Israel, Russia, and the US—ticagrelor fared worse.”

Victor Serebruany, MD, from Johns Hopkins University, said he was initially impressed by the trial results but became skeptical after noticing inconsistencies and anomalies in the data. He filed a complaint with the US District Court in the District of Columbia, suggesting that the cardiovascular events in the study “may have been manipulated.”

 

US Department of Justice Investigation

The US Department of Justice (DOJ) opened an investigation in 2013 and closed it in 2014 with no further action. Serebruany continues to publish critiques of the trial 15 years later but told The BMJ he has little hope that the questions will be resolved unless the DOJ re-engages with an investigation.

Doshi also points out discrepancies in the data reported. In the 2009 paper, published as an intent-to-treat analysis, investigators said there were 905 total deaths from any cause among all randomized patients. “An internal company report states, however, that 983 patients had died at this point. While 33 deaths occurred after the follow-up period, the NEJM tally still leaves out 45 deaths ‘discovered after withdrawal of consent,’” he reports.

The NEJM responded to Doshi that while it didn’t dispute the error in the number of deaths, it was uncertain about publishing a correction, citing new — not yet published — guidelines from the International Committee of Medical Journal Editors. NEJM Editor-in-Chief Eric Rubin told The BMJ that “for older manuscripts, correction is not necessarily appropriate unless there would be an effect on clinical practice.”

Doshi’s investigation includes an interview with Eric Bates, MD, professor of internal medicine at the University of Michigan in Ann Arbor, and a co-author of the US guidelines that recommend ticagrelor, who said he was “increasingly disturbed by how trial after trial came out as being not dramatically positive in any way.” Bates is now calling for a review of ticagrelor’s recommendation in guidelines, according to the report.

AstraZeneca declined to be interviewed for the BMJ investigation, according to Doshi, and a spokesperson from the company told the journal by email that they have “nothing to add,” directing editors to its 2014 public statement after the DOJ’s investigation into PLATO. The BMJ said PLATO trial co-chairs Robert A. Harrington, MD, and Lars Wallentin, MD, did not respond to The BMJ’s requests for comment.

 

Will the Guidelines Be Changed Now?

“I know and have worked with Drs Wallentin and Harrington,” Bates told Medscape Medical News, “and find them to be honest, intelligent clinical scientists with the highest ethical standards who manage conflicts of interest as well as can be done in the clinical research arena, where industry support is required to develop new knowledge,” he said.

“If there is a concern that AstraZeneca was manipulating the dataset and FDA submission, that is an important issue,” Bates said. “The US paradox and the failure of any other antiplatelet trial to find a comparative mortality advantage are two unexplained issues with PLATO that provide good fodder for conspiracy theories. I agree with the NEJM that this trial is 15 years old and may not be worth readjudicating in the current treatment era.”

Other calls for revisiting guidelines have come after disappointing postlicensure studies have repeatedly demonstrated that ticagrelor has “similar efficacy to clopidogrel but with increased bleeding and [dyspnea],” Doshi reports.

“My concern is the marketing spin by AstraZeneca and the promotion of ticagrelor by six to eight ‘thought leaders’ consistently funded by AstraZeneca over the past 10 years,” said Bates. “They have flooded the literature with supportive subset and post hoc analyses, review articles, and ‘meta-analyses’ flawed by selection and intellectual bias, and public interviews that consistently discount the findings of the many subsequent randomized controlled trials that have not supported the superiority of ticagrelor over clopidogrel or prasugrel.”

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

TOPLINE:

Elevated levels of N-terminal pro–B-type natriuretic peptide (NT-proBNP), a key biomarker for diagnosing heart failure, show a nearly fourfold increased risk for atrial fibrillation (AF) in at-risk individuals. The utility of this biomarker was particularly evident in older adults and when serum-based measurements were used.

METHODOLOGY:

• Researchers conducted a meta-analysis of prospective cohort, case-cohort, or nested case-control studies to examine the association between NT-proBNP and the incidence of AF.
• They also explored the potential of NT-proBNP in improving risk prediction models for AF.
• Overall, 136,089 adults were included from 16 cohorts, and 8017 cases of incident AF were reported over a median follow-up of 4-20 years.
• Most of the included cohorts were from Europe (n = 12), followed by America (n = 3) and Asia (n = 1).
• The accuracy of the risk prediction models was evaluated using C-indexes, with values in the range of 0.50-0.70, low accuracy; 0.70-0.90, moderate accuracy; and > 0.90, high accuracy.

TAKEAWAY:

• Elevated NT-proBNP levels showed a strong association with the risk for AF, with individuals in the highest quintile of NT-proBNP facing a 3.84-fold higher risk for incident AF (pooled relative risk [RR], 3.84; 95% CI, 3.03-4.87) than those in the lowest quintile.
• The risk increased by 9% for each 10 pg/mL increase in NT-proBNP (RR, 1.09; 95% CI, 1.04-1.14), with a significant nonlinear dose-response association found between NT-proBNP and the risk for AF (P for nonlinearity < .001).
• The association was stronger in the subgroups of older adults and when the biomarker was measured in serum samples.
• The addition of NT-proBNP to traditional risk prediction models for AF may improve predictive accuracy, with the ΔC-indexes ranging from 0.010 to 0.060.

IN PRACTICE:

“The significance of NT-proBNP in enhancing AF risk stratification deserves greater attention, with potential expansion to routine health screening,” the authors wrote.

SOURCE:

The study was led by Wanyue Wang, Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, and was published online on December 06, 2024, in Heart.

LIMITATIONS:

Significant heterogeneity was observed in this meta-analysis, with the subgroup articles only providing exploratory and indicative findings. Due to the observational nature of this study, residual confounding could not be excluded. None of the prospective studies included differentiated subtypes of AF, such as paroxysmal and asymptomatic forms, which might have influenced the observed outcomes.

DISCLOSURES:

This study was supported by grants from the National Key Research and Development Program of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Natural Science Foundation of China, and National High Level Hospital Clinical Research Funding. The authors declared no conflicts of interest.

This article was created 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.

TOPLINE:

Elevated levels of N-terminal pro–B-type natriuretic peptide (NT-proBNP), a key biomarker for diagnosing heart failure, show a nearly fourfold increased risk for atrial fibrillation (AF) in at-risk individuals. The utility of this biomarker was particularly evident in older adults and when serum-based measurements were used.

METHODOLOGY:

• Researchers conducted a meta-analysis of prospective cohort, case-cohort, or nested case-control studies to examine the association between NT-proBNP and the incidence of AF.
• They also explored the potential of NT-proBNP in improving risk prediction models for AF.
• Overall, 136,089 adults were included from 16 cohorts, and 8017 cases of incident AF were reported over a median follow-up of 4-20 years.
• Most of the included cohorts were from Europe (n = 12), followed by America (n = 3) and Asia (n = 1).
• The accuracy of the risk prediction models was evaluated using C-indexes, with values in the range of 0.50-0.70, low accuracy; 0.70-0.90, moderate accuracy; and > 0.90, high accuracy.

TAKEAWAY:

• Elevated NT-proBNP levels showed a strong association with the risk for AF, with individuals in the highest quintile of NT-proBNP facing a 3.84-fold higher risk for incident AF (pooled relative risk [RR], 3.84; 95% CI, 3.03-4.87) than those in the lowest quintile.
• The risk increased by 9% for each 10 pg/mL increase in NT-proBNP (RR, 1.09; 95% CI, 1.04-1.14), with a significant nonlinear dose-response association found between NT-proBNP and the risk for AF (P for nonlinearity < .001).
• The association was stronger in the subgroups of older adults and when the biomarker was measured in serum samples.
• The addition of NT-proBNP to traditional risk prediction models for AF may improve predictive accuracy, with the ΔC-indexes ranging from 0.010 to 0.060.

IN PRACTICE:

“The significance of NT-proBNP in enhancing AF risk stratification deserves greater attention, with potential expansion to routine health screening,” the authors wrote.

SOURCE:

The study was led by Wanyue Wang, Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, and was published online on December 06, 2024, in Heart.

LIMITATIONS:

Significant heterogeneity was observed in this meta-analysis, with the subgroup articles only providing exploratory and indicative findings. Due to the observational nature of this study, residual confounding could not be excluded. None of the prospective studies included differentiated subtypes of AF, such as paroxysmal and asymptomatic forms, which might have influenced the observed outcomes.

DISCLOSURES:

This study was supported by grants from the National Key Research and Development Program of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Natural Science Foundation of China, and National High Level Hospital Clinical Research Funding. The authors declared no conflicts of interest.

This article was created 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.

TOPLINE:

Elevated levels of N-terminal pro–B-type natriuretic peptide (NT-proBNP), a key biomarker for diagnosing heart failure, show a nearly fourfold increased risk for atrial fibrillation (AF) in at-risk individuals. The utility of this biomarker was particularly evident in older adults and when serum-based measurements were used.

METHODOLOGY:

• Researchers conducted a meta-analysis of prospective cohort, case-cohort, or nested case-control studies to examine the association between NT-proBNP and the incidence of AF.
• They also explored the potential of NT-proBNP in improving risk prediction models for AF.
• Overall, 136,089 adults were included from 16 cohorts, and 8017 cases of incident AF were reported over a median follow-up of 4-20 years.
• Most of the included cohorts were from Europe (n = 12), followed by America (n = 3) and Asia (n = 1).
• The accuracy of the risk prediction models was evaluated using C-indexes, with values in the range of 0.50-0.70, low accuracy; 0.70-0.90, moderate accuracy; and > 0.90, high accuracy.

TAKEAWAY:

• Elevated NT-proBNP levels showed a strong association with the risk for AF, with individuals in the highest quintile of NT-proBNP facing a 3.84-fold higher risk for incident AF (pooled relative risk [RR], 3.84; 95% CI, 3.03-4.87) than those in the lowest quintile.
• The risk increased by 9% for each 10 pg/mL increase in NT-proBNP (RR, 1.09; 95% CI, 1.04-1.14), with a significant nonlinear dose-response association found between NT-proBNP and the risk for AF (P for nonlinearity < .001).
• The association was stronger in the subgroups of older adults and when the biomarker was measured in serum samples.
• The addition of NT-proBNP to traditional risk prediction models for AF may improve predictive accuracy, with the ΔC-indexes ranging from 0.010 to 0.060.

IN PRACTICE:

“The significance of NT-proBNP in enhancing AF risk stratification deserves greater attention, with potential expansion to routine health screening,” the authors wrote.

SOURCE:

The study was led by Wanyue Wang, Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, and was published online on December 06, 2024, in Heart.

LIMITATIONS:

Significant heterogeneity was observed in this meta-analysis, with the subgroup articles only providing exploratory and indicative findings. Due to the observational nature of this study, residual confounding could not be excluded. None of the prospective studies included differentiated subtypes of AF, such as paroxysmal and asymptomatic forms, which might have influenced the observed outcomes.

DISCLOSURES:

This study was supported by grants from the National Key Research and Development Program of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Natural Science Foundation of China, and National High Level Hospital Clinical Research Funding. The authors declared no conflicts of interest.

This article was created 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.

Instead of sitting behind a laptop during patient visits, the pediatrician directly faces the patient and parent, relying on an ambient artificial intelligence (AI) scribe to capture the conversation for the electronic health record (EHR). A geriatrician doing rounds at the senior living facility plugs each patient’s medications into an AI tool, checking for drug interactions. And a busy hospital radiology department runs all its emergency head CTs through an AI algorithm, triaging potential stroke patients to ensure they receive the highest priority. None of these physicians have been sued for malpractice for AI usage, but they wonder if they’re at risk.

In a recent Medscape report, AI Adoption in Healthcare, 224 physicians responded to the statement: “I want to do more with AI but I worry about malpractice risk if I move too fast.” Seventeen percent said that they strongly agreed while 23% said they agreed — a full 40% were concerned about using the technology for legal reasons.  

Malpractice and AI are on many minds in healthcare, especially in large health systems, Deepika Srivastava, chief operating officer at The Doctors Company, told this news organization. “AI is at the forefront of the conversation, and they’re [large health systems] raising questions. Larger systems want to protect themselves.” 

The good news is there’s currently no sign of legal action over the clinical use of AI. “We’re not seeing even a few AI-related suits just yet,” but the risk is growing, Srivastava said, “and that’s why we’re talking about it. The legal system will need to adapt to address the role of AI in healthcare.”

 

How Doctors Are Using AI

Healthcare is incorporating AI in multiple ways based on the type of tool and function needed. Narrow AI is popular in fields like radiology, comparing two large data sets to find differences between them. Narrow AI can help differentiate between normal and abnormal tissue, such as breast or lung tumors. Almost 900 AI health tools have Food and Drug Administration approval as of July 2024, discerning abnormalities and recognizing patterns better than many humans, said Robert Pearl, MD, author of ChatGPT, MD: How AI-Empowered Patients & Doctors Can Take Back Control of American Medicine and former CEO of The Permanente Medical Group.

Narrow AI can improve diagnostic speed and accuracy for other specialties, too, including dermatology and ophthalmology, Pearl said. “It’s less clear to me if it will be very beneficial in primary care, neurology, and psychiatry, areas of medicine that involve a lot of words.” In those specialties, some may use generative AI as a repository of resources. In clinical practice, ambient AI is also used to create health records based on patient/clinician conversations.

In clinical administration, AI is used for scheduling, billing, and submitting insurance claims. On the insurer side, denying claims based on AI algorithms has been at the heart of legal actions, making recent headlines. 

 

Malpractice Risks When Using AI

Accuracy and privacy should be at the top of the list for malpractice concerns with AI. With accuracy, liability could partially be determined by use type. If a diagnostic application makes the wrong diagnosis, “the company has legal accountability because it created and had to test it specific to the application that it’s being recommended for,” Pearl said. 

However, keeping a human in the loop is a smart move when using AI diagnostic tools. The physician should still choose the AI-suggested diagnosis or a different one. If it’s the wrong diagnosis, “it’s really hard to currently say where is the source of the error? Was it the physician? Was it the tool?” Srivastava added.

With an incorrect diagnosis by generative AI, liability is more apparent. “You’re taking that accountability,” Pearl said. Generative AI operates in a black box, predicting the correct answer based on information stored in a database. “Generative AI tries to draw a correlation between what it has seen and predicting the next output,” said Alex Shahrestani, managing partner of Promise Legal PLLC, a law firm in Austin, Texas. He serves on the State Bar of Texas’s Taskforce on AI and the Law and has participated in advisory groups related to AI policies with the National Institute of Standards and Technology. “A doctor should know to validate information given back to them by AI,” applying their own medical training and judgment.

Generative AI can provide ideas. Pearl shared a story about a surgeon who was unable to remove a breathing tube that was stuck in a patients’ throat at the end of a procedure. The surgeon checked ChatGPT in the operating room, finding a similar case. Adrenaline in the anesthetic restricted the blood vessels, causing the vocal cords to stick together. Following the AI information, the surgeon allowed more time for the anesthesia to diffuse. As it wore off, the vocal cords separated, easing the removal of the breathing tube. “That is the kind of expertise it can provide,” Pearl said.

Privacy is a common AI concern, but it may be more problematic than it should be. “Many think if you talk to an AI system, you’re surrendering personal information the model can learn from,” said Shahrestani. Platforms offer opt-outs. Even without opting out, the model won’t automatically ingest your interactions. That’s not a privacy feature, but a concern by the developer that the information may not help the model. 

“If you do use these opt-out mechanisms, and you have the requisite amount of confidentiality, you can use ChatGPT without too much concern about the patient information being released into the wild,” Shahrestani said. Or use systems with stricter requirements that keep all data on site.

 

Malpractice Insurance Policies and AI

Currently, malpractice policies do not specify AI coverage. “We don’t ask right now to list all the technology you’re using,” said Srivastava. Many EHR systems already incorporate AI. If a human provider is in the loop, already vetted and insured, “we should be okay when it comes to the risk of malpractice when doctors are using AI because it’s still the risk that we’re ensuring.”

Insurers are paying attention, though. “Traditional medical malpractice law does require re-evaluation because the rapid pace of AI development has outpaced the efforts to integrate it into the legal system,” Srivastava said.

Some, including Pearl, believe AI will actually lower the malpractice risk. Having more data points to consider can make doctors’ jobs faster, easier, and more accurate. “I believe the technology will decrease lawsuits, not increase them,” said Pearl.

 

Meanwhile, How Can Doctors Protect Themselves From an AI Malpractice Suit?

Know your tool: Providers should understand the tool they’re deploying, what it provides, how it was built and trained (including potential biases), how it was tested, and the guidelines for how to use it or not use it, said Srivastava. Evaluate each tool, use case, and risk separately. “Don’t just say it’s all AI.” 

With generative AI, users will have better success requesting information that has been available longer and is more widely accessed. “It’s more likely to come back correctly,” said Shahrestani. If the information sought is fairly new or not widespread, the tool may try to draw problematic conclusions. 

Document: “Document, document, document. Just making sure you have good documentation can really help you if litigation comes up and it’s related to the AI tools,” Srivastava said.

Try it out: “I recommend you use [generative AI] a lot so you understand its strengths and shortcomings,” said Shahrestani. “If you wait until things settle, you’ll be further behind.” 

Pretend you’re the patient and give the tool the information you’d give a doctor and see the results, said Pearl. It will provide you with an idea of what it can do. “No one would sue you because you went to the library to look up information in the textbooks,” he said — using generative AI is similar. Try the free versions first; if you begin relying on it more, the paid versions have better features and are inexpensive. 

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

Instead of sitting behind a laptop during patient visits, the pediatrician directly faces the patient and parent, relying on an ambient artificial intelligence (AI) scribe to capture the conversation for the electronic health record (EHR). A geriatrician doing rounds at the senior living facility plugs each patient’s medications into an AI tool, checking for drug interactions. And a busy hospital radiology department runs all its emergency head CTs through an AI algorithm, triaging potential stroke patients to ensure they receive the highest priority. None of these physicians have been sued for malpractice for AI usage, but they wonder if they’re at risk.

In a recent Medscape report, AI Adoption in Healthcare, 224 physicians responded to the statement: “I want to do more with AI but I worry about malpractice risk if I move too fast.” Seventeen percent said that they strongly agreed while 23% said they agreed — a full 40% were concerned about using the technology for legal reasons.  

Malpractice and AI are on many minds in healthcare, especially in large health systems, Deepika Srivastava, chief operating officer at The Doctors Company, told this news organization. “AI is at the forefront of the conversation, and they’re [large health systems] raising questions. Larger systems want to protect themselves.” 

The good news is there’s currently no sign of legal action over the clinical use of AI. “We’re not seeing even a few AI-related suits just yet,” but the risk is growing, Srivastava said, “and that’s why we’re talking about it. The legal system will need to adapt to address the role of AI in healthcare.”

 

How Doctors Are Using AI

Healthcare is incorporating AI in multiple ways based on the type of tool and function needed. Narrow AI is popular in fields like radiology, comparing two large data sets to find differences between them. Narrow AI can help differentiate between normal and abnormal tissue, such as breast or lung tumors. Almost 900 AI health tools have Food and Drug Administration approval as of July 2024, discerning abnormalities and recognizing patterns better than many humans, said Robert Pearl, MD, author of ChatGPT, MD: How AI-Empowered Patients & Doctors Can Take Back Control of American Medicine and former CEO of The Permanente Medical Group.

Narrow AI can improve diagnostic speed and accuracy for other specialties, too, including dermatology and ophthalmology, Pearl said. “It’s less clear to me if it will be very beneficial in primary care, neurology, and psychiatry, areas of medicine that involve a lot of words.” In those specialties, some may use generative AI as a repository of resources. In clinical practice, ambient AI is also used to create health records based on patient/clinician conversations.

In clinical administration, AI is used for scheduling, billing, and submitting insurance claims. On the insurer side, denying claims based on AI algorithms has been at the heart of legal actions, making recent headlines. 

 

Malpractice Risks When Using AI

Accuracy and privacy should be at the top of the list for malpractice concerns with AI. With accuracy, liability could partially be determined by use type. If a diagnostic application makes the wrong diagnosis, “the company has legal accountability because it created and had to test it specific to the application that it’s being recommended for,” Pearl said. 

However, keeping a human in the loop is a smart move when using AI diagnostic tools. The physician should still choose the AI-suggested diagnosis or a different one. If it’s the wrong diagnosis, “it’s really hard to currently say where is the source of the error? Was it the physician? Was it the tool?” Srivastava added.

With an incorrect diagnosis by generative AI, liability is more apparent. “You’re taking that accountability,” Pearl said. Generative AI operates in a black box, predicting the correct answer based on information stored in a database. “Generative AI tries to draw a correlation between what it has seen and predicting the next output,” said Alex Shahrestani, managing partner of Promise Legal PLLC, a law firm in Austin, Texas. He serves on the State Bar of Texas’s Taskforce on AI and the Law and has participated in advisory groups related to AI policies with the National Institute of Standards and Technology. “A doctor should know to validate information given back to them by AI,” applying their own medical training and judgment.

Generative AI can provide ideas. Pearl shared a story about a surgeon who was unable to remove a breathing tube that was stuck in a patients’ throat at the end of a procedure. The surgeon checked ChatGPT in the operating room, finding a similar case. Adrenaline in the anesthetic restricted the blood vessels, causing the vocal cords to stick together. Following the AI information, the surgeon allowed more time for the anesthesia to diffuse. As it wore off, the vocal cords separated, easing the removal of the breathing tube. “That is the kind of expertise it can provide,” Pearl said.

Privacy is a common AI concern, but it may be more problematic than it should be. “Many think if you talk to an AI system, you’re surrendering personal information the model can learn from,” said Shahrestani. Platforms offer opt-outs. Even without opting out, the model won’t automatically ingest your interactions. That’s not a privacy feature, but a concern by the developer that the information may not help the model. 

“If you do use these opt-out mechanisms, and you have the requisite amount of confidentiality, you can use ChatGPT without too much concern about the patient information being released into the wild,” Shahrestani said. Or use systems with stricter requirements that keep all data on site.

 

Malpractice Insurance Policies and AI

Currently, malpractice policies do not specify AI coverage. “We don’t ask right now to list all the technology you’re using,” said Srivastava. Many EHR systems already incorporate AI. If a human provider is in the loop, already vetted and insured, “we should be okay when it comes to the risk of malpractice when doctors are using AI because it’s still the risk that we’re ensuring.”

Insurers are paying attention, though. “Traditional medical malpractice law does require re-evaluation because the rapid pace of AI development has outpaced the efforts to integrate it into the legal system,” Srivastava said.

Some, including Pearl, believe AI will actually lower the malpractice risk. Having more data points to consider can make doctors’ jobs faster, easier, and more accurate. “I believe the technology will decrease lawsuits, not increase them,” said Pearl.

 

Meanwhile, How Can Doctors Protect Themselves From an AI Malpractice Suit?

Know your tool: Providers should understand the tool they’re deploying, what it provides, how it was built and trained (including potential biases), how it was tested, and the guidelines for how to use it or not use it, said Srivastava. Evaluate each tool, use case, and risk separately. “Don’t just say it’s all AI.” 

With generative AI, users will have better success requesting information that has been available longer and is more widely accessed. “It’s more likely to come back correctly,” said Shahrestani. If the information sought is fairly new or not widespread, the tool may try to draw problematic conclusions. 

Document: “Document, document, document. Just making sure you have good documentation can really help you if litigation comes up and it’s related to the AI tools,” Srivastava said.

Try it out: “I recommend you use [generative AI] a lot so you understand its strengths and shortcomings,” said Shahrestani. “If you wait until things settle, you’ll be further behind.” 

Pretend you’re the patient and give the tool the information you’d give a doctor and see the results, said Pearl. It will provide you with an idea of what it can do. “No one would sue you because you went to the library to look up information in the textbooks,” he said — using generative AI is similar. Try the free versions first; if you begin relying on it more, the paid versions have better features and are inexpensive. 

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

Instead of sitting behind a laptop during patient visits, the pediatrician directly faces the patient and parent, relying on an ambient artificial intelligence (AI) scribe to capture the conversation for the electronic health record (EHR). A geriatrician doing rounds at the senior living facility plugs each patient’s medications into an AI tool, checking for drug interactions. And a busy hospital radiology department runs all its emergency head CTs through an AI algorithm, triaging potential stroke patients to ensure they receive the highest priority. None of these physicians have been sued for malpractice for AI usage, but they wonder if they’re at risk.

In a recent Medscape report, AI Adoption in Healthcare, 224 physicians responded to the statement: “I want to do more with AI but I worry about malpractice risk if I move too fast.” Seventeen percent said that they strongly agreed while 23% said they agreed — a full 40% were concerned about using the technology for legal reasons.  

Malpractice and AI are on many minds in healthcare, especially in large health systems, Deepika Srivastava, chief operating officer at The Doctors Company, told this news organization. “AI is at the forefront of the conversation, and they’re [large health systems] raising questions. Larger systems want to protect themselves.” 

The good news is there’s currently no sign of legal action over the clinical use of AI. “We’re not seeing even a few AI-related suits just yet,” but the risk is growing, Srivastava said, “and that’s why we’re talking about it. The legal system will need to adapt to address the role of AI in healthcare.”

 

How Doctors Are Using AI

Healthcare is incorporating AI in multiple ways based on the type of tool and function needed. Narrow AI is popular in fields like radiology, comparing two large data sets to find differences between them. Narrow AI can help differentiate between normal and abnormal tissue, such as breast or lung tumors. Almost 900 AI health tools have Food and Drug Administration approval as of July 2024, discerning abnormalities and recognizing patterns better than many humans, said Robert Pearl, MD, author of ChatGPT, MD: How AI-Empowered Patients & Doctors Can Take Back Control of American Medicine and former CEO of The Permanente Medical Group.

Narrow AI can improve diagnostic speed and accuracy for other specialties, too, including dermatology and ophthalmology, Pearl said. “It’s less clear to me if it will be very beneficial in primary care, neurology, and psychiatry, areas of medicine that involve a lot of words.” In those specialties, some may use generative AI as a repository of resources. In clinical practice, ambient AI is also used to create health records based on patient/clinician conversations.

In clinical administration, AI is used for scheduling, billing, and submitting insurance claims. On the insurer side, denying claims based on AI algorithms has been at the heart of legal actions, making recent headlines. 

 

Malpractice Risks When Using AI

Accuracy and privacy should be at the top of the list for malpractice concerns with AI. With accuracy, liability could partially be determined by use type. If a diagnostic application makes the wrong diagnosis, “the company has legal accountability because it created and had to test it specific to the application that it’s being recommended for,” Pearl said. 

However, keeping a human in the loop is a smart move when using AI diagnostic tools. The physician should still choose the AI-suggested diagnosis or a different one. If it’s the wrong diagnosis, “it’s really hard to currently say where is the source of the error? Was it the physician? Was it the tool?” Srivastava added.

With an incorrect diagnosis by generative AI, liability is more apparent. “You’re taking that accountability,” Pearl said. Generative AI operates in a black box, predicting the correct answer based on information stored in a database. “Generative AI tries to draw a correlation between what it has seen and predicting the next output,” said Alex Shahrestani, managing partner of Promise Legal PLLC, a law firm in Austin, Texas. He serves on the State Bar of Texas’s Taskforce on AI and the Law and has participated in advisory groups related to AI policies with the National Institute of Standards and Technology. “A doctor should know to validate information given back to them by AI,” applying their own medical training and judgment.

Generative AI can provide ideas. Pearl shared a story about a surgeon who was unable to remove a breathing tube that was stuck in a patients’ throat at the end of a procedure. The surgeon checked ChatGPT in the operating room, finding a similar case. Adrenaline in the anesthetic restricted the blood vessels, causing the vocal cords to stick together. Following the AI information, the surgeon allowed more time for the anesthesia to diffuse. As it wore off, the vocal cords separated, easing the removal of the breathing tube. “That is the kind of expertise it can provide,” Pearl said.

Privacy is a common AI concern, but it may be more problematic than it should be. “Many think if you talk to an AI system, you’re surrendering personal information the model can learn from,” said Shahrestani. Platforms offer opt-outs. Even without opting out, the model won’t automatically ingest your interactions. That’s not a privacy feature, but a concern by the developer that the information may not help the model. 

“If you do use these opt-out mechanisms, and you have the requisite amount of confidentiality, you can use ChatGPT without too much concern about the patient information being released into the wild,” Shahrestani said. Or use systems with stricter requirements that keep all data on site.

 

Malpractice Insurance Policies and AI

Currently, malpractice policies do not specify AI coverage. “We don’t ask right now to list all the technology you’re using,” said Srivastava. Many EHR systems already incorporate AI. If a human provider is in the loop, already vetted and insured, “we should be okay when it comes to the risk of malpractice when doctors are using AI because it’s still the risk that we’re ensuring.”

Insurers are paying attention, though. “Traditional medical malpractice law does require re-evaluation because the rapid pace of AI development has outpaced the efforts to integrate it into the legal system,” Srivastava said.

Some, including Pearl, believe AI will actually lower the malpractice risk. Having more data points to consider can make doctors’ jobs faster, easier, and more accurate. “I believe the technology will decrease lawsuits, not increase them,” said Pearl.

 

Meanwhile, How Can Doctors Protect Themselves From an AI Malpractice Suit?

Know your tool: Providers should understand the tool they’re deploying, what it provides, how it was built and trained (including potential biases), how it was tested, and the guidelines for how to use it or not use it, said Srivastava. Evaluate each tool, use case, and risk separately. “Don’t just say it’s all AI.” 

With generative AI, users will have better success requesting information that has been available longer and is more widely accessed. “It’s more likely to come back correctly,” said Shahrestani. If the information sought is fairly new or not widespread, the tool may try to draw problematic conclusions. 

Document: “Document, document, document. Just making sure you have good documentation can really help you if litigation comes up and it’s related to the AI tools,” Srivastava said.

Try it out: “I recommend you use [generative AI] a lot so you understand its strengths and shortcomings,” said Shahrestani. “If you wait until things settle, you’ll be further behind.” 

Pretend you’re the patient and give the tool the information you’d give a doctor and see the results, said Pearl. It will provide you with an idea of what it can do. “No one would sue you because you went to the library to look up information in the textbooks,” he said — using generative AI is similar. Try the free versions first; if you begin relying on it more, the paid versions have better features and are inexpensive. 

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

The question may seem simple: Could paying for weight loss medications — especially the pricey glucagon-like peptide 1 receptor agonists (GLP-1s), tirzepatide (Zepbound) and semaglutide (Wegovy) — be more cost-effective than paying for obesity care and the complications of obesity, such as cardiovascular disease and diabetes?

It’s a question that’s getting an increased amount of attention.

And for good reason — more than two in five US adults have obesity, according to the Centers for Disease Control and Prevention, and costs to treat obesity, in 2019 dollars, approached $173 billion, including productivity losses. Adults with obesity have annual healthcare costs of $1861 more than those at healthier weights.

Among recent developments:

• A proposed new rule, announced on November 26 by the Biden administration, expands coverage of anti-obesity medication for Americans who have Medicare and Medicaid. If it takes effect, an estimated 3.4 million Medicare recipients and about 4 million adult Medicaid enrollees could get access to the medications.
• As Medicare coverage goes, private insurers often follow. Observers predict that if the Centers for Medicare & Medicaid Services (CMS) covers anti-obesity drugs, more private employers may soon do the same. Recently, however, some private plans have done the opposite and dropped coverage of the pricey GLP-1s, which can cost $1000 a month or more out-of-pocket, citing excess costs for their company.
• Among the analyses about the value of weight loss on healthcare cost savings is a report published on December 5 in JAMA Network Open. Emory University experts looked at privately insured adults and adult Medicare beneficiaries with a body mass index (BMI) of ≥ 25 (classified as overweight). The conclusion: Projected annual savings from weight loss among US adults with obesity were substantial for both employee-based insurance and Medicare recipients.
• Besides helping obesity and obesity-related conditions, access to GLP-1s could have a favorable effect on productivity, others claim. That’s one focus of a 5-year partnership between the University of Manchester in England, and Eli Lilly and Company. Called SURMOUNT-REAL UK, the study will evaluate the effectiveness of tirzepatide in weight loss, diabetes prevention, and prevention of obesity-related complications in adults with obesity. It also aims to look at changes in health-related quality of life with weight loss and with changes in employment status and sick days.

CMS Proposal

In a statement announcing the proposal for Medicare and Medicaid to offer weight loss drugs, the White House noted that “tens of millions of Americans struggle with obesity” but that currently Medicare only covers the anti-obesity medications for certain conditions such as diabetes. The new proposal would expand that access to those with obesity. As of August, just 13 states cover GLP-1s in Medicaid programs, and North Carolina was the latest to do so.

Organizations advocating for health equity and recognition that obesity is a chronic disease came out in strong support of the proposal.

Kenneth E. Thorpe, PhD, a health policy expert at Emory University in Atlanta, who coauthored the recent analysis finding that weight loss offsets healthcare costs on an individual basis, told this news organization: “If finalized, this broad new coverage [by Medicare and Medicaid] would have a profound impact on the ability of Americans to access these novel medications that could significantly reduce obesity-related healthcare spending and improve overall health.”

The proposal “is modernizing the coverage of Medicare and Medicaid for obesity treatment,” agreed John Cawley, PhD, professor of economics and public policy at Cornell University in Ithaca, New York, who has researched the direct medical costs of obesity in the United States. “In this HHS rule, they talk about the scientific and medical consensus that having obesity is a chronic condition.”

The proposal requires a 60-day comment period that ends January 27, 2025, taking the timeline into the beginning of the Trump administration. Cawley and others pointed out that Trump’s pick for Health and Human Services Secretary, Robert F. Kennedy Jr, has been an outspoken opponent of the anti-obesity medicines, suggesting instead that Americans simply eat better.

 

Expert Analyses: Emory, Cornell, Southern California

So would paying for the pricey GLP-1s be smart in the long term? Analyses don’t agree.

Weight loss among those with obesity produces healthcare cost savings, said Thorpe and Peter Joski, MSPH, an associate research professor at Emory University. The two compared annual healthcare spending among privately insured adults and adult Medicare beneficiaries with a BMI of ≥ 25, using data from the Medical Expenditure Panel Survey — Household Component from April 1 to June 20, 2024.

The researchers looked at 3774 adults insured with Medicare and 13,435 with employer-sponsored insurance. Overall, those with private insurance with a weight loss of 5% spent an estimated average of $670 less on healthcare. Those with a weight loss of 25% spent an estimated $2849 less on healthcare. Among those with Medicare who had one or more comorbidities, a 5% weight loss reduced spending by $1262 on average; a 25% loss reduced it by an estimated $5442, or 31%.

Thorpe called the savings substantial. In an email interview, Thorpe said, “So yes, weight loss for people living with obesity does lower healthcare costs, as my research shows, but it also lowers other costs as well.”

These include costs associated with disability, workers’ compensation, presenteeism/absenteeism, and everyday costs, he said. He contends that “those other costs should factor into decisions about preventing and treating obesity of payors and policymakers and enhance the case for cost-effectiveness of treating obesity.”

Other research suggests it’s important to target the use of the anti-obesity medications to the BMI range that would get the most benefit. For people just barely above the BMI threshold of 30, no cost savings are expected, Cawley found in his research. But he has found substantial cost reduction if the BMI was 35-40.

However, as Cawley pointed out, as the drugs get cheaper and more options become available, the entire scenario is expected to shift.

 

The Congressional Budget Office View

In October, the nonpartisan Congressional Budget Office issued a report, “How Would Authorizing Medicare to Cover Anti-Obesity Medications Affect the Federal Budget?” Among the conclusions: Covering the anti-obesity medications would increase federal spending, on net, by about $35 billion from 2026 to 2034. Total direct federal costs of covering the medication would increase from $1.6 billion in 2026 to $7.1 billion in 2034. And it said total savings from improved health of the beneficiaries would be small, less than $50 million in 2026 and rising to $1 billion in 2034.

Covering the medications would cost $5600 per user in 2026, then down to $4300 in 2034. The offset of savings per user would be about $50 in 2026, then $650 in 2034.

 

Expert Analysis: USC Schaeffer Center

“The costs offsets come over time,” said Alison Sexton Ward, PhD, an economist at the University of Southern California’s Leonard D. Schaeffer Center, Los Angeles, and an expert on the topic. “If we look at the average annual medical cost over a lifetime, we do see cost offsets there.”

However, treating obesity means people will live longer, “and living longer costs more,” she said.

She took issue with some of the calculations in the CBO report, such as not considering the effect of semaglutide’s patent expiring in 2033.

In a white paper published in April 2023, Sexton Ward and her coauthors modeled potential social benefits and medical cost offsets from granting access to the newer weight loss drugs. The cumulative social benefits of providing coverage over the next decade would reach nearly $1 trillion, they said. Benefits would increase if private insurance expanded coverage. “In the first 10 years alone, covering weight loss therapies would save Medicare $175 billion-$245 billion, depending on whether private insurance joins Medicare in providing coverage for younger populations.”

While much focus is on Medicare coverage, Sexton Ward and others pointed out the need to expand coverage to younger ages, with the aim of preventing or delaying obesity-related complications.

 

Lilly UK Trial

A spokesperson for Lilly declined to comment further on the UK study, explaining that the study was just launching.

Besides tracking weight loss, researchers will evaluate the effect of the weight loss on sick days from work and employment. Obesity is shown to affect a person’s ability to work, leading to more absenteeism, so treating the obesity may improve productivity.

 

Beyond Health: The Value of Weight Loss

“I love the idea of studying whether access to obesity medications helps people stay employed and do their job,” said Cristy Gallagher, associate director of Research and Policy at STOP Obesity Alliance at the Milken Institute School of Public Health, George Washington University, Washington, DC. The alliance includes more than 50 organizations advocating for adult obesity treatment.

“One of our big arguments is [that] access to care, and to obesity care, will also help other conditions — comorbidities like heart disease and diabetes.”

However, access to the anti-obesity medications, by itself, is not enough, Gallagher said. Other components, such as intensive behavioral therapy and guidance about diet and exercise, are needed, she said. So, too, for those who need it, is access to bariatric surgery, she said. And medication access should include other options besides the GLP-1s, she said. “Not every medication is right for everybody.”

Cawley, Gallagher, Thorpe, and Sexton Ward had no disclosures.
 

A version of this article appeared on Medscape.com.

The question may seem simple: Could paying for weight loss medications — especially the pricey glucagon-like peptide 1 receptor agonists (GLP-1s), tirzepatide (Zepbound) and semaglutide (Wegovy) — be more cost-effective than paying for obesity care and the complications of obesity, such as cardiovascular disease and diabetes?

It’s a question that’s getting an increased amount of attention.

And for good reason — more than two in five US adults have obesity, according to the Centers for Disease Control and Prevention, and costs to treat obesity, in 2019 dollars, approached $173 billion, including productivity losses. Adults with obesity have annual healthcare costs of $1861 more than those at healthier weights.

Among recent developments:

• A proposed new rule, announced on November 26 by the Biden administration, expands coverage of anti-obesity medication for Americans who have Medicare and Medicaid. If it takes effect, an estimated 3.4 million Medicare recipients and about 4 million adult Medicaid enrollees could get access to the medications.
• As Medicare coverage goes, private insurers often follow. Observers predict that if the Centers for Medicare & Medicaid Services (CMS) covers anti-obesity drugs, more private employers may soon do the same. Recently, however, some private plans have done the opposite and dropped coverage of the pricey GLP-1s, which can cost $1000 a month or more out-of-pocket, citing excess costs for their company.
• Among the analyses about the value of weight loss on healthcare cost savings is a report published on December 5 in JAMA Network Open. Emory University experts looked at privately insured adults and adult Medicare beneficiaries with a body mass index (BMI) of ≥ 25 (classified as overweight). The conclusion: Projected annual savings from weight loss among US adults with obesity were substantial for both employee-based insurance and Medicare recipients.
• Besides helping obesity and obesity-related conditions, access to GLP-1s could have a favorable effect on productivity, others claim. That’s one focus of a 5-year partnership between the University of Manchester in England, and Eli Lilly and Company. Called SURMOUNT-REAL UK, the study will evaluate the effectiveness of tirzepatide in weight loss, diabetes prevention, and prevention of obesity-related complications in adults with obesity. It also aims to look at changes in health-related quality of life with weight loss and with changes in employment status and sick days.

CMS Proposal

In a statement announcing the proposal for Medicare and Medicaid to offer weight loss drugs, the White House noted that “tens of millions of Americans struggle with obesity” but that currently Medicare only covers the anti-obesity medications for certain conditions such as diabetes. The new proposal would expand that access to those with obesity. As of August, just 13 states cover GLP-1s in Medicaid programs, and North Carolina was the latest to do so.

Organizations advocating for health equity and recognition that obesity is a chronic disease came out in strong support of the proposal.

Kenneth E. Thorpe, PhD, a health policy expert at Emory University in Atlanta, who coauthored the recent analysis finding that weight loss offsets healthcare costs on an individual basis, told this news organization: “If finalized, this broad new coverage [by Medicare and Medicaid] would have a profound impact on the ability of Americans to access these novel medications that could significantly reduce obesity-related healthcare spending and improve overall health.”

The proposal “is modernizing the coverage of Medicare and Medicaid for obesity treatment,” agreed John Cawley, PhD, professor of economics and public policy at Cornell University in Ithaca, New York, who has researched the direct medical costs of obesity in the United States. “In this HHS rule, they talk about the scientific and medical consensus that having obesity is a chronic condition.”

The proposal requires a 60-day comment period that ends January 27, 2025, taking the timeline into the beginning of the Trump administration. Cawley and others pointed out that Trump’s pick for Health and Human Services Secretary, Robert F. Kennedy Jr, has been an outspoken opponent of the anti-obesity medicines, suggesting instead that Americans simply eat better.

 

Expert Analyses: Emory, Cornell, Southern California

So would paying for the pricey GLP-1s be smart in the long term? Analyses don’t agree.

Weight loss among those with obesity produces healthcare cost savings, said Thorpe and Peter Joski, MSPH, an associate research professor at Emory University. The two compared annual healthcare spending among privately insured adults and adult Medicare beneficiaries with a BMI of ≥ 25, using data from the Medical Expenditure Panel Survey — Household Component from April 1 to June 20, 2024.

The researchers looked at 3774 adults insured with Medicare and 13,435 with employer-sponsored insurance. Overall, those with private insurance with a weight loss of 5% spent an estimated average of $670 less on healthcare. Those with a weight loss of 25% spent an estimated $2849 less on healthcare. Among those with Medicare who had one or more comorbidities, a 5% weight loss reduced spending by $1262 on average; a 25% loss reduced it by an estimated $5442, or 31%.

Thorpe called the savings substantial. In an email interview, Thorpe said, “So yes, weight loss for people living with obesity does lower healthcare costs, as my research shows, but it also lowers other costs as well.”

These include costs associated with disability, workers’ compensation, presenteeism/absenteeism, and everyday costs, he said. He contends that “those other costs should factor into decisions about preventing and treating obesity of payors and policymakers and enhance the case for cost-effectiveness of treating obesity.”

Other research suggests it’s important to target the use of the anti-obesity medications to the BMI range that would get the most benefit. For people just barely above the BMI threshold of 30, no cost savings are expected, Cawley found in his research. But he has found substantial cost reduction if the BMI was 35-40.

However, as Cawley pointed out, as the drugs get cheaper and more options become available, the entire scenario is expected to shift.

 

The Congressional Budget Office View

In October, the nonpartisan Congressional Budget Office issued a report, “How Would Authorizing Medicare to Cover Anti-Obesity Medications Affect the Federal Budget?” Among the conclusions: Covering the anti-obesity medications would increase federal spending, on net, by about $35 billion from 2026 to 2034. Total direct federal costs of covering the medication would increase from $1.6 billion in 2026 to $7.1 billion in 2034. And it said total savings from improved health of the beneficiaries would be small, less than $50 million in 2026 and rising to $1 billion in 2034.

Covering the medications would cost $5600 per user in 2026, then down to $4300 in 2034. The offset of savings per user would be about $50 in 2026, then $650 in 2034.

 

Expert Analysis: USC Schaeffer Center

“The costs offsets come over time,” said Alison Sexton Ward, PhD, an economist at the University of Southern California’s Leonard D. Schaeffer Center, Los Angeles, and an expert on the topic. “If we look at the average annual medical cost over a lifetime, we do see cost offsets there.”

However, treating obesity means people will live longer, “and living longer costs more,” she said.

She took issue with some of the calculations in the CBO report, such as not considering the effect of semaglutide’s patent expiring in 2033.

In a white paper published in April 2023, Sexton Ward and her coauthors modeled potential social benefits and medical cost offsets from granting access to the newer weight loss drugs. The cumulative social benefits of providing coverage over the next decade would reach nearly $1 trillion, they said. Benefits would increase if private insurance expanded coverage. “In the first 10 years alone, covering weight loss therapies would save Medicare $175 billion-$245 billion, depending on whether private insurance joins Medicare in providing coverage for younger populations.”

While much focus is on Medicare coverage, Sexton Ward and others pointed out the need to expand coverage to younger ages, with the aim of preventing or delaying obesity-related complications.

 

Lilly UK Trial

A spokesperson for Lilly declined to comment further on the UK study, explaining that the study was just launching.

Besides tracking weight loss, researchers will evaluate the effect of the weight loss on sick days from work and employment. Obesity is shown to affect a person’s ability to work, leading to more absenteeism, so treating the obesity may improve productivity.

 

Beyond Health: The Value of Weight Loss

“I love the idea of studying whether access to obesity medications helps people stay employed and do their job,” said Cristy Gallagher, associate director of Research and Policy at STOP Obesity Alliance at the Milken Institute School of Public Health, George Washington University, Washington, DC. The alliance includes more than 50 organizations advocating for adult obesity treatment.

“One of our big arguments is [that] access to care, and to obesity care, will also help other conditions — comorbidities like heart disease and diabetes.”

However, access to the anti-obesity medications, by itself, is not enough, Gallagher said. Other components, such as intensive behavioral therapy and guidance about diet and exercise, are needed, she said. So, too, for those who need it, is access to bariatric surgery, she said. And medication access should include other options besides the GLP-1s, she said. “Not every medication is right for everybody.”

Cawley, Gallagher, Thorpe, and Sexton Ward had no disclosures.
 

A version of this article appeared on Medscape.com.

The question may seem simple: Could paying for weight loss medications — especially the pricey glucagon-like peptide 1 receptor agonists (GLP-1s), tirzepatide (Zepbound) and semaglutide (Wegovy) — be more cost-effective than paying for obesity care and the complications of obesity, such as cardiovascular disease and diabetes?

It’s a question that’s getting an increased amount of attention.

And for good reason — more than two in five US adults have obesity, according to the Centers for Disease Control and Prevention, and costs to treat obesity, in 2019 dollars, approached $173 billion, including productivity losses. Adults with obesity have annual healthcare costs of $1861 more than those at healthier weights.

Among recent developments:

• A proposed new rule, announced on November 26 by the Biden administration, expands coverage of anti-obesity medication for Americans who have Medicare and Medicaid. If it takes effect, an estimated 3.4 million Medicare recipients and about 4 million adult Medicaid enrollees could get access to the medications.
• As Medicare coverage goes, private insurers often follow. Observers predict that if the Centers for Medicare & Medicaid Services (CMS) covers anti-obesity drugs, more private employers may soon do the same. Recently, however, some private plans have done the opposite and dropped coverage of the pricey GLP-1s, which can cost $1000 a month or more out-of-pocket, citing excess costs for their company.
• Among the analyses about the value of weight loss on healthcare cost savings is a report published on December 5 in JAMA Network Open. Emory University experts looked at privately insured adults and adult Medicare beneficiaries with a body mass index (BMI) of ≥ 25 (classified as overweight). The conclusion: Projected annual savings from weight loss among US adults with obesity were substantial for both employee-based insurance and Medicare recipients.
• Besides helping obesity and obesity-related conditions, access to GLP-1s could have a favorable effect on productivity, others claim. That’s one focus of a 5-year partnership between the University of Manchester in England, and Eli Lilly and Company. Called SURMOUNT-REAL UK, the study will evaluate the effectiveness of tirzepatide in weight loss, diabetes prevention, and prevention of obesity-related complications in adults with obesity. It also aims to look at changes in health-related quality of life with weight loss and with changes in employment status and sick days.

CMS Proposal

In a statement announcing the proposal for Medicare and Medicaid to offer weight loss drugs, the White House noted that “tens of millions of Americans struggle with obesity” but that currently Medicare only covers the anti-obesity medications for certain conditions such as diabetes. The new proposal would expand that access to those with obesity. As of August, just 13 states cover GLP-1s in Medicaid programs, and North Carolina was the latest to do so.

Organizations advocating for health equity and recognition that obesity is a chronic disease came out in strong support of the proposal.

Kenneth E. Thorpe, PhD, a health policy expert at Emory University in Atlanta, who coauthored the recent analysis finding that weight loss offsets healthcare costs on an individual basis, told this news organization: “If finalized, this broad new coverage [by Medicare and Medicaid] would have a profound impact on the ability of Americans to access these novel medications that could significantly reduce obesity-related healthcare spending and improve overall health.”

The proposal “is modernizing the coverage of Medicare and Medicaid for obesity treatment,” agreed John Cawley, PhD, professor of economics and public policy at Cornell University in Ithaca, New York, who has researched the direct medical costs of obesity in the United States. “In this HHS rule, they talk about the scientific and medical consensus that having obesity is a chronic condition.”

The proposal requires a 60-day comment period that ends January 27, 2025, taking the timeline into the beginning of the Trump administration. Cawley and others pointed out that Trump’s pick for Health and Human Services Secretary, Robert F. Kennedy Jr, has been an outspoken opponent of the anti-obesity medicines, suggesting instead that Americans simply eat better.

 

Expert Analyses: Emory, Cornell, Southern California

So would paying for the pricey GLP-1s be smart in the long term? Analyses don’t agree.

Weight loss among those with obesity produces healthcare cost savings, said Thorpe and Peter Joski, MSPH, an associate research professor at Emory University. The two compared annual healthcare spending among privately insured adults and adult Medicare beneficiaries with a BMI of ≥ 25, using data from the Medical Expenditure Panel Survey — Household Component from April 1 to June 20, 2024.

The researchers looked at 3774 adults insured with Medicare and 13,435 with employer-sponsored insurance. Overall, those with private insurance with a weight loss of 5% spent an estimated average of $670 less on healthcare. Those with a weight loss of 25% spent an estimated $2849 less on healthcare. Among those with Medicare who had one or more comorbidities, a 5% weight loss reduced spending by $1262 on average; a 25% loss reduced it by an estimated $5442, or 31%.

Thorpe called the savings substantial. In an email interview, Thorpe said, “So yes, weight loss for people living with obesity does lower healthcare costs, as my research shows, but it also lowers other costs as well.”

These include costs associated with disability, workers’ compensation, presenteeism/absenteeism, and everyday costs, he said. He contends that “those other costs should factor into decisions about preventing and treating obesity of payors and policymakers and enhance the case for cost-effectiveness of treating obesity.”

Other research suggests it’s important to target the use of the anti-obesity medications to the BMI range that would get the most benefit. For people just barely above the BMI threshold of 30, no cost savings are expected, Cawley found in his research. But he has found substantial cost reduction if the BMI was 35-40.

However, as Cawley pointed out, as the drugs get cheaper and more options become available, the entire scenario is expected to shift.

 

The Congressional Budget Office View

In October, the nonpartisan Congressional Budget Office issued a report, “How Would Authorizing Medicare to Cover Anti-Obesity Medications Affect the Federal Budget?” Among the conclusions: Covering the anti-obesity medications would increase federal spending, on net, by about $35 billion from 2026 to 2034. Total direct federal costs of covering the medication would increase from $1.6 billion in 2026 to $7.1 billion in 2034. And it said total savings from improved health of the beneficiaries would be small, less than $50 million in 2026 and rising to $1 billion in 2034.

Covering the medications would cost $5600 per user in 2026, then down to $4300 in 2034. The offset of savings per user would be about $50 in 2026, then $650 in 2034.

 

Expert Analysis: USC Schaeffer Center

“The costs offsets come over time,” said Alison Sexton Ward, PhD, an economist at the University of Southern California’s Leonard D. Schaeffer Center, Los Angeles, and an expert on the topic. “If we look at the average annual medical cost over a lifetime, we do see cost offsets there.”

However, treating obesity means people will live longer, “and living longer costs more,” she said.

She took issue with some of the calculations in the CBO report, such as not considering the effect of semaglutide’s patent expiring in 2033.

In a white paper published in April 2023, Sexton Ward and her coauthors modeled potential social benefits and medical cost offsets from granting access to the newer weight loss drugs. The cumulative social benefits of providing coverage over the next decade would reach nearly $1 trillion, they said. Benefits would increase if private insurance expanded coverage. “In the first 10 years alone, covering weight loss therapies would save Medicare $175 billion-$245 billion, depending on whether private insurance joins Medicare in providing coverage for younger populations.”

While much focus is on Medicare coverage, Sexton Ward and others pointed out the need to expand coverage to younger ages, with the aim of preventing or delaying obesity-related complications.

 

Lilly UK Trial

A spokesperson for Lilly declined to comment further on the UK study, explaining that the study was just launching.

Besides tracking weight loss, researchers will evaluate the effect of the weight loss on sick days from work and employment. Obesity is shown to affect a person’s ability to work, leading to more absenteeism, so treating the obesity may improve productivity.

 

Beyond Health: The Value of Weight Loss

“I love the idea of studying whether access to obesity medications helps people stay employed and do their job,” said Cristy Gallagher, associate director of Research and Policy at STOP Obesity Alliance at the Milken Institute School of Public Health, George Washington University, Washington, DC. The alliance includes more than 50 organizations advocating for adult obesity treatment.

“One of our big arguments is [that] access to care, and to obesity care, will also help other conditions — comorbidities like heart disease and diabetes.”

However, access to the anti-obesity medications, by itself, is not enough, Gallagher said. Other components, such as intensive behavioral therapy and guidance about diet and exercise, are needed, she said. So, too, for those who need it, is access to bariatric surgery, she said. And medication access should include other options besides the GLP-1s, she said. “Not every medication is right for everybody.”

Cawley, Gallagher, Thorpe, and Sexton Ward had no disclosures.
 

A version of this article appeared on Medscape.com.