MDedge Neurology

The Food and Drug Administration has warned two manufacturers about illegal marketing of drugs containing cannabidiol (CBD) for over-the-counter use without an approved new drug application, for using substandard manufacturing processes, and for failure to comply with current good manufacturing practices. These warnings add to 51 previous warning letters issued by the FDA since 2015 to other manufacturers of products containing CBD who were violating the Federal Food, Drug, and Cosmetic Act.

In a news release, the agency explained that its two most recent letters, sent to Honest Globe Inc. on March 15 and BioLyte Laboratories LLC on March 18, were issued because CBD has “known pharmacologic effects on humans, with demonstrated risks, it cannot be legally marketed as an inactive ingredient in OTC drug products that are not reviewed and approved by the FDA.” They also describe the companies’ failures to comply with current good manufacturing practices.

“The FDA continues to alert the public to potential safety and efficacy concerns with unapproved CBD products sold online and in stores across the country,” FDA Principal Deputy Commissioner Amy P. Abernethy, MD, PhD, said in the release. “It’s important that consumers understand that the FDA has only approved one drug containing CBD as an ingredient [Epidiolex]. These other, unapproved, CBD products may have dangerous health impacts and side effects. We remain focused on exploring potential pathways for CBD products to be lawfully marketed while also educating the public about these outstanding questions of CBD’s safety. Meanwhile, we will continue to monitor and take action, as needed, against companies that unlawfully market their products – prioritizing those that pose a risk to public health.”

The specific products from Santa Ana, Calif.–based Honest Globe that the FDA called unapproved new drugs and misbranded under the Federal Food, Drug, and Cosmetic Act included Elixicure Original Pain Relief and Elixicure Lavender Pain Relief, both of which were described as containing CBD. Products from Grand Rapids, Mich.–based BioLyte Laboratories LLC that the FDA similarly cited for violations included Silver Gel, Silver Gel with Aloe, Silver Liquid Supplement, Therapeutic Pain Gel, Pain Relief Cream, and Magnesium Oil Spray.

The agency has asked the two companies to respond to its letters within 15 working days, “stating how they will address these violations or providing their reasoning and supporting information as to why they believe these products are not in violation of the law. Failure to adequately address the violations promptly may result in legal action, including product seizure and/or injunction.”

[email protected]

The Food and Drug Administration has warned two manufacturers about illegal marketing of drugs containing cannabidiol (CBD) for over-the-counter use without an approved new drug application, for using substandard manufacturing processes, and for failure to comply with current good manufacturing practices. These warnings add to 51 previous warning letters issued by the FDA since 2015 to other manufacturers of products containing CBD who were violating the Federal Food, Drug, and Cosmetic Act.

In a news release, the agency explained that its two most recent letters, sent to Honest Globe Inc. on March 15 and BioLyte Laboratories LLC on March 18, were issued because CBD has “known pharmacologic effects on humans, with demonstrated risks, it cannot be legally marketed as an inactive ingredient in OTC drug products that are not reviewed and approved by the FDA.” They also describe the companies’ failures to comply with current good manufacturing practices.

“The FDA continues to alert the public to potential safety and efficacy concerns with unapproved CBD products sold online and in stores across the country,” FDA Principal Deputy Commissioner Amy P. Abernethy, MD, PhD, said in the release. “It’s important that consumers understand that the FDA has only approved one drug containing CBD as an ingredient [Epidiolex]. These other, unapproved, CBD products may have dangerous health impacts and side effects. We remain focused on exploring potential pathways for CBD products to be lawfully marketed while also educating the public about these outstanding questions of CBD’s safety. Meanwhile, we will continue to monitor and take action, as needed, against companies that unlawfully market their products – prioritizing those that pose a risk to public health.”

The specific products from Santa Ana, Calif.–based Honest Globe that the FDA called unapproved new drugs and misbranded under the Federal Food, Drug, and Cosmetic Act included Elixicure Original Pain Relief and Elixicure Lavender Pain Relief, both of which were described as containing CBD. Products from Grand Rapids, Mich.–based BioLyte Laboratories LLC that the FDA similarly cited for violations included Silver Gel, Silver Gel with Aloe, Silver Liquid Supplement, Therapeutic Pain Gel, Pain Relief Cream, and Magnesium Oil Spray.

The agency has asked the two companies to respond to its letters within 15 working days, “stating how they will address these violations or providing their reasoning and supporting information as to why they believe these products are not in violation of the law. Failure to adequately address the violations promptly may result in legal action, including product seizure and/or injunction.”

[email protected]

The Food and Drug Administration has warned two manufacturers about illegal marketing of drugs containing cannabidiol (CBD) for over-the-counter use without an approved new drug application, for using substandard manufacturing processes, and for failure to comply with current good manufacturing practices. These warnings add to 51 previous warning letters issued by the FDA since 2015 to other manufacturers of products containing CBD who were violating the Federal Food, Drug, and Cosmetic Act.

In a news release, the agency explained that its two most recent letters, sent to Honest Globe Inc. on March 15 and BioLyte Laboratories LLC on March 18, were issued because CBD has “known pharmacologic effects on humans, with demonstrated risks, it cannot be legally marketed as an inactive ingredient in OTC drug products that are not reviewed and approved by the FDA.” They also describe the companies’ failures to comply with current good manufacturing practices.

“The FDA continues to alert the public to potential safety and efficacy concerns with unapproved CBD products sold online and in stores across the country,” FDA Principal Deputy Commissioner Amy P. Abernethy, MD, PhD, said in the release. “It’s important that consumers understand that the FDA has only approved one drug containing CBD as an ingredient [Epidiolex]. These other, unapproved, CBD products may have dangerous health impacts and side effects. We remain focused on exploring potential pathways for CBD products to be lawfully marketed while also educating the public about these outstanding questions of CBD’s safety. Meanwhile, we will continue to monitor and take action, as needed, against companies that unlawfully market their products – prioritizing those that pose a risk to public health.”

The specific products from Santa Ana, Calif.–based Honest Globe that the FDA called unapproved new drugs and misbranded under the Federal Food, Drug, and Cosmetic Act included Elixicure Original Pain Relief and Elixicure Lavender Pain Relief, both of which were described as containing CBD. Products from Grand Rapids, Mich.–based BioLyte Laboratories LLC that the FDA similarly cited for violations included Silver Gel, Silver Gel with Aloe, Silver Liquid Supplement, Therapeutic Pain Gel, Pain Relief Cream, and Magnesium Oil Spray.

The agency has asked the two companies to respond to its letters within 15 working days, “stating how they will address these violations or providing their reasoning and supporting information as to why they believe these products are not in violation of the law. Failure to adequately address the violations promptly may result in legal action, including product seizure and/or injunction.”

[email protected]

Memantine (aka Namenda) is Food and Drug Administration–approved for Alzheimer’s disease, though its benefits are modest, at best.

It’s also, 18 years after first coming to market, relatively inexpensive.

I occasionally use it off label, as neurologists tend to do with a wide variety of medications. There are small studies that suggest it’s effective for migraine prevention and painful neuropathies. It also has a relatively benign side-effect profile.

As a result, once in a while I prescribe it for migraines or neuropathy where more typical agents haven’t helped. Like any of these drugs, sometimes it works, sometimes it doesn’t. A lot of neurology, as one of my colleagues puts it, is “guessing and voodoo.”

Since I’ve started this, however, I’ve noticed an unusual, and somewhat scary, side effect – one that has nothing to do the drug reactions.

While I don’t use any type of commercial chart system, most doctors in my area do, as well as all the hospitals. So I often see my patients’ notes from their general practitioners or after they’ve been in the hospital for whatever reason.

Those notes often list – as they should – current medications. Which includes the memantine I’ve prescribed.

But in the patient problem list I often then see “Alzheimer’s disease” or “dementia” show up, even in people who clearly have no history of such.

I’ve seen it way too many times to think it’s an accident. So one of two things is happening:

1. The computer chart system, when it sees “memantine” entered, searches its database, finds what it’s FDA-approved for, and automatically puts that in a list of current diagnoses.

2. The person entering the data, upon hearing the patient takes memantine, just enters the more commonly used indication as well, without bothering to ask the patient why they’re taking it.

Neither of these is good.

At the very least, they show a lack of proper history taking (or interest in doing so) by the person entering things in the chart (which these days could be someone with no medical training at all). It doesn’t take that much effort to say “what are you on this for?” I do it several times a day. It’s part of my job.

It’s bad form for any incorrect diagnosis to get into a chart. It can have serious repercussions on someone’s ability to get health, disability, or life insurance, not to mention the immediate impact on their care when that shows up. Someone who doesn’t know the patient opens the chart and immediately assumes it’s what they’ve got. I mean, it’s the chart. People treat it like it’s infallible and inviolable.

Once something is in a chart, it’s impossible to get it out. This isn’t a new issue – I trained at the VA when sometimes an H&P simply said “see old chart” and there were four volumes of it. But now, in the age of digital records, entries are forever. The toe you fractured surfing 8 years ago still shows up as a “current problem,” and will likely follow you to the grave. The same with any other diagnosis entered – it’s yours to keep, regardless of accuracy.

Medicine, like life, is mostly gray. But computers, and many times those who enter their data, only see things as black and white. In this field that’s liable to backfire. I’m just seeing the tip of the iceberg by using memantine off-label.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Memantine (aka Namenda) is Food and Drug Administration–approved for Alzheimer’s disease, though its benefits are modest, at best.

It’s also, 18 years after first coming to market, relatively inexpensive.

I occasionally use it off label, as neurologists tend to do with a wide variety of medications. There are small studies that suggest it’s effective for migraine prevention and painful neuropathies. It also has a relatively benign side-effect profile.

As a result, once in a while I prescribe it for migraines or neuropathy where more typical agents haven’t helped. Like any of these drugs, sometimes it works, sometimes it doesn’t. A lot of neurology, as one of my colleagues puts it, is “guessing and voodoo.”

Since I’ve started this, however, I’ve noticed an unusual, and somewhat scary, side effect – one that has nothing to do the drug reactions.

While I don’t use any type of commercial chart system, most doctors in my area do, as well as all the hospitals. So I often see my patients’ notes from their general practitioners or after they’ve been in the hospital for whatever reason.

Those notes often list – as they should – current medications. Which includes the memantine I’ve prescribed.

But in the patient problem list I often then see “Alzheimer’s disease” or “dementia” show up, even in people who clearly have no history of such.

I’ve seen it way too many times to think it’s an accident. So one of two things is happening:

1. The computer chart system, when it sees “memantine” entered, searches its database, finds what it’s FDA-approved for, and automatically puts that in a list of current diagnoses.

2. The person entering the data, upon hearing the patient takes memantine, just enters the more commonly used indication as well, without bothering to ask the patient why they’re taking it.

Neither of these is good.

At the very least, they show a lack of proper history taking (or interest in doing so) by the person entering things in the chart (which these days could be someone with no medical training at all). It doesn’t take that much effort to say “what are you on this for?” I do it several times a day. It’s part of my job.

It’s bad form for any incorrect diagnosis to get into a chart. It can have serious repercussions on someone’s ability to get health, disability, or life insurance, not to mention the immediate impact on their care when that shows up. Someone who doesn’t know the patient opens the chart and immediately assumes it’s what they’ve got. I mean, it’s the chart. People treat it like it’s infallible and inviolable.

Once something is in a chart, it’s impossible to get it out. This isn’t a new issue – I trained at the VA when sometimes an H&P simply said “see old chart” and there were four volumes of it. But now, in the age of digital records, entries are forever. The toe you fractured surfing 8 years ago still shows up as a “current problem,” and will likely follow you to the grave. The same with any other diagnosis entered – it’s yours to keep, regardless of accuracy.

Medicine, like life, is mostly gray. But computers, and many times those who enter their data, only see things as black and white. In this field that’s liable to backfire. I’m just seeing the tip of the iceberg by using memantine off-label.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Memantine (aka Namenda) is Food and Drug Administration–approved for Alzheimer’s disease, though its benefits are modest, at best.

It’s also, 18 years after first coming to market, relatively inexpensive.

I occasionally use it off label, as neurologists tend to do with a wide variety of medications. There are small studies that suggest it’s effective for migraine prevention and painful neuropathies. It also has a relatively benign side-effect profile.

As a result, once in a while I prescribe it for migraines or neuropathy where more typical agents haven’t helped. Like any of these drugs, sometimes it works, sometimes it doesn’t. A lot of neurology, as one of my colleagues puts it, is “guessing and voodoo.”

Since I’ve started this, however, I’ve noticed an unusual, and somewhat scary, side effect – one that has nothing to do the drug reactions.

While I don’t use any type of commercial chart system, most doctors in my area do, as well as all the hospitals. So I often see my patients’ notes from their general practitioners or after they’ve been in the hospital for whatever reason.

Those notes often list – as they should – current medications. Which includes the memantine I’ve prescribed.

But in the patient problem list I often then see “Alzheimer’s disease” or “dementia” show up, even in people who clearly have no history of such.

I’ve seen it way too many times to think it’s an accident. So one of two things is happening:

1. The computer chart system, when it sees “memantine” entered, searches its database, finds what it’s FDA-approved for, and automatically puts that in a list of current diagnoses.

2. The person entering the data, upon hearing the patient takes memantine, just enters the more commonly used indication as well, without bothering to ask the patient why they’re taking it.

Neither of these is good.

At the very least, they show a lack of proper history taking (or interest in doing so) by the person entering things in the chart (which these days could be someone with no medical training at all). It doesn’t take that much effort to say “what are you on this for?” I do it several times a day. It’s part of my job.

It’s bad form for any incorrect diagnosis to get into a chart. It can have serious repercussions on someone’s ability to get health, disability, or life insurance, not to mention the immediate impact on their care when that shows up. Someone who doesn’t know the patient opens the chart and immediately assumes it’s what they’ve got. I mean, it’s the chart. People treat it like it’s infallible and inviolable.

Once something is in a chart, it’s impossible to get it out. This isn’t a new issue – I trained at the VA when sometimes an H&P simply said “see old chart” and there were four volumes of it. But now, in the age of digital records, entries are forever. The toe you fractured surfing 8 years ago still shows up as a “current problem,” and will likely follow you to the grave. The same with any other diagnosis entered – it’s yours to keep, regardless of accuracy.

Medicine, like life, is mostly gray. But computers, and many times those who enter their data, only see things as black and white. In this field that’s liable to backfire. I’m just seeing the tip of the iceberg by using memantine off-label.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

The new SARS-CoV-2 variants are not just problems for humans. 

New research shows they can also infect animals, and for the first time, variants have been able to infect mice, a development that may complicate efforts to rein in the global spread of the virus.

In addition, two new studies have implications for pets. Veterinarians in Texas and the United Kingdom have documented infections of B.1.1.7 – the fast-spreading variant first found in the United Kingdom – in dogs and cats. The animals in the U.K. study also had heart damage, but it’s unclear if the damage was caused by the virus or was already there and was found as a result of their infections.

Animal studies of SARS-CoV-2 and its emerging variants are urgent, said Sarah Hamer, DVM, PhD, a veterinarian and epidemiologist at Texas A&M University, College Station. 

She’s part of a network of scientists who are swabbing the pets of people who are diagnosed with COVID-19 to find out how often the virus passes from people to animals.

The collaboration is part of the One Health initiative through the Centers for Disease Control and Prevention. One Health aims to tackle infectious diseases by recognizing that people can’t be fully protected from pathogens unless animals and the environment are also safeguarded. “Over 70% of emerging diseases of humans have their origins in animal populations,” Dr. Hamer said. “So if we are only focusing on studying disease as it emerges in humans and ignoring where those pathogens have been transmitted or circulating for years, then we might miss the ability to detect early emergence. We might miss the ability to control these diseases before they become problems for human health.”
 

Variants move to mice

In new work, researchers at the Institut Pasteur in Paris have shown that the B.1.351 and P.1 variants of concern, which were first identified in South Africa and Brazil, respectively, can infect mice, giving the virus a potential new host. Older versions of the virus couldn’t infect mice because they weren’t able bind to receptors on their cells. These two variants can.

On one hand, that’s a good thing, because it will help scientists more easily conduct experiments in mice. Before, if they wanted to do an experiment with SARS-CoV-2 in mice, they had to use a special strain of mouse that was bred to carry human ACE2 receptors on their lung cells. Now that mice can become naturally infected, any breed will do, making it less costly and time-consuming to study the virus in animals.

On the other hand, the idea that the virus could have more and different ways to spread isn’t good news.

“From the beginning of the epidemic and since human coronaviruses emerged from animals, it has been very important to establish in which species the virus can replicate, in particular the species that live close to humans,” said Xavier Montagutelli, DVM, PhD, head of the Mouse Genetics Laboratory at the Institut Pasteur. His study was published as a preprint ahead of peer review on BioRXIV.

Once a virus establishes itself within a population of animals, it will continue to spread and change and may eventually be passed back to humans. It’s the reason that birds and pigs are closely monitored for influenza viruses.

So far, with SARS-CoV-2, only one animal has been found to catch and spread the virus and pass it back to people – farmed mink. Researchers have also documented SARS-CoV-2 antibodies in escaped mink living near mink farms in Utah, suggesting the virus has the potential to be transmitted to wild populations.

And the move of the virus into mice suggests that SARS-CoV-2 could establish itself in a population of wild animals that live close to humans.

“At this point, we have no evidence that wild mice are infected, or can become infected from humans,” Dr. Montagutelli said. He added that his findings emphasize the need to regularly test animals for signs of the infection. He said these surveys will need to be updated as more variants emerge.

“So far, we’ve been lucky that our livestock species aren’t really susceptible to this,” said Scott Weese, DVM, a professor at Ontario Veterinary College at the University of Guelph, who studies emerging infectious diseases that pass between animals and people.

While the outbreaks on mink farms have been bad, imagine what would happen, Dr. Weese said, if the virus moved to pigs.

“If this infects a barn with a few thousand pigs – which is like the mink scenario – but we have a lot more pig farms than mink farms,” he said.

“With these variants, we have to reset,” he said. “We’ve figured all this about animals and how it spreads or how it doesn’t, but now we need to repeat all those studies to make sure it’s the same thing.”
 

Pets catch variants, too

Pets living with people who are infected with SARS-CoV-2 can catch it from their owners, and cats are particularly susceptible, Dr. Weese said. 

Contact tracing studies, which also tested animals for signs of the virus, have found that about half of cats living with infected people have signs of infection, while 20%-30% of dogs were sick.

“It’s quite common,” for pets to get COVID, Dr. Weese said.

Now, two new studies have shown that pets can also be infected by the newer B.1.1.7 variant.

The first study, from researchers at Texas A&M, documented the variant in a dog and a cat from Brazos County, Texas. Neither the older black Lab mix or the older domestic shorthair cat had symptoms of COVID-19. They were tested as part of a project funded by the CDC.

Dr. Weese said pets are at risk by people who are infected, but they don’t seem to play a big role in spreading the disease to humans. So if you have pets, there’s no reason to worry that they could bring the virus home to you. You’re more likely to be a risk to them.

The second study, from a specialty animal hospital in southeast England, documented infection by the B.1.1.7 virus variant in 11 dogs and cats. Most of the pets had unusual symptoms, including inflamed hearts and heart damage.

Dr. Weese called this study interesting and said its findings deserve more investigation, but pointed out that the study can’t determine whether the infection caused the heart damage, or whether it was already there.

“This is a human virus. There’s no doubt about it. It can affect other species, but it likes people a lot better,” he said. “If you think about the big picture and what is the potential role of animals, pets are pretty low risk.”
 

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

The new SARS-CoV-2 variants are not just problems for humans. 

New research shows they can also infect animals, and for the first time, variants have been able to infect mice, a development that may complicate efforts to rein in the global spread of the virus.

In addition, two new studies have implications for pets. Veterinarians in Texas and the United Kingdom have documented infections of B.1.1.7 – the fast-spreading variant first found in the United Kingdom – in dogs and cats. The animals in the U.K. study also had heart damage, but it’s unclear if the damage was caused by the virus or was already there and was found as a result of their infections.

Animal studies of SARS-CoV-2 and its emerging variants are urgent, said Sarah Hamer, DVM, PhD, a veterinarian and epidemiologist at Texas A&M University, College Station. 

She’s part of a network of scientists who are swabbing the pets of people who are diagnosed with COVID-19 to find out how often the virus passes from people to animals.

The collaboration is part of the One Health initiative through the Centers for Disease Control and Prevention. One Health aims to tackle infectious diseases by recognizing that people can’t be fully protected from pathogens unless animals and the environment are also safeguarded. “Over 70% of emerging diseases of humans have their origins in animal populations,” Dr. Hamer said. “So if we are only focusing on studying disease as it emerges in humans and ignoring where those pathogens have been transmitted or circulating for years, then we might miss the ability to detect early emergence. We might miss the ability to control these diseases before they become problems for human health.”
 

Variants move to mice

In new work, researchers at the Institut Pasteur in Paris have shown that the B.1.351 and P.1 variants of concern, which were first identified in South Africa and Brazil, respectively, can infect mice, giving the virus a potential new host. Older versions of the virus couldn’t infect mice because they weren’t able bind to receptors on their cells. These two variants can.

On one hand, that’s a good thing, because it will help scientists more easily conduct experiments in mice. Before, if they wanted to do an experiment with SARS-CoV-2 in mice, they had to use a special strain of mouse that was bred to carry human ACE2 receptors on their lung cells. Now that mice can become naturally infected, any breed will do, making it less costly and time-consuming to study the virus in animals.

On the other hand, the idea that the virus could have more and different ways to spread isn’t good news.

“From the beginning of the epidemic and since human coronaviruses emerged from animals, it has been very important to establish in which species the virus can replicate, in particular the species that live close to humans,” said Xavier Montagutelli, DVM, PhD, head of the Mouse Genetics Laboratory at the Institut Pasteur. His study was published as a preprint ahead of peer review on BioRXIV.

Once a virus establishes itself within a population of animals, it will continue to spread and change and may eventually be passed back to humans. It’s the reason that birds and pigs are closely monitored for influenza viruses.

So far, with SARS-CoV-2, only one animal has been found to catch and spread the virus and pass it back to people – farmed mink. Researchers have also documented SARS-CoV-2 antibodies in escaped mink living near mink farms in Utah, suggesting the virus has the potential to be transmitted to wild populations.

And the move of the virus into mice suggests that SARS-CoV-2 could establish itself in a population of wild animals that live close to humans.

“At this point, we have no evidence that wild mice are infected, or can become infected from humans,” Dr. Montagutelli said. He added that his findings emphasize the need to regularly test animals for signs of the infection. He said these surveys will need to be updated as more variants emerge.

“So far, we’ve been lucky that our livestock species aren’t really susceptible to this,” said Scott Weese, DVM, a professor at Ontario Veterinary College at the University of Guelph, who studies emerging infectious diseases that pass between animals and people.

While the outbreaks on mink farms have been bad, imagine what would happen, Dr. Weese said, if the virus moved to pigs.

“If this infects a barn with a few thousand pigs – which is like the mink scenario – but we have a lot more pig farms than mink farms,” he said.

“With these variants, we have to reset,” he said. “We’ve figured all this about animals and how it spreads or how it doesn’t, but now we need to repeat all those studies to make sure it’s the same thing.”
 

Pets catch variants, too

Pets living with people who are infected with SARS-CoV-2 can catch it from their owners, and cats are particularly susceptible, Dr. Weese said. 

Contact tracing studies, which also tested animals for signs of the virus, have found that about half of cats living with infected people have signs of infection, while 20%-30% of dogs were sick.

“It’s quite common,” for pets to get COVID, Dr. Weese said.

Now, two new studies have shown that pets can also be infected by the newer B.1.1.7 variant.

The first study, from researchers at Texas A&M, documented the variant in a dog and a cat from Brazos County, Texas. Neither the older black Lab mix or the older domestic shorthair cat had symptoms of COVID-19. They were tested as part of a project funded by the CDC.

Dr. Weese said pets are at risk by people who are infected, but they don’t seem to play a big role in spreading the disease to humans. So if you have pets, there’s no reason to worry that they could bring the virus home to you. You’re more likely to be a risk to them.

The second study, from a specialty animal hospital in southeast England, documented infection by the B.1.1.7 virus variant in 11 dogs and cats. Most of the pets had unusual symptoms, including inflamed hearts and heart damage.

Dr. Weese called this study interesting and said its findings deserve more investigation, but pointed out that the study can’t determine whether the infection caused the heart damage, or whether it was already there.

“This is a human virus. There’s no doubt about it. It can affect other species, but it likes people a lot better,” he said. “If you think about the big picture and what is the potential role of animals, pets are pretty low risk.”
 

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

The new SARS-CoV-2 variants are not just problems for humans. 

New research shows they can also infect animals, and for the first time, variants have been able to infect mice, a development that may complicate efforts to rein in the global spread of the virus.

In addition, two new studies have implications for pets. Veterinarians in Texas and the United Kingdom have documented infections of B.1.1.7 – the fast-spreading variant first found in the United Kingdom – in dogs and cats. The animals in the U.K. study also had heart damage, but it’s unclear if the damage was caused by the virus or was already there and was found as a result of their infections.

Animal studies of SARS-CoV-2 and its emerging variants are urgent, said Sarah Hamer, DVM, PhD, a veterinarian and epidemiologist at Texas A&M University, College Station. 

She’s part of a network of scientists who are swabbing the pets of people who are diagnosed with COVID-19 to find out how often the virus passes from people to animals.

The collaboration is part of the One Health initiative through the Centers for Disease Control and Prevention. One Health aims to tackle infectious diseases by recognizing that people can’t be fully protected from pathogens unless animals and the environment are also safeguarded. “Over 70% of emerging diseases of humans have their origins in animal populations,” Dr. Hamer said. “So if we are only focusing on studying disease as it emerges in humans and ignoring where those pathogens have been transmitted or circulating for years, then we might miss the ability to detect early emergence. We might miss the ability to control these diseases before they become problems for human health.”
 

Variants move to mice

In new work, researchers at the Institut Pasteur in Paris have shown that the B.1.351 and P.1 variants of concern, which were first identified in South Africa and Brazil, respectively, can infect mice, giving the virus a potential new host. Older versions of the virus couldn’t infect mice because they weren’t able bind to receptors on their cells. These two variants can.

On one hand, that’s a good thing, because it will help scientists more easily conduct experiments in mice. Before, if they wanted to do an experiment with SARS-CoV-2 in mice, they had to use a special strain of mouse that was bred to carry human ACE2 receptors on their lung cells. Now that mice can become naturally infected, any breed will do, making it less costly and time-consuming to study the virus in animals.

On the other hand, the idea that the virus could have more and different ways to spread isn’t good news.

“From the beginning of the epidemic and since human coronaviruses emerged from animals, it has been very important to establish in which species the virus can replicate, in particular the species that live close to humans,” said Xavier Montagutelli, DVM, PhD, head of the Mouse Genetics Laboratory at the Institut Pasteur. His study was published as a preprint ahead of peer review on BioRXIV.

Once a virus establishes itself within a population of animals, it will continue to spread and change and may eventually be passed back to humans. It’s the reason that birds and pigs are closely monitored for influenza viruses.

So far, with SARS-CoV-2, only one animal has been found to catch and spread the virus and pass it back to people – farmed mink. Researchers have also documented SARS-CoV-2 antibodies in escaped mink living near mink farms in Utah, suggesting the virus has the potential to be transmitted to wild populations.

And the move of the virus into mice suggests that SARS-CoV-2 could establish itself in a population of wild animals that live close to humans.

“At this point, we have no evidence that wild mice are infected, or can become infected from humans,” Dr. Montagutelli said. He added that his findings emphasize the need to regularly test animals for signs of the infection. He said these surveys will need to be updated as more variants emerge.

“So far, we’ve been lucky that our livestock species aren’t really susceptible to this,” said Scott Weese, DVM, a professor at Ontario Veterinary College at the University of Guelph, who studies emerging infectious diseases that pass between animals and people.

While the outbreaks on mink farms have been bad, imagine what would happen, Dr. Weese said, if the virus moved to pigs.

“If this infects a barn with a few thousand pigs – which is like the mink scenario – but we have a lot more pig farms than mink farms,” he said.

“With these variants, we have to reset,” he said. “We’ve figured all this about animals and how it spreads or how it doesn’t, but now we need to repeat all those studies to make sure it’s the same thing.”
 

Pets catch variants, too

Pets living with people who are infected with SARS-CoV-2 can catch it from their owners, and cats are particularly susceptible, Dr. Weese said. 

Contact tracing studies, which also tested animals for signs of the virus, have found that about half of cats living with infected people have signs of infection, while 20%-30% of dogs were sick.

“It’s quite common,” for pets to get COVID, Dr. Weese said.

Now, two new studies have shown that pets can also be infected by the newer B.1.1.7 variant.

The first study, from researchers at Texas A&M, documented the variant in a dog and a cat from Brazos County, Texas. Neither the older black Lab mix or the older domestic shorthair cat had symptoms of COVID-19. They were tested as part of a project funded by the CDC.

Dr. Weese said pets are at risk by people who are infected, but they don’t seem to play a big role in spreading the disease to humans. So if you have pets, there’s no reason to worry that they could bring the virus home to you. You’re more likely to be a risk to them.

The second study, from a specialty animal hospital in southeast England, documented infection by the B.1.1.7 virus variant in 11 dogs and cats. Most of the pets had unusual symptoms, including inflamed hearts and heart damage.

Dr. Weese called this study interesting and said its findings deserve more investigation, but pointed out that the study can’t determine whether the infection caused the heart damage, or whether it was already there.

“This is a human virus. There’s no doubt about it. It can affect other species, but it likes people a lot better,” he said. “If you think about the big picture and what is the potential role of animals, pets are pretty low risk.”
 

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

New research underscores the importance of folic acid supplementation for pregnant women with epilepsy who are taking antiepileptic drugs (AEDs).

Dietary folate alone, even in the United States, where food is fortified with folic acid, is “not sufficient” to improve cognitive outcomes for children of women who take AEDs during pregnancy, the researchers report.

“We found that dietary folate was not related to outcomes,” study investigator Kimford Meador, MD, professor of neurology and neurologic sciences, Stanford (Calif.) University, told this news organization.

“Only when the mother was taking extra folate did we see an improvement in child outcomes,” he added.

The findings were published online Feb. 23 in Epilepsy and Behavior.
 

Cognitive boost

“Daily folate is recommended to women in the general populations to reduce congenital malformations,” Dr. Meador said. In addition, periconceptional use of folate has been shown in previous research to improve neurodevelopmental outcomes for children of mothers with epilepsy who are taking AEDs.

Whether folate-fortified food alone, without supplements, has any effect on cognitive outcomes in this population of children has not been examined previously.

To investigate, the researchers assessed 117 children from the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study, a prospective, observational study of women with epilepsy who were taking one of four AEDs: carbamazepine, lamotrigine, phenytoin, or valproate.

Results showed that dietary folate from fortified food alone, without supplements, had no significant impact on IQ at age 6 years among children with prenatal exposure to AEDs.

In contrast, use of periconceptual folate supplements was significantly associated with a 10-point higher IQ at age 6 in the adjusted analyses (95% confidence interval, 5.2-15.0; P < .001).

These six other nutrients from food and supplements had no significant association with IQ at age 6 years: vitamins C, D, and E, omega-3, gamma tocopherol, and vitamin B12.
 

Optimal dose unclear

The findings indicate that folates, including natural folate and folic acid, in food do not have positive cognitive effects for children of women with epilepsy who take AEDs, the researchers write.

Dr. Meador noted that the optimal dose of folic acid supplementation to provide a cognitive benefit remains unclear.

The U.S. Centers for Disease Control recommends 0.4 mg/d for the general population of women of childbearing age. In Europe, the recommendation is 1 mg/d.

“Higher doses are recommended if there is a personal or family history of spina bifida in prior pregnancies, but there is some concern that very high doses of folate may be detrimental,” Dr. Meador said.

For women with epilepsy, he would recommend “at least 1 mg/d and not more than 4 mg/d.”
 

Proves a point?

Commenting on the study for this news organization, Derek Chong, MD, vice chair of neurology and director of epilepsy at Lenox Hill Hospital, New York, said the finding that folate fortification of food alone is not adequate for women with epilepsy is “not groundbreaking” but does prove something previously thought.

“Folic acid is important for all women, but it does seem like folic acid may be even more important in the epilepsy population,” said Dr. Chong, who was not involved with the research.

He cautioned that the current analysis included only four medications, three of which are not used very often anymore.

“Lamotrigine is probably the most commonly used one now. It’s unfortunate that this study did not include Keppra [levetiracetam], which probably is the number one medication that we use now,” Dr. Chong said.

The research was supported by the National Institutes of Health. Dr. Meador and Dr. Chong have reported no relevant financial relationships.

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

New research underscores the importance of folic acid supplementation for pregnant women with epilepsy who are taking antiepileptic drugs (AEDs).

Dietary folate alone, even in the United States, where food is fortified with folic acid, is “not sufficient” to improve cognitive outcomes for children of women who take AEDs during pregnancy, the researchers report.

“We found that dietary folate was not related to outcomes,” study investigator Kimford Meador, MD, professor of neurology and neurologic sciences, Stanford (Calif.) University, told this news organization.

“Only when the mother was taking extra folate did we see an improvement in child outcomes,” he added.

The findings were published online Feb. 23 in Epilepsy and Behavior.
 

Cognitive boost

“Daily folate is recommended to women in the general populations to reduce congenital malformations,” Dr. Meador said. In addition, periconceptional use of folate has been shown in previous research to improve neurodevelopmental outcomes for children of mothers with epilepsy who are taking AEDs.

Whether folate-fortified food alone, without supplements, has any effect on cognitive outcomes in this population of children has not been examined previously.

To investigate, the researchers assessed 117 children from the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study, a prospective, observational study of women with epilepsy who were taking one of four AEDs: carbamazepine, lamotrigine, phenytoin, or valproate.

Results showed that dietary folate from fortified food alone, without supplements, had no significant impact on IQ at age 6 years among children with prenatal exposure to AEDs.

In contrast, use of periconceptual folate supplements was significantly associated with a 10-point higher IQ at age 6 in the adjusted analyses (95% confidence interval, 5.2-15.0; P < .001).

These six other nutrients from food and supplements had no significant association with IQ at age 6 years: vitamins C, D, and E, omega-3, gamma tocopherol, and vitamin B12.
 

Optimal dose unclear

The findings indicate that folates, including natural folate and folic acid, in food do not have positive cognitive effects for children of women with epilepsy who take AEDs, the researchers write.

Dr. Meador noted that the optimal dose of folic acid supplementation to provide a cognitive benefit remains unclear.

The U.S. Centers for Disease Control recommends 0.4 mg/d for the general population of women of childbearing age. In Europe, the recommendation is 1 mg/d.

“Higher doses are recommended if there is a personal or family history of spina bifida in prior pregnancies, but there is some concern that very high doses of folate may be detrimental,” Dr. Meador said.

For women with epilepsy, he would recommend “at least 1 mg/d and not more than 4 mg/d.”
 

Proves a point?

Commenting on the study for this news organization, Derek Chong, MD, vice chair of neurology and director of epilepsy at Lenox Hill Hospital, New York, said the finding that folate fortification of food alone is not adequate for women with epilepsy is “not groundbreaking” but does prove something previously thought.

“Folic acid is important for all women, but it does seem like folic acid may be even more important in the epilepsy population,” said Dr. Chong, who was not involved with the research.

He cautioned that the current analysis included only four medications, three of which are not used very often anymore.

“Lamotrigine is probably the most commonly used one now. It’s unfortunate that this study did not include Keppra [levetiracetam], which probably is the number one medication that we use now,” Dr. Chong said.

The research was supported by the National Institutes of Health. Dr. Meador and Dr. Chong have reported no relevant financial relationships.

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

New research underscores the importance of folic acid supplementation for pregnant women with epilepsy who are taking antiepileptic drugs (AEDs).

Dietary folate alone, even in the United States, where food is fortified with folic acid, is “not sufficient” to improve cognitive outcomes for children of women who take AEDs during pregnancy, the researchers report.

“We found that dietary folate was not related to outcomes,” study investigator Kimford Meador, MD, professor of neurology and neurologic sciences, Stanford (Calif.) University, told this news organization.

“Only when the mother was taking extra folate did we see an improvement in child outcomes,” he added.

The findings were published online Feb. 23 in Epilepsy and Behavior.
 

Cognitive boost

“Daily folate is recommended to women in the general populations to reduce congenital malformations,” Dr. Meador said. In addition, periconceptional use of folate has been shown in previous research to improve neurodevelopmental outcomes for children of mothers with epilepsy who are taking AEDs.

Whether folate-fortified food alone, without supplements, has any effect on cognitive outcomes in this population of children has not been examined previously.

To investigate, the researchers assessed 117 children from the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study, a prospective, observational study of women with epilepsy who were taking one of four AEDs: carbamazepine, lamotrigine, phenytoin, or valproate.

Results showed that dietary folate from fortified food alone, without supplements, had no significant impact on IQ at age 6 years among children with prenatal exposure to AEDs.

In contrast, use of periconceptual folate supplements was significantly associated with a 10-point higher IQ at age 6 in the adjusted analyses (95% confidence interval, 5.2-15.0; P < .001).

These six other nutrients from food and supplements had no significant association with IQ at age 6 years: vitamins C, D, and E, omega-3, gamma tocopherol, and vitamin B12.
 

Optimal dose unclear

The findings indicate that folates, including natural folate and folic acid, in food do not have positive cognitive effects for children of women with epilepsy who take AEDs, the researchers write.

Dr. Meador noted that the optimal dose of folic acid supplementation to provide a cognitive benefit remains unclear.

The U.S. Centers for Disease Control recommends 0.4 mg/d for the general population of women of childbearing age. In Europe, the recommendation is 1 mg/d.

“Higher doses are recommended if there is a personal or family history of spina bifida in prior pregnancies, but there is some concern that very high doses of folate may be detrimental,” Dr. Meador said.

For women with epilepsy, he would recommend “at least 1 mg/d and not more than 4 mg/d.”
 

Proves a point?

Commenting on the study for this news organization, Derek Chong, MD, vice chair of neurology and director of epilepsy at Lenox Hill Hospital, New York, said the finding that folate fortification of food alone is not adequate for women with epilepsy is “not groundbreaking” but does prove something previously thought.

“Folic acid is important for all women, but it does seem like folic acid may be even more important in the epilepsy population,” said Dr. Chong, who was not involved with the research.

He cautioned that the current analysis included only four medications, three of which are not used very often anymore.

“Lamotrigine is probably the most commonly used one now. It’s unfortunate that this study did not include Keppra [levetiracetam], which probably is the number one medication that we use now,” Dr. Chong said.

The research was supported by the National Institutes of Health. Dr. Meador and Dr. Chong have reported no relevant financial relationships.

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

For patients with dementia, cannabinoids may be a promising intervention for treating neuropsychiatric symptoms (NPS) and the refusing of food, new research suggests.

AndreyPopov/Getty Images

Results of a systematic literature review, presented at the 2021 meeting of the American Association for Geriatric Psychiatry, showed that cannabinoids were associated with reduced agitation, longer sleep, and lower NPS. They were also linked to increased meal consumption and weight gain.

Refusing food is a common problem for patients with dementia, often resulting in worsening sleep, agitation, and mood, study investigator Niraj Asthana, MD, a second-year resident in the department of psychiatry, University of California, San Diego, said in an interview. Dr. Asthana noted that certain cannabinoid analogues are now used to stimulate appetite for patients undergoing chemotherapy.
 

Filling a treatment gap

After years of legal and other problems affecting cannabinoid research, there is renewed interest in investigating its use for patients with dementia. Early evidence suggests that cannabinoids may also be beneficial for pain, sleep, and aggression.

The researchers noted that cannabinoids may be especially valuable in areas where there are currently limited therapies, including food refusal and NPS.

“Unfortunately, there are limited treatments available for food refusal, so we’re left with appetite stimulants and electroconvulsive therapy, and although atypical antipsychotics are commonly used to treat NPS, they’re associated with an increased risk of serious adverse events and mortality in older patients,” said Dr. Asthana.

Dr. Asthana and colleague Dan Sewell, MD, carried out a systematic literature review of relevant studies of the use of cannabinoids for dementia patients.

“We found there are lot of studies, but they’re small scale; I’d say the largest was probably about 50 patients, with most studies having 10-50 patients,” said Dr. Asthana. In part, this may be because, until very recently, research on cannabinoids was controversial.

To review the current literature on the potential applications of cannabinoids in the treatment of food refusal and NPS in dementia patients, the researchers conducted a literature review.

They identified 23 relevant studies of the use of synthetic cannabinoids, including dronabinol and nabilone, for dementia patients. These products contain tetrahydrocannabinol (THC), the main psychoactive compound in cannabis.
 

More research coming

Several studies showed that cannabinoid use was associated with reduced nighttime motor activity, improved sleep duration, reduced agitation, and lower Neuropsychiatric Inventory scores.

Several studies revealed a link between cannabinoids use and increased appetite and the consumption of more meals. One crossover placebo-controlled trial showed an overall increase in body weight among dementia patients who took dronabinol.

This suggests there might be something to the “colloquial cultural association between cannabinoids and the munchies,” said Dr. Asthana.

Possible mechanisms for the effects on appetite may be that cannabinoids increase levels of the hormone ghrelin, which is also known as the “hunger hormone,” and decrease leptin levels, a hormone that inhibits hunger. Dr. Asthana noted that, in these studies, the dose of THC was low and that overall, cannabinoids appeared to be safe.

“We found that, at least in these small-scale studies, cannabinoid analogues are well tolerated,” possibly because of the relatively low doses of THC, said Dr. Asthana. “They generally don’t seem to have a ton of side effects; they may make people a little sleepy, which is actually good, because these patents also have a lot of trouble sleeping.”

He noted that more recent research suggests cannabidiol oil may reduce agitation by up to 40%.

“Now that cannabis is losing a lot of its stigma, both culturally and in the scientific community, you’re seeing a lot of grant applications for clinical trials,” said Dr. Asthana. “I’m excited to see what we find in the next 5-10 years.”

In a comment, Kirsten Wilkins, MD, associate professor of psychiatry, Yale University, New Haven, Conn., who is also a geriatric psychiatrist at the Veterans Affairs Connecticut Health Care System, welcomed the new research in this area.

“With limited safe and effective treatments for food refusal and neuropsychiatric symptoms of dementia, Dr. Asthana and Dr. Sewell highlight the growing body of literature suggesting cannabinoids may be a novel treatment option,” she said.

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

For patients with dementia, cannabinoids may be a promising intervention for treating neuropsychiatric symptoms (NPS) and the refusing of food, new research suggests.

AndreyPopov/Getty Images

Results of a systematic literature review, presented at the 2021 meeting of the American Association for Geriatric Psychiatry, showed that cannabinoids were associated with reduced agitation, longer sleep, and lower NPS. They were also linked to increased meal consumption and weight gain.

Refusing food is a common problem for patients with dementia, often resulting in worsening sleep, agitation, and mood, study investigator Niraj Asthana, MD, a second-year resident in the department of psychiatry, University of California, San Diego, said in an interview. Dr. Asthana noted that certain cannabinoid analogues are now used to stimulate appetite for patients undergoing chemotherapy.
 

Filling a treatment gap

After years of legal and other problems affecting cannabinoid research, there is renewed interest in investigating its use for patients with dementia. Early evidence suggests that cannabinoids may also be beneficial for pain, sleep, and aggression.

The researchers noted that cannabinoids may be especially valuable in areas where there are currently limited therapies, including food refusal and NPS.

“Unfortunately, there are limited treatments available for food refusal, so we’re left with appetite stimulants and electroconvulsive therapy, and although atypical antipsychotics are commonly used to treat NPS, they’re associated with an increased risk of serious adverse events and mortality in older patients,” said Dr. Asthana.

Dr. Asthana and colleague Dan Sewell, MD, carried out a systematic literature review of relevant studies of the use of cannabinoids for dementia patients.

“We found there are lot of studies, but they’re small scale; I’d say the largest was probably about 50 patients, with most studies having 10-50 patients,” said Dr. Asthana. In part, this may be because, until very recently, research on cannabinoids was controversial.

To review the current literature on the potential applications of cannabinoids in the treatment of food refusal and NPS in dementia patients, the researchers conducted a literature review.

They identified 23 relevant studies of the use of synthetic cannabinoids, including dronabinol and nabilone, for dementia patients. These products contain tetrahydrocannabinol (THC), the main psychoactive compound in cannabis.
 

More research coming

Several studies showed that cannabinoid use was associated with reduced nighttime motor activity, improved sleep duration, reduced agitation, and lower Neuropsychiatric Inventory scores.

Several studies revealed a link between cannabinoids use and increased appetite and the consumption of more meals. One crossover placebo-controlled trial showed an overall increase in body weight among dementia patients who took dronabinol.

This suggests there might be something to the “colloquial cultural association between cannabinoids and the munchies,” said Dr. Asthana.

Possible mechanisms for the effects on appetite may be that cannabinoids increase levels of the hormone ghrelin, which is also known as the “hunger hormone,” and decrease leptin levels, a hormone that inhibits hunger. Dr. Asthana noted that, in these studies, the dose of THC was low and that overall, cannabinoids appeared to be safe.

“We found that, at least in these small-scale studies, cannabinoid analogues are well tolerated,” possibly because of the relatively low doses of THC, said Dr. Asthana. “They generally don’t seem to have a ton of side effects; they may make people a little sleepy, which is actually good, because these patents also have a lot of trouble sleeping.”

He noted that more recent research suggests cannabidiol oil may reduce agitation by up to 40%.

“Now that cannabis is losing a lot of its stigma, both culturally and in the scientific community, you’re seeing a lot of grant applications for clinical trials,” said Dr. Asthana. “I’m excited to see what we find in the next 5-10 years.”

In a comment, Kirsten Wilkins, MD, associate professor of psychiatry, Yale University, New Haven, Conn., who is also a geriatric psychiatrist at the Veterans Affairs Connecticut Health Care System, welcomed the new research in this area.

“With limited safe and effective treatments for food refusal and neuropsychiatric symptoms of dementia, Dr. Asthana and Dr. Sewell highlight the growing body of literature suggesting cannabinoids may be a novel treatment option,” she said.

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

For patients with dementia, cannabinoids may be a promising intervention for treating neuropsychiatric symptoms (NPS) and the refusing of food, new research suggests.

AndreyPopov/Getty Images

Results of a systematic literature review, presented at the 2021 meeting of the American Association for Geriatric Psychiatry, showed that cannabinoids were associated with reduced agitation, longer sleep, and lower NPS. They were also linked to increased meal consumption and weight gain.

Refusing food is a common problem for patients with dementia, often resulting in worsening sleep, agitation, and mood, study investigator Niraj Asthana, MD, a second-year resident in the department of psychiatry, University of California, San Diego, said in an interview. Dr. Asthana noted that certain cannabinoid analogues are now used to stimulate appetite for patients undergoing chemotherapy.
 

Filling a treatment gap

After years of legal and other problems affecting cannabinoid research, there is renewed interest in investigating its use for patients with dementia. Early evidence suggests that cannabinoids may also be beneficial for pain, sleep, and aggression.

The researchers noted that cannabinoids may be especially valuable in areas where there are currently limited therapies, including food refusal and NPS.

“Unfortunately, there are limited treatments available for food refusal, so we’re left with appetite stimulants and electroconvulsive therapy, and although atypical antipsychotics are commonly used to treat NPS, they’re associated with an increased risk of serious adverse events and mortality in older patients,” said Dr. Asthana.

Dr. Asthana and colleague Dan Sewell, MD, carried out a systematic literature review of relevant studies of the use of cannabinoids for dementia patients.

“We found there are lot of studies, but they’re small scale; I’d say the largest was probably about 50 patients, with most studies having 10-50 patients,” said Dr. Asthana. In part, this may be because, until very recently, research on cannabinoids was controversial.

To review the current literature on the potential applications of cannabinoids in the treatment of food refusal and NPS in dementia patients, the researchers conducted a literature review.

They identified 23 relevant studies of the use of synthetic cannabinoids, including dronabinol and nabilone, for dementia patients. These products contain tetrahydrocannabinol (THC), the main psychoactive compound in cannabis.
 

More research coming

Several studies showed that cannabinoid use was associated with reduced nighttime motor activity, improved sleep duration, reduced agitation, and lower Neuropsychiatric Inventory scores.

Several studies revealed a link between cannabinoids use and increased appetite and the consumption of more meals. One crossover placebo-controlled trial showed an overall increase in body weight among dementia patients who took dronabinol.

This suggests there might be something to the “colloquial cultural association between cannabinoids and the munchies,” said Dr. Asthana.

Possible mechanisms for the effects on appetite may be that cannabinoids increase levels of the hormone ghrelin, which is also known as the “hunger hormone,” and decrease leptin levels, a hormone that inhibits hunger. Dr. Asthana noted that, in these studies, the dose of THC was low and that overall, cannabinoids appeared to be safe.

“We found that, at least in these small-scale studies, cannabinoid analogues are well tolerated,” possibly because of the relatively low doses of THC, said Dr. Asthana. “They generally don’t seem to have a ton of side effects; they may make people a little sleepy, which is actually good, because these patents also have a lot of trouble sleeping.”

He noted that more recent research suggests cannabidiol oil may reduce agitation by up to 40%.

“Now that cannabis is losing a lot of its stigma, both culturally and in the scientific community, you’re seeing a lot of grant applications for clinical trials,” said Dr. Asthana. “I’m excited to see what we find in the next 5-10 years.”

In a comment, Kirsten Wilkins, MD, associate professor of psychiatry, Yale University, New Haven, Conn., who is also a geriatric psychiatrist at the Veterans Affairs Connecticut Health Care System, welcomed the new research in this area.

“With limited safe and effective treatments for food refusal and neuropsychiatric symptoms of dementia, Dr. Asthana and Dr. Sewell highlight the growing body of literature suggesting cannabinoids may be a novel treatment option,” she said.

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

Patients with suspected large-vessel occlusion stroke who were taken directly to the angiography suite, bypassing the emergency department, received endovascular treatment faster and had better 90-day functional outcomes in a new study.

Results of the ANGIO-CAT trial were presented at the International Stroke Conference sponsored by the American Heart Association.

The study involved patients suspected of having a large-vessel occlusion, as assessed in the prehospital setting by paramedics using the Rapid Arterial Occlusion Evaluation (RACE) score.

In his presentation, Manuel Requena, PhD, a neurologist and neurointerventionalist fellow at Vall d’Hebron Hospital, Barcelona, explained that, if patients were within 6 hours of symptom onset with a RACE scale score greater than 4, paramedics called ahead to a stroke neurologist, who met the patient directly at the hospital.

If on clinical examination the National Institutes of Health Stroke Scale (NIHSS) score was greater than 10, patients could be enrolled into the study. Upon enrollment, they were randomly assigned either to be taken directly to the angiography suite or to receive standard care.
 

Bypassing the emergency department

Dr. Requena noted that, at his center, patients who receive standard care are transferred to the CT imaging suite, where they are evaluated with noncontrast CT and CT angiography. CT perfusion is also performed if the treating physician deems it necessary.

If a large-vessel occlusion is confirmed, patients are then transferred to the angiography suite for endovascular treatment. He added that in many centers, patients are evaluated in the ED before undergoing CT scanning.

Patients in the direct angiography group received a “flat-panel” noncontrast CT in the angiography suite to rule out intracranial hemorrhage or a large, established infarct. The large-vessel occlusion would be confirmed by arteriography before the endovascular procedure was performed.

After CT scanning, patients received thrombolysis as recommended in the guidelines.

The current interim analysis includes the 174 patients who have been enrolled so far in the study. The median RACE score for these patients was 7, and the median NIHSS score was 17. Large-vessel occlusion was confirmed in 84% of patients, and 8% had an intracerebral hemorrhage.

Results showed that of the 147 patients who received endovascular therapy, puncture time was shorter for those who were taken directly to angiography (median, 18 min vs. 42 min), as was time to reperfusion (median, 57 min vs. 84 min).

The primary outcome was a shift analysis of the Modified Rankin Scale functional outcome scale at 90 days (odds of 1-point improvement or more). In the direct angiography group, the adjusted odds ratio for an improved functional outcome was 2.2 (95% confidence interval, 1.2-.1).

There were no significant differences in safety endpoints. There was a trend toward more procedural complications in those receiving endovascular therapy in the direct angiography group (8.1% vs. 2.7%; P = .6), but there was also a trend toward lower 90-day mortality in this group (20.2% vs. 32.9%; P = .07)

Dr. Requena reported no significant difference in safety outcomes among those with a hemorrhagic stroke.

“Our study is the first clinical trial that shows the superiority of direct transfer to an angiography suite,” said Dr. Requena. “Our findings were close to what we expected, and we were surprised that they occurred so early in the study. We trust that they will be confirmed in ongoing, multicenter, international trials.”

Stroke patients who were transferred directly to an angiography suite were also less likely to be dependent on assistance with daily activities than were those who received the current standard of care, Dr. Requena said. “More frequent and more rapid treatment can help improve outcomes for our stroke patients.”

A limitation of this study is that the hospital had extensive experience with immediate angiography, so findings may differ at hospitals or care centers with less angiography expertise or experience, Dr. Requena said.

He added that retrospective studies conducted in hospitals in the United States, Germany, and Switzerland show that this kind of protocol can be developed in any high-volume stroke center, although multicenter, international trials are needed.
 

The cost of speed

Commenting on the ANGIO-CAT study, Michael Hill, MD, a professor at the University of Calgary (Alta.), said the 27-minute improvement in door-to-reperfusion time achieved in the study was meaningful and correlates with the degree of improved outcomes observed. “So, the improvement in speed of treatment resulting in better outcomes makes sense,” he added.

He cautioned that this strategy would only be feasible in certain centers with selected patients and that cost will be a fundamental issue.

“If you identify patients at angiography, you risk having some patients with no target large-vessel occlusion,” Dr. Hill added. “The real question is, how many of these patients without a large-vessel occlusion can the system tolerate before it becomes uneconomical and not fruitful or harmful, given that groin puncture is not totally harmless?”

The moderator of the ISC news conference on the study, Mitchell Elkind, MD, professor of neurology at Columbia University, New York, who is also president of the American Stroke Association, said the study reflects the growing recognition of the importance of speed when treating stroke. “If we can shorten time to treatment using rapid evaluation and imaging protocols, this will help save brain,” he said.

Also commenting on the study, Louisa McCullough, MD, PhD, chief of neurology at Memorial Hermann Hospital–Texas Medical Center, Houston, who is the ISC meeting chair, said she thought the study would be relevant to the United States. “Speed is really of the essence. Whenever we can reduce delays, that will make a big difference to patients.”

Referring to this study on improving hospital systems, as well as a second study that was presented at the meeting that showed benefits from delivery of prehospital thrombolysis via a mobile stroke unit, Dr. McCullough added that “we need to set up models so we can get the best of both these worlds. These studies are really leading the way on how we can change the stroke systems of care.”

The study was funded by Vall d’Hebron Research Institute. Dr. Requena disclosed no relevant financial relationships.

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

Patients with suspected large-vessel occlusion stroke who were taken directly to the angiography suite, bypassing the emergency department, received endovascular treatment faster and had better 90-day functional outcomes in a new study.

Results of the ANGIO-CAT trial were presented at the International Stroke Conference sponsored by the American Heart Association.

The study involved patients suspected of having a large-vessel occlusion, as assessed in the prehospital setting by paramedics using the Rapid Arterial Occlusion Evaluation (RACE) score.

In his presentation, Manuel Requena, PhD, a neurologist and neurointerventionalist fellow at Vall d’Hebron Hospital, Barcelona, explained that, if patients were within 6 hours of symptom onset with a RACE scale score greater than 4, paramedics called ahead to a stroke neurologist, who met the patient directly at the hospital.

If on clinical examination the National Institutes of Health Stroke Scale (NIHSS) score was greater than 10, patients could be enrolled into the study. Upon enrollment, they were randomly assigned either to be taken directly to the angiography suite or to receive standard care.
 

Bypassing the emergency department

Dr. Requena noted that, at his center, patients who receive standard care are transferred to the CT imaging suite, where they are evaluated with noncontrast CT and CT angiography. CT perfusion is also performed if the treating physician deems it necessary.

If a large-vessel occlusion is confirmed, patients are then transferred to the angiography suite for endovascular treatment. He added that in many centers, patients are evaluated in the ED before undergoing CT scanning.

Patients in the direct angiography group received a “flat-panel” noncontrast CT in the angiography suite to rule out intracranial hemorrhage or a large, established infarct. The large-vessel occlusion would be confirmed by arteriography before the endovascular procedure was performed.

After CT scanning, patients received thrombolysis as recommended in the guidelines.

The current interim analysis includes the 174 patients who have been enrolled so far in the study. The median RACE score for these patients was 7, and the median NIHSS score was 17. Large-vessel occlusion was confirmed in 84% of patients, and 8% had an intracerebral hemorrhage.

Results showed that of the 147 patients who received endovascular therapy, puncture time was shorter for those who were taken directly to angiography (median, 18 min vs. 42 min), as was time to reperfusion (median, 57 min vs. 84 min).

The primary outcome was a shift analysis of the Modified Rankin Scale functional outcome scale at 90 days (odds of 1-point improvement or more). In the direct angiography group, the adjusted odds ratio for an improved functional outcome was 2.2 (95% confidence interval, 1.2-.1).

There were no significant differences in safety endpoints. There was a trend toward more procedural complications in those receiving endovascular therapy in the direct angiography group (8.1% vs. 2.7%; P = .6), but there was also a trend toward lower 90-day mortality in this group (20.2% vs. 32.9%; P = .07)

Dr. Requena reported no significant difference in safety outcomes among those with a hemorrhagic stroke.

“Our study is the first clinical trial that shows the superiority of direct transfer to an angiography suite,” said Dr. Requena. “Our findings were close to what we expected, and we were surprised that they occurred so early in the study. We trust that they will be confirmed in ongoing, multicenter, international trials.”

Stroke patients who were transferred directly to an angiography suite were also less likely to be dependent on assistance with daily activities than were those who received the current standard of care, Dr. Requena said. “More frequent and more rapid treatment can help improve outcomes for our stroke patients.”

A limitation of this study is that the hospital had extensive experience with immediate angiography, so findings may differ at hospitals or care centers with less angiography expertise or experience, Dr. Requena said.

He added that retrospective studies conducted in hospitals in the United States, Germany, and Switzerland show that this kind of protocol can be developed in any high-volume stroke center, although multicenter, international trials are needed.
 

The cost of speed

Commenting on the ANGIO-CAT study, Michael Hill, MD, a professor at the University of Calgary (Alta.), said the 27-minute improvement in door-to-reperfusion time achieved in the study was meaningful and correlates with the degree of improved outcomes observed. “So, the improvement in speed of treatment resulting in better outcomes makes sense,” he added.

He cautioned that this strategy would only be feasible in certain centers with selected patients and that cost will be a fundamental issue.

“If you identify patients at angiography, you risk having some patients with no target large-vessel occlusion,” Dr. Hill added. “The real question is, how many of these patients without a large-vessel occlusion can the system tolerate before it becomes uneconomical and not fruitful or harmful, given that groin puncture is not totally harmless?”

The moderator of the ISC news conference on the study, Mitchell Elkind, MD, professor of neurology at Columbia University, New York, who is also president of the American Stroke Association, said the study reflects the growing recognition of the importance of speed when treating stroke. “If we can shorten time to treatment using rapid evaluation and imaging protocols, this will help save brain,” he said.

Also commenting on the study, Louisa McCullough, MD, PhD, chief of neurology at Memorial Hermann Hospital–Texas Medical Center, Houston, who is the ISC meeting chair, said she thought the study would be relevant to the United States. “Speed is really of the essence. Whenever we can reduce delays, that will make a big difference to patients.”

Referring to this study on improving hospital systems, as well as a second study that was presented at the meeting that showed benefits from delivery of prehospital thrombolysis via a mobile stroke unit, Dr. McCullough added that “we need to set up models so we can get the best of both these worlds. These studies are really leading the way on how we can change the stroke systems of care.”

The study was funded by Vall d’Hebron Research Institute. Dr. Requena disclosed no relevant financial relationships.

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

Patients with suspected large-vessel occlusion stroke who were taken directly to the angiography suite, bypassing the emergency department, received endovascular treatment faster and had better 90-day functional outcomes in a new study.

Results of the ANGIO-CAT trial were presented at the International Stroke Conference sponsored by the American Heart Association.

The study involved patients suspected of having a large-vessel occlusion, as assessed in the prehospital setting by paramedics using the Rapid Arterial Occlusion Evaluation (RACE) score.

In his presentation, Manuel Requena, PhD, a neurologist and neurointerventionalist fellow at Vall d’Hebron Hospital, Barcelona, explained that, if patients were within 6 hours of symptom onset with a RACE scale score greater than 4, paramedics called ahead to a stroke neurologist, who met the patient directly at the hospital.

If on clinical examination the National Institutes of Health Stroke Scale (NIHSS) score was greater than 10, patients could be enrolled into the study. Upon enrollment, they were randomly assigned either to be taken directly to the angiography suite or to receive standard care.
 

Bypassing the emergency department

Dr. Requena noted that, at his center, patients who receive standard care are transferred to the CT imaging suite, where they are evaluated with noncontrast CT and CT angiography. CT perfusion is also performed if the treating physician deems it necessary.

If a large-vessel occlusion is confirmed, patients are then transferred to the angiography suite for endovascular treatment. He added that in many centers, patients are evaluated in the ED before undergoing CT scanning.

Patients in the direct angiography group received a “flat-panel” noncontrast CT in the angiography suite to rule out intracranial hemorrhage or a large, established infarct. The large-vessel occlusion would be confirmed by arteriography before the endovascular procedure was performed.

After CT scanning, patients received thrombolysis as recommended in the guidelines.

The current interim analysis includes the 174 patients who have been enrolled so far in the study. The median RACE score for these patients was 7, and the median NIHSS score was 17. Large-vessel occlusion was confirmed in 84% of patients, and 8% had an intracerebral hemorrhage.

Results showed that of the 147 patients who received endovascular therapy, puncture time was shorter for those who were taken directly to angiography (median, 18 min vs. 42 min), as was time to reperfusion (median, 57 min vs. 84 min).

The primary outcome was a shift analysis of the Modified Rankin Scale functional outcome scale at 90 days (odds of 1-point improvement or more). In the direct angiography group, the adjusted odds ratio for an improved functional outcome was 2.2 (95% confidence interval, 1.2-.1).

There were no significant differences in safety endpoints. There was a trend toward more procedural complications in those receiving endovascular therapy in the direct angiography group (8.1% vs. 2.7%; P = .6), but there was also a trend toward lower 90-day mortality in this group (20.2% vs. 32.9%; P = .07)

Dr. Requena reported no significant difference in safety outcomes among those with a hemorrhagic stroke.

“Our study is the first clinical trial that shows the superiority of direct transfer to an angiography suite,” said Dr. Requena. “Our findings were close to what we expected, and we were surprised that they occurred so early in the study. We trust that they will be confirmed in ongoing, multicenter, international trials.”

Stroke patients who were transferred directly to an angiography suite were also less likely to be dependent on assistance with daily activities than were those who received the current standard of care, Dr. Requena said. “More frequent and more rapid treatment can help improve outcomes for our stroke patients.”

A limitation of this study is that the hospital had extensive experience with immediate angiography, so findings may differ at hospitals or care centers with less angiography expertise or experience, Dr. Requena said.

He added that retrospective studies conducted in hospitals in the United States, Germany, and Switzerland show that this kind of protocol can be developed in any high-volume stroke center, although multicenter, international trials are needed.
 

The cost of speed

Commenting on the ANGIO-CAT study, Michael Hill, MD, a professor at the University of Calgary (Alta.), said the 27-minute improvement in door-to-reperfusion time achieved in the study was meaningful and correlates with the degree of improved outcomes observed. “So, the improvement in speed of treatment resulting in better outcomes makes sense,” he added.

He cautioned that this strategy would only be feasible in certain centers with selected patients and that cost will be a fundamental issue.

“If you identify patients at angiography, you risk having some patients with no target large-vessel occlusion,” Dr. Hill added. “The real question is, how many of these patients without a large-vessel occlusion can the system tolerate before it becomes uneconomical and not fruitful or harmful, given that groin puncture is not totally harmless?”

The moderator of the ISC news conference on the study, Mitchell Elkind, MD, professor of neurology at Columbia University, New York, who is also president of the American Stroke Association, said the study reflects the growing recognition of the importance of speed when treating stroke. “If we can shorten time to treatment using rapid evaluation and imaging protocols, this will help save brain,” he said.

Also commenting on the study, Louisa McCullough, MD, PhD, chief of neurology at Memorial Hermann Hospital–Texas Medical Center, Houston, who is the ISC meeting chair, said she thought the study would be relevant to the United States. “Speed is really of the essence. Whenever we can reduce delays, that will make a big difference to patients.”

Referring to this study on improving hospital systems, as well as a second study that was presented at the meeting that showed benefits from delivery of prehospital thrombolysis via a mobile stroke unit, Dr. McCullough added that “we need to set up models so we can get the best of both these worlds. These studies are really leading the way on how we can change the stroke systems of care.”

The study was funded by Vall d’Hebron Research Institute. Dr. Requena disclosed no relevant financial relationships.

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

A noninvasive imaging method for identifying whether the source of a patient’s primary aldosteronism is from unilateral or bilateral adrenal adenomas worked as well as the standard method, invasive adrenal vein sampling, in a head-to-head comparison with 143 patients.

‘This is a first step.’

“This study is a first step. It will take lots more data for endocrinologists to buy into a scan over AVS,” commented David A. D’Alessio, MD, professor and chief of the division of endocrinology and metabolism at Duke University in Durham, N.C.

But Dr. D’Alessio also acknowledged the clear benefits from a safe and effective alternative to AVS.

“A reliable, less invasive, and less technical means of lateralizing excess aldosterone production would increase the number of people [with a unilateral PA source] going to surgery. The reality is that, if you are not a patient at the Mayo Clinic . . .or the National Institutes of Health, then AVS is a bit of crap shoot” that is very operator and institution dependent for its accuracy, Dr. D’Alessio said in an interview.

Metomidate specifically binds to key enzymes of the adrenal corticosteroid biosynthetic pathway, making it a precise targeting agent for a radioactive tag as documented almost a decade ago. One limitation is that this radiotracer labeling of metomidate has a 20-minute half life, which means it must be produced on site, thereby making the technology out of reach for locations that can’t set up this capability.

MATCHing imaging against AVS

To test the clinical utility of metomidate-based PET-CT directly against AVS, Dr. Wu and her associates enrolled 143 adults with confirmed PA and hypertension at two centers in London and one in Cambridge, England. The MATCH study cohort averaged 53 years of age; two-thirds were men, 58% were White, and 30% were Black. Their median blood pressure was 147/91 mm Hg, and they were maintained on a median of two antihypertensive drugs.

The researchers assessed every patient with both the imaging method and AVS, performed in random order and blindly scored. They then began each patient on a 1-month regimen with an MRA (usually spironolactone but eplerenone [Inspra] was also an option) to test the responsiveness of each patient’s hypertension to this drug class and to gauge their likely response to adrenalectomy. After the MRA test, the researchers assessed the lateralization tests and determined that 78 patients were appropriate candidates for unilateral adrenalectomy while the remaining 65 patients were not and continued on the MRA regimen. They recommended surgery if patients were clear positives by AVS, by PET-CT imaging, or both.

The study had four primary outcomes to assess the ability of the two diagnostic methods to predict the success of surgery based on four increasingly stringent postsurgical criteria calculated in hierarchical sequence: Partial or complete biochemical success, complete biochemical success, partial or complete clinical success (partial meaning any significant reduction in blood pressure), or complete clinical success (systolic pressure reduced to less than 135 mm Hg). Only one of the 78 patients treated with surgery failed to achieve at least a partial biochemical response.

SciePro/Shutterstock

Woefully low rates of PA assessment

But regardless of the success that PET-CT imaging has for identifying surgical candidates, the first step is to identify patients with PA, a diagnosis that’s woefully underperformed worldwide. One example: A separate report at ENDO 2021 retrospectively reviewed nearly 12,000 patients with hypertension and an indication of PA, such as treatment-resistant hypertension or early-onset hypertension, and managed at either of two university outpatient clinics in Michigan during 2010-2019. The report documented that 3% underwent PA assessment.

Diagnosis of patients with PA “is a major problem,” noted Dr. D’Alessio. “I think of PA as an underdiagnosed and undertreated condition, with a huge impact on morbidity and mortality. Any advance in this area is likely to be useful.” But, he added, “I’m dubious whether this [new imaging approach] will increase diagnosis of PA.” What’s needed is “getting more primary care physicians to do more screening” for PA among their patients with hypertension and a suggestion of a PA cause.

“Surgical cures are glamorous, but medical management is also very effective, and we have good, inexpensive drugs to do this,” the MRAs, Dr. D’Alessio said.

The study received no commercial funding. Dr. Wu and her coauthors had no disclosures. Dr. D’Alessio has been a speaker on behalf of Novo Nordisk, a consultant to Intarcia and Lilly, and has received research funding from Lilly and Merck.
 

[email protected]

A noninvasive imaging method for identifying whether the source of a patient’s primary aldosteronism is from unilateral or bilateral adrenal adenomas worked as well as the standard method, invasive adrenal vein sampling, in a head-to-head comparison with 143 patients.

‘This is a first step.’

“This study is a first step. It will take lots more data for endocrinologists to buy into a scan over AVS,” commented David A. D’Alessio, MD, professor and chief of the division of endocrinology and metabolism at Duke University in Durham, N.C.

But Dr. D’Alessio also acknowledged the clear benefits from a safe and effective alternative to AVS.

“A reliable, less invasive, and less technical means of lateralizing excess aldosterone production would increase the number of people [with a unilateral PA source] going to surgery. The reality is that, if you are not a patient at the Mayo Clinic . . .or the National Institutes of Health, then AVS is a bit of crap shoot” that is very operator and institution dependent for its accuracy, Dr. D’Alessio said in an interview.

Metomidate specifically binds to key enzymes of the adrenal corticosteroid biosynthetic pathway, making it a precise targeting agent for a radioactive tag as documented almost a decade ago. One limitation is that this radiotracer labeling of metomidate has a 20-minute half life, which means it must be produced on site, thereby making the technology out of reach for locations that can’t set up this capability.

MATCHing imaging against AVS

To test the clinical utility of metomidate-based PET-CT directly against AVS, Dr. Wu and her associates enrolled 143 adults with confirmed PA and hypertension at two centers in London and one in Cambridge, England. The MATCH study cohort averaged 53 years of age; two-thirds were men, 58% were White, and 30% were Black. Their median blood pressure was 147/91 mm Hg, and they were maintained on a median of two antihypertensive drugs.

The researchers assessed every patient with both the imaging method and AVS, performed in random order and blindly scored. They then began each patient on a 1-month regimen with an MRA (usually spironolactone but eplerenone [Inspra] was also an option) to test the responsiveness of each patient’s hypertension to this drug class and to gauge their likely response to adrenalectomy. After the MRA test, the researchers assessed the lateralization tests and determined that 78 patients were appropriate candidates for unilateral adrenalectomy while the remaining 65 patients were not and continued on the MRA regimen. They recommended surgery if patients were clear positives by AVS, by PET-CT imaging, or both.

The study had four primary outcomes to assess the ability of the two diagnostic methods to predict the success of surgery based on four increasingly stringent postsurgical criteria calculated in hierarchical sequence: Partial or complete biochemical success, complete biochemical success, partial or complete clinical success (partial meaning any significant reduction in blood pressure), or complete clinical success (systolic pressure reduced to less than 135 mm Hg). Only one of the 78 patients treated with surgery failed to achieve at least a partial biochemical response.

SciePro/Shutterstock

Woefully low rates of PA assessment

But regardless of the success that PET-CT imaging has for identifying surgical candidates, the first step is to identify patients with PA, a diagnosis that’s woefully underperformed worldwide. One example: A separate report at ENDO 2021 retrospectively reviewed nearly 12,000 patients with hypertension and an indication of PA, such as treatment-resistant hypertension or early-onset hypertension, and managed at either of two university outpatient clinics in Michigan during 2010-2019. The report documented that 3% underwent PA assessment.

Diagnosis of patients with PA “is a major problem,” noted Dr. D’Alessio. “I think of PA as an underdiagnosed and undertreated condition, with a huge impact on morbidity and mortality. Any advance in this area is likely to be useful.” But, he added, “I’m dubious whether this [new imaging approach] will increase diagnosis of PA.” What’s needed is “getting more primary care physicians to do more screening” for PA among their patients with hypertension and a suggestion of a PA cause.

“Surgical cures are glamorous, but medical management is also very effective, and we have good, inexpensive drugs to do this,” the MRAs, Dr. D’Alessio said.

The study received no commercial funding. Dr. Wu and her coauthors had no disclosures. Dr. D’Alessio has been a speaker on behalf of Novo Nordisk, a consultant to Intarcia and Lilly, and has received research funding from Lilly and Merck.
 

[email protected]

A noninvasive imaging method for identifying whether the source of a patient’s primary aldosteronism is from unilateral or bilateral adrenal adenomas worked as well as the standard method, invasive adrenal vein sampling, in a head-to-head comparison with 143 patients.

‘This is a first step.’

“This study is a first step. It will take lots more data for endocrinologists to buy into a scan over AVS,” commented David A. D’Alessio, MD, professor and chief of the division of endocrinology and metabolism at Duke University in Durham, N.C.

But Dr. D’Alessio also acknowledged the clear benefits from a safe and effective alternative to AVS.

“A reliable, less invasive, and less technical means of lateralizing excess aldosterone production would increase the number of people [with a unilateral PA source] going to surgery. The reality is that, if you are not a patient at the Mayo Clinic . . .or the National Institutes of Health, then AVS is a bit of crap shoot” that is very operator and institution dependent for its accuracy, Dr. D’Alessio said in an interview.

Metomidate specifically binds to key enzymes of the adrenal corticosteroid biosynthetic pathway, making it a precise targeting agent for a radioactive tag as documented almost a decade ago. One limitation is that this radiotracer labeling of metomidate has a 20-minute half life, which means it must be produced on site, thereby making the technology out of reach for locations that can’t set up this capability.

MATCHing imaging against AVS

To test the clinical utility of metomidate-based PET-CT directly against AVS, Dr. Wu and her associates enrolled 143 adults with confirmed PA and hypertension at two centers in London and one in Cambridge, England. The MATCH study cohort averaged 53 years of age; two-thirds were men, 58% were White, and 30% were Black. Their median blood pressure was 147/91 mm Hg, and they were maintained on a median of two antihypertensive drugs.

The researchers assessed every patient with both the imaging method and AVS, performed in random order and blindly scored. They then began each patient on a 1-month regimen with an MRA (usually spironolactone but eplerenone [Inspra] was also an option) to test the responsiveness of each patient’s hypertension to this drug class and to gauge their likely response to adrenalectomy. After the MRA test, the researchers assessed the lateralization tests and determined that 78 patients were appropriate candidates for unilateral adrenalectomy while the remaining 65 patients were not and continued on the MRA regimen. They recommended surgery if patients were clear positives by AVS, by PET-CT imaging, or both.

The study had four primary outcomes to assess the ability of the two diagnostic methods to predict the success of surgery based on four increasingly stringent postsurgical criteria calculated in hierarchical sequence: Partial or complete biochemical success, complete biochemical success, partial or complete clinical success (partial meaning any significant reduction in blood pressure), or complete clinical success (systolic pressure reduced to less than 135 mm Hg). Only one of the 78 patients treated with surgery failed to achieve at least a partial biochemical response.

SciePro/Shutterstock

Woefully low rates of PA assessment

But regardless of the success that PET-CT imaging has for identifying surgical candidates, the first step is to identify patients with PA, a diagnosis that’s woefully underperformed worldwide. One example: A separate report at ENDO 2021 retrospectively reviewed nearly 12,000 patients with hypertension and an indication of PA, such as treatment-resistant hypertension or early-onset hypertension, and managed at either of two university outpatient clinics in Michigan during 2010-2019. The report documented that 3% underwent PA assessment.

Diagnosis of patients with PA “is a major problem,” noted Dr. D’Alessio. “I think of PA as an underdiagnosed and undertreated condition, with a huge impact on morbidity and mortality. Any advance in this area is likely to be useful.” But, he added, “I’m dubious whether this [new imaging approach] will increase diagnosis of PA.” What’s needed is “getting more primary care physicians to do more screening” for PA among their patients with hypertension and a suggestion of a PA cause.

“Surgical cures are glamorous, but medical management is also very effective, and we have good, inexpensive drugs to do this,” the MRAs, Dr. D’Alessio said.

The study received no commercial funding. Dr. Wu and her coauthors had no disclosures. Dr. D’Alessio has been a speaker on behalf of Novo Nordisk, a consultant to Intarcia and Lilly, and has received research funding from Lilly and Merck.
 

[email protected]

The National Resident Matching Program (NRMP) announced March 19 that this year’s Main Residency Match was the largest in its history.

A total of 38,106 positions were offered, up 850 spots (2.3%) from 2020. Of those, 35,194 were first-year (PGY-1) positions, which was 928 more than the previous year (2.7%). A record 5,915 programs were part of the Match, 88 more than 2020.

“The application and recruitment cycle was upended as a result of the pandemic, yet the results of the Match continue to demonstrate strong and consistent outcomes for participants,” Donna L. Lamb, DHSc, MBA, BSN, NRMP president and CEO, said in a new release.

The report comes amid a year of Zoom interview fatigue, canceled testing, and virus fears and work-arounds, which the NMRP has never had to wrestle with since it was established in 1952.

Despite challenges, fill rates increased across the board. Of the 38,106 total positions offered, 36,179 were filled, representing a 2.6% increase over 2020. Of the 35,194 first-year positions available, 33,535 were filled, representing a 2.9% increase.

Those rates drove the percentage of all positions filled to 94.9% (up from 94.6%) and the percentage of PGY-1 positions filled to 94.8% (also up from 94.6%). There were 1,927 unfilled positions, a decline of 71 (3.6%) from 2020.
 

Primary care results strong

Of the first-year positions offered, 17,649 (49.6%) were in family medicine, internal medicine, and pediatrics. That’s an increase of 514 positions (3%) over 2020.

Of first-year positions offered in 2021, 16,860 (95.5%) were filled. U.S. seniors took 11,013 (65.3%) of those slots; that represents a slight decline (0.3%) from 2020. Family medicine saw a gain of 63 U.S. MD seniors who matched, and internal medicine saw a gain of 93 U.S. DO seniors who matched.
 

Some specialties filled all positions

PGY-1 specialties with 30 positions or more that filled all available positions include dermatology, medicine – emergency medicine, medicine – pediatrics, neurologic surgery, otolaryngology, integrated plastic surgery, and vascular surgery.*

PGY-1 specialties with 30 positions or more that filled more than 90% with U.S. seniors include dermatology (100%), medicine – emergency medicine (93.6%), medicine – pediatrics (93.5%), otolaryngology (93.2%), orthopedic surgery (92.8%), and integrated plastic surgery (90.4%).*

PGY-1 specialties with at least 30 positions that filled less than 50% with U.S. seniors include pathology (41.4 %) and surgery–preliminary (28%).

The number of U.S. citizen international medical graduates who submitted rank-ordered lists was 5,295, an increase of 128 (2.5%) over 2020 and the highest in 6 years; 3,152 of them matched to first-year positions, down two PGY-1 matched applicants over last year.

Full data are available on the NRMP’s website.

Correction, 3/22/21: An earlier version of this article misstated the affected specialties.

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

The National Resident Matching Program (NRMP) announced March 19 that this year’s Main Residency Match was the largest in its history.

A total of 38,106 positions were offered, up 850 spots (2.3%) from 2020. Of those, 35,194 were first-year (PGY-1) positions, which was 928 more than the previous year (2.7%). A record 5,915 programs were part of the Match, 88 more than 2020.

“The application and recruitment cycle was upended as a result of the pandemic, yet the results of the Match continue to demonstrate strong and consistent outcomes for participants,” Donna L. Lamb, DHSc, MBA, BSN, NRMP president and CEO, said in a new release.

The report comes amid a year of Zoom interview fatigue, canceled testing, and virus fears and work-arounds, which the NMRP has never had to wrestle with since it was established in 1952.

Despite challenges, fill rates increased across the board. Of the 38,106 total positions offered, 36,179 were filled, representing a 2.6% increase over 2020. Of the 35,194 first-year positions available, 33,535 were filled, representing a 2.9% increase.

Those rates drove the percentage of all positions filled to 94.9% (up from 94.6%) and the percentage of PGY-1 positions filled to 94.8% (also up from 94.6%). There were 1,927 unfilled positions, a decline of 71 (3.6%) from 2020.
 

Primary care results strong

Of the first-year positions offered, 17,649 (49.6%) were in family medicine, internal medicine, and pediatrics. That’s an increase of 514 positions (3%) over 2020.

Of first-year positions offered in 2021, 16,860 (95.5%) were filled. U.S. seniors took 11,013 (65.3%) of those slots; that represents a slight decline (0.3%) from 2020. Family medicine saw a gain of 63 U.S. MD seniors who matched, and internal medicine saw a gain of 93 U.S. DO seniors who matched.
 

Some specialties filled all positions

PGY-1 specialties with 30 positions or more that filled all available positions include dermatology, medicine – emergency medicine, medicine – pediatrics, neurologic surgery, otolaryngology, integrated plastic surgery, and vascular surgery.*

PGY-1 specialties with 30 positions or more that filled more than 90% with U.S. seniors include dermatology (100%), medicine – emergency medicine (93.6%), medicine – pediatrics (93.5%), otolaryngology (93.2%), orthopedic surgery (92.8%), and integrated plastic surgery (90.4%).*

PGY-1 specialties with at least 30 positions that filled less than 50% with U.S. seniors include pathology (41.4 %) and surgery–preliminary (28%).

The number of U.S. citizen international medical graduates who submitted rank-ordered lists was 5,295, an increase of 128 (2.5%) over 2020 and the highest in 6 years; 3,152 of them matched to first-year positions, down two PGY-1 matched applicants over last year.

Full data are available on the NRMP’s website.

Correction, 3/22/21: An earlier version of this article misstated the affected specialties.

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

The National Resident Matching Program (NRMP) announced March 19 that this year’s Main Residency Match was the largest in its history.

A total of 38,106 positions were offered, up 850 spots (2.3%) from 2020. Of those, 35,194 were first-year (PGY-1) positions, which was 928 more than the previous year (2.7%). A record 5,915 programs were part of the Match, 88 more than 2020.

“The application and recruitment cycle was upended as a result of the pandemic, yet the results of the Match continue to demonstrate strong and consistent outcomes for participants,” Donna L. Lamb, DHSc, MBA, BSN, NRMP president and CEO, said in a new release.

The report comes amid a year of Zoom interview fatigue, canceled testing, and virus fears and work-arounds, which the NMRP has never had to wrestle with since it was established in 1952.

Despite challenges, fill rates increased across the board. Of the 38,106 total positions offered, 36,179 were filled, representing a 2.6% increase over 2020. Of the 35,194 first-year positions available, 33,535 were filled, representing a 2.9% increase.

Those rates drove the percentage of all positions filled to 94.9% (up from 94.6%) and the percentage of PGY-1 positions filled to 94.8% (also up from 94.6%). There were 1,927 unfilled positions, a decline of 71 (3.6%) from 2020.
 

Primary care results strong

Of the first-year positions offered, 17,649 (49.6%) were in family medicine, internal medicine, and pediatrics. That’s an increase of 514 positions (3%) over 2020.

Of first-year positions offered in 2021, 16,860 (95.5%) were filled. U.S. seniors took 11,013 (65.3%) of those slots; that represents a slight decline (0.3%) from 2020. Family medicine saw a gain of 63 U.S. MD seniors who matched, and internal medicine saw a gain of 93 U.S. DO seniors who matched.
 

Some specialties filled all positions

PGY-1 specialties with 30 positions or more that filled all available positions include dermatology, medicine – emergency medicine, medicine – pediatrics, neurologic surgery, otolaryngology, integrated plastic surgery, and vascular surgery.*

PGY-1 specialties with 30 positions or more that filled more than 90% with U.S. seniors include dermatology (100%), medicine – emergency medicine (93.6%), medicine – pediatrics (93.5%), otolaryngology (93.2%), orthopedic surgery (92.8%), and integrated plastic surgery (90.4%).*

PGY-1 specialties with at least 30 positions that filled less than 50% with U.S. seniors include pathology (41.4 %) and surgery–preliminary (28%).

The number of U.S. citizen international medical graduates who submitted rank-ordered lists was 5,295, an increase of 128 (2.5%) over 2020 and the highest in 6 years; 3,152 of them matched to first-year positions, down two PGY-1 matched applicants over last year.

Full data are available on the NRMP’s website.

Correction, 3/22/21: An earlier version of this article misstated the affected specialties.

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

In January, as Mississippi health officials planned for their incoming shipments of COVID-19 vaccine, they assessed the state’s most vulnerable: health care workers, of course, and elderly people in nursing homes. But among those who needed urgent protection from the virus ripping across the Magnolia State were 1 million Mississippians with obesity.

Obesity and weight-related illnesses have been deadly liabilities in the COVID era. A report released this month by the World Obesity Federation found that increased body weight is the second-greatest predictor of COVID-related hospitalization and death across the globe, trailing only old age as a risk factor.

As a fixture of life in the American South – home to 9 of the nation’s 12 heaviest states – obesity is playing a role not only in COVID outcomes, but in the calculus of the vaccination rollout. Mississippi was one of the first states to add a body mass index of 30 or more (a rough gauge of obesity tied to height and weight) to the list of qualifying medical conditions for a shot. About 40% of the state’s adults meet that definition, according to federal health survey data, and combined with the risk group already eligible for vaccination – residents 65 and older – that means fully half of Mississippi’s adults are entitled to vie for a restricted allotment of shots.

At least 29 states have green-lighted obesity for inclusion in the first phases of the vaccine rollout, according to KFF – a vast widening of eligibility that has the potential to overwhelm government efforts and heighten competition for scarce doses.

“We have a lifesaving intervention, and we don’t have enough of it,” said Jen Kates, PhD, director of global health and HIV policy for Kaiser Family Foundation. “Hard choices are being made about who should go first, and there is no right answer.”

The sheer prevalence of obesity in the nation – two in three Americans exceed what is considered a healthy weight – was a public health concern well before the pandemic. But COVID-19 dramatically fast-tracked the discussion from warnings about the long-term damage excess fat tissue can pose to heart, lung and metabolic functions to far more immediate threats.

In the United Kingdom, for example, overweight COVID patients were 67% more likely to require intensive care, and obese patients three times likelier, according to the World Obesity Federation report. A Centers for Disease Control and Prevention study released Monday found a similar trend among U.S. patients and noted that the risk of COVID-related hospitalization, ventilation and death increased with patients’ obesity level.

The counties that hug the southern Mississippi River are home to some of the most concentrated pockets of extreme obesity in the United States. Coronavirus infections began surging in Southern states early last summer, and hospitalizations rose in step.

Deaths in rural stretches of Arkansas, Louisiana, Mississippi, and Tennessee have been overshadowed by the sheer number of deaths in metropolitan areas like New York, Los Angeles, and Essex County, N.J. But as a share of the population, the coronavirus has been similarly unsparing in many Southern communities. In sparsely populated Claiborne County, Miss., on the floodplains of the Mississippi River, 30 residents – about 1 in 300 – had died as of early March. In East Feliciana Parish, La., north of Baton Rouge, with 106 deaths, about 1 in 180 had died by then.

“It’s just math. If the population is more obese and obesity clearly contributes to worse outcomes, then neighborhoods, cities, states and countries that are more obese will have a greater toll from COVID,” said Dr. James de Lemos, MD, a professor of internal medicine at UT Southwestern Medical Center in Dallas who led a study of hospitalized COVID patients published in the medical journal Circulation.

And, because in the U.S. obesity rates tend to be relatively high among African Americans and Latinos who are poor, with diminished access to health care, “it’s a triple whammy,” Dr. de Lemos said. “All these things intersect.”

Poverty and limited access to medical care are common features in the South, where residents like Michelle Antonyshyn, a former registered nurse and mother of seven in Salem, Ark., say they are afraid of the virus. Ms. Antonyshyn, 49, has obesity and debilitating pain in her knees and back, though she does not have high blood pressure or diabetes, two underlying conditions that federal health officials have determined are added risk factors for severe cases of COVID-19.

Still, she said, she “was very concerned just knowing that being obese puts you more at risk for bad outcomes such as being on a ventilator and death.” As a precaution, Ms. Antonyshyn said, she and her large brood locked down early and stopped attending church services in person, watching online instead.

“It’s not the same as having fellowship, but the risk for me was enough,” said Ms. Antonyshyn.

Governors throughout the South seem to recognize that weight can contribute to COVID-19 complications and have pushed for vaccine eligibility rules that prioritize obesity. But on the ground, local health officials are girding for having to tell newly eligible people who qualify as obese that there aren’t enough shots to go around.

In Port Gibson, Miss., Mheja Williams, MD, medical director of the Claiborne County Family Health Center, has been receiving barely enough doses to inoculate the health workers and oldest seniors in her county of 9,600. One week in early February, she received 100 doses.

Obesity and extreme obesity are endemic in Claiborne County, and health officials say the “normalization” of obesity means people often don’t register their weight as a risk factor, whether for COVID or other health issues. The risks are exacerbated by a general flouting of pandemic etiquette: Dr. Williams said that middle-aged and younger residents are not especially vigilant about physical distancing and that mask use is rare.

The rise of obesity in the United States is well documented over the past half-century, as the nation turned from a diet of fruits, vegetables and limited meats to one laden with ultra-processed foods and rich with salt, fat, sugar, and flavorings, along with copious amounts of meat, fast food, and soda. The U.S. has generally led the global obesity race, setting records as even toddlers and young children grew implausibly, dangerously overweight.

Well before COVID, obesity was a leading cause of preventable death in the United States. The National Institutes of Health declared it a disease in 1998, one that fosters heart disease, stroke, type 2 diabetes, and breast, colon, and other cancers.

Researchers say it is no coincidence that nations like the United States, the United Kingdom, and Italy, with relatively high obesity rates, have proved particularly vulnerable to the novel coronavirus.

They believe the virus may exploit underlying metabolic and physiological impairments that often exist in concert with obesity. Extra fat can lead to a cascade of metabolic disruptions, chronic systemic inflammation, and hormonal dysregulation that may thwart the body’s response to infection.

Other respiratory viruses, like influenza and SARS, which appeared in China in 2002, rely on cholesterol to spread enveloped RNA virus to neighboring cells, and researchers have proposed that a similar mechanism may play a role in the spread of the novel coronavirus.

There are also practical problems for coronavirus patients with obesity admitted to the hospital. They can be more difficult to intubate because of excess central weight pressing down on the diaphragm, making breathing with infected lungs even more difficult.

Physicians who specialize in treating patients with obesity say public health officials need to be more forthright and urgent in their messaging, telegraphing the risks of this COVID era.

“It should be explicit and direct,” said Fatima Stanford, MD, an obesity medicine specialist at Massachusetts General Hospital, Boston, and a Harvard Medical School instructor.

Dr. Stanford denounces the fat-shaming and bullying that people with obesity often experience. But telling patients – and the public – that obesity increases the risk of hospitalization and death is crucial, she said.

“I don’t think it’s stigmatizing,” she said. “If you tell them in that way, it’s not to scare you, it’s just giving information. Sometimes people are just unaware.”



KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

In January, as Mississippi health officials planned for their incoming shipments of COVID-19 vaccine, they assessed the state’s most vulnerable: health care workers, of course, and elderly people in nursing homes. But among those who needed urgent protection from the virus ripping across the Magnolia State were 1 million Mississippians with obesity.

Obesity and weight-related illnesses have been deadly liabilities in the COVID era. A report released this month by the World Obesity Federation found that increased body weight is the second-greatest predictor of COVID-related hospitalization and death across the globe, trailing only old age as a risk factor.

As a fixture of life in the American South – home to 9 of the nation’s 12 heaviest states – obesity is playing a role not only in COVID outcomes, but in the calculus of the vaccination rollout. Mississippi was one of the first states to add a body mass index of 30 or more (a rough gauge of obesity tied to height and weight) to the list of qualifying medical conditions for a shot. About 40% of the state’s adults meet that definition, according to federal health survey data, and combined with the risk group already eligible for vaccination – residents 65 and older – that means fully half of Mississippi’s adults are entitled to vie for a restricted allotment of shots.

At least 29 states have green-lighted obesity for inclusion in the first phases of the vaccine rollout, according to KFF – a vast widening of eligibility that has the potential to overwhelm government efforts and heighten competition for scarce doses.

“We have a lifesaving intervention, and we don’t have enough of it,” said Jen Kates, PhD, director of global health and HIV policy for Kaiser Family Foundation. “Hard choices are being made about who should go first, and there is no right answer.”

The sheer prevalence of obesity in the nation – two in three Americans exceed what is considered a healthy weight – was a public health concern well before the pandemic. But COVID-19 dramatically fast-tracked the discussion from warnings about the long-term damage excess fat tissue can pose to heart, lung and metabolic functions to far more immediate threats.

In the United Kingdom, for example, overweight COVID patients were 67% more likely to require intensive care, and obese patients three times likelier, according to the World Obesity Federation report. A Centers for Disease Control and Prevention study released Monday found a similar trend among U.S. patients and noted that the risk of COVID-related hospitalization, ventilation and death increased with patients’ obesity level.

The counties that hug the southern Mississippi River are home to some of the most concentrated pockets of extreme obesity in the United States. Coronavirus infections began surging in Southern states early last summer, and hospitalizations rose in step.

Deaths in rural stretches of Arkansas, Louisiana, Mississippi, and Tennessee have been overshadowed by the sheer number of deaths in metropolitan areas like New York, Los Angeles, and Essex County, N.J. But as a share of the population, the coronavirus has been similarly unsparing in many Southern communities. In sparsely populated Claiborne County, Miss., on the floodplains of the Mississippi River, 30 residents – about 1 in 300 – had died as of early March. In East Feliciana Parish, La., north of Baton Rouge, with 106 deaths, about 1 in 180 had died by then.

“It’s just math. If the population is more obese and obesity clearly contributes to worse outcomes, then neighborhoods, cities, states and countries that are more obese will have a greater toll from COVID,” said Dr. James de Lemos, MD, a professor of internal medicine at UT Southwestern Medical Center in Dallas who led a study of hospitalized COVID patients published in the medical journal Circulation.

And, because in the U.S. obesity rates tend to be relatively high among African Americans and Latinos who are poor, with diminished access to health care, “it’s a triple whammy,” Dr. de Lemos said. “All these things intersect.”

Poverty and limited access to medical care are common features in the South, where residents like Michelle Antonyshyn, a former registered nurse and mother of seven in Salem, Ark., say they are afraid of the virus. Ms. Antonyshyn, 49, has obesity and debilitating pain in her knees and back, though she does not have high blood pressure or diabetes, two underlying conditions that federal health officials have determined are added risk factors for severe cases of COVID-19.

Still, she said, she “was very concerned just knowing that being obese puts you more at risk for bad outcomes such as being on a ventilator and death.” As a precaution, Ms. Antonyshyn said, she and her large brood locked down early and stopped attending church services in person, watching online instead.

“It’s not the same as having fellowship, but the risk for me was enough,” said Ms. Antonyshyn.

Governors throughout the South seem to recognize that weight can contribute to COVID-19 complications and have pushed for vaccine eligibility rules that prioritize obesity. But on the ground, local health officials are girding for having to tell newly eligible people who qualify as obese that there aren’t enough shots to go around.

In Port Gibson, Miss., Mheja Williams, MD, medical director of the Claiborne County Family Health Center, has been receiving barely enough doses to inoculate the health workers and oldest seniors in her county of 9,600. One week in early February, she received 100 doses.

Obesity and extreme obesity are endemic in Claiborne County, and health officials say the “normalization” of obesity means people often don’t register their weight as a risk factor, whether for COVID or other health issues. The risks are exacerbated by a general flouting of pandemic etiquette: Dr. Williams said that middle-aged and younger residents are not especially vigilant about physical distancing and that mask use is rare.

The rise of obesity in the United States is well documented over the past half-century, as the nation turned from a diet of fruits, vegetables and limited meats to one laden with ultra-processed foods and rich with salt, fat, sugar, and flavorings, along with copious amounts of meat, fast food, and soda. The U.S. has generally led the global obesity race, setting records as even toddlers and young children grew implausibly, dangerously overweight.

Well before COVID, obesity was a leading cause of preventable death in the United States. The National Institutes of Health declared it a disease in 1998, one that fosters heart disease, stroke, type 2 diabetes, and breast, colon, and other cancers.

Researchers say it is no coincidence that nations like the United States, the United Kingdom, and Italy, with relatively high obesity rates, have proved particularly vulnerable to the novel coronavirus.

They believe the virus may exploit underlying metabolic and physiological impairments that often exist in concert with obesity. Extra fat can lead to a cascade of metabolic disruptions, chronic systemic inflammation, and hormonal dysregulation that may thwart the body’s response to infection.

Other respiratory viruses, like influenza and SARS, which appeared in China in 2002, rely on cholesterol to spread enveloped RNA virus to neighboring cells, and researchers have proposed that a similar mechanism may play a role in the spread of the novel coronavirus.

There are also practical problems for coronavirus patients with obesity admitted to the hospital. They can be more difficult to intubate because of excess central weight pressing down on the diaphragm, making breathing with infected lungs even more difficult.

Physicians who specialize in treating patients with obesity say public health officials need to be more forthright and urgent in their messaging, telegraphing the risks of this COVID era.

“It should be explicit and direct,” said Fatima Stanford, MD, an obesity medicine specialist at Massachusetts General Hospital, Boston, and a Harvard Medical School instructor.

Dr. Stanford denounces the fat-shaming and bullying that people with obesity often experience. But telling patients – and the public – that obesity increases the risk of hospitalization and death is crucial, she said.

“I don’t think it’s stigmatizing,” she said. “If you tell them in that way, it’s not to scare you, it’s just giving information. Sometimes people are just unaware.”



KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

In January, as Mississippi health officials planned for their incoming shipments of COVID-19 vaccine, they assessed the state’s most vulnerable: health care workers, of course, and elderly people in nursing homes. But among those who needed urgent protection from the virus ripping across the Magnolia State were 1 million Mississippians with obesity.

Obesity and weight-related illnesses have been deadly liabilities in the COVID era. A report released this month by the World Obesity Federation found that increased body weight is the second-greatest predictor of COVID-related hospitalization and death across the globe, trailing only old age as a risk factor.

As a fixture of life in the American South – home to 9 of the nation’s 12 heaviest states – obesity is playing a role not only in COVID outcomes, but in the calculus of the vaccination rollout. Mississippi was one of the first states to add a body mass index of 30 or more (a rough gauge of obesity tied to height and weight) to the list of qualifying medical conditions for a shot. About 40% of the state’s adults meet that definition, according to federal health survey data, and combined with the risk group already eligible for vaccination – residents 65 and older – that means fully half of Mississippi’s adults are entitled to vie for a restricted allotment of shots.

At least 29 states have green-lighted obesity for inclusion in the first phases of the vaccine rollout, according to KFF – a vast widening of eligibility that has the potential to overwhelm government efforts and heighten competition for scarce doses.

“We have a lifesaving intervention, and we don’t have enough of it,” said Jen Kates, PhD, director of global health and HIV policy for Kaiser Family Foundation. “Hard choices are being made about who should go first, and there is no right answer.”

The sheer prevalence of obesity in the nation – two in three Americans exceed what is considered a healthy weight – was a public health concern well before the pandemic. But COVID-19 dramatically fast-tracked the discussion from warnings about the long-term damage excess fat tissue can pose to heart, lung and metabolic functions to far more immediate threats.

In the United Kingdom, for example, overweight COVID patients were 67% more likely to require intensive care, and obese patients three times likelier, according to the World Obesity Federation report. A Centers for Disease Control and Prevention study released Monday found a similar trend among U.S. patients and noted that the risk of COVID-related hospitalization, ventilation and death increased with patients’ obesity level.

The counties that hug the southern Mississippi River are home to some of the most concentrated pockets of extreme obesity in the United States. Coronavirus infections began surging in Southern states early last summer, and hospitalizations rose in step.

Deaths in rural stretches of Arkansas, Louisiana, Mississippi, and Tennessee have been overshadowed by the sheer number of deaths in metropolitan areas like New York, Los Angeles, and Essex County, N.J. But as a share of the population, the coronavirus has been similarly unsparing in many Southern communities. In sparsely populated Claiborne County, Miss., on the floodplains of the Mississippi River, 30 residents – about 1 in 300 – had died as of early March. In East Feliciana Parish, La., north of Baton Rouge, with 106 deaths, about 1 in 180 had died by then.

“It’s just math. If the population is more obese and obesity clearly contributes to worse outcomes, then neighborhoods, cities, states and countries that are more obese will have a greater toll from COVID,” said Dr. James de Lemos, MD, a professor of internal medicine at UT Southwestern Medical Center in Dallas who led a study of hospitalized COVID patients published in the medical journal Circulation.

And, because in the U.S. obesity rates tend to be relatively high among African Americans and Latinos who are poor, with diminished access to health care, “it’s a triple whammy,” Dr. de Lemos said. “All these things intersect.”

Poverty and limited access to medical care are common features in the South, where residents like Michelle Antonyshyn, a former registered nurse and mother of seven in Salem, Ark., say they are afraid of the virus. Ms. Antonyshyn, 49, has obesity and debilitating pain in her knees and back, though she does not have high blood pressure or diabetes, two underlying conditions that federal health officials have determined are added risk factors for severe cases of COVID-19.

Still, she said, she “was very concerned just knowing that being obese puts you more at risk for bad outcomes such as being on a ventilator and death.” As a precaution, Ms. Antonyshyn said, she and her large brood locked down early and stopped attending church services in person, watching online instead.

“It’s not the same as having fellowship, but the risk for me was enough,” said Ms. Antonyshyn.

Governors throughout the South seem to recognize that weight can contribute to COVID-19 complications and have pushed for vaccine eligibility rules that prioritize obesity. But on the ground, local health officials are girding for having to tell newly eligible people who qualify as obese that there aren’t enough shots to go around.

In Port Gibson, Miss., Mheja Williams, MD, medical director of the Claiborne County Family Health Center, has been receiving barely enough doses to inoculate the health workers and oldest seniors in her county of 9,600. One week in early February, she received 100 doses.

Obesity and extreme obesity are endemic in Claiborne County, and health officials say the “normalization” of obesity means people often don’t register their weight as a risk factor, whether for COVID or other health issues. The risks are exacerbated by a general flouting of pandemic etiquette: Dr. Williams said that middle-aged and younger residents are not especially vigilant about physical distancing and that mask use is rare.

The rise of obesity in the United States is well documented over the past half-century, as the nation turned from a diet of fruits, vegetables and limited meats to one laden with ultra-processed foods and rich with salt, fat, sugar, and flavorings, along with copious amounts of meat, fast food, and soda. The U.S. has generally led the global obesity race, setting records as even toddlers and young children grew implausibly, dangerously overweight.

Well before COVID, obesity was a leading cause of preventable death in the United States. The National Institutes of Health declared it a disease in 1998, one that fosters heart disease, stroke, type 2 diabetes, and breast, colon, and other cancers.

Researchers say it is no coincidence that nations like the United States, the United Kingdom, and Italy, with relatively high obesity rates, have proved particularly vulnerable to the novel coronavirus.

They believe the virus may exploit underlying metabolic and physiological impairments that often exist in concert with obesity. Extra fat can lead to a cascade of metabolic disruptions, chronic systemic inflammation, and hormonal dysregulation that may thwart the body’s response to infection.

Other respiratory viruses, like influenza and SARS, which appeared in China in 2002, rely on cholesterol to spread enveloped RNA virus to neighboring cells, and researchers have proposed that a similar mechanism may play a role in the spread of the novel coronavirus.

There are also practical problems for coronavirus patients with obesity admitted to the hospital. They can be more difficult to intubate because of excess central weight pressing down on the diaphragm, making breathing with infected lungs even more difficult.

Physicians who specialize in treating patients with obesity say public health officials need to be more forthright and urgent in their messaging, telegraphing the risks of this COVID era.

“It should be explicit and direct,” said Fatima Stanford, MD, an obesity medicine specialist at Massachusetts General Hospital, Boston, and a Harvard Medical School instructor.

Dr. Stanford denounces the fat-shaming and bullying that people with obesity often experience. But telling patients – and the public – that obesity increases the risk of hospitalization and death is crucial, she said.

“I don’t think it’s stigmatizing,” she said. “If you tell them in that way, it’s not to scare you, it’s just giving information. Sometimes people are just unaware.”



KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

In a summary of abstracts presented at the ACTRIMS Forum 2021, Dr. Mark Freedman shares that he and his colleagues found no apparent increased risk of COVID-19 with long-term use of interferon β-1a in patients with multiple sclerosis (MS).

Dr. Freedman also highlights several abstracts examining the use of cladribine and ocrelizumab in older patients with MS.

A post hoc analysis of lymphocyte subsets in the combined safety populations of CLARITY, CLARITY Extension, and ORACLE-MS found that by week 96, the effects of cladribine tablets 3.5 mg/kg on CD19+ B, CD4+ T, and CD8+ T lymphocytes in younger and older patients with MS were similar, with steady recovery following nadir.

Another study on younger and older patients treated with cladribine tablets 3.5 mg/kg found that around a quarter of both groups had transient periods of Grade ≥3 lymphopenia during the study, and the rate of certain infection-related treatment-emergent adverse events was higher in the older patients.

A single-center study found that 25% of patients in the older population stopped ocrelizumab, the most common reasons being disease progression and repeated or severe infections.

Lastly, an evaluation of older patients with progressive MS found no statistical difference in 2-year clinical endpoints for patients taking ocrelizumab compared to prior to anti-CD20 therapy.

--

Mark S. Freedman, MSc, MD is a Professor, Department of Neurology, University of Ottawa and The Ottawa Hospital Research Institute; and Director, Multiple Sclerosis Research Unit, The Ottawa Hospital–General Campus.

Mark S. Freedman, MSc, MD, has disclosed the following relevant financial relationships:

Serve(d) on the advisory board, board of directors, or other similar groups for: Actelion (Janssen/Johnson and Johnson); Alexion; Atara Biotherapeutics; Bayer Healthcare; Biogen Idec; Celgene; Clene Nanomedicine; GRI Bio; Hoffmann-La Roche; Magenta Therapeutics; Merck Serono; MedDay Pharmaceuticals; Novartis; Sanofi Genzyme; Teva Canada.

Serve(d) as a member of a speakers bureau for: Sanofi Genzyme; EMD Serono.

Received honoraria or consultation fees for: Actelion (Janssen/Johnson and Johnson); Alexion; Biogen Idec; Celgene (BMS); EMD Inc; Sanofi Genzyme; Hoffmann-La Roche; Merck Serono; Novartis; Teva Canada.

Received research or educational grants from: EMD Inc; Hoffmann-La Roche; Sanofi Genzyme Canada.

In a summary of abstracts presented at the ACTRIMS Forum 2021, Dr. Mark Freedman shares that he and his colleagues found no apparent increased risk of COVID-19 with long-term use of interferon β-1a in patients with multiple sclerosis (MS).

Dr. Freedman also highlights several abstracts examining the use of cladribine and ocrelizumab in older patients with MS.

A post hoc analysis of lymphocyte subsets in the combined safety populations of CLARITY, CLARITY Extension, and ORACLE-MS found that by week 96, the effects of cladribine tablets 3.5 mg/kg on CD19+ B, CD4+ T, and CD8+ T lymphocytes in younger and older patients with MS were similar, with steady recovery following nadir.

Another study on younger and older patients treated with cladribine tablets 3.5 mg/kg found that around a quarter of both groups had transient periods of Grade ≥3 lymphopenia during the study, and the rate of certain infection-related treatment-emergent adverse events was higher in the older patients.

A single-center study found that 25% of patients in the older population stopped ocrelizumab, the most common reasons being disease progression and repeated or severe infections.

Lastly, an evaluation of older patients with progressive MS found no statistical difference in 2-year clinical endpoints for patients taking ocrelizumab compared to prior to anti-CD20 therapy.

--

Mark S. Freedman, MSc, MD is a Professor, Department of Neurology, University of Ottawa and The Ottawa Hospital Research Institute; and Director, Multiple Sclerosis Research Unit, The Ottawa Hospital–General Campus.

Mark S. Freedman, MSc, MD, has disclosed the following relevant financial relationships:

Serve(d) on the advisory board, board of directors, or other similar groups for: Actelion (Janssen/Johnson and Johnson); Alexion; Atara Biotherapeutics; Bayer Healthcare; Biogen Idec; Celgene; Clene Nanomedicine; GRI Bio; Hoffmann-La Roche; Magenta Therapeutics; Merck Serono; MedDay Pharmaceuticals; Novartis; Sanofi Genzyme; Teva Canada.

Serve(d) as a member of a speakers bureau for: Sanofi Genzyme; EMD Serono.

Received honoraria or consultation fees for: Actelion (Janssen/Johnson and Johnson); Alexion; Biogen Idec; Celgene (BMS); EMD Inc; Sanofi Genzyme; Hoffmann-La Roche; Merck Serono; Novartis; Teva Canada.

Received research or educational grants from: EMD Inc; Hoffmann-La Roche; Sanofi Genzyme Canada.

In a summary of abstracts presented at the ACTRIMS Forum 2021, Dr. Mark Freedman shares that he and his colleagues found no apparent increased risk of COVID-19 with long-term use of interferon β-1a in patients with multiple sclerosis (MS).

Dr. Freedman also highlights several abstracts examining the use of cladribine and ocrelizumab in older patients with MS.

A post hoc analysis of lymphocyte subsets in the combined safety populations of CLARITY, CLARITY Extension, and ORACLE-MS found that by week 96, the effects of cladribine tablets 3.5 mg/kg on CD19+ B, CD4+ T, and CD8+ T lymphocytes in younger and older patients with MS were similar, with steady recovery following nadir.

Another study on younger and older patients treated with cladribine tablets 3.5 mg/kg found that around a quarter of both groups had transient periods of Grade ≥3 lymphopenia during the study, and the rate of certain infection-related treatment-emergent adverse events was higher in the older patients.

A single-center study found that 25% of patients in the older population stopped ocrelizumab, the most common reasons being disease progression and repeated or severe infections.

Lastly, an evaluation of older patients with progressive MS found no statistical difference in 2-year clinical endpoints for patients taking ocrelizumab compared to prior to anti-CD20 therapy.

--

Mark S. Freedman, MSc, MD is a Professor, Department of Neurology, University of Ottawa and The Ottawa Hospital Research Institute; and Director, Multiple Sclerosis Research Unit, The Ottawa Hospital–General Campus.

Mark S. Freedman, MSc, MD, has disclosed the following relevant financial relationships:

Serve(d) on the advisory board, board of directors, or other similar groups for: Actelion (Janssen/Johnson and Johnson); Alexion; Atara Biotherapeutics; Bayer Healthcare; Biogen Idec; Celgene; Clene Nanomedicine; GRI Bio; Hoffmann-La Roche; Magenta Therapeutics; Merck Serono; MedDay Pharmaceuticals; Novartis; Sanofi Genzyme; Teva Canada.

Serve(d) as a member of a speakers bureau for: Sanofi Genzyme; EMD Serono.

Received honoraria or consultation fees for: Actelion (Janssen/Johnson and Johnson); Alexion; Biogen Idec; Celgene (BMS); EMD Inc; Sanofi Genzyme; Hoffmann-La Roche; Merck Serono; Novartis; Teva Canada.

Received research or educational grants from: EMD Inc; Hoffmann-La Roche; Sanofi Genzyme Canada.