Rheumatology News

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.”

jevans@mdedge.com

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.”

jevans@mdedge.com

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.”

jevans@mdedge.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.

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.

More sleep at night, fewer or no sleep problems, and low levels of professional burnout were associated with a lower risk of developing COVID-19 among health care workers considered to be at high risk for exposure to patients with COVID-19, new evidence reveals.

PRImageFactory/iStock/Getty Images

For each additional hour of sleep at night, for example, risk for COVID-19 dropped by 12% in a study of 2844 frontline health care workers.

Furthermore, those who reported experiencing work-related burnout every day were 2.6 times more likely to report having COVID-19, to report having COVID-19 for a longer time, and to experience COVID-19 of more severity.

“This study underscores the importance of non–hygiene-related risk factors for COVID-19 and supports a holistic approach to health – including optimal sleep and job stress reduction to protect our health care workers from this and future pandemics,” senior author Sara B. Seidelmann, MD, said in an interview.

“Our findings add to the literature that sleep duration at night, sleep problems, and burnout may be risk factors for viral illnesses like COVID-19,” wrote Dr. Seidelmann and colleagues.

This is the first study to link COVID-19 risk to sleep habits – including number of hours of sleep at night, daytime napping hours, and severe sleep problems – among health care workers across multiple countries.

The study was published online March 22 in BMJ Nutrition, Prevention, and Health.

The researchers surveyed health care professionals in specialties considered to place personnel at high risk for exposure to SARS-CoV-2: critical care, emergency care, and internal medicine.

The association between sleep and burnout risk factors and COVID-19 did not vary significantly by specialty. “We didn’t detect any significant interactions between age, sex, specialty, or country,” said Dr. Seidelmann, assistant professor of clinical medicine at Columbia University College of Physicians and Surgeons, New York, and an internist at Stamford (Conn.) Hospital.

In addition to the 12% lower risk associated with each additional hour of sleep at night, each 1 additional hour of daytime napping was linked with a 6% increased risk for COVID-19 in an adjusted analysis (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.01-1.12).

Daytime napping slightly increased risk for COVID-19 in five of the six countries included in the study: France, Germany, Italy, the United Kingdom, and the United States. In contrast, in Spain, napping had a nonsignificant protective effect.

The survey asked health care workers to recall nighttime sleep duration, sleep disorders, and burnout in the year prior to onset of the COVID-19 pandemic.
 

‘Significant, close contact’ with COVID-19?

Lead author Hyunju Kim, NP, Dr. Seidelmann, and colleagues conducted the population-based, case-control study from July 17 to Sept. 25, 2020. They identified health care workers from the SurveyHealthcareGlobus (SHG) network.

Of the respondents, 72% were men. The mean age of the participants was 48 years, and the study population was 77% White, 12% Asian, 6% mixed background, 2% Black, and 1% other. (The remainder preferred not to say).

The 568 health care workers considered to have COVID-19 were classified on the basis of self-reported symptoms. Control participants had no symptoms associated with COVID-19.

All 2,844 participants answered yes to a question about having “significant close contact” with COVID-19 patients in their workplace.

Compared to reporting no sleep problems, having three such problems – difficulty sleeping at night, poor sleep continuity, and frequent use of sleeping pills – was associated with 88% greater odds of COVID-19 (OR, 1.88; 95% CI, 1.17–3.01).

Having one sleep problem was not associated with COVID-19.
 

More burnout, greater risk

The health care workers reported the severity of any work-related burnout. “There was a significant dose-response relationship between frequency of burnout and COVID-19,” the researchers noted.

Those who reported having burnout rarely or weekly had a 1.3-1.4 greater chance of reporting COVID-19 compared to those who reported having no burnout, for example.

In addition, reporting a high level of burnout was linked to about three times the risk for having COVID-19 of longer duration and of greater severity.

What drives the association between sleep problems, burnout, and higher risk for COVID-19 and severe COVID-19 remains unknown.

“The mechanism underlying these associations isn’t clear, but suboptimal sleep, sleep disorders, and stress may result in immune system dysregulation, increased inflammation, and alterations in hormones such as cortisol and melatonin that may increase vulnerability to viral infections,” Dr. Seidelmann said.
 

Strengths and limitations

Using a large network of health care workers in the early phase of the pandemic is a strength of the study. How generalizable the findings are outside the SHG database of 1.5 million health care workers remains unknown.

Another limitation was reliance on self-reporting of COVID-19 patient exposure, outcomes, and covariates, which could have introduced bias.

“However,” the researchers noted, “health care workers are likely a reliable source of information.”
 

Insomnia a common challenge

A 2020 meta-analysis examined the effect of insomnia and psychological factors on COVID-19 risk among health care workers. Lead author Kavita Batra, PhD, of the University of Nevada, Las Vegas (UNLV), and colleagues found that the pooled prevalence of insomnia was almost 28%.

“The recent six-country study by Kim and colleagues also underscores this relationship between lack of sleep and having higher odds of COVID-19 infection,” Manoj Sharma, MBBS, PhD, professor of social and behavioral health in the UNLV department of environmental and occupational health, and one of the study authors, said in an interview.

More research is warranted to learn the direction of the association, he said. Does reduced sleep lower immunity and make a health care worker more susceptible to SARS-CoV-2 infection, or does the anxiety associated with COVID-19 contribute to insomnia?

“Practicing sleep hygiene is a must not only for health workers but also for everyone,” Dr. Sharma added. Recommendations include having fixed hours of going to bed, fixed hours of waking up, not overdoing naps, having at least 30 minutes of winding down before sleeping, having a dark bedroom devoid of all electronics and other disturbances, avoiding smoking, alcohol, and stimulants (such as caffeine) before sleeping, and practicing relaxation right before sleeping, he said.

“It is hard for some health care workers, especially those who work night shifts, but it must be a priority to follow as many sleep hygiene measures as possible,” Dr. Sharma said. “After all, if you do not take care of yourself how can you take care of others?”

Dr. Seidelmann, Dr. Batra, and Dr. Sharma have disclosed no relevant financial relationships.

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

More sleep at night, fewer or no sleep problems, and low levels of professional burnout were associated with a lower risk of developing COVID-19 among health care workers considered to be at high risk for exposure to patients with COVID-19, new evidence reveals.

PRImageFactory/iStock/Getty Images

For each additional hour of sleep at night, for example, risk for COVID-19 dropped by 12% in a study of 2844 frontline health care workers.

Furthermore, those who reported experiencing work-related burnout every day were 2.6 times more likely to report having COVID-19, to report having COVID-19 for a longer time, and to experience COVID-19 of more severity.

“This study underscores the importance of non–hygiene-related risk factors for COVID-19 and supports a holistic approach to health – including optimal sleep and job stress reduction to protect our health care workers from this and future pandemics,” senior author Sara B. Seidelmann, MD, said in an interview.

“Our findings add to the literature that sleep duration at night, sleep problems, and burnout may be risk factors for viral illnesses like COVID-19,” wrote Dr. Seidelmann and colleagues.

This is the first study to link COVID-19 risk to sleep habits – including number of hours of sleep at night, daytime napping hours, and severe sleep problems – among health care workers across multiple countries.

The study was published online March 22 in BMJ Nutrition, Prevention, and Health.

The researchers surveyed health care professionals in specialties considered to place personnel at high risk for exposure to SARS-CoV-2: critical care, emergency care, and internal medicine.

The association between sleep and burnout risk factors and COVID-19 did not vary significantly by specialty. “We didn’t detect any significant interactions between age, sex, specialty, or country,” said Dr. Seidelmann, assistant professor of clinical medicine at Columbia University College of Physicians and Surgeons, New York, and an internist at Stamford (Conn.) Hospital.

In addition to the 12% lower risk associated with each additional hour of sleep at night, each 1 additional hour of daytime napping was linked with a 6% increased risk for COVID-19 in an adjusted analysis (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.01-1.12).

Daytime napping slightly increased risk for COVID-19 in five of the six countries included in the study: France, Germany, Italy, the United Kingdom, and the United States. In contrast, in Spain, napping had a nonsignificant protective effect.

The survey asked health care workers to recall nighttime sleep duration, sleep disorders, and burnout in the year prior to onset of the COVID-19 pandemic.
 

‘Significant, close contact’ with COVID-19?

Lead author Hyunju Kim, NP, Dr. Seidelmann, and colleagues conducted the population-based, case-control study from July 17 to Sept. 25, 2020. They identified health care workers from the SurveyHealthcareGlobus (SHG) network.

Of the respondents, 72% were men. The mean age of the participants was 48 years, and the study population was 77% White, 12% Asian, 6% mixed background, 2% Black, and 1% other. (The remainder preferred not to say).

The 568 health care workers considered to have COVID-19 were classified on the basis of self-reported symptoms. Control participants had no symptoms associated with COVID-19.

All 2,844 participants answered yes to a question about having “significant close contact” with COVID-19 patients in their workplace.

Compared to reporting no sleep problems, having three such problems – difficulty sleeping at night, poor sleep continuity, and frequent use of sleeping pills – was associated with 88% greater odds of COVID-19 (OR, 1.88; 95% CI, 1.17–3.01).

Having one sleep problem was not associated with COVID-19.
 

More burnout, greater risk

The health care workers reported the severity of any work-related burnout. “There was a significant dose-response relationship between frequency of burnout and COVID-19,” the researchers noted.

Those who reported having burnout rarely or weekly had a 1.3-1.4 greater chance of reporting COVID-19 compared to those who reported having no burnout, for example.

In addition, reporting a high level of burnout was linked to about three times the risk for having COVID-19 of longer duration and of greater severity.

What drives the association between sleep problems, burnout, and higher risk for COVID-19 and severe COVID-19 remains unknown.

“The mechanism underlying these associations isn’t clear, but suboptimal sleep, sleep disorders, and stress may result in immune system dysregulation, increased inflammation, and alterations in hormones such as cortisol and melatonin that may increase vulnerability to viral infections,” Dr. Seidelmann said.
 

Strengths and limitations

Using a large network of health care workers in the early phase of the pandemic is a strength of the study. How generalizable the findings are outside the SHG database of 1.5 million health care workers remains unknown.

Another limitation was reliance on self-reporting of COVID-19 patient exposure, outcomes, and covariates, which could have introduced bias.

“However,” the researchers noted, “health care workers are likely a reliable source of information.”
 

Insomnia a common challenge

A 2020 meta-analysis examined the effect of insomnia and psychological factors on COVID-19 risk among health care workers. Lead author Kavita Batra, PhD, of the University of Nevada, Las Vegas (UNLV), and colleagues found that the pooled prevalence of insomnia was almost 28%.

“The recent six-country study by Kim and colleagues also underscores this relationship between lack of sleep and having higher odds of COVID-19 infection,” Manoj Sharma, MBBS, PhD, professor of social and behavioral health in the UNLV department of environmental and occupational health, and one of the study authors, said in an interview.

More research is warranted to learn the direction of the association, he said. Does reduced sleep lower immunity and make a health care worker more susceptible to SARS-CoV-2 infection, or does the anxiety associated with COVID-19 contribute to insomnia?

“Practicing sleep hygiene is a must not only for health workers but also for everyone,” Dr. Sharma added. Recommendations include having fixed hours of going to bed, fixed hours of waking up, not overdoing naps, having at least 30 minutes of winding down before sleeping, having a dark bedroom devoid of all electronics and other disturbances, avoiding smoking, alcohol, and stimulants (such as caffeine) before sleeping, and practicing relaxation right before sleeping, he said.

“It is hard for some health care workers, especially those who work night shifts, but it must be a priority to follow as many sleep hygiene measures as possible,” Dr. Sharma said. “After all, if you do not take care of yourself how can you take care of others?”

Dr. Seidelmann, Dr. Batra, and Dr. Sharma have disclosed no relevant financial relationships.

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

More sleep at night, fewer or no sleep problems, and low levels of professional burnout were associated with a lower risk of developing COVID-19 among health care workers considered to be at high risk for exposure to patients with COVID-19, new evidence reveals.

PRImageFactory/iStock/Getty Images

For each additional hour of sleep at night, for example, risk for COVID-19 dropped by 12% in a study of 2844 frontline health care workers.

Furthermore, those who reported experiencing work-related burnout every day were 2.6 times more likely to report having COVID-19, to report having COVID-19 for a longer time, and to experience COVID-19 of more severity.

“This study underscores the importance of non–hygiene-related risk factors for COVID-19 and supports a holistic approach to health – including optimal sleep and job stress reduction to protect our health care workers from this and future pandemics,” senior author Sara B. Seidelmann, MD, said in an interview.

“Our findings add to the literature that sleep duration at night, sleep problems, and burnout may be risk factors for viral illnesses like COVID-19,” wrote Dr. Seidelmann and colleagues.

This is the first study to link COVID-19 risk to sleep habits – including number of hours of sleep at night, daytime napping hours, and severe sleep problems – among health care workers across multiple countries.

The study was published online March 22 in BMJ Nutrition, Prevention, and Health.

The researchers surveyed health care professionals in specialties considered to place personnel at high risk for exposure to SARS-CoV-2: critical care, emergency care, and internal medicine.

The association between sleep and burnout risk factors and COVID-19 did not vary significantly by specialty. “We didn’t detect any significant interactions between age, sex, specialty, or country,” said Dr. Seidelmann, assistant professor of clinical medicine at Columbia University College of Physicians and Surgeons, New York, and an internist at Stamford (Conn.) Hospital.

In addition to the 12% lower risk associated with each additional hour of sleep at night, each 1 additional hour of daytime napping was linked with a 6% increased risk for COVID-19 in an adjusted analysis (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.01-1.12).

Daytime napping slightly increased risk for COVID-19 in five of the six countries included in the study: France, Germany, Italy, the United Kingdom, and the United States. In contrast, in Spain, napping had a nonsignificant protective effect.

The survey asked health care workers to recall nighttime sleep duration, sleep disorders, and burnout in the year prior to onset of the COVID-19 pandemic.
 

‘Significant, close contact’ with COVID-19?

Lead author Hyunju Kim, NP, Dr. Seidelmann, and colleagues conducted the population-based, case-control study from July 17 to Sept. 25, 2020. They identified health care workers from the SurveyHealthcareGlobus (SHG) network.

Of the respondents, 72% were men. The mean age of the participants was 48 years, and the study population was 77% White, 12% Asian, 6% mixed background, 2% Black, and 1% other. (The remainder preferred not to say).

The 568 health care workers considered to have COVID-19 were classified on the basis of self-reported symptoms. Control participants had no symptoms associated with COVID-19.

All 2,844 participants answered yes to a question about having “significant close contact” with COVID-19 patients in their workplace.

Compared to reporting no sleep problems, having three such problems – difficulty sleeping at night, poor sleep continuity, and frequent use of sleeping pills – was associated with 88% greater odds of COVID-19 (OR, 1.88; 95% CI, 1.17–3.01).

Having one sleep problem was not associated with COVID-19.
 

More burnout, greater risk

The health care workers reported the severity of any work-related burnout. “There was a significant dose-response relationship between frequency of burnout and COVID-19,” the researchers noted.

Those who reported having burnout rarely or weekly had a 1.3-1.4 greater chance of reporting COVID-19 compared to those who reported having no burnout, for example.

In addition, reporting a high level of burnout was linked to about three times the risk for having COVID-19 of longer duration and of greater severity.

What drives the association between sleep problems, burnout, and higher risk for COVID-19 and severe COVID-19 remains unknown.

“The mechanism underlying these associations isn’t clear, but suboptimal sleep, sleep disorders, and stress may result in immune system dysregulation, increased inflammation, and alterations in hormones such as cortisol and melatonin that may increase vulnerability to viral infections,” Dr. Seidelmann said.
 

Strengths and limitations

Using a large network of health care workers in the early phase of the pandemic is a strength of the study. How generalizable the findings are outside the SHG database of 1.5 million health care workers remains unknown.

Another limitation was reliance on self-reporting of COVID-19 patient exposure, outcomes, and covariates, which could have introduced bias.

“However,” the researchers noted, “health care workers are likely a reliable source of information.”
 

Insomnia a common challenge

A 2020 meta-analysis examined the effect of insomnia and psychological factors on COVID-19 risk among health care workers. Lead author Kavita Batra, PhD, of the University of Nevada, Las Vegas (UNLV), and colleagues found that the pooled prevalence of insomnia was almost 28%.

“The recent six-country study by Kim and colleagues also underscores this relationship between lack of sleep and having higher odds of COVID-19 infection,” Manoj Sharma, MBBS, PhD, professor of social and behavioral health in the UNLV department of environmental and occupational health, and one of the study authors, said in an interview.

More research is warranted to learn the direction of the association, he said. Does reduced sleep lower immunity and make a health care worker more susceptible to SARS-CoV-2 infection, or does the anxiety associated with COVID-19 contribute to insomnia?

“Practicing sleep hygiene is a must not only for health workers but also for everyone,” Dr. Sharma added. Recommendations include having fixed hours of going to bed, fixed hours of waking up, not overdoing naps, having at least 30 minutes of winding down before sleeping, having a dark bedroom devoid of all electronics and other disturbances, avoiding smoking, alcohol, and stimulants (such as caffeine) before sleeping, and practicing relaxation right before sleeping, he said.

“It is hard for some health care workers, especially those who work night shifts, but it must be a priority to follow as many sleep hygiene measures as possible,” Dr. Sharma said. “After all, if you do not take care of yourself how can you take care of others?”

Dr. Seidelmann, Dr. Batra, and Dr. Sharma have disclosed no relevant financial relationships.

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

Severe COVID-19 infection was more likely in hospitalized patients with systemic lupus erythematosus (SLE) who had comorbidities and risk factors associated with severe infection in the general population, notably older age, male gender, and hypertension, based on data from a nationwide epidemiologic study of inpatients in France.

“Recently, anti-interferon antibodies have been implicated in severe SARS-CoV-2 infection while it has been known for decades that patients with SLE may produce such autoantibodies,” but large-scale data on the risk of severe COVID-19 infection in SLE patients are limited, Arthur Mageau, MD, of Bichat–Claude Bernard Hospital in Paris, and colleagues wrote.

In a research letter published in Annals of the Rheumatic Diseases, the researchers used the French health care database Programme de Médicalisation des Systèmes d’Information to identify 11,055 adult SLE patients who had at least one hospital stay between March 1, 2020, and Oct.31, 2020. Of these, 1,411 (12.8%) also were diagnosed with COVID-19, and these patients had a total of 1,721 hospital stays.

Overall, in-hospital mortality was approximately four times higher among SLE patients with COVID-19 infection, compared with SLE patients without COVID-19 infection (9.5% vs. 2.4%, P < .001), and 293 (17%) of the COVID-19 hospital stays involved an intensive care unit. In the ICU, 78 (26.7%) of the COVID-19 patients required invasive ventilation, and 71 (24.7%) required noninvasive mechanical ventilation.

The SLE patients with COVID-19 who died were significantly more likely than the SLE patients with COVID-19 who recovered to be older and male, and to have conditions including chronic kidney disease, high blood pressure, chronic pulmonary disease, and a history of cardiovascular events or lupus nephritis. The study findings were limited by the focus on hospitalized patients only, so the results cannot be generalized to all lupus patients, the researchers said.

“Interestingly, while the overall mortality rate was lower in SLE/COVID-19–positive inpatients as compared with the total population admitted for SARS-CoV-2 infection in France during the same period (9.5% vs 15.7%, P < .0001), the mortality rate at a younger age tended to be higher in patients with SLE,” the researchers wrote, but the difference for these younger patients was not statistically significant. This disparity may be caused by the reduced need for immunosuppressive drugs in SLE patients as they age, and the observed increased mortality in younger SLE patients, compared with the general population, suggests that SLE may promote poor outcomes from COVID-19 infection.

Dr. Mageau received PhD fellowship support from the Agence Nationale pour la recherche. He and the other researchers had no financial conflicts to disclose. The study received no outside funding.

Severe COVID-19 infection was more likely in hospitalized patients with systemic lupus erythematosus (SLE) who had comorbidities and risk factors associated with severe infection in the general population, notably older age, male gender, and hypertension, based on data from a nationwide epidemiologic study of inpatients in France.

“Recently, anti-interferon antibodies have been implicated in severe SARS-CoV-2 infection while it has been known for decades that patients with SLE may produce such autoantibodies,” but large-scale data on the risk of severe COVID-19 infection in SLE patients are limited, Arthur Mageau, MD, of Bichat–Claude Bernard Hospital in Paris, and colleagues wrote.

In a research letter published in Annals of the Rheumatic Diseases, the researchers used the French health care database Programme de Médicalisation des Systèmes d’Information to identify 11,055 adult SLE patients who had at least one hospital stay between March 1, 2020, and Oct.31, 2020. Of these, 1,411 (12.8%) also were diagnosed with COVID-19, and these patients had a total of 1,721 hospital stays.

Overall, in-hospital mortality was approximately four times higher among SLE patients with COVID-19 infection, compared with SLE patients without COVID-19 infection (9.5% vs. 2.4%, P < .001), and 293 (17%) of the COVID-19 hospital stays involved an intensive care unit. In the ICU, 78 (26.7%) of the COVID-19 patients required invasive ventilation, and 71 (24.7%) required noninvasive mechanical ventilation.

The SLE patients with COVID-19 who died were significantly more likely than the SLE patients with COVID-19 who recovered to be older and male, and to have conditions including chronic kidney disease, high blood pressure, chronic pulmonary disease, and a history of cardiovascular events or lupus nephritis. The study findings were limited by the focus on hospitalized patients only, so the results cannot be generalized to all lupus patients, the researchers said.

“Interestingly, while the overall mortality rate was lower in SLE/COVID-19–positive inpatients as compared with the total population admitted for SARS-CoV-2 infection in France during the same period (9.5% vs 15.7%, P < .0001), the mortality rate at a younger age tended to be higher in patients with SLE,” the researchers wrote, but the difference for these younger patients was not statistically significant. This disparity may be caused by the reduced need for immunosuppressive drugs in SLE patients as they age, and the observed increased mortality in younger SLE patients, compared with the general population, suggests that SLE may promote poor outcomes from COVID-19 infection.

Dr. Mageau received PhD fellowship support from the Agence Nationale pour la recherche. He and the other researchers had no financial conflicts to disclose. The study received no outside funding.

Severe COVID-19 infection was more likely in hospitalized patients with systemic lupus erythematosus (SLE) who had comorbidities and risk factors associated with severe infection in the general population, notably older age, male gender, and hypertension, based on data from a nationwide epidemiologic study of inpatients in France.

“Recently, anti-interferon antibodies have been implicated in severe SARS-CoV-2 infection while it has been known for decades that patients with SLE may produce such autoantibodies,” but large-scale data on the risk of severe COVID-19 infection in SLE patients are limited, Arthur Mageau, MD, of Bichat–Claude Bernard Hospital in Paris, and colleagues wrote.

In a research letter published in Annals of the Rheumatic Diseases, the researchers used the French health care database Programme de Médicalisation des Systèmes d’Information to identify 11,055 adult SLE patients who had at least one hospital stay between March 1, 2020, and Oct.31, 2020. Of these, 1,411 (12.8%) also were diagnosed with COVID-19, and these patients had a total of 1,721 hospital stays.

Overall, in-hospital mortality was approximately four times higher among SLE patients with COVID-19 infection, compared with SLE patients without COVID-19 infection (9.5% vs. 2.4%, P < .001), and 293 (17%) of the COVID-19 hospital stays involved an intensive care unit. In the ICU, 78 (26.7%) of the COVID-19 patients required invasive ventilation, and 71 (24.7%) required noninvasive mechanical ventilation.

The SLE patients with COVID-19 who died were significantly more likely than the SLE patients with COVID-19 who recovered to be older and male, and to have conditions including chronic kidney disease, high blood pressure, chronic pulmonary disease, and a history of cardiovascular events or lupus nephritis. The study findings were limited by the focus on hospitalized patients only, so the results cannot be generalized to all lupus patients, the researchers said.

“Interestingly, while the overall mortality rate was lower in SLE/COVID-19–positive inpatients as compared with the total population admitted for SARS-CoV-2 infection in France during the same period (9.5% vs 15.7%, P < .0001), the mortality rate at a younger age tended to be higher in patients with SLE,” the researchers wrote, but the difference for these younger patients was not statistically significant. This disparity may be caused by the reduced need for immunosuppressive drugs in SLE patients as they age, and the observed increased mortality in younger SLE patients, compared with the general population, suggests that SLE may promote poor outcomes from COVID-19 infection.

Dr. Mageau received PhD fellowship support from the Agence Nationale pour la recherche. He and the other researchers had no financial conflicts to disclose. The study received no outside funding.

Federal regulators on March 23 said they were “concerned” that drug maker AstraZeneca included “outdated information” in its announcement the previous day that the company’s COVID-19 vaccine was effective.

The federal Data and Safety Monitoring Board shared those concerns with the company as well as with the National Institute of Allergy and Infectious Diseases, and the U.S. Biomedical Advanced Research and Development Authority, according to a statement from NIAID issued early March 23.

“We urge the company to work with the DSMB to review the efficacy data and ensure the most accurate, up-to-date efficacy data be made public as quickly as possible,” the agency said.

The NIAID statement does not say what data may have been outdated or how it may have changed the results. The company said March 22 it plans to see U.S. authorization for the vaccine in April.

The statement from NIAID comes a day after AstraZeneca said the interim results of their phase III U.S. study found it was 79% effective against symptomatic COVID-19, 80% effective in people 65 years and older, and 100% effective against severe or critical disease and hospitalization.

Company officials and clinical trial investigators on March 22 also addressed the recent concerns about blood clots, how well the vaccine will perform against variants, and provided a timeline for seeking regulatory approval.

“There are many countries in Europe and throughout the world that have already authorized this. The fact that a United States-run study has confirmed the efficacy and safety of this vaccine, I think is an important contribution to global health in general,” Anthony Fauci, MD, chief medical advisor to President Joe Biden, said during a White House press briefing March 22.

Andy Slavitt, White House senior advisor for the COVID-19 Response Team, had a more tempered reaction.

“It’s important to remind everyone we cannot and will not get ahead of the FDA,” he said. “While we would certainly call today’s news encouraging, it’s the kind of thing we like to see, we have a rigorous process that will come once an EUA is submitted and that will give us more information.”

With 30 million doses at the ready, the company plans to file for FDA emergency use authorization “within weeks,” Menelas Pangalos, executive vice president of biopharmaceuticals research and development at AstraZeneca, said during a media briefing March 22.
 

Risk of thrombosis addressed

Regarding highly publicized reports of problems with blood clots from the AstraZeneca vaccine, the World Health Organization found the vaccine creates no greater risks, as did the European Medicines Agency

“We’ve had absolute confidence in the efficacy of the vaccine. Seeing this data now I hope gives others increased confidence that this is a very safe and effective vaccine,” Mr. Pangalos said.

“We’re glad this is being investigated really thoroughly,” Magda Sobieszczyk, MD, an infectious disease specialist at Columbia University In New York City, said. “It’s incredibly reassuring that the regulatory agencies have looked at the data thoroughly and there is no enhanced signal above what is seen in the population.”

“There were no concerning signals noted in the U.S. data,” she added.

Regarding the risk of blood clots, “These data are therefore timely in further addressing any safety concerns that could undermine vaccine uptake.” Andrew Garrett, PhD, executive vice president of scientific operations at ICON Clinical Research, agreed.

The vaccine was well-tolerated, the company reported, with no serious adverse events. Temporary pain and tenderness at the injection site, mild-to-moderate headaches, fatigue, chills, fever, muscle aches. and malaise were among the reported reactions.

The phase III interim results show 141 cases of symptomatic COVID-19 in the study of 32,449 adults. “We don’t have the whole breakdown yet . . . these are the high-level results we just got this week,” Mr. Pangalos said. Further information on rates of mild to moderate COVID-19 illness between groups is not yet available, for example.

The company explained that participants were randomly assigned to vaccine or placebo, with twice as many receiving the actual vaccine.

The trial is ongoing, so the FDA will receive information on more than the 141 COVID-19 symptomatic cases when the company submits a full primary analysis to the agency, Mr. Pangalos said.

In the phase III study, patients received two doses 4 weeks apart.

Beyond the U.S. study, the company has additional information, including real-world data from the United Kingdom, that it intends to submit to the FDA. Part of this evidence suggests increased efficacy when a second dose is administered at 3 months
 

‘Robust’ findings

“This is a large study, so these results can be expected to be robust. They could be expected to be even more so if there were more cases to compare between the groups, but 141 is still a substantial number of cases,” said Peter English, MD, of Horsham, United Kingdom, who is immediate past chair of the British Medical Association Public Health Medicine Committee.

Experts welcomed the 80% efficacy in people 65 and older in particular. “Importantly, the trial provides further support for efficacy in the elderly where previous clinical trial data, other than immunologic data, had been lacking,” Dr. Garrett said.

“It is clear this vaccine has very good efficacy. Remember that 60% was, prior to any trials being started, regarded as a good target,” said Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine. “This efficacy does not show a notable decline at older ages. This was expected and the speculation that it was ineffective or quasi-ineffective at older ages was totally unjustified.

“This is good news for the global community and one hopes that any political statements around this good news are avoided,” he added.
 

Efficacy against variants?

Regarding virus variants, Mr. Pangalos noted the study was conducted when several variants of concern were in circulation.

“What I can say is given this study was conducted much later in terms of timing, it’s very encouraging that we’ve got such high efficacy numbers when undoubtedly there are variants of concern in circulation in this study,” Mr. Pangalos said.

“It also highlights why we believe that against severe disease, our vaccine will be effective against all variants of concern,” he added.

Once the company submits its EUA to the FDA, the company is ready to immediately distribute 30 million doses of the vaccine and expects to ship 50 million total within the first month, Ruud Dobber, PhD, AstraZeneca executive vice president and president of the AZ Biopharmaceuticals Business Unit, said during the briefing.

The vaccine can be stored at 2 to 8 degrees Celsius for at least 6 months. Like other COVID-19 vaccines already authorized for emergency use, the duration of protection with the AstraZeneca product remains unknown.

This article was updated March 23, 2021.

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

Federal regulators on March 23 said they were “concerned” that drug maker AstraZeneca included “outdated information” in its announcement the previous day that the company’s COVID-19 vaccine was effective.

The federal Data and Safety Monitoring Board shared those concerns with the company as well as with the National Institute of Allergy and Infectious Diseases, and the U.S. Biomedical Advanced Research and Development Authority, according to a statement from NIAID issued early March 23.

“We urge the company to work with the DSMB to review the efficacy data and ensure the most accurate, up-to-date efficacy data be made public as quickly as possible,” the agency said.

The NIAID statement does not say what data may have been outdated or how it may have changed the results. The company said March 22 it plans to see U.S. authorization for the vaccine in April.

The statement from NIAID comes a day after AstraZeneca said the interim results of their phase III U.S. study found it was 79% effective against symptomatic COVID-19, 80% effective in people 65 years and older, and 100% effective against severe or critical disease and hospitalization.

Company officials and clinical trial investigators on March 22 also addressed the recent concerns about blood clots, how well the vaccine will perform against variants, and provided a timeline for seeking regulatory approval.

“There are many countries in Europe and throughout the world that have already authorized this. The fact that a United States-run study has confirmed the efficacy and safety of this vaccine, I think is an important contribution to global health in general,” Anthony Fauci, MD, chief medical advisor to President Joe Biden, said during a White House press briefing March 22.

Andy Slavitt, White House senior advisor for the COVID-19 Response Team, had a more tempered reaction.

“It’s important to remind everyone we cannot and will not get ahead of the FDA,” he said. “While we would certainly call today’s news encouraging, it’s the kind of thing we like to see, we have a rigorous process that will come once an EUA is submitted and that will give us more information.”

With 30 million doses at the ready, the company plans to file for FDA emergency use authorization “within weeks,” Menelas Pangalos, executive vice president of biopharmaceuticals research and development at AstraZeneca, said during a media briefing March 22.
 

Risk of thrombosis addressed

Regarding highly publicized reports of problems with blood clots from the AstraZeneca vaccine, the World Health Organization found the vaccine creates no greater risks, as did the European Medicines Agency

“We’ve had absolute confidence in the efficacy of the vaccine. Seeing this data now I hope gives others increased confidence that this is a very safe and effective vaccine,” Mr. Pangalos said.

“We’re glad this is being investigated really thoroughly,” Magda Sobieszczyk, MD, an infectious disease specialist at Columbia University In New York City, said. “It’s incredibly reassuring that the regulatory agencies have looked at the data thoroughly and there is no enhanced signal above what is seen in the population.”

“There were no concerning signals noted in the U.S. data,” she added.

Regarding the risk of blood clots, “These data are therefore timely in further addressing any safety concerns that could undermine vaccine uptake.” Andrew Garrett, PhD, executive vice president of scientific operations at ICON Clinical Research, agreed.

The vaccine was well-tolerated, the company reported, with no serious adverse events. Temporary pain and tenderness at the injection site, mild-to-moderate headaches, fatigue, chills, fever, muscle aches. and malaise were among the reported reactions.

The phase III interim results show 141 cases of symptomatic COVID-19 in the study of 32,449 adults. “We don’t have the whole breakdown yet . . . these are the high-level results we just got this week,” Mr. Pangalos said. Further information on rates of mild to moderate COVID-19 illness between groups is not yet available, for example.

The company explained that participants were randomly assigned to vaccine or placebo, with twice as many receiving the actual vaccine.

The trial is ongoing, so the FDA will receive information on more than the 141 COVID-19 symptomatic cases when the company submits a full primary analysis to the agency, Mr. Pangalos said.

In the phase III study, patients received two doses 4 weeks apart.

Beyond the U.S. study, the company has additional information, including real-world data from the United Kingdom, that it intends to submit to the FDA. Part of this evidence suggests increased efficacy when a second dose is administered at 3 months
 

‘Robust’ findings

“This is a large study, so these results can be expected to be robust. They could be expected to be even more so if there were more cases to compare between the groups, but 141 is still a substantial number of cases,” said Peter English, MD, of Horsham, United Kingdom, who is immediate past chair of the British Medical Association Public Health Medicine Committee.

Experts welcomed the 80% efficacy in people 65 and older in particular. “Importantly, the trial provides further support for efficacy in the elderly where previous clinical trial data, other than immunologic data, had been lacking,” Dr. Garrett said.

“It is clear this vaccine has very good efficacy. Remember that 60% was, prior to any trials being started, regarded as a good target,” said Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine. “This efficacy does not show a notable decline at older ages. This was expected and the speculation that it was ineffective or quasi-ineffective at older ages was totally unjustified.

“This is good news for the global community and one hopes that any political statements around this good news are avoided,” he added.
 

Efficacy against variants?

Regarding virus variants, Mr. Pangalos noted the study was conducted when several variants of concern were in circulation.

“What I can say is given this study was conducted much later in terms of timing, it’s very encouraging that we’ve got such high efficacy numbers when undoubtedly there are variants of concern in circulation in this study,” Mr. Pangalos said.

“It also highlights why we believe that against severe disease, our vaccine will be effective against all variants of concern,” he added.

Once the company submits its EUA to the FDA, the company is ready to immediately distribute 30 million doses of the vaccine and expects to ship 50 million total within the first month, Ruud Dobber, PhD, AstraZeneca executive vice president and president of the AZ Biopharmaceuticals Business Unit, said during the briefing.

The vaccine can be stored at 2 to 8 degrees Celsius for at least 6 months. Like other COVID-19 vaccines already authorized for emergency use, the duration of protection with the AstraZeneca product remains unknown.

This article was updated March 23, 2021.

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

Federal regulators on March 23 said they were “concerned” that drug maker AstraZeneca included “outdated information” in its announcement the previous day that the company’s COVID-19 vaccine was effective.

The federal Data and Safety Monitoring Board shared those concerns with the company as well as with the National Institute of Allergy and Infectious Diseases, and the U.S. Biomedical Advanced Research and Development Authority, according to a statement from NIAID issued early March 23.

“We urge the company to work with the DSMB to review the efficacy data and ensure the most accurate, up-to-date efficacy data be made public as quickly as possible,” the agency said.

The NIAID statement does not say what data may have been outdated or how it may have changed the results. The company said March 22 it plans to see U.S. authorization for the vaccine in April.

The statement from NIAID comes a day after AstraZeneca said the interim results of their phase III U.S. study found it was 79% effective against symptomatic COVID-19, 80% effective in people 65 years and older, and 100% effective against severe or critical disease and hospitalization.

Company officials and clinical trial investigators on March 22 also addressed the recent concerns about blood clots, how well the vaccine will perform against variants, and provided a timeline for seeking regulatory approval.

“There are many countries in Europe and throughout the world that have already authorized this. The fact that a United States-run study has confirmed the efficacy and safety of this vaccine, I think is an important contribution to global health in general,” Anthony Fauci, MD, chief medical advisor to President Joe Biden, said during a White House press briefing March 22.

Andy Slavitt, White House senior advisor for the COVID-19 Response Team, had a more tempered reaction.

“It’s important to remind everyone we cannot and will not get ahead of the FDA,” he said. “While we would certainly call today’s news encouraging, it’s the kind of thing we like to see, we have a rigorous process that will come once an EUA is submitted and that will give us more information.”

With 30 million doses at the ready, the company plans to file for FDA emergency use authorization “within weeks,” Menelas Pangalos, executive vice president of biopharmaceuticals research and development at AstraZeneca, said during a media briefing March 22.
 

Risk of thrombosis addressed

Regarding highly publicized reports of problems with blood clots from the AstraZeneca vaccine, the World Health Organization found the vaccine creates no greater risks, as did the European Medicines Agency

“We’ve had absolute confidence in the efficacy of the vaccine. Seeing this data now I hope gives others increased confidence that this is a very safe and effective vaccine,” Mr. Pangalos said.

“We’re glad this is being investigated really thoroughly,” Magda Sobieszczyk, MD, an infectious disease specialist at Columbia University In New York City, said. “It’s incredibly reassuring that the regulatory agencies have looked at the data thoroughly and there is no enhanced signal above what is seen in the population.”

“There were no concerning signals noted in the U.S. data,” she added.

Regarding the risk of blood clots, “These data are therefore timely in further addressing any safety concerns that could undermine vaccine uptake.” Andrew Garrett, PhD, executive vice president of scientific operations at ICON Clinical Research, agreed.

The vaccine was well-tolerated, the company reported, with no serious adverse events. Temporary pain and tenderness at the injection site, mild-to-moderate headaches, fatigue, chills, fever, muscle aches. and malaise were among the reported reactions.

The phase III interim results show 141 cases of symptomatic COVID-19 in the study of 32,449 adults. “We don’t have the whole breakdown yet . . . these are the high-level results we just got this week,” Mr. Pangalos said. Further information on rates of mild to moderate COVID-19 illness between groups is not yet available, for example.

The company explained that participants were randomly assigned to vaccine or placebo, with twice as many receiving the actual vaccine.

The trial is ongoing, so the FDA will receive information on more than the 141 COVID-19 symptomatic cases when the company submits a full primary analysis to the agency, Mr. Pangalos said.

In the phase III study, patients received two doses 4 weeks apart.

Beyond the U.S. study, the company has additional information, including real-world data from the United Kingdom, that it intends to submit to the FDA. Part of this evidence suggests increased efficacy when a second dose is administered at 3 months
 

‘Robust’ findings

“This is a large study, so these results can be expected to be robust. They could be expected to be even more so if there were more cases to compare between the groups, but 141 is still a substantial number of cases,” said Peter English, MD, of Horsham, United Kingdom, who is immediate past chair of the British Medical Association Public Health Medicine Committee.

Experts welcomed the 80% efficacy in people 65 and older in particular. “Importantly, the trial provides further support for efficacy in the elderly where previous clinical trial data, other than immunologic data, had been lacking,” Dr. Garrett said.

“It is clear this vaccine has very good efficacy. Remember that 60% was, prior to any trials being started, regarded as a good target,” said Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine. “This efficacy does not show a notable decline at older ages. This was expected and the speculation that it was ineffective or quasi-ineffective at older ages was totally unjustified.

“This is good news for the global community and one hopes that any political statements around this good news are avoided,” he added.
 

Efficacy against variants?

Regarding virus variants, Mr. Pangalos noted the study was conducted when several variants of concern were in circulation.

“What I can say is given this study was conducted much later in terms of timing, it’s very encouraging that we’ve got such high efficacy numbers when undoubtedly there are variants of concern in circulation in this study,” Mr. Pangalos said.

“It also highlights why we believe that against severe disease, our vaccine will be effective against all variants of concern,” he added.

Once the company submits its EUA to the FDA, the company is ready to immediately distribute 30 million doses of the vaccine and expects to ship 50 million total within the first month, Ruud Dobber, PhD, AstraZeneca executive vice president and president of the AZ Biopharmaceuticals Business Unit, said during the briefing.

The vaccine can be stored at 2 to 8 degrees Celsius for at least 6 months. Like other COVID-19 vaccines already authorized for emergency use, the duration of protection with the AstraZeneca product remains unknown.

This article was updated March 23, 2021.

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

A new study has found that older men with high levels of abdominal aortic calcification (AAC) and a prevalent vertebral fracture – both of which can be assessed via lateral spine radiographs – are at increased risk of hip, clinical vertebral, and major osteoporotic fractures.

“The results of this study and others suggest that it may be appropriate to expand lateral spine imaging to include those with a significant pre-test probability of higher AAC being present,” wrote John T. Schousboe, MD, of the Park Nicollet Clinic and HealthPartners Institute in Bloomington, Minn. The study was published in the Journal of Bone and Mineral Research.

To determine the impact of prevalent vertebral fractures and AAC on fracture risk, the researchers assessed the lateral spine radiographs of 5,365 men who were enrolled in the Osteoporotic Fractures in Men (MrOS) study. All participants were 65 years or older, community dwelling, able to walk without assistance, and without bilateral hip arthroplasties. They split patients’ 24-point AAC (ACC-24) scores at the baseline visit into four levels: 0-1, 2-4, 5-8, and greater than 9. Self-reports of fractures were solicited from the cohort every 4 months.

Of all participants, 7.6% (n = 407) had a prevalent vertebral fracture at baseline. They were, on average, 1.5 years older than participants without a fracture; they were also more likely to be white and to have a prior nonspine fracture, along with having a lower femoral neck BMD (0.718 g/cm², compared with 0.787 g/cm²; P < .001). In addition, significantly more men with a prevalent vertebral fracture had an AAC score greater than 9 (27% vs. 21.2%).

After an average follow-up period of 12.4 years (standard deviation, 5.2), 634 men had a major osteoporotic fracture, 283 had a hip fracture, 206 had a clinical vertebral fracture, and 2,626 died without having any of the three. After adjustment for risk factors such as age, prior nonspine fracture, and prevalent vertebral fracture, men with higher AAC-24 scores had a higher risk of major osteoporotic fracture, compared with men who had scores of 0-1: a hazard ratio of 1.38 (95% confidence interval, 1.10-1.73; P < .001) for scores 2-4, a HR of 1.45 (95% CI, 1.14-1.84; P < .001) for scores 5-8, and a HR of 1.65 (95% CI, 1.29-2.10; P < .001) for scores greater than 9.

Similar findings were reported regarding risk of hip fractures: a HR of 1.54 (95% CI, 1.07-2.20; P < .001) for men with AAC-24 scores 2-4, a HR of 1.40 (95% CI, 0.96-2.06; P < .001) for scores 5-8, and a HR of 2.17 (95% CI, 1.50-3.13; P < .001) for scores greater than 9. AAC-24 score severity was not associated with a higher risk of clinical vertebral fractures.

After adjustment for risk factors and AAC-24 score, men with prevalent vertebral fractures had an increased risk of all three fracture outcomes, compared with men without any fractures at baseline: a HR of 1.56 (95% CI, 1.12-2.16; P < .001) for hip fracture, a HR of 1.85 (95% CI, 1.48-2.31; P < .001) for major osteoporotic fracture, and a HR of 2.76 (95% CI, 1.94-3.91; P < .001) for clinical vertebral fracture.

Adjusting for competing mortality produced similar results: men with higher levels of AAC had increased risk of major osteoporotic fracture and hip fracture, although AAC-24 score was not associated with higher risk of clinical vertebral fractures. Prevalent vertebral fractures were also still associated with higher risk of hip (subdistribution HR, 1.42; 95% CI, 1.01-2.00; P = .004), major osteoporotic fracture (SHR, 1.71; 95% CI, 1.36-2.14; P < .001), and clinical vertebral fracture (SHR, 2.46; 95% CI, 1.72-3.52; P < .001).

Fracture risk assessment proves to be “a nice proof of concept”

“It’s well known that prevalent fractures predict future fractures,” said Thomas M. Link, MD, PhD, chief of the musculoskeletal imaging section in the department of radiology and biomedical imaging at the University of California, San Francisco, in an interview. “The new finding is that aortic calcifications combined with prevalent fractures perform better in predicting major osteoporotic fractures. Traditionally on radiographs, we note that patients who have more calcifications in vessels have less density or calcium in the bone, so this is a nice proof of concept.”

“While the study shows excellent reproducibility, it is not clear how the AAC-24 score was validated,” he added. “Theoretically, abdominal CT could be used for this.”

Along with validation of the AAC-24 score on lateral spine radiographs, he expressed a desire that future research would be “clearer regarding how this would potentially impact patient management. Prevalent fractures already are an indication to treat patients with osteoporosis-specific drugs. How would the results of this study impact management beyond that?”

The authors acknowledged their study’s other potential limitations, including limits in their ability to estimate absolute and relative hip fracture risk in men with low AAC scores but a prevalent vertebral fracture. In addition, they noted that their cohort was “mostly white, healthy, community-dwelling older men” and therefore may not be generalizable to other populations.

The study was supported by the National Institutes of Health, including grants from the National Institute on Aging, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Center for Advancing Translational Sciences, and the NIH Roadmap for Medical Research. One author reported being supported by a National Heart Foundation of Australia Future Leader Fellowship. The others disclosed no potential conflicts of interest.

A new study has found that older men with high levels of abdominal aortic calcification (AAC) and a prevalent vertebral fracture – both of which can be assessed via lateral spine radiographs – are at increased risk of hip, clinical vertebral, and major osteoporotic fractures.

“The results of this study and others suggest that it may be appropriate to expand lateral spine imaging to include those with a significant pre-test probability of higher AAC being present,” wrote John T. Schousboe, MD, of the Park Nicollet Clinic and HealthPartners Institute in Bloomington, Minn. The study was published in the Journal of Bone and Mineral Research.

To determine the impact of prevalent vertebral fractures and AAC on fracture risk, the researchers assessed the lateral spine radiographs of 5,365 men who were enrolled in the Osteoporotic Fractures in Men (MrOS) study. All participants were 65 years or older, community dwelling, able to walk without assistance, and without bilateral hip arthroplasties. They split patients’ 24-point AAC (ACC-24) scores at the baseline visit into four levels: 0-1, 2-4, 5-8, and greater than 9. Self-reports of fractures were solicited from the cohort every 4 months.

Of all participants, 7.6% (n = 407) had a prevalent vertebral fracture at baseline. They were, on average, 1.5 years older than participants without a fracture; they were also more likely to be white and to have a prior nonspine fracture, along with having a lower femoral neck BMD (0.718 g/cm², compared with 0.787 g/cm²; P < .001). In addition, significantly more men with a prevalent vertebral fracture had an AAC score greater than 9 (27% vs. 21.2%).

After an average follow-up period of 12.4 years (standard deviation, 5.2), 634 men had a major osteoporotic fracture, 283 had a hip fracture, 206 had a clinical vertebral fracture, and 2,626 died without having any of the three. After adjustment for risk factors such as age, prior nonspine fracture, and prevalent vertebral fracture, men with higher AAC-24 scores had a higher risk of major osteoporotic fracture, compared with men who had scores of 0-1: a hazard ratio of 1.38 (95% confidence interval, 1.10-1.73; P < .001) for scores 2-4, a HR of 1.45 (95% CI, 1.14-1.84; P < .001) for scores 5-8, and a HR of 1.65 (95% CI, 1.29-2.10; P < .001) for scores greater than 9.

Similar findings were reported regarding risk of hip fractures: a HR of 1.54 (95% CI, 1.07-2.20; P < .001) for men with AAC-24 scores 2-4, a HR of 1.40 (95% CI, 0.96-2.06; P < .001) for scores 5-8, and a HR of 2.17 (95% CI, 1.50-3.13; P < .001) for scores greater than 9. AAC-24 score severity was not associated with a higher risk of clinical vertebral fractures.

After adjustment for risk factors and AAC-24 score, men with prevalent vertebral fractures had an increased risk of all three fracture outcomes, compared with men without any fractures at baseline: a HR of 1.56 (95% CI, 1.12-2.16; P < .001) for hip fracture, a HR of 1.85 (95% CI, 1.48-2.31; P < .001) for major osteoporotic fracture, and a HR of 2.76 (95% CI, 1.94-3.91; P < .001) for clinical vertebral fracture.

Adjusting for competing mortality produced similar results: men with higher levels of AAC had increased risk of major osteoporotic fracture and hip fracture, although AAC-24 score was not associated with higher risk of clinical vertebral fractures. Prevalent vertebral fractures were also still associated with higher risk of hip (subdistribution HR, 1.42; 95% CI, 1.01-2.00; P = .004), major osteoporotic fracture (SHR, 1.71; 95% CI, 1.36-2.14; P < .001), and clinical vertebral fracture (SHR, 2.46; 95% CI, 1.72-3.52; P < .001).

Fracture risk assessment proves to be “a nice proof of concept”

“It’s well known that prevalent fractures predict future fractures,” said Thomas M. Link, MD, PhD, chief of the musculoskeletal imaging section in the department of radiology and biomedical imaging at the University of California, San Francisco, in an interview. “The new finding is that aortic calcifications combined with prevalent fractures perform better in predicting major osteoporotic fractures. Traditionally on radiographs, we note that patients who have more calcifications in vessels have less density or calcium in the bone, so this is a nice proof of concept.”

“While the study shows excellent reproducibility, it is not clear how the AAC-24 score was validated,” he added. “Theoretically, abdominal CT could be used for this.”

Along with validation of the AAC-24 score on lateral spine radiographs, he expressed a desire that future research would be “clearer regarding how this would potentially impact patient management. Prevalent fractures already are an indication to treat patients with osteoporosis-specific drugs. How would the results of this study impact management beyond that?”

The authors acknowledged their study’s other potential limitations, including limits in their ability to estimate absolute and relative hip fracture risk in men with low AAC scores but a prevalent vertebral fracture. In addition, they noted that their cohort was “mostly white, healthy, community-dwelling older men” and therefore may not be generalizable to other populations.

The study was supported by the National Institutes of Health, including grants from the National Institute on Aging, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Center for Advancing Translational Sciences, and the NIH Roadmap for Medical Research. One author reported being supported by a National Heart Foundation of Australia Future Leader Fellowship. The others disclosed no potential conflicts of interest.

A new study has found that older men with high levels of abdominal aortic calcification (AAC) and a prevalent vertebral fracture – both of which can be assessed via lateral spine radiographs – are at increased risk of hip, clinical vertebral, and major osteoporotic fractures.

“The results of this study and others suggest that it may be appropriate to expand lateral spine imaging to include those with a significant pre-test probability of higher AAC being present,” wrote John T. Schousboe, MD, of the Park Nicollet Clinic and HealthPartners Institute in Bloomington, Minn. The study was published in the Journal of Bone and Mineral Research.

To determine the impact of prevalent vertebral fractures and AAC on fracture risk, the researchers assessed the lateral spine radiographs of 5,365 men who were enrolled in the Osteoporotic Fractures in Men (MrOS) study. All participants were 65 years or older, community dwelling, able to walk without assistance, and without bilateral hip arthroplasties. They split patients’ 24-point AAC (ACC-24) scores at the baseline visit into four levels: 0-1, 2-4, 5-8, and greater than 9. Self-reports of fractures were solicited from the cohort every 4 months.

Of all participants, 7.6% (n = 407) had a prevalent vertebral fracture at baseline. They were, on average, 1.5 years older than participants without a fracture; they were also more likely to be white and to have a prior nonspine fracture, along with having a lower femoral neck BMD (0.718 g/cm², compared with 0.787 g/cm²; P < .001). In addition, significantly more men with a prevalent vertebral fracture had an AAC score greater than 9 (27% vs. 21.2%).

After an average follow-up period of 12.4 years (standard deviation, 5.2), 634 men had a major osteoporotic fracture, 283 had a hip fracture, 206 had a clinical vertebral fracture, and 2,626 died without having any of the three. After adjustment for risk factors such as age, prior nonspine fracture, and prevalent vertebral fracture, men with higher AAC-24 scores had a higher risk of major osteoporotic fracture, compared with men who had scores of 0-1: a hazard ratio of 1.38 (95% confidence interval, 1.10-1.73; P < .001) for scores 2-4, a HR of 1.45 (95% CI, 1.14-1.84; P < .001) for scores 5-8, and a HR of 1.65 (95% CI, 1.29-2.10; P < .001) for scores greater than 9.

Similar findings were reported regarding risk of hip fractures: a HR of 1.54 (95% CI, 1.07-2.20; P < .001) for men with AAC-24 scores 2-4, a HR of 1.40 (95% CI, 0.96-2.06; P < .001) for scores 5-8, and a HR of 2.17 (95% CI, 1.50-3.13; P < .001) for scores greater than 9. AAC-24 score severity was not associated with a higher risk of clinical vertebral fractures.

After adjustment for risk factors and AAC-24 score, men with prevalent vertebral fractures had an increased risk of all three fracture outcomes, compared with men without any fractures at baseline: a HR of 1.56 (95% CI, 1.12-2.16; P < .001) for hip fracture, a HR of 1.85 (95% CI, 1.48-2.31; P < .001) for major osteoporotic fracture, and a HR of 2.76 (95% CI, 1.94-3.91; P < .001) for clinical vertebral fracture.

Adjusting for competing mortality produced similar results: men with higher levels of AAC had increased risk of major osteoporotic fracture and hip fracture, although AAC-24 score was not associated with higher risk of clinical vertebral fractures. Prevalent vertebral fractures were also still associated with higher risk of hip (subdistribution HR, 1.42; 95% CI, 1.01-2.00; P = .004), major osteoporotic fracture (SHR, 1.71; 95% CI, 1.36-2.14; P < .001), and clinical vertebral fracture (SHR, 2.46; 95% CI, 1.72-3.52; P < .001).

Fracture risk assessment proves to be “a nice proof of concept”

“It’s well known that prevalent fractures predict future fractures,” said Thomas M. Link, MD, PhD, chief of the musculoskeletal imaging section in the department of radiology and biomedical imaging at the University of California, San Francisco, in an interview. “The new finding is that aortic calcifications combined with prevalent fractures perform better in predicting major osteoporotic fractures. Traditionally on radiographs, we note that patients who have more calcifications in vessels have less density or calcium in the bone, so this is a nice proof of concept.”

“While the study shows excellent reproducibility, it is not clear how the AAC-24 score was validated,” he added. “Theoretically, abdominal CT could be used for this.”

Along with validation of the AAC-24 score on lateral spine radiographs, he expressed a desire that future research would be “clearer regarding how this would potentially impact patient management. Prevalent fractures already are an indication to treat patients with osteoporosis-specific drugs. How would the results of this study impact management beyond that?”

The authors acknowledged their study’s other potential limitations, including limits in their ability to estimate absolute and relative hip fracture risk in men with low AAC scores but a prevalent vertebral fracture. In addition, they noted that their cohort was “mostly white, healthy, community-dwelling older men” and therefore may not be generalizable to other populations.

The study was supported by the National Institutes of Health, including grants from the National Institute on Aging, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Center for Advancing Translational Sciences, and the NIH Roadmap for Medical Research. One author reported being supported by a National Heart Foundation of Australia Future Leader Fellowship. The others disclosed no potential conflicts of interest.

Family physician Mitchell A. Kaminski, MD, MBA, was still awash in feelings of joy and relief at recently being vaccinated against COVID-19 when a patient’s comments stopped him cold. The patient, a middle-aged man with several comorbidities had just declined the pneumonia vaccine – and he added, without prompting, that he wouldn’t be getting the COVID vaccine either. This patient had heard getting vaccinated could kill him.

Dr. Kaminski countered with medical facts, including that the very rare side effects hadn’t killed anyone in the United States but COVID was killing thousands of people every day. “Well then, I’ll just risk getting COVID,” Dr. Kaminski recalled the patient saying. Conversation over.

That experience caused Dr. Kaminski, who is program director for population health at Thomas Jefferson University, Philadelphia, to rethink the way he talks to patients who are uncertain or skeptical about getting a COVID-19 vaccine. Now, if he saw that patient who seemed fearful of dying from a vaccination, Dr. Kaminski said he would be more curious.

Instead of outright contradicting the beliefs of a patient who is reluctant to get vaccinated, Dr. Kaminski now gently asks about the reasons for their discomfort and offers information about the vaccines. But mostly, he listens.

©Sean Warren/iStockphoto.com

Conversations between physicians and patients about the risks that come with getting a COVID-19 vaccine are becoming more common in general as eligibility for immunizations expands. Physicians are using a variety of methods to communicate about the safety and importance of getting vaccinated that they think will lead to more of their patients getting a COVID-19 vaccine.

About 80% of Americans say that they are most likely to turn to doctors, nurses and other health professionals for help in deciding whether to get the COVID vaccine, according to research by the Kaiser Family Foundation.
 

Getting beyond the distrust

While patients often feel a strong connection with their health providers, distrust in the medical establishment still exists, especially among some populations. The Kaiser Family Foundation reported that a third of Black respondents are taking a “wait-and-see” approach, while 23% said they will get it only if it’s required – or not at all.

Distrust persists from historical racist events in medicine, such as the infamous Tuskegee experiments in which treatment was withheld from Black men with syphilis. But physicians shouldn’t assume that all Black patients have the same reasons for vaccine hesitancy, said Krys Foster, MD, MPH, a family physician at Thomas Jefferson University.

“In my experience caring for patients who are uncertain or have concerns about receiving the vaccine, I’ve learned that many are just seeking more information, or even my approval to say that it is safe to proceed given their medical history,” she said.

Sources such as the COVID Racial Data Tracker have found that Black Americans have a higher COVID death rate than other racial or ethnic groups, making vaccination even more vital. Yet fear of the vaccine could be triggered by misinformation that can be found in various places online, Dr. Foster said.

To encourage people to get vaccinated and dispel false information, Dr. Foster takes time to discuss how safe it is to get a COVID-19 vaccine and the vaccines’ side effects, then quickly pivots to discussing how to get vaccinated.

It can be difficult for some people to find appointments or access testing sites. The failure to get the vaccine shouldn’t automatically be attributed to “hesitancy,” she said. “The onus is on the medical community to help fix the health injustices inflicted on communities of color by providing equitable information and access and stop placing blame on them for having the ‘wrong’ vaccine attitude.”
 

Give your testimonial

Jamie Loehr, MD, of Cayuga Family Medicine in Ithaca, N.Y., said he has always had a higher-than-average number of patients who refused or delayed their children’s vaccines. He does not kick them out of his practice but politely continues to educate them about the vaccines.

When patients ask Dr. Loehr if he trusts the vaccine, he responds with confidence: “I not only believe in it, I got it and I recommend it to anyone who can possibly get it.”

He was surprised recently when a mother who has expressed reluctance to vaccinate her young children came for a checkup and told him she had already received a COVID vaccine. “She made the decision on her own that this was important enough that she wanted to get it,” he said.
 

Health care worker hesitancy

Some health care workers’ unease about being at the front of the line for vaccines may be another source of vaccine hesitancy among members of the general population that physicians need to address. In a survey of almost 3,500 health care workers conducted in October and November 2020 and published in January 2021 in Vaccines, only about a third (36%) said they would get the vaccine as soon as it became available. By mid- to late-February, 54% of health care workers reported having been vaccinated and another 10% planned to get the vaccine as soon as possible, according to the Kaiser Family Foundation COVID-19 Vaccine Monitor.

Resolving doubts about the vaccines requires a thoughtful approach toward health care colleagues, said Eileen Barrett, MD, MPH, an internist and hospitalist who was a coauthor of the Vaccines paper and who serves on the editorial advisory board of Internal Medicine News. “We should meet people where they are and do our best to hear their concerns, listening thoughtfully without condescension. Validate how important their role is in endorsing vaccination and also validate asking questions.”

There’s power in the strong personal testimonial of physicians and other health care workers – not just to influence patients, but as a model for fellow health professionals, as well, noted Dr. Barrett, who cares for COVID-19 patients and is associate professor in the division of hospital medicine, department of internal medicine, at the University of New Mexico, Albuquerque.
 

‘Do it for your loved ones’

The Reagan-Udall Foundation, a nonprofit organization created by Congress to support the Food and Drug Administration, tested some messaging with focus groups. Participants responded favorably to this statement about why the vaccines were developed so quickly: “Vaccine development moved faster than normal because everyone’s making it their highest priority.”

People did not feel motivated to get the vaccine out of a sense of civic duty, said Susan Winckler, RPh, Esq, who is CEO of the foundation. But they did think the following was a good reason to get vaccinated: “By getting a vaccine, I could protect my children, my parents, and other loved ones.”

Physicians also can work with community influencers, such as faith leaders, to build confidence in vaccines. That’s part of the strategy of Roll Up Your Sleeves, a campaign spearheaded by agilon health, a company that partners with physician practices to develop value-based care for Medicare Advantage patients.

For example, Wilmington Health in North Carolina answered questions about the vaccines in Facebook Live events and created a Spanish-language video to boost vaccine confidence in the Latinx community. Additionally, PriMED Physicians in Dayton, Ohio, reached out to Black churches to provide a vaccine-awareness video and a PriMED doctor participated in a webinar sponsored by the Nigerian Women Cultural Organization to help dispel myths about COVID-19 and the vaccines.

“This is a way to deepen our relationship with our patients,” said Ben Kornitzer, MD, chief medical officer of agilon. “It’s helping to walk them through this door where on one side is the pandemic and social isolation and on the other side is a return to their life and loved ones.”

The messages provided by primary care physicians can be powerful and affirming, said Ms. Winckler.

“The path forward is to make a space for people to ask questions,” she continued, noting that the Reagan-Udall Foundation provides charts that show how the timeline for vaccine development was compressed without skipping any steps.

Strategies and background information on how to reinforce confidence in COVID-19 vaccines are also available on a page of the Centers for Disease Control and Prevention’s website.

None of the experts interviewed reported any relevant conflicts of interest. The Reagan-Udall Foundation has received sponsorships from Johnson & Johnson and AstraZeneca and has had a safety surveillance contract with Pfizer.

Family physician Mitchell A. Kaminski, MD, MBA, was still awash in feelings of joy and relief at recently being vaccinated against COVID-19 when a patient’s comments stopped him cold. The patient, a middle-aged man with several comorbidities had just declined the pneumonia vaccine – and he added, without prompting, that he wouldn’t be getting the COVID vaccine either. This patient had heard getting vaccinated could kill him.

Dr. Kaminski countered with medical facts, including that the very rare side effects hadn’t killed anyone in the United States but COVID was killing thousands of people every day. “Well then, I’ll just risk getting COVID,” Dr. Kaminski recalled the patient saying. Conversation over.

That experience caused Dr. Kaminski, who is program director for population health at Thomas Jefferson University, Philadelphia, to rethink the way he talks to patients who are uncertain or skeptical about getting a COVID-19 vaccine. Now, if he saw that patient who seemed fearful of dying from a vaccination, Dr. Kaminski said he would be more curious.

Instead of outright contradicting the beliefs of a patient who is reluctant to get vaccinated, Dr. Kaminski now gently asks about the reasons for their discomfort and offers information about the vaccines. But mostly, he listens.

©Sean Warren/iStockphoto.com

Conversations between physicians and patients about the risks that come with getting a COVID-19 vaccine are becoming more common in general as eligibility for immunizations expands. Physicians are using a variety of methods to communicate about the safety and importance of getting vaccinated that they think will lead to more of their patients getting a COVID-19 vaccine.

About 80% of Americans say that they are most likely to turn to doctors, nurses and other health professionals for help in deciding whether to get the COVID vaccine, according to research by the Kaiser Family Foundation.
 

Getting beyond the distrust

While patients often feel a strong connection with their health providers, distrust in the medical establishment still exists, especially among some populations. The Kaiser Family Foundation reported that a third of Black respondents are taking a “wait-and-see” approach, while 23% said they will get it only if it’s required – or not at all.

Distrust persists from historical racist events in medicine, such as the infamous Tuskegee experiments in which treatment was withheld from Black men with syphilis. But physicians shouldn’t assume that all Black patients have the same reasons for vaccine hesitancy, said Krys Foster, MD, MPH, a family physician at Thomas Jefferson University.

“In my experience caring for patients who are uncertain or have concerns about receiving the vaccine, I’ve learned that many are just seeking more information, or even my approval to say that it is safe to proceed given their medical history,” she said.

Sources such as the COVID Racial Data Tracker have found that Black Americans have a higher COVID death rate than other racial or ethnic groups, making vaccination even more vital. Yet fear of the vaccine could be triggered by misinformation that can be found in various places online, Dr. Foster said.

To encourage people to get vaccinated and dispel false information, Dr. Foster takes time to discuss how safe it is to get a COVID-19 vaccine and the vaccines’ side effects, then quickly pivots to discussing how to get vaccinated.

It can be difficult for some people to find appointments or access testing sites. The failure to get the vaccine shouldn’t automatically be attributed to “hesitancy,” she said. “The onus is on the medical community to help fix the health injustices inflicted on communities of color by providing equitable information and access and stop placing blame on them for having the ‘wrong’ vaccine attitude.”
 

Give your testimonial

Jamie Loehr, MD, of Cayuga Family Medicine in Ithaca, N.Y., said he has always had a higher-than-average number of patients who refused or delayed their children’s vaccines. He does not kick them out of his practice but politely continues to educate them about the vaccines.

When patients ask Dr. Loehr if he trusts the vaccine, he responds with confidence: “I not only believe in it, I got it and I recommend it to anyone who can possibly get it.”

He was surprised recently when a mother who has expressed reluctance to vaccinate her young children came for a checkup and told him she had already received a COVID vaccine. “She made the decision on her own that this was important enough that she wanted to get it,” he said.
 

Health care worker hesitancy

Some health care workers’ unease about being at the front of the line for vaccines may be another source of vaccine hesitancy among members of the general population that physicians need to address. In a survey of almost 3,500 health care workers conducted in October and November 2020 and published in January 2021 in Vaccines, only about a third (36%) said they would get the vaccine as soon as it became available. By mid- to late-February, 54% of health care workers reported having been vaccinated and another 10% planned to get the vaccine as soon as possible, according to the Kaiser Family Foundation COVID-19 Vaccine Monitor.

Resolving doubts about the vaccines requires a thoughtful approach toward health care colleagues, said Eileen Barrett, MD, MPH, an internist and hospitalist who was a coauthor of the Vaccines paper and who serves on the editorial advisory board of Internal Medicine News. “We should meet people where they are and do our best to hear their concerns, listening thoughtfully without condescension. Validate how important their role is in endorsing vaccination and also validate asking questions.”

There’s power in the strong personal testimonial of physicians and other health care workers – not just to influence patients, but as a model for fellow health professionals, as well, noted Dr. Barrett, who cares for COVID-19 patients and is associate professor in the division of hospital medicine, department of internal medicine, at the University of New Mexico, Albuquerque.
 

‘Do it for your loved ones’

The Reagan-Udall Foundation, a nonprofit organization created by Congress to support the Food and Drug Administration, tested some messaging with focus groups. Participants responded favorably to this statement about why the vaccines were developed so quickly: “Vaccine development moved faster than normal because everyone’s making it their highest priority.”

People did not feel motivated to get the vaccine out of a sense of civic duty, said Susan Winckler, RPh, Esq, who is CEO of the foundation. But they did think the following was a good reason to get vaccinated: “By getting a vaccine, I could protect my children, my parents, and other loved ones.”

Physicians also can work with community influencers, such as faith leaders, to build confidence in vaccines. That’s part of the strategy of Roll Up Your Sleeves, a campaign spearheaded by agilon health, a company that partners with physician practices to develop value-based care for Medicare Advantage patients.

For example, Wilmington Health in North Carolina answered questions about the vaccines in Facebook Live events and created a Spanish-language video to boost vaccine confidence in the Latinx community. Additionally, PriMED Physicians in Dayton, Ohio, reached out to Black churches to provide a vaccine-awareness video and a PriMED doctor participated in a webinar sponsored by the Nigerian Women Cultural Organization to help dispel myths about COVID-19 and the vaccines.

“This is a way to deepen our relationship with our patients,” said Ben Kornitzer, MD, chief medical officer of agilon. “It’s helping to walk them through this door where on one side is the pandemic and social isolation and on the other side is a return to their life and loved ones.”

The messages provided by primary care physicians can be powerful and affirming, said Ms. Winckler.

“The path forward is to make a space for people to ask questions,” she continued, noting that the Reagan-Udall Foundation provides charts that show how the timeline for vaccine development was compressed without skipping any steps.

Strategies and background information on how to reinforce confidence in COVID-19 vaccines are also available on a page of the Centers for Disease Control and Prevention’s website.

None of the experts interviewed reported any relevant conflicts of interest. The Reagan-Udall Foundation has received sponsorships from Johnson & Johnson and AstraZeneca and has had a safety surveillance contract with Pfizer.

Family physician Mitchell A. Kaminski, MD, MBA, was still awash in feelings of joy and relief at recently being vaccinated against COVID-19 when a patient’s comments stopped him cold. The patient, a middle-aged man with several comorbidities had just declined the pneumonia vaccine – and he added, without prompting, that he wouldn’t be getting the COVID vaccine either. This patient had heard getting vaccinated could kill him.

Dr. Kaminski countered with medical facts, including that the very rare side effects hadn’t killed anyone in the United States but COVID was killing thousands of people every day. “Well then, I’ll just risk getting COVID,” Dr. Kaminski recalled the patient saying. Conversation over.

That experience caused Dr. Kaminski, who is program director for population health at Thomas Jefferson University, Philadelphia, to rethink the way he talks to patients who are uncertain or skeptical about getting a COVID-19 vaccine. Now, if he saw that patient who seemed fearful of dying from a vaccination, Dr. Kaminski said he would be more curious.

Instead of outright contradicting the beliefs of a patient who is reluctant to get vaccinated, Dr. Kaminski now gently asks about the reasons for their discomfort and offers information about the vaccines. But mostly, he listens.

©Sean Warren/iStockphoto.com

Conversations between physicians and patients about the risks that come with getting a COVID-19 vaccine are becoming more common in general as eligibility for immunizations expands. Physicians are using a variety of methods to communicate about the safety and importance of getting vaccinated that they think will lead to more of their patients getting a COVID-19 vaccine.

About 80% of Americans say that they are most likely to turn to doctors, nurses and other health professionals for help in deciding whether to get the COVID vaccine, according to research by the Kaiser Family Foundation.
 

Getting beyond the distrust

While patients often feel a strong connection with their health providers, distrust in the medical establishment still exists, especially among some populations. The Kaiser Family Foundation reported that a third of Black respondents are taking a “wait-and-see” approach, while 23% said they will get it only if it’s required – or not at all.

Distrust persists from historical racist events in medicine, such as the infamous Tuskegee experiments in which treatment was withheld from Black men with syphilis. But physicians shouldn’t assume that all Black patients have the same reasons for vaccine hesitancy, said Krys Foster, MD, MPH, a family physician at Thomas Jefferson University.

“In my experience caring for patients who are uncertain or have concerns about receiving the vaccine, I’ve learned that many are just seeking more information, or even my approval to say that it is safe to proceed given their medical history,” she said.

Sources such as the COVID Racial Data Tracker have found that Black Americans have a higher COVID death rate than other racial or ethnic groups, making vaccination even more vital. Yet fear of the vaccine could be triggered by misinformation that can be found in various places online, Dr. Foster said.

To encourage people to get vaccinated and dispel false information, Dr. Foster takes time to discuss how safe it is to get a COVID-19 vaccine and the vaccines’ side effects, then quickly pivots to discussing how to get vaccinated.

It can be difficult for some people to find appointments or access testing sites. The failure to get the vaccine shouldn’t automatically be attributed to “hesitancy,” she said. “The onus is on the medical community to help fix the health injustices inflicted on communities of color by providing equitable information and access and stop placing blame on them for having the ‘wrong’ vaccine attitude.”
 

Give your testimonial

Jamie Loehr, MD, of Cayuga Family Medicine in Ithaca, N.Y., said he has always had a higher-than-average number of patients who refused or delayed their children’s vaccines. He does not kick them out of his practice but politely continues to educate them about the vaccines.

When patients ask Dr. Loehr if he trusts the vaccine, he responds with confidence: “I not only believe in it, I got it and I recommend it to anyone who can possibly get it.”

He was surprised recently when a mother who has expressed reluctance to vaccinate her young children came for a checkup and told him she had already received a COVID vaccine. “She made the decision on her own that this was important enough that she wanted to get it,” he said.
 

Health care worker hesitancy

Some health care workers’ unease about being at the front of the line for vaccines may be another source of vaccine hesitancy among members of the general population that physicians need to address. In a survey of almost 3,500 health care workers conducted in October and November 2020 and published in January 2021 in Vaccines, only about a third (36%) said they would get the vaccine as soon as it became available. By mid- to late-February, 54% of health care workers reported having been vaccinated and another 10% planned to get the vaccine as soon as possible, according to the Kaiser Family Foundation COVID-19 Vaccine Monitor.

Resolving doubts about the vaccines requires a thoughtful approach toward health care colleagues, said Eileen Barrett, MD, MPH, an internist and hospitalist who was a coauthor of the Vaccines paper and who serves on the editorial advisory board of Internal Medicine News. “We should meet people where they are and do our best to hear their concerns, listening thoughtfully without condescension. Validate how important their role is in endorsing vaccination and also validate asking questions.”

There’s power in the strong personal testimonial of physicians and other health care workers – not just to influence patients, but as a model for fellow health professionals, as well, noted Dr. Barrett, who cares for COVID-19 patients and is associate professor in the division of hospital medicine, department of internal medicine, at the University of New Mexico, Albuquerque.
 

‘Do it for your loved ones’

The Reagan-Udall Foundation, a nonprofit organization created by Congress to support the Food and Drug Administration, tested some messaging with focus groups. Participants responded favorably to this statement about why the vaccines were developed so quickly: “Vaccine development moved faster than normal because everyone’s making it their highest priority.”

People did not feel motivated to get the vaccine out of a sense of civic duty, said Susan Winckler, RPh, Esq, who is CEO of the foundation. But they did think the following was a good reason to get vaccinated: “By getting a vaccine, I could protect my children, my parents, and other loved ones.”

Physicians also can work with community influencers, such as faith leaders, to build confidence in vaccines. That’s part of the strategy of Roll Up Your Sleeves, a campaign spearheaded by agilon health, a company that partners with physician practices to develop value-based care for Medicare Advantage patients.

For example, Wilmington Health in North Carolina answered questions about the vaccines in Facebook Live events and created a Spanish-language video to boost vaccine confidence in the Latinx community. Additionally, PriMED Physicians in Dayton, Ohio, reached out to Black churches to provide a vaccine-awareness video and a PriMED doctor participated in a webinar sponsored by the Nigerian Women Cultural Organization to help dispel myths about COVID-19 and the vaccines.

“This is a way to deepen our relationship with our patients,” said Ben Kornitzer, MD, chief medical officer of agilon. “It’s helping to walk them through this door where on one side is the pandemic and social isolation and on the other side is a return to their life and loved ones.”

The messages provided by primary care physicians can be powerful and affirming, said Ms. Winckler.

“The path forward is to make a space for people to ask questions,” she continued, noting that the Reagan-Udall Foundation provides charts that show how the timeline for vaccine development was compressed without skipping any steps.

Strategies and background information on how to reinforce confidence in COVID-19 vaccines are also available on a page of the Centers for Disease Control and Prevention’s website.

None of the experts interviewed reported any relevant conflicts of interest. The Reagan-Udall Foundation has received sponsorships from Johnson & Johnson and AstraZeneca and has had a safety surveillance contract with Pfizer.

On the basis of the quality of sustained bone growth achieved with vosoritide in dwarfism, studies are underway or being considered for more diseases that impair bone growth, according to discussion that followed the presentation of a phase 3 trial extension study at the annual meeting of the Endocrine Society.

After 1 year on active therapy in the randomized trial and another year in the extension study, patients in the vosoritide group had sustained growth velocity while placebo group patients who crossed over to active therapy caught up, reported Ravi Savarirayan, MD, Murdoch Children’s Research Institute, University of Melbourne, Australia.

Moreover, the quality and type of bone growth, such as the improvement in body segment ratios over the second year of the study, support a durable benefit. Dr. Savarirayan said that improvements in activities of daily living are expected from this improvement in upper-to-lower body segment ratios, as well as the growth seen in the limbs.

Currently there is no approved pharmacologic therapy for achondroplasia in the United States. Growth hormone has been approved in Japan, but Dr. Savarirayan said its effects have been limited. Surgery such as limb lengthening is another option, but this approach is not uniformly effective and carries risks.

The 52-week results from the multinational phase 3 trial with vosoritide, which stimulates bone growth, were published last year in The Lancet. In that trial, 121 patients between the ages of 5 and 18 years with achondroplasia were randomized to vosoritide at a dose of 15 μg/kg once daily or placebo.

Over the 1-year study period, the median growth velocity for those treated with vosoritide increased from about 4 cm per year to 6 cm per year. Relative to those in the placebo arm, which did not experience any change in growth, the median growth at the end of 52 weeks was 1.75 cm/year greater (6.71 vs. 3.99 cm).
 

After crossover, placebo patients catch up

In the extension study, the placebo patients were crossed over to the active therapy and both groups were followed for an additional 52 weeks. Over this period, velocity declined modestly in those in the group initially randomized to vosoritide but climbed steeply in the placebo group so that rates after 1 year were nearly identical (5.57 vs. 5.65 cm, respectively).

“The results suggest this medication may well have a durable effect,” said Dr. Savarirayan, who believes that the benefit is derived from stimulation of the growth plates. Based on the very similar efficacy observed in the placebo group once switched to active therapy, the response to vosoritide appears to be predictable.

Of the 60 patients initially randomized to vosoritide, 58 entered the extension. Of the patients who did not remain in the study, two left due to discomfort from injection-site reactions. All 61 patients initially assigned to placebo crossed over.

“We did not see any evidence of tachyphylaxis in the randomized study or in the extension,” Dr. Savarirayan said.

Although two more patients initiated on vosoritide discontinued treatment before the end of 2 years, there were no new adverse events observed. Rather, injection-site pain, which self-resolved in all patients, appears to be the most significant side effect.

“In children, the daily subcutaneous injections can be an issue,” Dr. Savarirayan acknowledged.
 

Injection site reactions most common adverse event

In a detailed evaluation of safety in a previously published dose-finding phase 2 study, injection-site reactions were also the most common of treatment-related adverse events, but there were no episodes of anaphylaxis or other grade 3 or higher hypersensitivity reactions (N Engl J Med. 2019 Jul 4;381:25-35).

Prior to clinical trials, continuous infusion of endogenous C-type natriuretic peptide demonstrated an ability to stimulate long-bone growth in experimental studies. Vosoritide, a recombinant analogue of C-type natriuretic peptide, appears to provide the same activity but offers a longer half-life.

Based on the benefits observed in achondroplasia, other applications are now being explored.

“When you evaluate the quality of the bone growth associated with vosoritide, it is normal,” said Melita Irving, MD, a consultant in clinical genetics at the Guy’s and St .Thomas’ NHS Trust, London. Dr. Irving has been involved in other research initiatives with this therapy and she cited a variety of evidence that has supported healthy bone development, including favorable changes in markers of bone growth such as type 10 collagen.

As a result, vosoritide, which is now under review by the U.S. Food and Drug Administration for treatment of dwarfism, is being pursued for several other diseases that result in abnormal bone growth, such as hypochondroplasia. Not least, clinical studies in idiopathic short stature have reached “early stages,” Dr. Irving said.

Dr. Savarirayan and Dr. Irving report no relevant conflicts of interest.

cenews@mdedge.com