MDedge Neurology

Childhood autism rates are at the highest level since the Centers for Disease Control and Prevention began tracking the disorder in 2000, new data released Dec. 2 show.

The increase likely reflects improvements in diagnosis and identification of autism spectrum disorder (ASD), not an increase in incidence, study authors with the CDC’s Autism and Developmental Disabilities Monitoring (ADDM) Network told this news organization.

Using a new surveillance methodology, researchers found that 2.3% of 8-year-olds in communities in 11 states across the United States had an autism diagnosis in 2018, up from 1.9% in 2016.

A separate report on early identification in 4-year-olds shows that children born in 2014 were 50% more likely to receive an autism diagnosis or ASD special education classification by 48 months of age than those born in 2010, signaling improved early diagnosis.

Taken together, the data suggest efforts to raise awareness about autism are working, though researchers were quick to say much work remains.

“It was not surprising to me and in fact it was reassuring that the number of children diagnosed with autism is higher and is actually approaching prevalence of autism that has been noted in some national surveys of parents,” Stuart Shapira, MD, PhD, associate director for science in CDC’s National Center on Birth Defects and Developmental Disability, told this news organization.

“It means we’re doing a better job of identifying children, which helps to get them into services earlier so they can achieve their best developmental outcome.”

The studies, published online in Morbidity and Mortality Weekly Report, are the first to use a new ASD surveillance protocol that relies on ASD diagnosis or special education classification and billing codes and eliminates comprehensive records analysis by trained clinician reviewers.

Racial disparities

The updated methodology was less labor intensive and reduced the time it took to produce the report, but it is not without its critics, who claim the new protocol will undercount the number of children with ASD.

Created in 2000 and funded by the CDC, the ADDM Network is the only surveillance program in the United States that tracks the number and characteristics of children with ASD in multiple communities in the U.S.

When ADDM released its first report in 2007 from six states and based on data from the year 2000, ASD prevalence was 6.7 per 1,000 children, or 1 in 150 children.

In the latest report, which includes data from 2018, the autism prevalence rate across 11 states was 23.0 per 1,000 children, or 1 in 44 children.

That rate is closer to reported autism prevalence from the National Survey of Children’s Health and the National Health Interview Survey, both of which rely on parent-reported ASD diagnoses.

For the report, researchers analyzed medical and special education records of 220,281 children who were born in 2010 in Arizona, Arkansas, California, Georgia, Maryland, Minnesota, Missouri, New Jersey, Tennessee, Utah, and Wisconsin.

Children were counted as having autism if their records included an ASD diagnosis, a special education classification of ASD, or an ASD International Classification of Diseases (ICD) code. A total of 5,058 children met those criteria.

Rates of ASD ranged from a low of 1.7% in Missouri to 3.9% in California and were 4.2 times higher in boys than in girls. Just under half of the children with ASD were evaluated by age 36 months.

Although the overall ASD prevalence was similar among White, Black, Hispanic, and Asian/Pacific Islander children, the report highlighted a number of other racial disparities overall and in individual states.

For example, among those with ASD and data on cognitive ability, 35.2% had an intelligence quotient score of 70 or lower. Black children with ASD were far more likely to have an IQ of 70 or less (49.8%) than Hispanic (33.1%) or White (29.7%) children.

“The persistent disparities in co-occurring intellectual disabilities in children with autism is something that we continue to see and suggests that we need to better understand exactly what’s happening,” Matthew Maenner, PhD, an epidemiologist and autism surveillance team lead with the CDC’s National Center on Birth Defects and Developmental Disabilities, told this news organization.

Another long-standing trend observed again in the new report on prevalence among 8-year-olds is low ASD prevalence among Hispanic children. While the overall estimate showed similar autism rates, a closer review of state-level data reveals a different picture.

“In almost half of the sites, Hispanic children were less likely to be identified as having ASD,” he said. “This gets lost if you look only at the overall estimate.”

New methodology

When ADDM released its first report in 2007, autism diagnosis was widely inadequate in the United States. Relying on only confirmed ASD diagnoses would significantly underestimate the number of children with the disorder, so the CDC added “active case finding” to the protocol.

Trained clinician reviewers analyzed individual notes from medical and educational records for every 8-year-old in ADDM Network sites, looking for evidence of characteristics and behaviors associated with autism. The process was labor- and time-intensive and took up to 4 years to complete.

In 2018, the CDC began investigating ways to speed the process and came up with the strategy used in the latest report. The new protocol was faster, easier, and less expensive. Although he says cost was never the deciding factor, Dr. Maenner acknowledges that had they stuck with the original protocol, they would have been forced to reduce the number of ADDM Network sites.

Dr. Maenner argues that a comparison of the two protocols shows the new method doesn’t compromise accuracy and may actually capture children who lacked the medical or educational records the previous protocol required for a count. But not everyone agrees.

“I thought the point was to be as accurate and complete as possible in doing the surveillance,” Walter Zahorodny, PhD, associate professor of pediatrics at Rutgers University, New Brunswick, N.J., and principal investigator of the New Jersey ADDM Network site, told this news organization. “In states where there’s a high detail of information in records, like New Jersey, it’s going to underestimate the count.”

Dr. Zahorodny says the latest data prove his point. In 2016, under the old methodology, ASD prevalence was 3.1% in the state. In 2018, under the new protocol, prevalence was 2.84%, a decrease of about 20% that Dr. Zahorodny pins squarely on the elimination of ADDM clinical reviewers.

But New Jersey is the only state that participated in both the 2016 and 2018 surveillance periods to report a decrease in ASD prevalence. The other eight states all found autism rates in their states went up.

Sydney Pettygrove, PhD, associate professor of public health and pediatrics at the University of Arizona, Tucson, and a principal investigator for the ADDM site in Arizona, told this news organization that when she first learned the CDC was rolling out a new methodology, she and other investigators were concerned.

“People were really upset. I was really upset,” she said. “I had formed an opinion based on the earlier data that this would not be a good idea.”

In 2000, when ASD surveillance began in Arizona, nearly 30% of children identified by ADDM clinical reviewers as having autism had no mention of the disorder in their records. Today, that percentage is closer to 5%.

“In 2000 it would have been catastrophic to try to estimate the prevalence of autism with the new protocol,” said Dr. Pettygrove. As it turns out, under the new protocol, prevalence rates in Arizona increased from 16.0 per 1,000 children in 2016 to 24.9 in 2018.

Built-in bias eliminated?

In addition to speeding up the process, the new methodology might have other benefits as well. Under the old ADDM surveillance protocol, children who lacked certain medical or educational records did not meet the ASD case definition and weren’t counted.

A 2019 study showed that this disproportionately affected Black and Hispanic children, who had significantly less access to health care professionals than White children.

As a result, “the old methodology had a bias built into it,” Maureen Durkin, PhD, DrPH, coauthor of that study and chair of population health sciences at the University of Wisconsin–Madison and principal investigator for the ADDM site in Wisconsin, told this news organization.

“Clinician reviewers ended up putting these children in the ‘suspected ASD’ category because they couldn’t call it a case under the case definition,” Dr. Durkin said. “There was a fairly large percentage of suspected cases and a disproportionate number of those kids were children of color.”

Although she can’t say for sure, Dr. Durkin said it’s possible the new protocol could eliminate some of that bias.

CDC researchers also attribute the new method to an expanded study of early diagnosis among 4-year-olds. In previous years, only a handful of the ADDM Network sites participating in the 8-year-old surveillance project also studied early diagnosis in 4-year-olds.

This year, all 11 sites took part in the early diagnosis analysis, tripling the number of children included in the analysis. That made it possible to include, for the first time, Asian/Pacific Islander children in this analysis.

In the past, ASD prevalence has trended higher in White children, compared with other racial groups. The new data found that ASD prevalence among 4-year-olds was significantly lower in White children (12.9 per 1,000 children) than in Black, Hispanic, or Asian/Pacific Islander children (16.6, 21.1, and 22.7 per 1,000, respectively). Prevalence in American Indian/Alaska Native children was the lowest among all racial groups (11.5 per 1,000).

It’s the first time researchers have seen this pattern in any ADDM report, Kelly Shaw, PhD, lead author of that study and an epidemiologist with the National Center on Birth Defects and Developmental Disability at the CDC, told this news organization.

These data don’t provide clues about the potential cause of that disparity, Dr. Shaw said. It’s likely an indication of better identification of ASD in those communities, she said, and not a sign of increased incidence of autism among Black, Hispanic, or Asian/Pacific Islander children.

“We don’t have any evidence to suggest or expect that autism would be increasing differentially among groups,” Dr. Shaw said.

The data suggest “we are making some progress but there certainly is still room for improvement,” Dr. Shaw said.

Study authors report no conflicts of interest.

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

Childhood autism rates are at the highest level since the Centers for Disease Control and Prevention began tracking the disorder in 2000, new data released Dec. 2 show.

The increase likely reflects improvements in diagnosis and identification of autism spectrum disorder (ASD), not an increase in incidence, study authors with the CDC’s Autism and Developmental Disabilities Monitoring (ADDM) Network told this news organization.

Using a new surveillance methodology, researchers found that 2.3% of 8-year-olds in communities in 11 states across the United States had an autism diagnosis in 2018, up from 1.9% in 2016.

A separate report on early identification in 4-year-olds shows that children born in 2014 were 50% more likely to receive an autism diagnosis or ASD special education classification by 48 months of age than those born in 2010, signaling improved early diagnosis.

Taken together, the data suggest efforts to raise awareness about autism are working, though researchers were quick to say much work remains.

“It was not surprising to me and in fact it was reassuring that the number of children diagnosed with autism is higher and is actually approaching prevalence of autism that has been noted in some national surveys of parents,” Stuart Shapira, MD, PhD, associate director for science in CDC’s National Center on Birth Defects and Developmental Disability, told this news organization.

“It means we’re doing a better job of identifying children, which helps to get them into services earlier so they can achieve their best developmental outcome.”

The studies, published online in Morbidity and Mortality Weekly Report, are the first to use a new ASD surveillance protocol that relies on ASD diagnosis or special education classification and billing codes and eliminates comprehensive records analysis by trained clinician reviewers.

Racial disparities

The updated methodology was less labor intensive and reduced the time it took to produce the report, but it is not without its critics, who claim the new protocol will undercount the number of children with ASD.

Created in 2000 and funded by the CDC, the ADDM Network is the only surveillance program in the United States that tracks the number and characteristics of children with ASD in multiple communities in the U.S.

When ADDM released its first report in 2007 from six states and based on data from the year 2000, ASD prevalence was 6.7 per 1,000 children, or 1 in 150 children.

In the latest report, which includes data from 2018, the autism prevalence rate across 11 states was 23.0 per 1,000 children, or 1 in 44 children.

That rate is closer to reported autism prevalence from the National Survey of Children’s Health and the National Health Interview Survey, both of which rely on parent-reported ASD diagnoses.

For the report, researchers analyzed medical and special education records of 220,281 children who were born in 2010 in Arizona, Arkansas, California, Georgia, Maryland, Minnesota, Missouri, New Jersey, Tennessee, Utah, and Wisconsin.

Children were counted as having autism if their records included an ASD diagnosis, a special education classification of ASD, or an ASD International Classification of Diseases (ICD) code. A total of 5,058 children met those criteria.

Rates of ASD ranged from a low of 1.7% in Missouri to 3.9% in California and were 4.2 times higher in boys than in girls. Just under half of the children with ASD were evaluated by age 36 months.

Although the overall ASD prevalence was similar among White, Black, Hispanic, and Asian/Pacific Islander children, the report highlighted a number of other racial disparities overall and in individual states.

For example, among those with ASD and data on cognitive ability, 35.2% had an intelligence quotient score of 70 or lower. Black children with ASD were far more likely to have an IQ of 70 or less (49.8%) than Hispanic (33.1%) or White (29.7%) children.

“The persistent disparities in co-occurring intellectual disabilities in children with autism is something that we continue to see and suggests that we need to better understand exactly what’s happening,” Matthew Maenner, PhD, an epidemiologist and autism surveillance team lead with the CDC’s National Center on Birth Defects and Developmental Disabilities, told this news organization.

Another long-standing trend observed again in the new report on prevalence among 8-year-olds is low ASD prevalence among Hispanic children. While the overall estimate showed similar autism rates, a closer review of state-level data reveals a different picture.

“In almost half of the sites, Hispanic children were less likely to be identified as having ASD,” he said. “This gets lost if you look only at the overall estimate.”

New methodology

When ADDM released its first report in 2007, autism diagnosis was widely inadequate in the United States. Relying on only confirmed ASD diagnoses would significantly underestimate the number of children with the disorder, so the CDC added “active case finding” to the protocol.

Trained clinician reviewers analyzed individual notes from medical and educational records for every 8-year-old in ADDM Network sites, looking for evidence of characteristics and behaviors associated with autism. The process was labor- and time-intensive and took up to 4 years to complete.

In 2018, the CDC began investigating ways to speed the process and came up with the strategy used in the latest report. The new protocol was faster, easier, and less expensive. Although he says cost was never the deciding factor, Dr. Maenner acknowledges that had they stuck with the original protocol, they would have been forced to reduce the number of ADDM Network sites.

Dr. Maenner argues that a comparison of the two protocols shows the new method doesn’t compromise accuracy and may actually capture children who lacked the medical or educational records the previous protocol required for a count. But not everyone agrees.

“I thought the point was to be as accurate and complete as possible in doing the surveillance,” Walter Zahorodny, PhD, associate professor of pediatrics at Rutgers University, New Brunswick, N.J., and principal investigator of the New Jersey ADDM Network site, told this news organization. “In states where there’s a high detail of information in records, like New Jersey, it’s going to underestimate the count.”

Dr. Zahorodny says the latest data prove his point. In 2016, under the old methodology, ASD prevalence was 3.1% in the state. In 2018, under the new protocol, prevalence was 2.84%, a decrease of about 20% that Dr. Zahorodny pins squarely on the elimination of ADDM clinical reviewers.

But New Jersey is the only state that participated in both the 2016 and 2018 surveillance periods to report a decrease in ASD prevalence. The other eight states all found autism rates in their states went up.

Sydney Pettygrove, PhD, associate professor of public health and pediatrics at the University of Arizona, Tucson, and a principal investigator for the ADDM site in Arizona, told this news organization that when she first learned the CDC was rolling out a new methodology, she and other investigators were concerned.

“People were really upset. I was really upset,” she said. “I had formed an opinion based on the earlier data that this would not be a good idea.”

In 2000, when ASD surveillance began in Arizona, nearly 30% of children identified by ADDM clinical reviewers as having autism had no mention of the disorder in their records. Today, that percentage is closer to 5%.

“In 2000 it would have been catastrophic to try to estimate the prevalence of autism with the new protocol,” said Dr. Pettygrove. As it turns out, under the new protocol, prevalence rates in Arizona increased from 16.0 per 1,000 children in 2016 to 24.9 in 2018.

Built-in bias eliminated?

In addition to speeding up the process, the new methodology might have other benefits as well. Under the old ADDM surveillance protocol, children who lacked certain medical or educational records did not meet the ASD case definition and weren’t counted.

A 2019 study showed that this disproportionately affected Black and Hispanic children, who had significantly less access to health care professionals than White children.

As a result, “the old methodology had a bias built into it,” Maureen Durkin, PhD, DrPH, coauthor of that study and chair of population health sciences at the University of Wisconsin–Madison and principal investigator for the ADDM site in Wisconsin, told this news organization.

“Clinician reviewers ended up putting these children in the ‘suspected ASD’ category because they couldn’t call it a case under the case definition,” Dr. Durkin said. “There was a fairly large percentage of suspected cases and a disproportionate number of those kids were children of color.”

Although she can’t say for sure, Dr. Durkin said it’s possible the new protocol could eliminate some of that bias.

CDC researchers also attribute the new method to an expanded study of early diagnosis among 4-year-olds. In previous years, only a handful of the ADDM Network sites participating in the 8-year-old surveillance project also studied early diagnosis in 4-year-olds.

This year, all 11 sites took part in the early diagnosis analysis, tripling the number of children included in the analysis. That made it possible to include, for the first time, Asian/Pacific Islander children in this analysis.

In the past, ASD prevalence has trended higher in White children, compared with other racial groups. The new data found that ASD prevalence among 4-year-olds was significantly lower in White children (12.9 per 1,000 children) than in Black, Hispanic, or Asian/Pacific Islander children (16.6, 21.1, and 22.7 per 1,000, respectively). Prevalence in American Indian/Alaska Native children was the lowest among all racial groups (11.5 per 1,000).

It’s the first time researchers have seen this pattern in any ADDM report, Kelly Shaw, PhD, lead author of that study and an epidemiologist with the National Center on Birth Defects and Developmental Disability at the CDC, told this news organization.

These data don’t provide clues about the potential cause of that disparity, Dr. Shaw said. It’s likely an indication of better identification of ASD in those communities, she said, and not a sign of increased incidence of autism among Black, Hispanic, or Asian/Pacific Islander children.

“We don’t have any evidence to suggest or expect that autism would be increasing differentially among groups,” Dr. Shaw said.

The data suggest “we are making some progress but there certainly is still room for improvement,” Dr. Shaw said.

Study authors report no conflicts of interest.

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

Childhood autism rates are at the highest level since the Centers for Disease Control and Prevention began tracking the disorder in 2000, new data released Dec. 2 show.

The increase likely reflects improvements in diagnosis and identification of autism spectrum disorder (ASD), not an increase in incidence, study authors with the CDC’s Autism and Developmental Disabilities Monitoring (ADDM) Network told this news organization.

Using a new surveillance methodology, researchers found that 2.3% of 8-year-olds in communities in 11 states across the United States had an autism diagnosis in 2018, up from 1.9% in 2016.

A separate report on early identification in 4-year-olds shows that children born in 2014 were 50% more likely to receive an autism diagnosis or ASD special education classification by 48 months of age than those born in 2010, signaling improved early diagnosis.

Taken together, the data suggest efforts to raise awareness about autism are working, though researchers were quick to say much work remains.

“It was not surprising to me and in fact it was reassuring that the number of children diagnosed with autism is higher and is actually approaching prevalence of autism that has been noted in some national surveys of parents,” Stuart Shapira, MD, PhD, associate director for science in CDC’s National Center on Birth Defects and Developmental Disability, told this news organization.

“It means we’re doing a better job of identifying children, which helps to get them into services earlier so they can achieve their best developmental outcome.”

The studies, published online in Morbidity and Mortality Weekly Report, are the first to use a new ASD surveillance protocol that relies on ASD diagnosis or special education classification and billing codes and eliminates comprehensive records analysis by trained clinician reviewers.

Racial disparities

The updated methodology was less labor intensive and reduced the time it took to produce the report, but it is not without its critics, who claim the new protocol will undercount the number of children with ASD.

Created in 2000 and funded by the CDC, the ADDM Network is the only surveillance program in the United States that tracks the number and characteristics of children with ASD in multiple communities in the U.S.

When ADDM released its first report in 2007 from six states and based on data from the year 2000, ASD prevalence was 6.7 per 1,000 children, or 1 in 150 children.

In the latest report, which includes data from 2018, the autism prevalence rate across 11 states was 23.0 per 1,000 children, or 1 in 44 children.

That rate is closer to reported autism prevalence from the National Survey of Children’s Health and the National Health Interview Survey, both of which rely on parent-reported ASD diagnoses.

For the report, researchers analyzed medical and special education records of 220,281 children who were born in 2010 in Arizona, Arkansas, California, Georgia, Maryland, Minnesota, Missouri, New Jersey, Tennessee, Utah, and Wisconsin.

Children were counted as having autism if their records included an ASD diagnosis, a special education classification of ASD, or an ASD International Classification of Diseases (ICD) code. A total of 5,058 children met those criteria.

Rates of ASD ranged from a low of 1.7% in Missouri to 3.9% in California and were 4.2 times higher in boys than in girls. Just under half of the children with ASD were evaluated by age 36 months.

Although the overall ASD prevalence was similar among White, Black, Hispanic, and Asian/Pacific Islander children, the report highlighted a number of other racial disparities overall and in individual states.

For example, among those with ASD and data on cognitive ability, 35.2% had an intelligence quotient score of 70 or lower. Black children with ASD were far more likely to have an IQ of 70 or less (49.8%) than Hispanic (33.1%) or White (29.7%) children.

“The persistent disparities in co-occurring intellectual disabilities in children with autism is something that we continue to see and suggests that we need to better understand exactly what’s happening,” Matthew Maenner, PhD, an epidemiologist and autism surveillance team lead with the CDC’s National Center on Birth Defects and Developmental Disabilities, told this news organization.

Another long-standing trend observed again in the new report on prevalence among 8-year-olds is low ASD prevalence among Hispanic children. While the overall estimate showed similar autism rates, a closer review of state-level data reveals a different picture.

“In almost half of the sites, Hispanic children were less likely to be identified as having ASD,” he said. “This gets lost if you look only at the overall estimate.”

New methodology

When ADDM released its first report in 2007, autism diagnosis was widely inadequate in the United States. Relying on only confirmed ASD diagnoses would significantly underestimate the number of children with the disorder, so the CDC added “active case finding” to the protocol.

Trained clinician reviewers analyzed individual notes from medical and educational records for every 8-year-old in ADDM Network sites, looking for evidence of characteristics and behaviors associated with autism. The process was labor- and time-intensive and took up to 4 years to complete.

In 2018, the CDC began investigating ways to speed the process and came up with the strategy used in the latest report. The new protocol was faster, easier, and less expensive. Although he says cost was never the deciding factor, Dr. Maenner acknowledges that had they stuck with the original protocol, they would have been forced to reduce the number of ADDM Network sites.

Dr. Maenner argues that a comparison of the two protocols shows the new method doesn’t compromise accuracy and may actually capture children who lacked the medical or educational records the previous protocol required for a count. But not everyone agrees.

“I thought the point was to be as accurate and complete as possible in doing the surveillance,” Walter Zahorodny, PhD, associate professor of pediatrics at Rutgers University, New Brunswick, N.J., and principal investigator of the New Jersey ADDM Network site, told this news organization. “In states where there’s a high detail of information in records, like New Jersey, it’s going to underestimate the count.”

Dr. Zahorodny says the latest data prove his point. In 2016, under the old methodology, ASD prevalence was 3.1% in the state. In 2018, under the new protocol, prevalence was 2.84%, a decrease of about 20% that Dr. Zahorodny pins squarely on the elimination of ADDM clinical reviewers.

But New Jersey is the only state that participated in both the 2016 and 2018 surveillance periods to report a decrease in ASD prevalence. The other eight states all found autism rates in their states went up.

Sydney Pettygrove, PhD, associate professor of public health and pediatrics at the University of Arizona, Tucson, and a principal investigator for the ADDM site in Arizona, told this news organization that when she first learned the CDC was rolling out a new methodology, she and other investigators were concerned.

“People were really upset. I was really upset,” she said. “I had formed an opinion based on the earlier data that this would not be a good idea.”

In 2000, when ASD surveillance began in Arizona, nearly 30% of children identified by ADDM clinical reviewers as having autism had no mention of the disorder in their records. Today, that percentage is closer to 5%.

“In 2000 it would have been catastrophic to try to estimate the prevalence of autism with the new protocol,” said Dr. Pettygrove. As it turns out, under the new protocol, prevalence rates in Arizona increased from 16.0 per 1,000 children in 2016 to 24.9 in 2018.

Built-in bias eliminated?

In addition to speeding up the process, the new methodology might have other benefits as well. Under the old ADDM surveillance protocol, children who lacked certain medical or educational records did not meet the ASD case definition and weren’t counted.

A 2019 study showed that this disproportionately affected Black and Hispanic children, who had significantly less access to health care professionals than White children.

As a result, “the old methodology had a bias built into it,” Maureen Durkin, PhD, DrPH, coauthor of that study and chair of population health sciences at the University of Wisconsin–Madison and principal investigator for the ADDM site in Wisconsin, told this news organization.

“Clinician reviewers ended up putting these children in the ‘suspected ASD’ category because they couldn’t call it a case under the case definition,” Dr. Durkin said. “There was a fairly large percentage of suspected cases and a disproportionate number of those kids were children of color.”

Although she can’t say for sure, Dr. Durkin said it’s possible the new protocol could eliminate some of that bias.

CDC researchers also attribute the new method to an expanded study of early diagnosis among 4-year-olds. In previous years, only a handful of the ADDM Network sites participating in the 8-year-old surveillance project also studied early diagnosis in 4-year-olds.

This year, all 11 sites took part in the early diagnosis analysis, tripling the number of children included in the analysis. That made it possible to include, for the first time, Asian/Pacific Islander children in this analysis.

In the past, ASD prevalence has trended higher in White children, compared with other racial groups. The new data found that ASD prevalence among 4-year-olds was significantly lower in White children (12.9 per 1,000 children) than in Black, Hispanic, or Asian/Pacific Islander children (16.6, 21.1, and 22.7 per 1,000, respectively). Prevalence in American Indian/Alaska Native children was the lowest among all racial groups (11.5 per 1,000).

It’s the first time researchers have seen this pattern in any ADDM report, Kelly Shaw, PhD, lead author of that study and an epidemiologist with the National Center on Birth Defects and Developmental Disability at the CDC, told this news organization.

These data don’t provide clues about the potential cause of that disparity, Dr. Shaw said. It’s likely an indication of better identification of ASD in those communities, she said, and not a sign of increased incidence of autism among Black, Hispanic, or Asian/Pacific Islander children.

“We don’t have any evidence to suggest or expect that autism would be increasing differentially among groups,” Dr. Shaw said.

The data suggest “we are making some progress but there certainly is still room for improvement,” Dr. Shaw said.

Study authors report no conflicts of interest.

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

A French population-based study provides further evidence that the BNT162b2 Pfizer-BioNTech mRNA COVID-19 vaccine does not increase the short-term risk for serious cardiovascular adverse events in older people.

The study showed no increased risk of myocardial infarction (MI), stroke, or pulmonary embolism (PE) following vaccination in adults aged 75 years or older in the 14 days following vaccination.

“These findings regarding the BNT162b2 vaccine’s short-term cardiovascular safety profile in older people are reassuring. They should be taken into account by doctors when considering implementing a third dose of the vaccine in older people,” Marie Joelle Jabagi, PharmD, PhD, with the French National Agency for Medicines and Health Products Safety, Saint-Denis, France, said in an interview.

Ridofranz/Getty Images

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

A French population-based study provides further evidence that the BNT162b2 Pfizer-BioNTech mRNA COVID-19 vaccine does not increase the short-term risk for serious cardiovascular adverse events in older people.

The study showed no increased risk of myocardial infarction (MI), stroke, or pulmonary embolism (PE) following vaccination in adults aged 75 years or older in the 14 days following vaccination.

“These findings regarding the BNT162b2 vaccine’s short-term cardiovascular safety profile in older people are reassuring. They should be taken into account by doctors when considering implementing a third dose of the vaccine in older people,” Marie Joelle Jabagi, PharmD, PhD, with the French National Agency for Medicines and Health Products Safety, Saint-Denis, France, said in an interview.

Ridofranz/Getty Images

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

A French population-based study provides further evidence that the BNT162b2 Pfizer-BioNTech mRNA COVID-19 vaccine does not increase the short-term risk for serious cardiovascular adverse events in older people.

The study showed no increased risk of myocardial infarction (MI), stroke, or pulmonary embolism (PE) following vaccination in adults aged 75 years or older in the 14 days following vaccination.

“These findings regarding the BNT162b2 vaccine’s short-term cardiovascular safety profile in older people are reassuring. They should be taken into account by doctors when considering implementing a third dose of the vaccine in older people,” Marie Joelle Jabagi, PharmD, PhD, with the French National Agency for Medicines and Health Products Safety, Saint-Denis, France, said in an interview.

Ridofranz/Getty Images

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

Early lab studies show that a COVID-19 antibody treatment developed by GlaxoSmithKline and Vir Biotechnology could be effective against the Omicron variant.

The companies said Dec. 2 that they tested the drug, called sotrovimab, against individual mutations found in the Omicron variant, according to The Wall Street Journal. The preliminary findings haven’t yet been peer-reviewed, and the drug will need to be tested against the whole spike protein on the virus to confirm results.

GlaxoSmithKline and Vir have previously tested sotrovimab against mutations on other variants, the newspaper reported. When the Omicron variant was identified, the companies looked at earlier research to find the tests they had done against mutations that are also found in Omicron.

Sotrovimab targets a spot on the spike protein that is found in other coronaviruses and is thought to be less likely to mutate, according to the newspaper. Omicron has at least two mutations that overlap with the drug’s target site, but researchers at the companies don’t think the mutations will affect the treatment’s ability to bind to the spike protein.

GlaxoSmithKline expects to see results from testing the drug against the full mutated spike protein in the next 2 to 3 weeks, the Journal reported.

Sotrovimab has been authorized in about a dozen countries, including the United States, which paid about $1 billion for hundreds of thousands of doses.

Other companies have also been testing their antibody treatments against the Omicron variant.

Regeneron announced Nov. 30 that its drug could be less effective, and it said further analyses will determine how much less effective by using the actual Omicron genetic sequence, according to Reuters.

Outside scientists have also said the antibody drug from Eli Lilly & Co. isn’t as effective against Omicron. The company told Reuters that it is still testing the treatment against the variant.

Another experimental antibody therapy developed by Adagio Therapeutics appears to work well against the new variant, the Journal reported, but the treatment is in late-stage clinical trials and isn’t yet authorized.

Antiviral drugs could also help prevent hospitalization and may be less vulnerable to new variants because they target a different part of the virus, the newspaper reported. Merck and Pfizer have developed antiviral pills, which still require FDA approval.

In addition, Gilead believes its approved IV therapy, called remdesivir, will continue to be effective against the variant, Reuters reported.

The FDA said Nov. 30 that it is looking at the effect that authorized COVID-19 vaccines can have on Omicron and expects to have more information in coming weeks, Reuters reported.

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

Early lab studies show that a COVID-19 antibody treatment developed by GlaxoSmithKline and Vir Biotechnology could be effective against the Omicron variant.

The companies said Dec. 2 that they tested the drug, called sotrovimab, against individual mutations found in the Omicron variant, according to The Wall Street Journal. The preliminary findings haven’t yet been peer-reviewed, and the drug will need to be tested against the whole spike protein on the virus to confirm results.

GlaxoSmithKline and Vir have previously tested sotrovimab against mutations on other variants, the newspaper reported. When the Omicron variant was identified, the companies looked at earlier research to find the tests they had done against mutations that are also found in Omicron.

Sotrovimab targets a spot on the spike protein that is found in other coronaviruses and is thought to be less likely to mutate, according to the newspaper. Omicron has at least two mutations that overlap with the drug’s target site, but researchers at the companies don’t think the mutations will affect the treatment’s ability to bind to the spike protein.

GlaxoSmithKline expects to see results from testing the drug against the full mutated spike protein in the next 2 to 3 weeks, the Journal reported.

Sotrovimab has been authorized in about a dozen countries, including the United States, which paid about $1 billion for hundreds of thousands of doses.

Other companies have also been testing their antibody treatments against the Omicron variant.

Regeneron announced Nov. 30 that its drug could be less effective, and it said further analyses will determine how much less effective by using the actual Omicron genetic sequence, according to Reuters.

Outside scientists have also said the antibody drug from Eli Lilly & Co. isn’t as effective against Omicron. The company told Reuters that it is still testing the treatment against the variant.

Another experimental antibody therapy developed by Adagio Therapeutics appears to work well against the new variant, the Journal reported, but the treatment is in late-stage clinical trials and isn’t yet authorized.

Antiviral drugs could also help prevent hospitalization and may be less vulnerable to new variants because they target a different part of the virus, the newspaper reported. Merck and Pfizer have developed antiviral pills, which still require FDA approval.

In addition, Gilead believes its approved IV therapy, called remdesivir, will continue to be effective against the variant, Reuters reported.

The FDA said Nov. 30 that it is looking at the effect that authorized COVID-19 vaccines can have on Omicron and expects to have more information in coming weeks, Reuters reported.

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

Early lab studies show that a COVID-19 antibody treatment developed by GlaxoSmithKline and Vir Biotechnology could be effective against the Omicron variant.

The companies said Dec. 2 that they tested the drug, called sotrovimab, against individual mutations found in the Omicron variant, according to The Wall Street Journal. The preliminary findings haven’t yet been peer-reviewed, and the drug will need to be tested against the whole spike protein on the virus to confirm results.

GlaxoSmithKline and Vir have previously tested sotrovimab against mutations on other variants, the newspaper reported. When the Omicron variant was identified, the companies looked at earlier research to find the tests they had done against mutations that are also found in Omicron.

Sotrovimab targets a spot on the spike protein that is found in other coronaviruses and is thought to be less likely to mutate, according to the newspaper. Omicron has at least two mutations that overlap with the drug’s target site, but researchers at the companies don’t think the mutations will affect the treatment’s ability to bind to the spike protein.

GlaxoSmithKline expects to see results from testing the drug against the full mutated spike protein in the next 2 to 3 weeks, the Journal reported.

Sotrovimab has been authorized in about a dozen countries, including the United States, which paid about $1 billion for hundreds of thousands of doses.

Other companies have also been testing their antibody treatments against the Omicron variant.

Regeneron announced Nov. 30 that its drug could be less effective, and it said further analyses will determine how much less effective by using the actual Omicron genetic sequence, according to Reuters.

Outside scientists have also said the antibody drug from Eli Lilly & Co. isn’t as effective against Omicron. The company told Reuters that it is still testing the treatment against the variant.

Another experimental antibody therapy developed by Adagio Therapeutics appears to work well against the new variant, the Journal reported, but the treatment is in late-stage clinical trials and isn’t yet authorized.

Antiviral drugs could also help prevent hospitalization and may be less vulnerable to new variants because they target a different part of the virus, the newspaper reported. Merck and Pfizer have developed antiviral pills, which still require FDA approval.

In addition, Gilead believes its approved IV therapy, called remdesivir, will continue to be effective against the variant, Reuters reported.

The FDA said Nov. 30 that it is looking at the effect that authorized COVID-19 vaccines can have on Omicron and expects to have more information in coming weeks, Reuters reported.

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

COVID-19’s relentless toll on the clinical workforce inspired four doctors to draft an action plan to stem the exits and help colleagues preserve their physical and mental health.

Indeed, a recent poll of 1,000 health care workers conducted Sept. 2-8 by Morning Consult, showed that 18% of medical workers polled quit their jobs during the pandemic. Additionally, 31% said they had at least thought about leaving their work.

“As physicians, educators, peers and friends of COVID-19 responders, we are gravely concerned about our colleagues’ exhaustion, burnout, and disillusionment,” wrote lead author Eileen Barrett, MD, and coauthors of the new action plan, which was published in the Annals of Internal Medicine.

The 10-point, one-page checklist includes providing “practical support in the areas that clinicians identify as causing emotional stress or moral injury,” such as managing anger and grief when patients have chosen not to be vaccinated or confronting misinformation.

“Those are the things that are making people’s mental health worse” psychiatrist Jessi Gold, MD, MS, said in an interview. “I don’t think I’ve seen that mentioned other places.”

Among the other action items are:

• Reduce administrative tasks that are not “mission critical,” such as mandatory training that has no evidence of improving patient outcomes and meetings that could be skipped.
• Offer free and confidential resources to support clinicians’ mental health, such as easy access to crisis hotlines and peer support groups.
• Maintain transparency about personal protective equipment and contingency plans when there are shortages to restore trust.
• Encourage clinicians to use vacation time; leaders should model this.
• Implement suicide prevention strategies, including wellness check-ins for clinicians in hard-hit areas.

The action plan was based on the authors’ own experiences and the stories of colleagues and information in literature. It includes 10 changes health care leaders could make to help retain providers who may be on the brink of leaving their jobs or leaving medicine

Action items intended to be easily achievable, low cost

Dr. Barrett, who is a hospitalist in Albuquerque, said the goal was to present easily achievable and low-cost action items that clinicians and health care leaders could use as a starting point when change seems insurmountable and evidence on what works is slow to come.

She said one of the things that spurred her to coauthor the list was becoming aware of other clinicians’ “secret shame” in thinking about leaving medicine.

“Maybe a person who is not being listened to could take this journal article and say ‘we don’t know where to start. It looks like we can start here,’ ” said Dr. Barrett, who is also an associate professor in the division of hospital medicine, department of internal medicine, at the University of New Mexico, Albuquerque.

She noted that some of the good ideas floated around did not make the list, because they required daunting budget commitments and too much time to put into place.

Numerous other proposed solutions were of the wrong tone, according to Dr. Barrett.

“It’s not just about a hug or a piece of pizza,” she said.

Dr. Gold, who is an assistant professor at Washington University, St. Louis, and specializes in the mental health of health care workers, noted that, even though the list was pared to 10 action items, it is still hard for health care organizations to prioritize mental health.

“Many hospitals are still struggling with the active bleed of the pandemic and financially recovering,” she said. “If you’re dealing with a full ER and people are still dying of COVID and you don’t have the resources to support them, it’s really hard to then find magic money to deal with mental health. I’d love for that to be true.”

Every organization, however, can start with removing questions about mental and physical health diagnoses from credentialing and employment applications, which is one of the items on the list, she said.

“It’s the lowest-bar thing that you can fix for making people in crisis not fear getting help,” she said. That change must come on a state-by-state and individual hospital level.

Favorable reactions to list

Dr. Barrett, who also serves on the editorial advisory board of Internal Medicine News, said the reactions to the checklist have been “overwhelmingly favorable and appreciative.”

Eric J. Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and editor-in-chief of Medscape Medical News, tweeted about this list: “For COVID-19, more than ever before, it’s vital to keep clinicians in the U.S. health care workforce. These are 10 steps that will help.” The tweet was retweeted more than 100 times.

Lotte Dyrbye, MD, MHPE, a primary care physician and codirector of the program on physician well-being at the Mayo Clinic in Rochester, Minn., said in an interview that managing the anger around patients who choose to be unvaccinated is critical and something that has gotten little notice since the vaccines became available.

“Physicians and nurses are working extremely hard and seeing a lot of suffering and are taking care of patients very sick with COVID-19, knowing they had access to the vaccine. That is causing anger and frustration. We haven’t prepared health care workers to deal with that,” she said.
 

Outside expert: Not all items may be easy to implement

Dr. Dyrbye said that, though she found adding time to address COVID misinformation questions in appointments is very important, it may be wishful thinking.

The authors suggested training other members of the care team to answer those questions to free up time, but she said, for patients who have been swayed by misinformation, hearing information from someone other than the physician they have a relationship with won’t be convincing.

According to Dr. Dyrbye, the items on the list are not easy to implement, but the action plan is worthwhile to consider adopting as a multipronged approach.

“Most of these things are hard and we need to be in it for the long run,” she said.

The need is clear for efforts to address the mental health of not just experienced clinicians but those in training as well, she noted.
 

Related research

A study that was also recently published in the Annals of Internal Medicine suggested that making a few simple changes can help improve the mental health of residents. The research, which included nearly 17,000 first-year residents who started training between 2007 and 2019, addressed indicators of mental health in light of interventions such as limiting residents’ work hours and providing more services.

The investigators found that, though depression remains high among residents, depressive symptoms among first-year residents dropped 24.4% from 2007 to 2019 in parallel with four main factors: an increase in mental health services; restrictions on work hours for residents; more sleep hours; and higher-quality feedback from faculty.

Dr. Barrett said she hopes her colleagues and health care workers everywhere will find some solace in seeing that the new checklist she coauthored was published in a prominent journal.

The message Dr. Barrett said she hopes they see is: “Someone is validating it is not in their head. They are validating we can do better. They are validating that we must.”

Dr. Barrett and coauthors had no conflicts of interest. Dr. Gold and Dr. Dyrbye also disclosed having no relevant financial relationships.

COVID-19’s relentless toll on the clinical workforce inspired four doctors to draft an action plan to stem the exits and help colleagues preserve their physical and mental health.

Indeed, a recent poll of 1,000 health care workers conducted Sept. 2-8 by Morning Consult, showed that 18% of medical workers polled quit their jobs during the pandemic. Additionally, 31% said they had at least thought about leaving their work.

“As physicians, educators, peers and friends of COVID-19 responders, we are gravely concerned about our colleagues’ exhaustion, burnout, and disillusionment,” wrote lead author Eileen Barrett, MD, and coauthors of the new action plan, which was published in the Annals of Internal Medicine.

The 10-point, one-page checklist includes providing “practical support in the areas that clinicians identify as causing emotional stress or moral injury,” such as managing anger and grief when patients have chosen not to be vaccinated or confronting misinformation.

“Those are the things that are making people’s mental health worse” psychiatrist Jessi Gold, MD, MS, said in an interview. “I don’t think I’ve seen that mentioned other places.”

Among the other action items are:

• Reduce administrative tasks that are not “mission critical,” such as mandatory training that has no evidence of improving patient outcomes and meetings that could be skipped.
• Offer free and confidential resources to support clinicians’ mental health, such as easy access to crisis hotlines and peer support groups.
• Maintain transparency about personal protective equipment and contingency plans when there are shortages to restore trust.
• Encourage clinicians to use vacation time; leaders should model this.
• Implement suicide prevention strategies, including wellness check-ins for clinicians in hard-hit areas.

The action plan was based on the authors’ own experiences and the stories of colleagues and information in literature. It includes 10 changes health care leaders could make to help retain providers who may be on the brink of leaving their jobs or leaving medicine

Action items intended to be easily achievable, low cost

Dr. Barrett, who is a hospitalist in Albuquerque, said the goal was to present easily achievable and low-cost action items that clinicians and health care leaders could use as a starting point when change seems insurmountable and evidence on what works is slow to come.

She said one of the things that spurred her to coauthor the list was becoming aware of other clinicians’ “secret shame” in thinking about leaving medicine.

“Maybe a person who is not being listened to could take this journal article and say ‘we don’t know where to start. It looks like we can start here,’ ” said Dr. Barrett, who is also an associate professor in the division of hospital medicine, department of internal medicine, at the University of New Mexico, Albuquerque.

She noted that some of the good ideas floated around did not make the list, because they required daunting budget commitments and too much time to put into place.

Numerous other proposed solutions were of the wrong tone, according to Dr. Barrett.

“It’s not just about a hug or a piece of pizza,” she said.

Dr. Gold, who is an assistant professor at Washington University, St. Louis, and specializes in the mental health of health care workers, noted that, even though the list was pared to 10 action items, it is still hard for health care organizations to prioritize mental health.

“Many hospitals are still struggling with the active bleed of the pandemic and financially recovering,” she said. “If you’re dealing with a full ER and people are still dying of COVID and you don’t have the resources to support them, it’s really hard to then find magic money to deal with mental health. I’d love for that to be true.”

Every organization, however, can start with removing questions about mental and physical health diagnoses from credentialing and employment applications, which is one of the items on the list, she said.

“It’s the lowest-bar thing that you can fix for making people in crisis not fear getting help,” she said. That change must come on a state-by-state and individual hospital level.

Favorable reactions to list

Dr. Barrett, who also serves on the editorial advisory board of Internal Medicine News, said the reactions to the checklist have been “overwhelmingly favorable and appreciative.”

Eric J. Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and editor-in-chief of Medscape Medical News, tweeted about this list: “For COVID-19, more than ever before, it’s vital to keep clinicians in the U.S. health care workforce. These are 10 steps that will help.” The tweet was retweeted more than 100 times.

Lotte Dyrbye, MD, MHPE, a primary care physician and codirector of the program on physician well-being at the Mayo Clinic in Rochester, Minn., said in an interview that managing the anger around patients who choose to be unvaccinated is critical and something that has gotten little notice since the vaccines became available.

“Physicians and nurses are working extremely hard and seeing a lot of suffering and are taking care of patients very sick with COVID-19, knowing they had access to the vaccine. That is causing anger and frustration. We haven’t prepared health care workers to deal with that,” she said.
 

Outside expert: Not all items may be easy to implement

Dr. Dyrbye said that, though she found adding time to address COVID misinformation questions in appointments is very important, it may be wishful thinking.

The authors suggested training other members of the care team to answer those questions to free up time, but she said, for patients who have been swayed by misinformation, hearing information from someone other than the physician they have a relationship with won’t be convincing.

According to Dr. Dyrbye, the items on the list are not easy to implement, but the action plan is worthwhile to consider adopting as a multipronged approach.

“Most of these things are hard and we need to be in it for the long run,” she said.

The need is clear for efforts to address the mental health of not just experienced clinicians but those in training as well, she noted.
 

Related research

A study that was also recently published in the Annals of Internal Medicine suggested that making a few simple changes can help improve the mental health of residents. The research, which included nearly 17,000 first-year residents who started training between 2007 and 2019, addressed indicators of mental health in light of interventions such as limiting residents’ work hours and providing more services.

The investigators found that, though depression remains high among residents, depressive symptoms among first-year residents dropped 24.4% from 2007 to 2019 in parallel with four main factors: an increase in mental health services; restrictions on work hours for residents; more sleep hours; and higher-quality feedback from faculty.

Dr. Barrett said she hopes her colleagues and health care workers everywhere will find some solace in seeing that the new checklist she coauthored was published in a prominent journal.

The message Dr. Barrett said she hopes they see is: “Someone is validating it is not in their head. They are validating we can do better. They are validating that we must.”

Dr. Barrett and coauthors had no conflicts of interest. Dr. Gold and Dr. Dyrbye also disclosed having no relevant financial relationships.

COVID-19’s relentless toll on the clinical workforce inspired four doctors to draft an action plan to stem the exits and help colleagues preserve their physical and mental health.

Indeed, a recent poll of 1,000 health care workers conducted Sept. 2-8 by Morning Consult, showed that 18% of medical workers polled quit their jobs during the pandemic. Additionally, 31% said they had at least thought about leaving their work.

“As physicians, educators, peers and friends of COVID-19 responders, we are gravely concerned about our colleagues’ exhaustion, burnout, and disillusionment,” wrote lead author Eileen Barrett, MD, and coauthors of the new action plan, which was published in the Annals of Internal Medicine.

The 10-point, one-page checklist includes providing “practical support in the areas that clinicians identify as causing emotional stress or moral injury,” such as managing anger and grief when patients have chosen not to be vaccinated or confronting misinformation.

“Those are the things that are making people’s mental health worse” psychiatrist Jessi Gold, MD, MS, said in an interview. “I don’t think I’ve seen that mentioned other places.”

Among the other action items are:

• Reduce administrative tasks that are not “mission critical,” such as mandatory training that has no evidence of improving patient outcomes and meetings that could be skipped.
• Offer free and confidential resources to support clinicians’ mental health, such as easy access to crisis hotlines and peer support groups.
• Maintain transparency about personal protective equipment and contingency plans when there are shortages to restore trust.
• Encourage clinicians to use vacation time; leaders should model this.
• Implement suicide prevention strategies, including wellness check-ins for clinicians in hard-hit areas.

The action plan was based on the authors’ own experiences and the stories of colleagues and information in literature. It includes 10 changes health care leaders could make to help retain providers who may be on the brink of leaving their jobs or leaving medicine

Action items intended to be easily achievable, low cost

Dr. Barrett, who is a hospitalist in Albuquerque, said the goal was to present easily achievable and low-cost action items that clinicians and health care leaders could use as a starting point when change seems insurmountable and evidence on what works is slow to come.

She said one of the things that spurred her to coauthor the list was becoming aware of other clinicians’ “secret shame” in thinking about leaving medicine.

“Maybe a person who is not being listened to could take this journal article and say ‘we don’t know where to start. It looks like we can start here,’ ” said Dr. Barrett, who is also an associate professor in the division of hospital medicine, department of internal medicine, at the University of New Mexico, Albuquerque.

She noted that some of the good ideas floated around did not make the list, because they required daunting budget commitments and too much time to put into place.

Numerous other proposed solutions were of the wrong tone, according to Dr. Barrett.

“It’s not just about a hug or a piece of pizza,” she said.

Dr. Gold, who is an assistant professor at Washington University, St. Louis, and specializes in the mental health of health care workers, noted that, even though the list was pared to 10 action items, it is still hard for health care organizations to prioritize mental health.

“Many hospitals are still struggling with the active bleed of the pandemic and financially recovering,” she said. “If you’re dealing with a full ER and people are still dying of COVID and you don’t have the resources to support them, it’s really hard to then find magic money to deal with mental health. I’d love for that to be true.”

Every organization, however, can start with removing questions about mental and physical health diagnoses from credentialing and employment applications, which is one of the items on the list, she said.

“It’s the lowest-bar thing that you can fix for making people in crisis not fear getting help,” she said. That change must come on a state-by-state and individual hospital level.

Favorable reactions to list

Dr. Barrett, who also serves on the editorial advisory board of Internal Medicine News, said the reactions to the checklist have been “overwhelmingly favorable and appreciative.”

Eric J. Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and editor-in-chief of Medscape Medical News, tweeted about this list: “For COVID-19, more than ever before, it’s vital to keep clinicians in the U.S. health care workforce. These are 10 steps that will help.” The tweet was retweeted more than 100 times.

Lotte Dyrbye, MD, MHPE, a primary care physician and codirector of the program on physician well-being at the Mayo Clinic in Rochester, Minn., said in an interview that managing the anger around patients who choose to be unvaccinated is critical and something that has gotten little notice since the vaccines became available.

“Physicians and nurses are working extremely hard and seeing a lot of suffering and are taking care of patients very sick with COVID-19, knowing they had access to the vaccine. That is causing anger and frustration. We haven’t prepared health care workers to deal with that,” she said.
 

Outside expert: Not all items may be easy to implement

Dr. Dyrbye said that, though she found adding time to address COVID misinformation questions in appointments is very important, it may be wishful thinking.

The authors suggested training other members of the care team to answer those questions to free up time, but she said, for patients who have been swayed by misinformation, hearing information from someone other than the physician they have a relationship with won’t be convincing.

According to Dr. Dyrbye, the items on the list are not easy to implement, but the action plan is worthwhile to consider adopting as a multipronged approach.

“Most of these things are hard and we need to be in it for the long run,” she said.

The need is clear for efforts to address the mental health of not just experienced clinicians but those in training as well, she noted.
 

Related research

A study that was also recently published in the Annals of Internal Medicine suggested that making a few simple changes can help improve the mental health of residents. The research, which included nearly 17,000 first-year residents who started training between 2007 and 2019, addressed indicators of mental health in light of interventions such as limiting residents’ work hours and providing more services.

The investigators found that, though depression remains high among residents, depressive symptoms among first-year residents dropped 24.4% from 2007 to 2019 in parallel with four main factors: an increase in mental health services; restrictions on work hours for residents; more sleep hours; and higher-quality feedback from faculty.

Dr. Barrett said she hopes her colleagues and health care workers everywhere will find some solace in seeing that the new checklist she coauthored was published in a prominent journal.

The message Dr. Barrett said she hopes they see is: “Someone is validating it is not in their head. They are validating we can do better. They are validating that we must.”

Dr. Barrett and coauthors had no conflicts of interest. Dr. Gold and Dr. Dyrbye also disclosed having no relevant financial relationships.

A second U.S. case of COVID-19 caused by the Omicron variant has been picked up by genetic testing in Minnesota.

The man, from Hennepin County, Minn., fell ill on Nov. 22 after attending the Anime NYC 2021 conference at the Javits Center in New York City a few days before.  He sought testing on Nov. 24.  His symptoms have resolved, according to a press release on the case from the Minnesota Department of Health.  The man was fully vaccinated, the department said.

He was advised to isolate from others, but it’s unclear if he had contact with anyone else before he learning he was infected.

“This news is concerning, but it is not a surprise,” said Governor Tim Walz in a news release. “We know that this virus is highly infectious and moves quickly throughout the world. Minnesotans know what to do to keep each other safe now — get the vaccine, get tested, wear a mask indoors, and get a booster. Together, we can fight this virus and help keep Minnesotans safe,”

The first case of COVID-19 caused by Omicron was detected Dec. 1 in California. That case was in a traveler who had recently returned from South Africa.

This breaking news story will be updated.

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

A second U.S. case of COVID-19 caused by the Omicron variant has been picked up by genetic testing in Minnesota.

The man, from Hennepin County, Minn., fell ill on Nov. 22 after attending the Anime NYC 2021 conference at the Javits Center in New York City a few days before.  He sought testing on Nov. 24.  His symptoms have resolved, according to a press release on the case from the Minnesota Department of Health.  The man was fully vaccinated, the department said.

He was advised to isolate from others, but it’s unclear if he had contact with anyone else before he learning he was infected.

“This news is concerning, but it is not a surprise,” said Governor Tim Walz in a news release. “We know that this virus is highly infectious and moves quickly throughout the world. Minnesotans know what to do to keep each other safe now — get the vaccine, get tested, wear a mask indoors, and get a booster. Together, we can fight this virus and help keep Minnesotans safe,”

The first case of COVID-19 caused by Omicron was detected Dec. 1 in California. That case was in a traveler who had recently returned from South Africa.

This breaking news story will be updated.

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

A second U.S. case of COVID-19 caused by the Omicron variant has been picked up by genetic testing in Minnesota.

The man, from Hennepin County, Minn., fell ill on Nov. 22 after attending the Anime NYC 2021 conference at the Javits Center in New York City a few days before.  He sought testing on Nov. 24.  His symptoms have resolved, according to a press release on the case from the Minnesota Department of Health.  The man was fully vaccinated, the department said.

He was advised to isolate from others, but it’s unclear if he had contact with anyone else before he learning he was infected.

“This news is concerning, but it is not a surprise,” said Governor Tim Walz in a news release. “We know that this virus is highly infectious and moves quickly throughout the world. Minnesotans know what to do to keep each other safe now — get the vaccine, get tested, wear a mask indoors, and get a booster. Together, we can fight this virus and help keep Minnesotans safe,”

The first case of COVID-19 caused by Omicron was detected Dec. 1 in California. That case was in a traveler who had recently returned from South Africa.

This breaking news story will be updated.

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

It isn’t autocorrect’s fault this time, we swear

We’ve come a long way with communication technology. Back in the day, when Gondor needed to call for aid, they had to pull off the greatest signal fire montage of all time. Now we can send each other texts back and forth in an instant. (“Hey Theoden, send army, need help pls” doesn’t quite have the same gravitas though.) The question is, how do our brains keep up with such rapidly advancing technology?

Deagreez/iStock/Getty Images Plus

Er, they don’t. Not really. Instead, our brains create shortcuts called “good-enough language processing,” which is exactly what it sounds like.

Psychologists and psycholinguists have been studying misinterpretations such as good-enough language processing since the 1970s. Recently, however, psycholinguists from the Centre for Language and Brain at Higher School of Economics in Moscow have found that, when it comes to reading comprehension over text, older adults are using their knowledge of the world over how it’s grammatically formed in the sentence.

In the study, 349 people were asked to read and interpret four sentences, the third of which (translated from Russian) was: “Misha met the firefighter’s dentist, who had put out a fire in the warehouse.” When asked who put the fire out, 79% of older adults (aged 55 years and older), utilizing good-enough language processing, said the firefighter put out the fire. You probably glossed over that sentence and assumed the same thing. But this time, the dentist was the real hero.

That said, adolescents (aged 13-17) and young adults (aged 20-30) weren’t much better, and got that particular sentence wrong 63%-68% of the time. According to the researchers, good-enough language processing forms in adolescence and intensifies throughout adulthood.

Moral of the story? We should utilize signal fires more often. Less room for misinterpretation. When the beacons of Minas Tirith were lit, Rohan answered.
 

Singing … your … lungs … out

There’s nothing quite like a karaoke bar to unleash your inner rock star. Hey, why not just go for it, everyone is just as bad at singing as you. That’s part of the fun.

lisegagne/E+/Getty Images

A 25-year-old man named Wang Zhe may have taken the karaoke concept a bit too far, however. While out with friends at a birthday party, Mr. Zhe let loose on a song with a particularly large number of high notes. He tried his best, gamely attacking the song until he felt a pain in his chest. He didn’t think much of it, although he did cut his performance short, but then he awoke the next morning unable to breathe properly.

After a trip to the hospital, he explained the sequence of events to the doctors, and an x-ray found that the culprit of the pain and difficulty breathing was a life-threatening condition in which air bubbles are created between the chest and lung. All the force Mr. Zhe had used trying to sing made air sacks in his lung burst, causing the air bubbles and his lung to be compressed to 15% of what it should be. Mr. Zhe needed surgery to remove the air bubbles, but fortunately turned out just fine.

So, if you’re ever at a karaoke bar, looking for a song to sing, maybe avoid the ones with super high notes and stick with something a little lower. We’re picturing something like Paul Robeson singing Ol’ Man River. That oughta do the trick.
 

And the word of the year is …

Flibbertigibbet. Bamboozle. Gobbledygook. If the LOTME staff had any say, those would be the words of the year every year, but sadly, we’re not in charge of such things. Instead, we’ll just have to defer to Oxford and Merriam-Webster, both of whom have recently chosen their words of the year. No word yet on whether or not they made their announcement at a red carpet gala dinner attended by all the most fashionable and powerful words out there, but we’re hoping that’s what happened.

NoSystem images/Getty Images

We’ll start with Oxford, since they did choose first. We all know Oxford is the bad boy of the dictionary world, so they’ve chosen a casual colloquialism related to the big COVID-sized elephant in the room (or should it be elephant-sized COVID in the room?): Vax. According to them, while vax has been hanging around since the 1980s, it’s only been in the past year that it’s exploded in popularity in a wide range of contexts (we can’t imagine what those would be). According to Oxford, “as a short pithy word, it appeals, perhaps especially to media commentators, when more formal alternatives are much more long-winded.”

Speaking of long-winded, that brings us to Merriam-Webster, the sheltered nerd of the dictionary world. Clearly they’re too good for vax, so they’ve gone with vaccine as their 2021 word of the year. Vaccine, according to Merriam-Webster, carries two big stories: The impressive and herculean feat of bringing a COVID-19 vaccine so quickly to so many people, and the complex political and social upheaval between vaccine supporters and deniers.

Vaccine also serves as a great bookend for Merriam-Webster’s 2020 word of the year: Pandemic. In 2020, the pandemic started, and in 2021, thanks to the vaccine, the pandemic ends. That’s how it works, right? We have a vaccine, it’s all over now. What’s that? Omicron? No! Bad COVID! You do that outside, not on the carpet!

It isn’t autocorrect’s fault this time, we swear

We’ve come a long way with communication technology. Back in the day, when Gondor needed to call for aid, they had to pull off the greatest signal fire montage of all time. Now we can send each other texts back and forth in an instant. (“Hey Theoden, send army, need help pls” doesn’t quite have the same gravitas though.) The question is, how do our brains keep up with such rapidly advancing technology?

Deagreez/iStock/Getty Images Plus

Er, they don’t. Not really. Instead, our brains create shortcuts called “good-enough language processing,” which is exactly what it sounds like.

Psychologists and psycholinguists have been studying misinterpretations such as good-enough language processing since the 1970s. Recently, however, psycholinguists from the Centre for Language and Brain at Higher School of Economics in Moscow have found that, when it comes to reading comprehension over text, older adults are using their knowledge of the world over how it’s grammatically formed in the sentence.

In the study, 349 people were asked to read and interpret four sentences, the third of which (translated from Russian) was: “Misha met the firefighter’s dentist, who had put out a fire in the warehouse.” When asked who put the fire out, 79% of older adults (aged 55 years and older), utilizing good-enough language processing, said the firefighter put out the fire. You probably glossed over that sentence and assumed the same thing. But this time, the dentist was the real hero.

That said, adolescents (aged 13-17) and young adults (aged 20-30) weren’t much better, and got that particular sentence wrong 63%-68% of the time. According to the researchers, good-enough language processing forms in adolescence and intensifies throughout adulthood.

Moral of the story? We should utilize signal fires more often. Less room for misinterpretation. When the beacons of Minas Tirith were lit, Rohan answered.
 

Singing … your … lungs … out

There’s nothing quite like a karaoke bar to unleash your inner rock star. Hey, why not just go for it, everyone is just as bad at singing as you. That’s part of the fun.

lisegagne/E+/Getty Images

A 25-year-old man named Wang Zhe may have taken the karaoke concept a bit too far, however. While out with friends at a birthday party, Mr. Zhe let loose on a song with a particularly large number of high notes. He tried his best, gamely attacking the song until he felt a pain in his chest. He didn’t think much of it, although he did cut his performance short, but then he awoke the next morning unable to breathe properly.

After a trip to the hospital, he explained the sequence of events to the doctors, and an x-ray found that the culprit of the pain and difficulty breathing was a life-threatening condition in which air bubbles are created between the chest and lung. All the force Mr. Zhe had used trying to sing made air sacks in his lung burst, causing the air bubbles and his lung to be compressed to 15% of what it should be. Mr. Zhe needed surgery to remove the air bubbles, but fortunately turned out just fine.

So, if you’re ever at a karaoke bar, looking for a song to sing, maybe avoid the ones with super high notes and stick with something a little lower. We’re picturing something like Paul Robeson singing Ol’ Man River. That oughta do the trick.
 

And the word of the year is …

Flibbertigibbet. Bamboozle. Gobbledygook. If the LOTME staff had any say, those would be the words of the year every year, but sadly, we’re not in charge of such things. Instead, we’ll just have to defer to Oxford and Merriam-Webster, both of whom have recently chosen their words of the year. No word yet on whether or not they made their announcement at a red carpet gala dinner attended by all the most fashionable and powerful words out there, but we’re hoping that’s what happened.

NoSystem images/Getty Images

We’ll start with Oxford, since they did choose first. We all know Oxford is the bad boy of the dictionary world, so they’ve chosen a casual colloquialism related to the big COVID-sized elephant in the room (or should it be elephant-sized COVID in the room?): Vax. According to them, while vax has been hanging around since the 1980s, it’s only been in the past year that it’s exploded in popularity in a wide range of contexts (we can’t imagine what those would be). According to Oxford, “as a short pithy word, it appeals, perhaps especially to media commentators, when more formal alternatives are much more long-winded.”

Speaking of long-winded, that brings us to Merriam-Webster, the sheltered nerd of the dictionary world. Clearly they’re too good for vax, so they’ve gone with vaccine as their 2021 word of the year. Vaccine, according to Merriam-Webster, carries two big stories: The impressive and herculean feat of bringing a COVID-19 vaccine so quickly to so many people, and the complex political and social upheaval between vaccine supporters and deniers.

Vaccine also serves as a great bookend for Merriam-Webster’s 2020 word of the year: Pandemic. In 2020, the pandemic started, and in 2021, thanks to the vaccine, the pandemic ends. That’s how it works, right? We have a vaccine, it’s all over now. What’s that? Omicron? No! Bad COVID! You do that outside, not on the carpet!

It isn’t autocorrect’s fault this time, we swear

We’ve come a long way with communication technology. Back in the day, when Gondor needed to call for aid, they had to pull off the greatest signal fire montage of all time. Now we can send each other texts back and forth in an instant. (“Hey Theoden, send army, need help pls” doesn’t quite have the same gravitas though.) The question is, how do our brains keep up with such rapidly advancing technology?

Deagreez/iStock/Getty Images Plus

Er, they don’t. Not really. Instead, our brains create shortcuts called “good-enough language processing,” which is exactly what it sounds like.

Psychologists and psycholinguists have been studying misinterpretations such as good-enough language processing since the 1970s. Recently, however, psycholinguists from the Centre for Language and Brain at Higher School of Economics in Moscow have found that, when it comes to reading comprehension over text, older adults are using their knowledge of the world over how it’s grammatically formed in the sentence.

In the study, 349 people were asked to read and interpret four sentences, the third of which (translated from Russian) was: “Misha met the firefighter’s dentist, who had put out a fire in the warehouse.” When asked who put the fire out, 79% of older adults (aged 55 years and older), utilizing good-enough language processing, said the firefighter put out the fire. You probably glossed over that sentence and assumed the same thing. But this time, the dentist was the real hero.

That said, adolescents (aged 13-17) and young adults (aged 20-30) weren’t much better, and got that particular sentence wrong 63%-68% of the time. According to the researchers, good-enough language processing forms in adolescence and intensifies throughout adulthood.

Moral of the story? We should utilize signal fires more often. Less room for misinterpretation. When the beacons of Minas Tirith were lit, Rohan answered.
 

Singing … your … lungs … out

There’s nothing quite like a karaoke bar to unleash your inner rock star. Hey, why not just go for it, everyone is just as bad at singing as you. That’s part of the fun.

lisegagne/E+/Getty Images

A 25-year-old man named Wang Zhe may have taken the karaoke concept a bit too far, however. While out with friends at a birthday party, Mr. Zhe let loose on a song with a particularly large number of high notes. He tried his best, gamely attacking the song until he felt a pain in his chest. He didn’t think much of it, although he did cut his performance short, but then he awoke the next morning unable to breathe properly.

After a trip to the hospital, he explained the sequence of events to the doctors, and an x-ray found that the culprit of the pain and difficulty breathing was a life-threatening condition in which air bubbles are created between the chest and lung. All the force Mr. Zhe had used trying to sing made air sacks in his lung burst, causing the air bubbles and his lung to be compressed to 15% of what it should be. Mr. Zhe needed surgery to remove the air bubbles, but fortunately turned out just fine.

So, if you’re ever at a karaoke bar, looking for a song to sing, maybe avoid the ones with super high notes and stick with something a little lower. We’re picturing something like Paul Robeson singing Ol’ Man River. That oughta do the trick.
 

And the word of the year is …

Flibbertigibbet. Bamboozle. Gobbledygook. If the LOTME staff had any say, those would be the words of the year every year, but sadly, we’re not in charge of such things. Instead, we’ll just have to defer to Oxford and Merriam-Webster, both of whom have recently chosen their words of the year. No word yet on whether or not they made their announcement at a red carpet gala dinner attended by all the most fashionable and powerful words out there, but we’re hoping that’s what happened.

NoSystem images/Getty Images

We’ll start with Oxford, since they did choose first. We all know Oxford is the bad boy of the dictionary world, so they’ve chosen a casual colloquialism related to the big COVID-sized elephant in the room (or should it be elephant-sized COVID in the room?): Vax. According to them, while vax has been hanging around since the 1980s, it’s only been in the past year that it’s exploded in popularity in a wide range of contexts (we can’t imagine what those would be). According to Oxford, “as a short pithy word, it appeals, perhaps especially to media commentators, when more formal alternatives are much more long-winded.”

Speaking of long-winded, that brings us to Merriam-Webster, the sheltered nerd of the dictionary world. Clearly they’re too good for vax, so they’ve gone with vaccine as their 2021 word of the year. Vaccine, according to Merriam-Webster, carries two big stories: The impressive and herculean feat of bringing a COVID-19 vaccine so quickly to so many people, and the complex political and social upheaval between vaccine supporters and deniers.

Vaccine also serves as a great bookend for Merriam-Webster’s 2020 word of the year: Pandemic. In 2020, the pandemic started, and in 2021, thanks to the vaccine, the pandemic ends. That’s how it works, right? We have a vaccine, it’s all over now. What’s that? Omicron? No! Bad COVID! You do that outside, not on the carpet!

The first case of the Omicron variant of the coronavirus in the United States was confirmed by officials today in an individual in California who had recently traveled to South Africa. He or she was fully vaccinated against COVID-19 and experienced only “mild symptoms that are improving,” officials with the Centers for Disease Control and Prevention said. 

The patient, who was not named in the CDC’s announcement of the first U.S. case of the Omicron variant Dec. 1, is self-quarantining.

“All close contacts have been contacted and have tested negative,” officials said. 

The announcement comes as no surprise to many as the Omicron variant, first identified in South Africa, has been reported in countries around the world in recent days. Hong Kong, the United Kingdom, and Germany each reported this variant, as have Italy and the Netherlands. Over the weekend, the first North American cases were identified in Canada.

Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, announced over the weekend that this newest variant was likely already in the United States, telling ABC’s This Week its appearance here was “inevitable.”

Similar to previous variants, this new strain likely started circulating in the United States before scientists could do genetic tests to confirm its presence.

The World Health Organization named Omicron a “variant of concern” on Nov. 26, even though much remains unknown about how well it spreads, how severe it can be, and how it may resist vaccines. In the meantime, the United States enacted travel bans from multiple South African countries.

It remains to be seen if Omicron will follow the pattern of the Delta variant, which was first identified in the United States in May and became the dominant strain by July. It’s also possible it will follow the path taken by the Mu variant. Mu emerged in March and April to much concern, only to fizzle out by September because it was unable to compete with the Delta variant.

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

The first case of the Omicron variant of the coronavirus in the United States was confirmed by officials today in an individual in California who had recently traveled to South Africa. He or she was fully vaccinated against COVID-19 and experienced only “mild symptoms that are improving,” officials with the Centers for Disease Control and Prevention said. 

The patient, who was not named in the CDC’s announcement of the first U.S. case of the Omicron variant Dec. 1, is self-quarantining.

“All close contacts have been contacted and have tested negative,” officials said. 

The announcement comes as no surprise to many as the Omicron variant, first identified in South Africa, has been reported in countries around the world in recent days. Hong Kong, the United Kingdom, and Germany each reported this variant, as have Italy and the Netherlands. Over the weekend, the first North American cases were identified in Canada.

Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, announced over the weekend that this newest variant was likely already in the United States, telling ABC’s This Week its appearance here was “inevitable.”

Similar to previous variants, this new strain likely started circulating in the United States before scientists could do genetic tests to confirm its presence.

The World Health Organization named Omicron a “variant of concern” on Nov. 26, even though much remains unknown about how well it spreads, how severe it can be, and how it may resist vaccines. In the meantime, the United States enacted travel bans from multiple South African countries.

It remains to be seen if Omicron will follow the pattern of the Delta variant, which was first identified in the United States in May and became the dominant strain by July. It’s also possible it will follow the path taken by the Mu variant. Mu emerged in March and April to much concern, only to fizzle out by September because it was unable to compete with the Delta variant.

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

The first case of the Omicron variant of the coronavirus in the United States was confirmed by officials today in an individual in California who had recently traveled to South Africa. He or she was fully vaccinated against COVID-19 and experienced only “mild symptoms that are improving,” officials with the Centers for Disease Control and Prevention said. 

The patient, who was not named in the CDC’s announcement of the first U.S. case of the Omicron variant Dec. 1, is self-quarantining.

“All close contacts have been contacted and have tested negative,” officials said. 

The announcement comes as no surprise to many as the Omicron variant, first identified in South Africa, has been reported in countries around the world in recent days. Hong Kong, the United Kingdom, and Germany each reported this variant, as have Italy and the Netherlands. Over the weekend, the first North American cases were identified in Canada.

Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, announced over the weekend that this newest variant was likely already in the United States, telling ABC’s This Week its appearance here was “inevitable.”

Similar to previous variants, this new strain likely started circulating in the United States before scientists could do genetic tests to confirm its presence.

The World Health Organization named Omicron a “variant of concern” on Nov. 26, even though much remains unknown about how well it spreads, how severe it can be, and how it may resist vaccines. In the meantime, the United States enacted travel bans from multiple South African countries.

It remains to be seen if Omicron will follow the pattern of the Delta variant, which was first identified in the United States in May and became the dominant strain by July. It’s also possible it will follow the path taken by the Mu variant. Mu emerged in March and April to much concern, only to fizzle out by September because it was unable to compete with the Delta variant.

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

The Moderna CEO says existing COVID-19 vaccines will likely be less effective against the new Omicron variant.

“There is no world, I think, where [the effectiveness] is the same level … we had with Delta,” Stephane Bancel told the Financial Times .

“I think it’s going to be a material drop,” he said. “I just don’t know how much, because we need to wait for the data. But all the scientists I’ve talked to … are like, ‘This is not going to be good.’”

Vaccine companies are now studying whether the new Omicron variant could evade the current shots. Some data is expected in about 2 weeks.

Mr. Bancel said that if a new vaccine is needed, it could take several months to produce at scale. He estimated that Moderna could make billions of vaccine doses in 2022.

“[Moderna] and Pfizer cannot get a billion doses next week. The math doesn’t work,” he said. “But could we get the billion doses out by the summer? Sure.”

The news caused some panic on Nov. 30, prompting financial markets to fall sharply, according to Reuters. But the markets recovered after European officials gave a more reassuring outlook.

“Even if the new variant becomes more widespread, the vaccines we have will continue to provide protection,” Emer Cooke, executive director of the European Medicines Agency, told the European Parliament.

Mr. Cooke said the agency could approve new vaccines that target the Omicron variant within 3 to 4 months, if needed. Moderna and Pfizer have announced they are beginning to tailor a shot to address the Omicron variant in case the data shows they are necessary.

Also on Nov. 30, the European Centre for Disease Prevention and Control announced that 42 Omicron cases had been identified in 10 European Union countries, according to Reuters.

The cases were mild or had no symptoms, although they were found in younger people who may have mild or no symptoms anyway.

“For the assessment of whether [Omicron] escapes immunity, we still have to wait until investigations in the laboratories with [blood samples] from people who have recovered have been carried out,” Andrea Ammon, MD, chair of the agency, said during an online conference.

The University of Oxford, which developed a COVID-19 vaccine with AstraZeneca, said Nov. 30 that there’s no evidence that vaccines won’t prevent severe disease from the Omicron variant, according to Reuters.

“Despite the appearance of new variants over the past year, vaccines have continued to provide very high levels of protection against severe disease and there is no evidence so far that Omicron is any different,” the university said in a statement. “However, we have the necessary tools and processes in place for rapid development of an updated COVID-19 vaccine if it should be necessary.”

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

The Moderna CEO says existing COVID-19 vaccines will likely be less effective against the new Omicron variant.

“There is no world, I think, where [the effectiveness] is the same level … we had with Delta,” Stephane Bancel told the Financial Times .

“I think it’s going to be a material drop,” he said. “I just don’t know how much, because we need to wait for the data. But all the scientists I’ve talked to … are like, ‘This is not going to be good.’”

Vaccine companies are now studying whether the new Omicron variant could evade the current shots. Some data is expected in about 2 weeks.

Mr. Bancel said that if a new vaccine is needed, it could take several months to produce at scale. He estimated that Moderna could make billions of vaccine doses in 2022.

“[Moderna] and Pfizer cannot get a billion doses next week. The math doesn’t work,” he said. “But could we get the billion doses out by the summer? Sure.”

The news caused some panic on Nov. 30, prompting financial markets to fall sharply, according to Reuters. But the markets recovered after European officials gave a more reassuring outlook.

“Even if the new variant becomes more widespread, the vaccines we have will continue to provide protection,” Emer Cooke, executive director of the European Medicines Agency, told the European Parliament.

Mr. Cooke said the agency could approve new vaccines that target the Omicron variant within 3 to 4 months, if needed. Moderna and Pfizer have announced they are beginning to tailor a shot to address the Omicron variant in case the data shows they are necessary.

Also on Nov. 30, the European Centre for Disease Prevention and Control announced that 42 Omicron cases had been identified in 10 European Union countries, according to Reuters.

The cases were mild or had no symptoms, although they were found in younger people who may have mild or no symptoms anyway.

“For the assessment of whether [Omicron] escapes immunity, we still have to wait until investigations in the laboratories with [blood samples] from people who have recovered have been carried out,” Andrea Ammon, MD, chair of the agency, said during an online conference.

The University of Oxford, which developed a COVID-19 vaccine with AstraZeneca, said Nov. 30 that there’s no evidence that vaccines won’t prevent severe disease from the Omicron variant, according to Reuters.

“Despite the appearance of new variants over the past year, vaccines have continued to provide very high levels of protection against severe disease and there is no evidence so far that Omicron is any different,” the university said in a statement. “However, we have the necessary tools and processes in place for rapid development of an updated COVID-19 vaccine if it should be necessary.”

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

The Moderna CEO says existing COVID-19 vaccines will likely be less effective against the new Omicron variant.

“There is no world, I think, where [the effectiveness] is the same level … we had with Delta,” Stephane Bancel told the Financial Times .

“I think it’s going to be a material drop,” he said. “I just don’t know how much, because we need to wait for the data. But all the scientists I’ve talked to … are like, ‘This is not going to be good.’”

Vaccine companies are now studying whether the new Omicron variant could evade the current shots. Some data is expected in about 2 weeks.

Mr. Bancel said that if a new vaccine is needed, it could take several months to produce at scale. He estimated that Moderna could make billions of vaccine doses in 2022.

“[Moderna] and Pfizer cannot get a billion doses next week. The math doesn’t work,” he said. “But could we get the billion doses out by the summer? Sure.”

The news caused some panic on Nov. 30, prompting financial markets to fall sharply, according to Reuters. But the markets recovered after European officials gave a more reassuring outlook.

“Even if the new variant becomes more widespread, the vaccines we have will continue to provide protection,” Emer Cooke, executive director of the European Medicines Agency, told the European Parliament.

Mr. Cooke said the agency could approve new vaccines that target the Omicron variant within 3 to 4 months, if needed. Moderna and Pfizer have announced they are beginning to tailor a shot to address the Omicron variant in case the data shows they are necessary.

Also on Nov. 30, the European Centre for Disease Prevention and Control announced that 42 Omicron cases had been identified in 10 European Union countries, according to Reuters.

The cases were mild or had no symptoms, although they were found in younger people who may have mild or no symptoms anyway.

“For the assessment of whether [Omicron] escapes immunity, we still have to wait until investigations in the laboratories with [blood samples] from people who have recovered have been carried out,” Andrea Ammon, MD, chair of the agency, said during an online conference.

The University of Oxford, which developed a COVID-19 vaccine with AstraZeneca, said Nov. 30 that there’s no evidence that vaccines won’t prevent severe disease from the Omicron variant, according to Reuters.

“Despite the appearance of new variants over the past year, vaccines have continued to provide very high levels of protection against severe disease and there is no evidence so far that Omicron is any different,” the university said in a statement. “However, we have the necessary tools and processes in place for rapid development of an updated COVID-19 vaccine if it should be necessary.”

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

An antiviral pill from Merck may help some high-risk patients survive a COVID-19 infection or help them stay out of the hospital, even though the risks of taking the drug aren’t yet fully known, according to a panel of experts that advises the Food and Drug Administration on its regulatory decisions for these types of drugs.

The FDA’s Antimicrobial Drugs Advisory Committee narrowly voted to authorize the drug molnupiravir, voting 13 to 10 to support emergency use, which requires a medication to meet a lower standard of evidence than does full approval.

The FDA is not bound by the committee’s vote but typically follows its advice.

If authorized by the agency, molnupiravir would be the first antiviral agent available as a pill to treat COVID-19. Other therapies to treat the infection are available — monoclonal antibodies and the drug remdesivir — but they are given by infusion.

The United Kingdom has already authorized the use of Merck’s drug.

“This was clearly a difficult decision,” said committee member Michael Green, MD, a pediatric infectious disease expert at the University of Pittsburg School of Medicine.

Green said he voted yes, and that the drug’s ability to prevent deaths in the study weighed heavily on his decision. He said given uncertainties around the drug both the company and FDA should keep a close eye on patients taking the drug going forward.

“Should an alternative oral agent become available that had a better safety profile and equal or better efficacy profile, the agency might reconsider its authorization,” he said.

Others didn’t agree that the drug should be allowed onto the market.

“I voted no,” said Jennifer Le, PharmD, a professor of clinical pharmacy at the University of California. Dr. Le said the modest benefit of the medication didn’t outweigh all the potential safety issues. “I think I just need more efficacy and safety data,” she said.

Initial results from the first half of people enrolled in the clinical trial found the pill cut the risk of hospitalization or death by 50% in patients at higher risk of severe outcomes from COVID-19.

But later results, released just days before the meeting, showed that the drug’s effectiveness had dropped to about 30%.

In the updated analysis, 48 patients out of the 709 who were taking the drug were hospitalized or died within 29 days compared to 68 out of 699 who randomly got the placebo. There was one death in the group that got molnupiravir compared to nine in the placebo group. Nearly all those deaths occurred during the first phase of the study.

On Nov. 30 Merck explained that the drug’s efficacy appeared to fall, in part, because the placebo group had experienced fewer hospitalizations and deaths than expected during the second half of the study, making the drug look less beneficial by comparison.

The company said it wasn’t sure why patients in the placebo group had fared so much better in later trial enrollments.

“The efficacy of this product is not overwhelmingly good,” said committee member David Hardy, MD, an infectious disease expert at Charles Drew University School of Medicine in Los Angeles. “And I think that makes all of us a little uncomfortable about whether this is an advanced therapeutic because it’s an oral medication rather than an intravenous medication,” he said during the panel’s deliberations.

“I think we have to be very careful about how we’re going to allow people to use this,” Dr. Hardy said.

Many who voted for authorization thought use of the drug should be restricted to unvaccinated people who were at high risk of severe COVID-19 outcomes, the same population enrolled in the clinical trial. People in the trial were considered at higher risk if they were over age 60, had cancer, chronic kidney disease, chronic obstructive pulmonary disease, were obese, or had heart disease or diabetes.

There are some significant limitations of the study that may affect how the drug is used. Vaccinated people couldn’t enroll in the study, so it’s not known if the medication would have any benefit for them. Nearly two-thirds of the U.S. population is fully vaccinated. The study found no additional benefit of the medication compared to the placebo in people who had detectable antibodies, presumably from a prior infection.

Animal studies found that the drug — which kills the virus by forcing it to make errors as it copies its genetic material inside cells — could disrupt bone formation. For that reason, the manufacturer and the FDA agreed that it should not be used in anyone younger than age 18.

Animal studies also indicated that the drug could cause birth defects. For that reason, the company said the drug shouldn’t be given to women who are pregnant or breastfeeding and said doctors should make sure women of childbearing age aren’t pregnant before taking the medication.

Some members of the panel felt that pregnant women and their doctors should be given the choice of whether or not to use the drug, given that pregnant women are at high risk for severe COVID-19 outcomes and infused therapies may not be available in all settings.

Other members of the committee said they were uncomfortable authorizing the drug given its potential to mutate the virus.

The drug, which forces the virus to mutate as it copies its RNA, eventually causes the virus to make so many errors in its genetic material that it can no longer make more of itself and the immune system clears it out of the body.

But it takes a few days to work — the drug is designed to be taken for 5 consecutive days -- and studies of the viral loads of patients taking the drug show that through the first 2 days, viral loads remain detectable as these mutations occur.

Studies by the FDA show some of those mutations in the spike protein are the same ones that have helped the virus become more transmissible and escape the protection of vaccines.

So the question is whether someone taking the medication could develop a dangerous mutation and then infect someone else, sparking the spread of a new variant.

Nicholas Kartsonis, MD, a vice president at Merck, said that the company was still analyzing data.

“Even if the probability is very low — 1 in 10,000 or 1 in 100,000 -- that this drug would induce an escape mutant for which the vaccines we have would not cover, that would be catastrophic for the whole world, actually,” said committee member James Hildreth, MD, an immunologist and president of Meharry Medical College, Nashville. “Do you have sufficient data on the likelihood of that happening?” he asked Dr. Kartsonis of Merck.

“So we don’t,” Dr. Kartsonis said.

He said, in theory, the risk of mutation with molnupiravir is the same as seen with the use of vaccines or monoclonal antibody therapies. Dr. Hildreth wasn’t satisfied with that answer.

“With all respect, the mechanism of your drug is to drive [genetic mutations], so it’s not the same as the vaccine. It’s not the same as monoclonal antibodies,” he said.

Dr. Hildreth later said he didn’t feel comfortable voting for authorization given the uncertainties around escape mutants. He voted no.

“It was an easy vote for me,” he said.

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

An antiviral pill from Merck may help some high-risk patients survive a COVID-19 infection or help them stay out of the hospital, even though the risks of taking the drug aren’t yet fully known, according to a panel of experts that advises the Food and Drug Administration on its regulatory decisions for these types of drugs.

The FDA’s Antimicrobial Drugs Advisory Committee narrowly voted to authorize the drug molnupiravir, voting 13 to 10 to support emergency use, which requires a medication to meet a lower standard of evidence than does full approval.

The FDA is not bound by the committee’s vote but typically follows its advice.

If authorized by the agency, molnupiravir would be the first antiviral agent available as a pill to treat COVID-19. Other therapies to treat the infection are available — monoclonal antibodies and the drug remdesivir — but they are given by infusion.

The United Kingdom has already authorized the use of Merck’s drug.

“This was clearly a difficult decision,” said committee member Michael Green, MD, a pediatric infectious disease expert at the University of Pittsburg School of Medicine.

Green said he voted yes, and that the drug’s ability to prevent deaths in the study weighed heavily on his decision. He said given uncertainties around the drug both the company and FDA should keep a close eye on patients taking the drug going forward.

“Should an alternative oral agent become available that had a better safety profile and equal or better efficacy profile, the agency might reconsider its authorization,” he said.

Others didn’t agree that the drug should be allowed onto the market.

“I voted no,” said Jennifer Le, PharmD, a professor of clinical pharmacy at the University of California. Dr. Le said the modest benefit of the medication didn’t outweigh all the potential safety issues. “I think I just need more efficacy and safety data,” she said.

Initial results from the first half of people enrolled in the clinical trial found the pill cut the risk of hospitalization or death by 50% in patients at higher risk of severe outcomes from COVID-19.

But later results, released just days before the meeting, showed that the drug’s effectiveness had dropped to about 30%.

In the updated analysis, 48 patients out of the 709 who were taking the drug were hospitalized or died within 29 days compared to 68 out of 699 who randomly got the placebo. There was one death in the group that got molnupiravir compared to nine in the placebo group. Nearly all those deaths occurred during the first phase of the study.

On Nov. 30 Merck explained that the drug’s efficacy appeared to fall, in part, because the placebo group had experienced fewer hospitalizations and deaths than expected during the second half of the study, making the drug look less beneficial by comparison.

The company said it wasn’t sure why patients in the placebo group had fared so much better in later trial enrollments.

“The efficacy of this product is not overwhelmingly good,” said committee member David Hardy, MD, an infectious disease expert at Charles Drew University School of Medicine in Los Angeles. “And I think that makes all of us a little uncomfortable about whether this is an advanced therapeutic because it’s an oral medication rather than an intravenous medication,” he said during the panel’s deliberations.

“I think we have to be very careful about how we’re going to allow people to use this,” Dr. Hardy said.

Many who voted for authorization thought use of the drug should be restricted to unvaccinated people who were at high risk of severe COVID-19 outcomes, the same population enrolled in the clinical trial. People in the trial were considered at higher risk if they were over age 60, had cancer, chronic kidney disease, chronic obstructive pulmonary disease, were obese, or had heart disease or diabetes.

There are some significant limitations of the study that may affect how the drug is used. Vaccinated people couldn’t enroll in the study, so it’s not known if the medication would have any benefit for them. Nearly two-thirds of the U.S. population is fully vaccinated. The study found no additional benefit of the medication compared to the placebo in people who had detectable antibodies, presumably from a prior infection.

Animal studies found that the drug — which kills the virus by forcing it to make errors as it copies its genetic material inside cells — could disrupt bone formation. For that reason, the manufacturer and the FDA agreed that it should not be used in anyone younger than age 18.

Animal studies also indicated that the drug could cause birth defects. For that reason, the company said the drug shouldn’t be given to women who are pregnant or breastfeeding and said doctors should make sure women of childbearing age aren’t pregnant before taking the medication.

Some members of the panel felt that pregnant women and their doctors should be given the choice of whether or not to use the drug, given that pregnant women are at high risk for severe COVID-19 outcomes and infused therapies may not be available in all settings.

Other members of the committee said they were uncomfortable authorizing the drug given its potential to mutate the virus.

The drug, which forces the virus to mutate as it copies its RNA, eventually causes the virus to make so many errors in its genetic material that it can no longer make more of itself and the immune system clears it out of the body.

But it takes a few days to work — the drug is designed to be taken for 5 consecutive days -- and studies of the viral loads of patients taking the drug show that through the first 2 days, viral loads remain detectable as these mutations occur.

Studies by the FDA show some of those mutations in the spike protein are the same ones that have helped the virus become more transmissible and escape the protection of vaccines.

So the question is whether someone taking the medication could develop a dangerous mutation and then infect someone else, sparking the spread of a new variant.

Nicholas Kartsonis, MD, a vice president at Merck, said that the company was still analyzing data.

“Even if the probability is very low — 1 in 10,000 or 1 in 100,000 -- that this drug would induce an escape mutant for which the vaccines we have would not cover, that would be catastrophic for the whole world, actually,” said committee member James Hildreth, MD, an immunologist and president of Meharry Medical College, Nashville. “Do you have sufficient data on the likelihood of that happening?” he asked Dr. Kartsonis of Merck.

“So we don’t,” Dr. Kartsonis said.

He said, in theory, the risk of mutation with molnupiravir is the same as seen with the use of vaccines or monoclonal antibody therapies. Dr. Hildreth wasn’t satisfied with that answer.

“With all respect, the mechanism of your drug is to drive [genetic mutations], so it’s not the same as the vaccine. It’s not the same as monoclonal antibodies,” he said.

Dr. Hildreth later said he didn’t feel comfortable voting for authorization given the uncertainties around escape mutants. He voted no.

“It was an easy vote for me,” he said.

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

An antiviral pill from Merck may help some high-risk patients survive a COVID-19 infection or help them stay out of the hospital, even though the risks of taking the drug aren’t yet fully known, according to a panel of experts that advises the Food and Drug Administration on its regulatory decisions for these types of drugs.

The FDA’s Antimicrobial Drugs Advisory Committee narrowly voted to authorize the drug molnupiravir, voting 13 to 10 to support emergency use, which requires a medication to meet a lower standard of evidence than does full approval.

The FDA is not bound by the committee’s vote but typically follows its advice.

If authorized by the agency, molnupiravir would be the first antiviral agent available as a pill to treat COVID-19. Other therapies to treat the infection are available — monoclonal antibodies and the drug remdesivir — but they are given by infusion.

The United Kingdom has already authorized the use of Merck’s drug.

“This was clearly a difficult decision,” said committee member Michael Green, MD, a pediatric infectious disease expert at the University of Pittsburg School of Medicine.

Green said he voted yes, and that the drug’s ability to prevent deaths in the study weighed heavily on his decision. He said given uncertainties around the drug both the company and FDA should keep a close eye on patients taking the drug going forward.

“Should an alternative oral agent become available that had a better safety profile and equal or better efficacy profile, the agency might reconsider its authorization,” he said.

Others didn’t agree that the drug should be allowed onto the market.

“I voted no,” said Jennifer Le, PharmD, a professor of clinical pharmacy at the University of California. Dr. Le said the modest benefit of the medication didn’t outweigh all the potential safety issues. “I think I just need more efficacy and safety data,” she said.

Initial results from the first half of people enrolled in the clinical trial found the pill cut the risk of hospitalization or death by 50% in patients at higher risk of severe outcomes from COVID-19.

But later results, released just days before the meeting, showed that the drug’s effectiveness had dropped to about 30%.

In the updated analysis, 48 patients out of the 709 who were taking the drug were hospitalized or died within 29 days compared to 68 out of 699 who randomly got the placebo. There was one death in the group that got molnupiravir compared to nine in the placebo group. Nearly all those deaths occurred during the first phase of the study.

On Nov. 30 Merck explained that the drug’s efficacy appeared to fall, in part, because the placebo group had experienced fewer hospitalizations and deaths than expected during the second half of the study, making the drug look less beneficial by comparison.

The company said it wasn’t sure why patients in the placebo group had fared so much better in later trial enrollments.

“The efficacy of this product is not overwhelmingly good,” said committee member David Hardy, MD, an infectious disease expert at Charles Drew University School of Medicine in Los Angeles. “And I think that makes all of us a little uncomfortable about whether this is an advanced therapeutic because it’s an oral medication rather than an intravenous medication,” he said during the panel’s deliberations.

“I think we have to be very careful about how we’re going to allow people to use this,” Dr. Hardy said.

Many who voted for authorization thought use of the drug should be restricted to unvaccinated people who were at high risk of severe COVID-19 outcomes, the same population enrolled in the clinical trial. People in the trial were considered at higher risk if they were over age 60, had cancer, chronic kidney disease, chronic obstructive pulmonary disease, were obese, or had heart disease or diabetes.

There are some significant limitations of the study that may affect how the drug is used. Vaccinated people couldn’t enroll in the study, so it’s not known if the medication would have any benefit for them. Nearly two-thirds of the U.S. population is fully vaccinated. The study found no additional benefit of the medication compared to the placebo in people who had detectable antibodies, presumably from a prior infection.

Animal studies found that the drug — which kills the virus by forcing it to make errors as it copies its genetic material inside cells — could disrupt bone formation. For that reason, the manufacturer and the FDA agreed that it should not be used in anyone younger than age 18.

Animal studies also indicated that the drug could cause birth defects. For that reason, the company said the drug shouldn’t be given to women who are pregnant or breastfeeding and said doctors should make sure women of childbearing age aren’t pregnant before taking the medication.

Some members of the panel felt that pregnant women and their doctors should be given the choice of whether or not to use the drug, given that pregnant women are at high risk for severe COVID-19 outcomes and infused therapies may not be available in all settings.

Other members of the committee said they were uncomfortable authorizing the drug given its potential to mutate the virus.

The drug, which forces the virus to mutate as it copies its RNA, eventually causes the virus to make so many errors in its genetic material that it can no longer make more of itself and the immune system clears it out of the body.

But it takes a few days to work — the drug is designed to be taken for 5 consecutive days -- and studies of the viral loads of patients taking the drug show that through the first 2 days, viral loads remain detectable as these mutations occur.

Studies by the FDA show some of those mutations in the spike protein are the same ones that have helped the virus become more transmissible and escape the protection of vaccines.

So the question is whether someone taking the medication could develop a dangerous mutation and then infect someone else, sparking the spread of a new variant.

Nicholas Kartsonis, MD, a vice president at Merck, said that the company was still analyzing data.

“Even if the probability is very low — 1 in 10,000 or 1 in 100,000 -- that this drug would induce an escape mutant for which the vaccines we have would not cover, that would be catastrophic for the whole world, actually,” said committee member James Hildreth, MD, an immunologist and president of Meharry Medical College, Nashville. “Do you have sufficient data on the likelihood of that happening?” he asked Dr. Kartsonis of Merck.

“So we don’t,” Dr. Kartsonis said.

He said, in theory, the risk of mutation with molnupiravir is the same as seen with the use of vaccines or monoclonal antibody therapies. Dr. Hildreth wasn’t satisfied with that answer.

“With all respect, the mechanism of your drug is to drive [genetic mutations], so it’s not the same as the vaccine. It’s not the same as monoclonal antibodies,” he said.

Dr. Hildreth later said he didn’t feel comfortable voting for authorization given the uncertainties around escape mutants. He voted no.

“It was an easy vote for me,” he said.

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

Though primary efficacy results have yet to be published, new safety findings from two large, randomized trials of aducanumab offer details on which patients are more likely to experience complications associated with the controversial Alzheimer’s drug.

Courtesy of Memory and Aging Program at Butler Hospital

Amyloid-related imaging abnormalities, or ARIA, have been seen linked to a variety of experimental amyloid-lowering treatments for Alzheimer’s disease. The abnormalities include brain bleeding (ARIA-H) and brain edema (ARIA-E), detected on magnetic resonance imaging.
 

Safety findings

In a study published Nov. 22 in JAMA Neurology, Stephen Salloway, MD, director of neurology and the memory and aging program at Butler Hospital and the Martin M. Zucker Professor of Psychiatry and Human Behavior and Professor of Neurology at the Warren Alpert Medical School of Brown University in Providence, R.I., and his colleagues, reported that 41% of 1,029 patients in the high-dose (10 mg/kg) treatment groups of aducanumab (Aduhelm, Biogen) developed ARIA.

Thirty-five percent of the high-dose patients (n = 362) developed ARIA-E, and 94 had symptoms, with headache the most commonly reported, followed by confusion. ARIA-E occurred only sporadically in the placebo groups, while ARIA-H was more common. Microbleeds were seen in 19% of the high-dose patients compared with 6.6% in the placebo group, while superficial siderosis occurred in about 15%, versus 2.2% on placebo. Most of the ARIA-E events occurred during the first eight doses of the infusion treatment. People with one or more copies of the APOE4 genetic variant saw higher risk of ARIA-E associated with treatment compared with noncarriers (hazard ratio [HR] 2.5; 95% confidence interval [CI], 1.90-3.20). Evidence of brain micro-hemorrhages at baseline was associated with higher risk of ARIA-E (HR 1.7; 95% CI, 1.31-2.27) compared with patients without MRI evidence of brain bleeds in the year before treatment began.

Older age independently increased risk of ARIA-H, with a risk that was seen increasing 6% with each additional year of age.

The identically designed EMERGE and ENGAGE trials of aducanumab enrolled nearly 3,300 patients worldwide (mean age 70.4, 52% female). Participants were screened to include only those with amyloid-positive mild cognitive impairment (81% of the cohort) or mild Alzheimer’s dementia. Both trials were halted early after a futility analysis concluded that treatment was unlikely to result in benefit.

A post hoc analysis later determined that patients in one trial, EMERGE, showed slight clinical benefit on follow-up in the high-dose group only. The Food and Drug Administration approved the drug in July 2021 on the basis of that finding, overriding the consensus of its independent advisory committee, which was not persuaded. Since then the drug has become synonymous with controversy, not aided by its high list price of more than $50,000 per year, with many insurers and large health care systems refusing to deliver it. The recent reported death of a woman participating in an open-label extension trial of aducanumab, who was admitted to the hospital with brain swelling, has added to safety concerns.
 

Brain bleeds and age affect risk

In an interview with MDedge Neurology, neurologist Madhav Thambisetty, MD, PhD, a senior investigator with the National Institute on Aging in Baltimore, and a member of the FDA advisory committee that recommended against approval for aducanumab, said that while physicians are aware that APOE4 carriers face higher risks of treatment-related complications, the new safety findings offer additional guidance on patient selection.

“The older you are the greater your risk of ARIA, and the more micro-hemorrhages you have at baseline the greater your risk. Those are important findings that were not previously well publicized before,” Dr. Thambisetty said.

In the EMERGE and ENGAGE trials, Dr. Thambisetty pointed out, patients with four or more micro-hemorrhages at baseline were excluded. The new findings reveal that even a small number of bleeds at baseline can contribute to ARIA risk.

“Patients in real-world clinical practice are going to be very different from the tightly controlled, well-screened participants who were enrolled in these trials. Microbleeds are very common in Alzheimer’s patients, occurring in 18-32%. Now that these findings are available, it’s important for a practicing physician to obtain a baseline MRI scan and really pay attention to microbleeds, because that will affect treatment decisions.”
 

Additional concerns

Dr. Thambisetty cautioned that the new results made no mention of another important safety outcome: loss of brain volume associated with treatment.

Changes in brain volume have been seen associated with other amyloid-lowering treatments, though the reasons for this are poorly understood. Participants in EMERGE and ENGAGE “received numerous MRI scans,” Dr. Thambisetty said. “This was one of the strengths of the trials. Thanks to an open-label extension we now have more than 2 years of MRI data from meticulously monitored patients, and there has been no mention of brain volume changes despite this being a prespecified outcome. This, for me, is one of the glaring omissions of this paper, and the fact that it’s not even mentioned is really worrisome.”

The sponsor of the aducanumab trials, Biogen, has yet to publish efficacy findings in a peer-reviewed journal, instead presenting them piecemeal at conferences.

“The current paper was a secondary analysis,” Dr. Thambisetty said. “The authors say the primary analysis will be published elsewhere. I think it’s important to reflect upon the fact that these clinical trials enrolled more than 3,000 participants at more than 300 trial centers in 20 countries. We now have an approved drug that’s commercially available. And yet we don’t have a single peer-reviewed publication discussing the efficacy data. None of this is in the interest of our patients, or in advancing the science.”

The EMERGE and ENGAGE trials were funded by Biogen. Eight of the current paper’s 14 authors are Biogen employees. Dr. Salloway, the lead author, disclosed financial support from Biogen and other manufacturers, as did two of his coauthors. Dr. Thambisetty disclosed no financial conflicts of interest.

Though primary efficacy results have yet to be published, new safety findings from two large, randomized trials of aducanumab offer details on which patients are more likely to experience complications associated with the controversial Alzheimer’s drug.

Courtesy of Memory and Aging Program at Butler Hospital

Amyloid-related imaging abnormalities, or ARIA, have been seen linked to a variety of experimental amyloid-lowering treatments for Alzheimer’s disease. The abnormalities include brain bleeding (ARIA-H) and brain edema (ARIA-E), detected on magnetic resonance imaging.
 

Safety findings

In a study published Nov. 22 in JAMA Neurology, Stephen Salloway, MD, director of neurology and the memory and aging program at Butler Hospital and the Martin M. Zucker Professor of Psychiatry and Human Behavior and Professor of Neurology at the Warren Alpert Medical School of Brown University in Providence, R.I., and his colleagues, reported that 41% of 1,029 patients in the high-dose (10 mg/kg) treatment groups of aducanumab (Aduhelm, Biogen) developed ARIA.

Thirty-five percent of the high-dose patients (n = 362) developed ARIA-E, and 94 had symptoms, with headache the most commonly reported, followed by confusion. ARIA-E occurred only sporadically in the placebo groups, while ARIA-H was more common. Microbleeds were seen in 19% of the high-dose patients compared with 6.6% in the placebo group, while superficial siderosis occurred in about 15%, versus 2.2% on placebo. Most of the ARIA-E events occurred during the first eight doses of the infusion treatment. People with one or more copies of the APOE4 genetic variant saw higher risk of ARIA-E associated with treatment compared with noncarriers (hazard ratio [HR] 2.5; 95% confidence interval [CI], 1.90-3.20). Evidence of brain micro-hemorrhages at baseline was associated with higher risk of ARIA-E (HR 1.7; 95% CI, 1.31-2.27) compared with patients without MRI evidence of brain bleeds in the year before treatment began.

Older age independently increased risk of ARIA-H, with a risk that was seen increasing 6% with each additional year of age.

The identically designed EMERGE and ENGAGE trials of aducanumab enrolled nearly 3,300 patients worldwide (mean age 70.4, 52% female). Participants were screened to include only those with amyloid-positive mild cognitive impairment (81% of the cohort) or mild Alzheimer’s dementia. Both trials were halted early after a futility analysis concluded that treatment was unlikely to result in benefit.

A post hoc analysis later determined that patients in one trial, EMERGE, showed slight clinical benefit on follow-up in the high-dose group only. The Food and Drug Administration approved the drug in July 2021 on the basis of that finding, overriding the consensus of its independent advisory committee, which was not persuaded. Since then the drug has become synonymous with controversy, not aided by its high list price of more than $50,000 per year, with many insurers and large health care systems refusing to deliver it. The recent reported death of a woman participating in an open-label extension trial of aducanumab, who was admitted to the hospital with brain swelling, has added to safety concerns.
 

Brain bleeds and age affect risk

In an interview with MDedge Neurology, neurologist Madhav Thambisetty, MD, PhD, a senior investigator with the National Institute on Aging in Baltimore, and a member of the FDA advisory committee that recommended against approval for aducanumab, said that while physicians are aware that APOE4 carriers face higher risks of treatment-related complications, the new safety findings offer additional guidance on patient selection.

“The older you are the greater your risk of ARIA, and the more micro-hemorrhages you have at baseline the greater your risk. Those are important findings that were not previously well publicized before,” Dr. Thambisetty said.

In the EMERGE and ENGAGE trials, Dr. Thambisetty pointed out, patients with four or more micro-hemorrhages at baseline were excluded. The new findings reveal that even a small number of bleeds at baseline can contribute to ARIA risk.

“Patients in real-world clinical practice are going to be very different from the tightly controlled, well-screened participants who were enrolled in these trials. Microbleeds are very common in Alzheimer’s patients, occurring in 18-32%. Now that these findings are available, it’s important for a practicing physician to obtain a baseline MRI scan and really pay attention to microbleeds, because that will affect treatment decisions.”
 

Additional concerns

Dr. Thambisetty cautioned that the new results made no mention of another important safety outcome: loss of brain volume associated with treatment.

Changes in brain volume have been seen associated with other amyloid-lowering treatments, though the reasons for this are poorly understood. Participants in EMERGE and ENGAGE “received numerous MRI scans,” Dr. Thambisetty said. “This was one of the strengths of the trials. Thanks to an open-label extension we now have more than 2 years of MRI data from meticulously monitored patients, and there has been no mention of brain volume changes despite this being a prespecified outcome. This, for me, is one of the glaring omissions of this paper, and the fact that it’s not even mentioned is really worrisome.”

The sponsor of the aducanumab trials, Biogen, has yet to publish efficacy findings in a peer-reviewed journal, instead presenting them piecemeal at conferences.

“The current paper was a secondary analysis,” Dr. Thambisetty said. “The authors say the primary analysis will be published elsewhere. I think it’s important to reflect upon the fact that these clinical trials enrolled more than 3,000 participants at more than 300 trial centers in 20 countries. We now have an approved drug that’s commercially available. And yet we don’t have a single peer-reviewed publication discussing the efficacy data. None of this is in the interest of our patients, or in advancing the science.”

The EMERGE and ENGAGE trials were funded by Biogen. Eight of the current paper’s 14 authors are Biogen employees. Dr. Salloway, the lead author, disclosed financial support from Biogen and other manufacturers, as did two of his coauthors. Dr. Thambisetty disclosed no financial conflicts of interest.

Though primary efficacy results have yet to be published, new safety findings from two large, randomized trials of aducanumab offer details on which patients are more likely to experience complications associated with the controversial Alzheimer’s drug.

Courtesy of Memory and Aging Program at Butler Hospital

Amyloid-related imaging abnormalities, or ARIA, have been seen linked to a variety of experimental amyloid-lowering treatments for Alzheimer’s disease. The abnormalities include brain bleeding (ARIA-H) and brain edema (ARIA-E), detected on magnetic resonance imaging.
 

Safety findings

In a study published Nov. 22 in JAMA Neurology, Stephen Salloway, MD, director of neurology and the memory and aging program at Butler Hospital and the Martin M. Zucker Professor of Psychiatry and Human Behavior and Professor of Neurology at the Warren Alpert Medical School of Brown University in Providence, R.I., and his colleagues, reported that 41% of 1,029 patients in the high-dose (10 mg/kg) treatment groups of aducanumab (Aduhelm, Biogen) developed ARIA.

Thirty-five percent of the high-dose patients (n = 362) developed ARIA-E, and 94 had symptoms, with headache the most commonly reported, followed by confusion. ARIA-E occurred only sporadically in the placebo groups, while ARIA-H was more common. Microbleeds were seen in 19% of the high-dose patients compared with 6.6% in the placebo group, while superficial siderosis occurred in about 15%, versus 2.2% on placebo. Most of the ARIA-E events occurred during the first eight doses of the infusion treatment. People with one or more copies of the APOE4 genetic variant saw higher risk of ARIA-E associated with treatment compared with noncarriers (hazard ratio [HR] 2.5; 95% confidence interval [CI], 1.90-3.20). Evidence of brain micro-hemorrhages at baseline was associated with higher risk of ARIA-E (HR 1.7; 95% CI, 1.31-2.27) compared with patients without MRI evidence of brain bleeds in the year before treatment began.

Older age independently increased risk of ARIA-H, with a risk that was seen increasing 6% with each additional year of age.

The identically designed EMERGE and ENGAGE trials of aducanumab enrolled nearly 3,300 patients worldwide (mean age 70.4, 52% female). Participants were screened to include only those with amyloid-positive mild cognitive impairment (81% of the cohort) or mild Alzheimer’s dementia. Both trials were halted early after a futility analysis concluded that treatment was unlikely to result in benefit.

A post hoc analysis later determined that patients in one trial, EMERGE, showed slight clinical benefit on follow-up in the high-dose group only. The Food and Drug Administration approved the drug in July 2021 on the basis of that finding, overriding the consensus of its independent advisory committee, which was not persuaded. Since then the drug has become synonymous with controversy, not aided by its high list price of more than $50,000 per year, with many insurers and large health care systems refusing to deliver it. The recent reported death of a woman participating in an open-label extension trial of aducanumab, who was admitted to the hospital with brain swelling, has added to safety concerns.
 

Brain bleeds and age affect risk

In an interview with MDedge Neurology, neurologist Madhav Thambisetty, MD, PhD, a senior investigator with the National Institute on Aging in Baltimore, and a member of the FDA advisory committee that recommended against approval for aducanumab, said that while physicians are aware that APOE4 carriers face higher risks of treatment-related complications, the new safety findings offer additional guidance on patient selection.

“The older you are the greater your risk of ARIA, and the more micro-hemorrhages you have at baseline the greater your risk. Those are important findings that were not previously well publicized before,” Dr. Thambisetty said.

In the EMERGE and ENGAGE trials, Dr. Thambisetty pointed out, patients with four or more micro-hemorrhages at baseline were excluded. The new findings reveal that even a small number of bleeds at baseline can contribute to ARIA risk.

“Patients in real-world clinical practice are going to be very different from the tightly controlled, well-screened participants who were enrolled in these trials. Microbleeds are very common in Alzheimer’s patients, occurring in 18-32%. Now that these findings are available, it’s important for a practicing physician to obtain a baseline MRI scan and really pay attention to microbleeds, because that will affect treatment decisions.”
 

Additional concerns

Dr. Thambisetty cautioned that the new results made no mention of another important safety outcome: loss of brain volume associated with treatment.

Changes in brain volume have been seen associated with other amyloid-lowering treatments, though the reasons for this are poorly understood. Participants in EMERGE and ENGAGE “received numerous MRI scans,” Dr. Thambisetty said. “This was one of the strengths of the trials. Thanks to an open-label extension we now have more than 2 years of MRI data from meticulously monitored patients, and there has been no mention of brain volume changes despite this being a prespecified outcome. This, for me, is one of the glaring omissions of this paper, and the fact that it’s not even mentioned is really worrisome.”

The sponsor of the aducanumab trials, Biogen, has yet to publish efficacy findings in a peer-reviewed journal, instead presenting them piecemeal at conferences.

“The current paper was a secondary analysis,” Dr. Thambisetty said. “The authors say the primary analysis will be published elsewhere. I think it’s important to reflect upon the fact that these clinical trials enrolled more than 3,000 participants at more than 300 trial centers in 20 countries. We now have an approved drug that’s commercially available. And yet we don’t have a single peer-reviewed publication discussing the efficacy data. None of this is in the interest of our patients, or in advancing the science.”

The EMERGE and ENGAGE trials were funded by Biogen. Eight of the current paper’s 14 authors are Biogen employees. Dr. Salloway, the lead author, disclosed financial support from Biogen and other manufacturers, as did two of his coauthors. Dr. Thambisetty disclosed no financial conflicts of interest.