MDedge Cardiology

The pandemic has created a hostile environment for pregnant people and their babies.

Stress levels among expectant mothers have soared. Pregnant women with COVID are 5 times as likely as uninfected pregnant people to require intensive care and 22 times as likely to die. Infected moms are four times as likely to have a stillborn child.

Yet some of the pandemic’s greatest threats to infants’ health may not be apparent for years or even decades.

That’s because babies of COVID-infected moms are 60% more likely to be born very prematurely, which increases the danger of infant mortality and long-term disabilities such as cerebral palsy, asthma, and hearing loss, as well as a child’s risk of adult disease, including depression, anxiety, heart disease, and kidney disease.

Studies have linked fever and infection during pregnancy to developmental and psychiatric conditions such as autism, depression, and schizophrenia.

“Some of these conditions do not show up until middle childhood or early adult life, but they have their origins in fetal life,” said Evdokia Anagnostou, MD, a child neurologist at Holland Bloorview Kids Rehabilitation Hospital and a pediatrics professor at the University of Toronto.

For fetuses exposed to COVID, the greatest danger is usually not the coronavirus itself, but the mother’s immune system.

Both severe COVID infections and the strain of the pandemic can expose fetuses to harmful inflammation, which can occur when a mother’s immune system is fighting a virus or when stress hormones send nonstop alarm signals.

Prenatal inflammation “changes the way the brain develops and, depending on the timing of the infection, it can change the way the heart or kidneys develop,” Dr. Anagnostou said.

Although health officials have strongly recommended COVID vaccines for pregnant people, only 35% are fully vaccinated.

At least 150,000 pregnant women have been diagnosed with COVID; more than 25,000 of them have been hospitalized, and 249 have died, according to the Centers for Disease Control and Prevention.

Although most babies will be fine, even a small increase in the percentage of children with special medical or educational needs could have a large effect on the population, given the huge number of COVID infections, Dr. Anagnostou said.

“If someone has a baby who is doing well, that is what they should focus on,” Dr. Anagnostou said. “But from a public health point of view, we need to follow women who experienced severe COVID and their babies to understand the impact.”

Learning from history

Researchers in the United States and other countries are already studying “the COVID generation” to see whether these children have more health issues than those conceived or born before 2020.

Previous crises have shown that the challenges fetuses face in the womb – such as maternal infections, hunger, stress, and hormone-disrupting chemicals – can leave a lasting imprint on their health, as well as that of their children and grandchildren, said Frederick Kaskel, MD, director of pediatric nephrology at the Children’s Hospital at Montefiore, New York.

People whose mothers were pregnant during surges in the 1918 influenza pandemic, for example, had poorer health throughout their lives, compared with Americans born at other times, said John McCarthy, who is a medical student at Albert Einstein College of Medicine, New York, and cowrote a recent review in JAMA Pediatrics with Dr. Kaskel.

Researchers don’t know exactly which moms were infected with pandemic flu, Mr. McCarthy said. But women who were pregnant during major surges – when infection was widespread – had children with higher rates of heart disease or diabetes. These children were also less successful in school, less economically productive, and more likely to live with a disability.

Because organ systems develop during different periods of pregnancy, fetuses exposed during the first trimester may face different risks than those exposed toward the end of pregnancy, Mr. McCarthy said. For example, people born in the fall of 1918 were 50% more likely than others to develop kidney disease; that may reflect an exposure to the pandemic in the third trimester, while the kidneys were still developing.

Nearly 2 years into the COVID pandemic, researchers have begun to publish preliminary observations of infants exposed to COVID infections and stress before birth.

Although Dr. Anagnostou noted that it’s too early to reach definitive conclusions, “there is evidence that babies born to moms with severe COVID infections have changes to their immune system,” she said. “It’s enough to make us worry a little bit.”

Damaging a fetal security system

The good news about the coronavirus is that it seldom crosses the placenta, the organ tasked with protecting a developing fetus from infections and providing it with oxygen. So moms with COVID rarely give the virus to their children before birth.

That’s important, because some viruses that directly infect the fetus – such as Zika – can cause devastating birth defects, said Karin Nielsen-Saines, MD, a specialist in pediatric infectious diseases at University of California, Los Angeles.

But studies also suggest that inflammation from a mother’s COVID infection can injure the placenta, said Jeffery Goldstein, MD, an assistant professor of pathology at Northwestern University, Chicago. In a study published in American Journal of Clinical Pathology , Dr. Goldstein and his coauthors found that placentas from COVID-infected moms had more abnormal blood vessels than placentas from patients without COVID, making it harder for them to deliver sufficient oxygen to the fetus.

Placental damage can also lead to preeclampsia, a serious complication of pregnancy that can cause a mother’s blood pressure to spike.

Preeclampsia occurs when blood vessels in the placenta don’t develop or function properly, forcing the mother’s heart to work harder to get blood to the fetus, which may not receive enough oxygen and nutrients. Preeclampsia also predisposes women to heart attacks and strokes later in life.

Rewiring the immune system

In some cases, COVID also appears to rewire a baby’s immune response, Dr. Nielsen-Saines said.

In an October study in the journal Cell Reports Medicine, Dr. Nielsen-Saines and her coauthors found that infants born to people with severe COVID infections had a different mix of immune cells and proteins than other babies. None of the newborns tested positive for the coronavirus.

The immune changes are concerning, Dr. Nielsen-Saines said, because this pattern of immune cells and proteins has previously been found in infants with respiratory problems and in some cases poor neurodevelopment.

Notably, all the babies in her study appear healthy, said Dr. Nielsen-Saines, who plans to follow them for 3 years to see whether these early signals translate into developmental delays, such as problems talking, walking, or interacting with others.

“How big of a difference does any of this make in the baby?” asked Dr. Anagnostou. “We won’t know for a few years. All we can do is try to be as prepared as possible.”

Increasing the risk for boys

Boys could face higher risks from COVID, even before birth.

Males are generally more vulnerable than females as fetuses and newborns; they’re more likely to be born prematurely and to die as infants. Preterm boys also have a higher risk of disability and death.

But coronavirus infection poses special dangers, said Sabra Klein, PhD, a professor of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health, Baltimore.

That’s because boys are disproportionately affected by conditions linked to maternal infections. Boys are four times as likely as girls to be diagnosed with autism or attention-deficit/hyperactivity disorder, for example, while men are 75% more likely than women to develop schizophrenia.

Scientists don’t fully understand why boys appear more fragile in the womb, although testosterone – which can dampen immune response – may play a role, said Kristina Adams Waldorf, MD, a professor of obstetrics and gynecology at the University of Washington.

Men generally mount weaker immune responses than women and more often develop severe COVID infections. Recent research suggests boys with COVID are more likely than girls to become seriously ill or develop a rare inflammatory condition called multisystem inflammatory syndrome.

New research on COVID could help illuminate this vulnerability.

In a study published in October, researchers found that the sex of a fetus influences the way its placenta responds to COVID, as well as how its mother’s immune system responds.

Pregnant people infected with COVID made fewer antibodies against the coronavirus if they were carrying male fetuses than if they were carrying females. Mothers also transferred fewer antibodies to boys than to girls, said Andrea Edlow, MD, senior author of the study and a maternal-fetal medicine specialist at Massachusetts General Hospital, Boston.

When examining the placentas of male fetuses after delivery, researchers found changes that could leave boys less protected against damaging inflammation.

The sex of a fetus can influence its mother’s response to other illnesses, as well.

For example, research shows that pregnant women with asthma have worse symptoms if they’re carrying a female. Women carrying males are slightly more likely to develop gestational diabetes.

Dr. Edlow said her findings raise questions about the “cross talk” between mother and baby. “The mom’s immune system is sensing there is a male fetus,” Dr. Edlow said. “And the fetus is actively communicating with the mom’s immune system.”

Boosting toxic stress

Rates of depression and stress among pregnant women have increased dramatically during the pandemic.

That’s concerning because chronic stress can lead to inflammation, affecting the babies of both infected and uninfected women, Dr. Anagnostou said.

Studies consistently show that infants born to mothers who experience significant stress during pregnancy have higher rates of short- and long-term health damage – including heart defects and obesity – than babies born to women with less stress.

“We know that inflammation directly influences the way a baby’s brain develops,” said Elinor Sullivan, PhD, an associate professor in psychiatry at Oregon Health & Science University, Portland.

Lockdowns, travel restrictions and physical distancing left many pregnant women without the support of family and friends. The stress of losing a loved one, a job, or a home further heightens the risks to moms and babies, said Dr. Sullivan, who is following children born during the pandemic for 5 years.

In research that has not yet been published, Dr. Sullivan found that babies of women who were pregnant during the pandemic showed more sadness and negative emotions in the first year of life, compared with infants of women who were pregnant before the pandemic.

The findings show the importance of helping and protecting pregnant people before and after delivery, said Dr. Sullivan, who conducted a separate study that found women who received more social support were less depressed.

Italian researchers are also studying the effect of maternal stress on infants’ behavior, as well as the way their genes are regulated.

Although stress-related inflammation doesn’t alter the structure of a baby’s genes, it can influence whether they’re turned on and off, said Livio Provenzi, PhD, a psychologist at the C. Mondino National Institute of Neurology Foundation in Pavia, Italy.

In Dr. Provenzi’s study of 163 mother-baby pairs he found differences in how genes that regulate the stress response were activated. Genes that help people respond to stress were more likely to be turned off in babies whose moms reported the most stress during pregnancy. The same moms also reported that their babies cried more and were fussier when they were 3 months old.

Researchers usually prefer to make in-person observations of babies as they interact with their mothers, Dr. Provenzi said. But because of the pandemic, Dr. Provenzi asked mothers to fill out questionnaires about infant behavior. He plans to observe mothers and babies in person when the children are 12 months old.

While vaccinating pregnant people is the best way to protect them and their fetuses from the virus, Dr. Anagnostou said, society needs to do more to preserve expectant mothers’ mental health.

“We can’t escape the fact that we’ve lived through 2 years of a pandemic,” Dr. Anagnostou said. “But we can think about opportunities for reducing the risk.”

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

The pandemic has created a hostile environment for pregnant people and their babies.

Stress levels among expectant mothers have soared. Pregnant women with COVID are 5 times as likely as uninfected pregnant people to require intensive care and 22 times as likely to die. Infected moms are four times as likely to have a stillborn child.

Yet some of the pandemic’s greatest threats to infants’ health may not be apparent for years or even decades.

That’s because babies of COVID-infected moms are 60% more likely to be born very prematurely, which increases the danger of infant mortality and long-term disabilities such as cerebral palsy, asthma, and hearing loss, as well as a child’s risk of adult disease, including depression, anxiety, heart disease, and kidney disease.

Studies have linked fever and infection during pregnancy to developmental and psychiatric conditions such as autism, depression, and schizophrenia.

“Some of these conditions do not show up until middle childhood or early adult life, but they have their origins in fetal life,” said Evdokia Anagnostou, MD, a child neurologist at Holland Bloorview Kids Rehabilitation Hospital and a pediatrics professor at the University of Toronto.

For fetuses exposed to COVID, the greatest danger is usually not the coronavirus itself, but the mother’s immune system.

Both severe COVID infections and the strain of the pandemic can expose fetuses to harmful inflammation, which can occur when a mother’s immune system is fighting a virus or when stress hormones send nonstop alarm signals.

Prenatal inflammation “changes the way the brain develops and, depending on the timing of the infection, it can change the way the heart or kidneys develop,” Dr. Anagnostou said.

Although health officials have strongly recommended COVID vaccines for pregnant people, only 35% are fully vaccinated.

At least 150,000 pregnant women have been diagnosed with COVID; more than 25,000 of them have been hospitalized, and 249 have died, according to the Centers for Disease Control and Prevention.

Although most babies will be fine, even a small increase in the percentage of children with special medical or educational needs could have a large effect on the population, given the huge number of COVID infections, Dr. Anagnostou said.

“If someone has a baby who is doing well, that is what they should focus on,” Dr. Anagnostou said. “But from a public health point of view, we need to follow women who experienced severe COVID and their babies to understand the impact.”

Learning from history

Researchers in the United States and other countries are already studying “the COVID generation” to see whether these children have more health issues than those conceived or born before 2020.

Previous crises have shown that the challenges fetuses face in the womb – such as maternal infections, hunger, stress, and hormone-disrupting chemicals – can leave a lasting imprint on their health, as well as that of their children and grandchildren, said Frederick Kaskel, MD, director of pediatric nephrology at the Children’s Hospital at Montefiore, New York.

People whose mothers were pregnant during surges in the 1918 influenza pandemic, for example, had poorer health throughout their lives, compared with Americans born at other times, said John McCarthy, who is a medical student at Albert Einstein College of Medicine, New York, and cowrote a recent review in JAMA Pediatrics with Dr. Kaskel.

Researchers don’t know exactly which moms were infected with pandemic flu, Mr. McCarthy said. But women who were pregnant during major surges – when infection was widespread – had children with higher rates of heart disease or diabetes. These children were also less successful in school, less economically productive, and more likely to live with a disability.

Because organ systems develop during different periods of pregnancy, fetuses exposed during the first trimester may face different risks than those exposed toward the end of pregnancy, Mr. McCarthy said. For example, people born in the fall of 1918 were 50% more likely than others to develop kidney disease; that may reflect an exposure to the pandemic in the third trimester, while the kidneys were still developing.

Nearly 2 years into the COVID pandemic, researchers have begun to publish preliminary observations of infants exposed to COVID infections and stress before birth.

Although Dr. Anagnostou noted that it’s too early to reach definitive conclusions, “there is evidence that babies born to moms with severe COVID infections have changes to their immune system,” she said. “It’s enough to make us worry a little bit.”

Damaging a fetal security system

The good news about the coronavirus is that it seldom crosses the placenta, the organ tasked with protecting a developing fetus from infections and providing it with oxygen. So moms with COVID rarely give the virus to their children before birth.

That’s important, because some viruses that directly infect the fetus – such as Zika – can cause devastating birth defects, said Karin Nielsen-Saines, MD, a specialist in pediatric infectious diseases at University of California, Los Angeles.

But studies also suggest that inflammation from a mother’s COVID infection can injure the placenta, said Jeffery Goldstein, MD, an assistant professor of pathology at Northwestern University, Chicago. In a study published in American Journal of Clinical Pathology , Dr. Goldstein and his coauthors found that placentas from COVID-infected moms had more abnormal blood vessels than placentas from patients without COVID, making it harder for them to deliver sufficient oxygen to the fetus.

Placental damage can also lead to preeclampsia, a serious complication of pregnancy that can cause a mother’s blood pressure to spike.

Preeclampsia occurs when blood vessels in the placenta don’t develop or function properly, forcing the mother’s heart to work harder to get blood to the fetus, which may not receive enough oxygen and nutrients. Preeclampsia also predisposes women to heart attacks and strokes later in life.

Rewiring the immune system

In some cases, COVID also appears to rewire a baby’s immune response, Dr. Nielsen-Saines said.

In an October study in the journal Cell Reports Medicine, Dr. Nielsen-Saines and her coauthors found that infants born to people with severe COVID infections had a different mix of immune cells and proteins than other babies. None of the newborns tested positive for the coronavirus.

The immune changes are concerning, Dr. Nielsen-Saines said, because this pattern of immune cells and proteins has previously been found in infants with respiratory problems and in some cases poor neurodevelopment.

Notably, all the babies in her study appear healthy, said Dr. Nielsen-Saines, who plans to follow them for 3 years to see whether these early signals translate into developmental delays, such as problems talking, walking, or interacting with others.

“How big of a difference does any of this make in the baby?” asked Dr. Anagnostou. “We won’t know for a few years. All we can do is try to be as prepared as possible.”

Increasing the risk for boys

Boys could face higher risks from COVID, even before birth.

Males are generally more vulnerable than females as fetuses and newborns; they’re more likely to be born prematurely and to die as infants. Preterm boys also have a higher risk of disability and death.

But coronavirus infection poses special dangers, said Sabra Klein, PhD, a professor of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health, Baltimore.

That’s because boys are disproportionately affected by conditions linked to maternal infections. Boys are four times as likely as girls to be diagnosed with autism or attention-deficit/hyperactivity disorder, for example, while men are 75% more likely than women to develop schizophrenia.

Scientists don’t fully understand why boys appear more fragile in the womb, although testosterone – which can dampen immune response – may play a role, said Kristina Adams Waldorf, MD, a professor of obstetrics and gynecology at the University of Washington.

Men generally mount weaker immune responses than women and more often develop severe COVID infections. Recent research suggests boys with COVID are more likely than girls to become seriously ill or develop a rare inflammatory condition called multisystem inflammatory syndrome.

New research on COVID could help illuminate this vulnerability.

In a study published in October, researchers found that the sex of a fetus influences the way its placenta responds to COVID, as well as how its mother’s immune system responds.

Pregnant people infected with COVID made fewer antibodies against the coronavirus if they were carrying male fetuses than if they were carrying females. Mothers also transferred fewer antibodies to boys than to girls, said Andrea Edlow, MD, senior author of the study and a maternal-fetal medicine specialist at Massachusetts General Hospital, Boston.

When examining the placentas of male fetuses after delivery, researchers found changes that could leave boys less protected against damaging inflammation.

The sex of a fetus can influence its mother’s response to other illnesses, as well.

For example, research shows that pregnant women with asthma have worse symptoms if they’re carrying a female. Women carrying males are slightly more likely to develop gestational diabetes.

Dr. Edlow said her findings raise questions about the “cross talk” between mother and baby. “The mom’s immune system is sensing there is a male fetus,” Dr. Edlow said. “And the fetus is actively communicating with the mom’s immune system.”

Boosting toxic stress

Rates of depression and stress among pregnant women have increased dramatically during the pandemic.

That’s concerning because chronic stress can lead to inflammation, affecting the babies of both infected and uninfected women, Dr. Anagnostou said.

Studies consistently show that infants born to mothers who experience significant stress during pregnancy have higher rates of short- and long-term health damage – including heart defects and obesity – than babies born to women with less stress.

“We know that inflammation directly influences the way a baby’s brain develops,” said Elinor Sullivan, PhD, an associate professor in psychiatry at Oregon Health & Science University, Portland.

Lockdowns, travel restrictions and physical distancing left many pregnant women without the support of family and friends. The stress of losing a loved one, a job, or a home further heightens the risks to moms and babies, said Dr. Sullivan, who is following children born during the pandemic for 5 years.

In research that has not yet been published, Dr. Sullivan found that babies of women who were pregnant during the pandemic showed more sadness and negative emotions in the first year of life, compared with infants of women who were pregnant before the pandemic.

The findings show the importance of helping and protecting pregnant people before and after delivery, said Dr. Sullivan, who conducted a separate study that found women who received more social support were less depressed.

Italian researchers are also studying the effect of maternal stress on infants’ behavior, as well as the way their genes are regulated.

Although stress-related inflammation doesn’t alter the structure of a baby’s genes, it can influence whether they’re turned on and off, said Livio Provenzi, PhD, a psychologist at the C. Mondino National Institute of Neurology Foundation in Pavia, Italy.

In Dr. Provenzi’s study of 163 mother-baby pairs he found differences in how genes that regulate the stress response were activated. Genes that help people respond to stress were more likely to be turned off in babies whose moms reported the most stress during pregnancy. The same moms also reported that their babies cried more and were fussier when they were 3 months old.

Researchers usually prefer to make in-person observations of babies as they interact with their mothers, Dr. Provenzi said. But because of the pandemic, Dr. Provenzi asked mothers to fill out questionnaires about infant behavior. He plans to observe mothers and babies in person when the children are 12 months old.

While vaccinating pregnant people is the best way to protect them and their fetuses from the virus, Dr. Anagnostou said, society needs to do more to preserve expectant mothers’ mental health.

“We can’t escape the fact that we’ve lived through 2 years of a pandemic,” Dr. Anagnostou said. “But we can think about opportunities for reducing the risk.”

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

The pandemic has created a hostile environment for pregnant people and their babies.

Stress levels among expectant mothers have soared. Pregnant women with COVID are 5 times as likely as uninfected pregnant people to require intensive care and 22 times as likely to die. Infected moms are four times as likely to have a stillborn child.

Yet some of the pandemic’s greatest threats to infants’ health may not be apparent for years or even decades.

That’s because babies of COVID-infected moms are 60% more likely to be born very prematurely, which increases the danger of infant mortality and long-term disabilities such as cerebral palsy, asthma, and hearing loss, as well as a child’s risk of adult disease, including depression, anxiety, heart disease, and kidney disease.

Studies have linked fever and infection during pregnancy to developmental and psychiatric conditions such as autism, depression, and schizophrenia.

“Some of these conditions do not show up until middle childhood or early adult life, but they have their origins in fetal life,” said Evdokia Anagnostou, MD, a child neurologist at Holland Bloorview Kids Rehabilitation Hospital and a pediatrics professor at the University of Toronto.

For fetuses exposed to COVID, the greatest danger is usually not the coronavirus itself, but the mother’s immune system.

Both severe COVID infections and the strain of the pandemic can expose fetuses to harmful inflammation, which can occur when a mother’s immune system is fighting a virus or when stress hormones send nonstop alarm signals.

Prenatal inflammation “changes the way the brain develops and, depending on the timing of the infection, it can change the way the heart or kidneys develop,” Dr. Anagnostou said.

Although health officials have strongly recommended COVID vaccines for pregnant people, only 35% are fully vaccinated.

At least 150,000 pregnant women have been diagnosed with COVID; more than 25,000 of them have been hospitalized, and 249 have died, according to the Centers for Disease Control and Prevention.

Although most babies will be fine, even a small increase in the percentage of children with special medical or educational needs could have a large effect on the population, given the huge number of COVID infections, Dr. Anagnostou said.

“If someone has a baby who is doing well, that is what they should focus on,” Dr. Anagnostou said. “But from a public health point of view, we need to follow women who experienced severe COVID and their babies to understand the impact.”

Learning from history

Researchers in the United States and other countries are already studying “the COVID generation” to see whether these children have more health issues than those conceived or born before 2020.

Previous crises have shown that the challenges fetuses face in the womb – such as maternal infections, hunger, stress, and hormone-disrupting chemicals – can leave a lasting imprint on their health, as well as that of their children and grandchildren, said Frederick Kaskel, MD, director of pediatric nephrology at the Children’s Hospital at Montefiore, New York.

People whose mothers were pregnant during surges in the 1918 influenza pandemic, for example, had poorer health throughout their lives, compared with Americans born at other times, said John McCarthy, who is a medical student at Albert Einstein College of Medicine, New York, and cowrote a recent review in JAMA Pediatrics with Dr. Kaskel.

Researchers don’t know exactly which moms were infected with pandemic flu, Mr. McCarthy said. But women who were pregnant during major surges – when infection was widespread – had children with higher rates of heart disease or diabetes. These children were also less successful in school, less economically productive, and more likely to live with a disability.

Because organ systems develop during different periods of pregnancy, fetuses exposed during the first trimester may face different risks than those exposed toward the end of pregnancy, Mr. McCarthy said. For example, people born in the fall of 1918 were 50% more likely than others to develop kidney disease; that may reflect an exposure to the pandemic in the third trimester, while the kidneys were still developing.

Nearly 2 years into the COVID pandemic, researchers have begun to publish preliminary observations of infants exposed to COVID infections and stress before birth.

Although Dr. Anagnostou noted that it’s too early to reach definitive conclusions, “there is evidence that babies born to moms with severe COVID infections have changes to their immune system,” she said. “It’s enough to make us worry a little bit.”

Damaging a fetal security system

The good news about the coronavirus is that it seldom crosses the placenta, the organ tasked with protecting a developing fetus from infections and providing it with oxygen. So moms with COVID rarely give the virus to their children before birth.

That’s important, because some viruses that directly infect the fetus – such as Zika – can cause devastating birth defects, said Karin Nielsen-Saines, MD, a specialist in pediatric infectious diseases at University of California, Los Angeles.

But studies also suggest that inflammation from a mother’s COVID infection can injure the placenta, said Jeffery Goldstein, MD, an assistant professor of pathology at Northwestern University, Chicago. In a study published in American Journal of Clinical Pathology , Dr. Goldstein and his coauthors found that placentas from COVID-infected moms had more abnormal blood vessels than placentas from patients without COVID, making it harder for them to deliver sufficient oxygen to the fetus.

Placental damage can also lead to preeclampsia, a serious complication of pregnancy that can cause a mother’s blood pressure to spike.

Preeclampsia occurs when blood vessels in the placenta don’t develop or function properly, forcing the mother’s heart to work harder to get blood to the fetus, which may not receive enough oxygen and nutrients. Preeclampsia also predisposes women to heart attacks and strokes later in life.

Rewiring the immune system

In some cases, COVID also appears to rewire a baby’s immune response, Dr. Nielsen-Saines said.

In an October study in the journal Cell Reports Medicine, Dr. Nielsen-Saines and her coauthors found that infants born to people with severe COVID infections had a different mix of immune cells and proteins than other babies. None of the newborns tested positive for the coronavirus.

The immune changes are concerning, Dr. Nielsen-Saines said, because this pattern of immune cells and proteins has previously been found in infants with respiratory problems and in some cases poor neurodevelopment.

Notably, all the babies in her study appear healthy, said Dr. Nielsen-Saines, who plans to follow them for 3 years to see whether these early signals translate into developmental delays, such as problems talking, walking, or interacting with others.

“How big of a difference does any of this make in the baby?” asked Dr. Anagnostou. “We won’t know for a few years. All we can do is try to be as prepared as possible.”

Increasing the risk for boys

Boys could face higher risks from COVID, even before birth.

Males are generally more vulnerable than females as fetuses and newborns; they’re more likely to be born prematurely and to die as infants. Preterm boys also have a higher risk of disability and death.

But coronavirus infection poses special dangers, said Sabra Klein, PhD, a professor of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health, Baltimore.

That’s because boys are disproportionately affected by conditions linked to maternal infections. Boys are four times as likely as girls to be diagnosed with autism or attention-deficit/hyperactivity disorder, for example, while men are 75% more likely than women to develop schizophrenia.

Scientists don’t fully understand why boys appear more fragile in the womb, although testosterone – which can dampen immune response – may play a role, said Kristina Adams Waldorf, MD, a professor of obstetrics and gynecology at the University of Washington.

Men generally mount weaker immune responses than women and more often develop severe COVID infections. Recent research suggests boys with COVID are more likely than girls to become seriously ill or develop a rare inflammatory condition called multisystem inflammatory syndrome.

New research on COVID could help illuminate this vulnerability.

In a study published in October, researchers found that the sex of a fetus influences the way its placenta responds to COVID, as well as how its mother’s immune system responds.

Pregnant people infected with COVID made fewer antibodies against the coronavirus if they were carrying male fetuses than if they were carrying females. Mothers also transferred fewer antibodies to boys than to girls, said Andrea Edlow, MD, senior author of the study and a maternal-fetal medicine specialist at Massachusetts General Hospital, Boston.

When examining the placentas of male fetuses after delivery, researchers found changes that could leave boys less protected against damaging inflammation.

The sex of a fetus can influence its mother’s response to other illnesses, as well.

For example, research shows that pregnant women with asthma have worse symptoms if they’re carrying a female. Women carrying males are slightly more likely to develop gestational diabetes.

Dr. Edlow said her findings raise questions about the “cross talk” between mother and baby. “The mom’s immune system is sensing there is a male fetus,” Dr. Edlow said. “And the fetus is actively communicating with the mom’s immune system.”

Boosting toxic stress

Rates of depression and stress among pregnant women have increased dramatically during the pandemic.

That’s concerning because chronic stress can lead to inflammation, affecting the babies of both infected and uninfected women, Dr. Anagnostou said.

Studies consistently show that infants born to mothers who experience significant stress during pregnancy have higher rates of short- and long-term health damage – including heart defects and obesity – than babies born to women with less stress.

“We know that inflammation directly influences the way a baby’s brain develops,” said Elinor Sullivan, PhD, an associate professor in psychiatry at Oregon Health & Science University, Portland.

Lockdowns, travel restrictions and physical distancing left many pregnant women without the support of family and friends. The stress of losing a loved one, a job, or a home further heightens the risks to moms and babies, said Dr. Sullivan, who is following children born during the pandemic for 5 years.

In research that has not yet been published, Dr. Sullivan found that babies of women who were pregnant during the pandemic showed more sadness and negative emotions in the first year of life, compared with infants of women who were pregnant before the pandemic.

The findings show the importance of helping and protecting pregnant people before and after delivery, said Dr. Sullivan, who conducted a separate study that found women who received more social support were less depressed.

Italian researchers are also studying the effect of maternal stress on infants’ behavior, as well as the way their genes are regulated.

Although stress-related inflammation doesn’t alter the structure of a baby’s genes, it can influence whether they’re turned on and off, said Livio Provenzi, PhD, a psychologist at the C. Mondino National Institute of Neurology Foundation in Pavia, Italy.

In Dr. Provenzi’s study of 163 mother-baby pairs he found differences in how genes that regulate the stress response were activated. Genes that help people respond to stress were more likely to be turned off in babies whose moms reported the most stress during pregnancy. The same moms also reported that their babies cried more and were fussier when they were 3 months old.

Researchers usually prefer to make in-person observations of babies as they interact with their mothers, Dr. Provenzi said. But because of the pandemic, Dr. Provenzi asked mothers to fill out questionnaires about infant behavior. He plans to observe mothers and babies in person when the children are 12 months old.

While vaccinating pregnant people is the best way to protect them and their fetuses from the virus, Dr. Anagnostou said, society needs to do more to preserve expectant mothers’ mental health.

“We can’t escape the fact that we’ve lived through 2 years of a pandemic,” Dr. Anagnostou said. “But we can think about opportunities for reducing the risk.”

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

Older adults who participate in even light physical activity (LPA) may have a lower risk of developing dementia, new research suggests.

In a retrospective analysis of more than 62,000 individuals aged 65 or older without preexisting dementia, 6% developed dementia.

Compared with inactive individuals, “insufficiently active,” “active,” and “highly active” individuals all had a 10%, 20%, and 28% lower risk for dementia, respectively. And this association was consistent regardless of age, sex, other comorbidities, or after the researchers censored for stroke.

Even the lowest amount of LPA was associated with reduced dementia risk, investigators noted.

“In older adults, an increased physical activity level, including a low amount of LPA, was associated with a reduced risk of dementia,” Minjae Yoon, MD, division of cardiology, Severance Cardiovascular Hospital, Yonsei University, Seoul, South Korea, and colleagues wrote.

“Promotion of LPA might reduce the risk of dementia in older adults,” they added.

The findings were published online in JAMA Network Open.
 

Reverse causation?

Physical activity has been shown previously to be associated with reduced dementia risk. Current World Health Organization guidelines recommend that adults with normal cognition should engage in PA to reduce their risk for cognitive decline.

However, some studies have not yielded this result, “suggesting that previous findings showing a lower risk of dementia in physically active people could be attributed to reverse causation,” the investigators noted. Additionally, previous research regarding exercise intensity has been “inconsistent” concerning the role of LPA in reducing dementia risk.

Many older adults with frailty and comorbidity cannot perform intense or even moderate PA, therefore “these adults would have to gain the benefits of physical activity from LPA,” the researchers noted.

To clarify the potential association between PA and new-onset dementia, they focused specifically on the “dose-response association” between PA and dementia – especially LPA.

Between 2009 and 2012, the investigators enrolled 62,286 older individuals (60.4% women; mean age, 73.2 years) with available health checkup data from the National Health Insurance Service–Senior Database of Korea. All had no history of dementia.

Leisure-time PA was assessed with self-report questionnaires that used a 7-day recall method and included three questions regarding usual frequency (in days per week):

• Vigorous PA (VPA) for at least 20 minutes
• Moderate-intensity PA (MPA) for at least 30 minutes 
• LPA for at least 30 minutes

VPA was defined as “intense exercise that caused severe shortness of breath, MPA was defined as activity causing mild shortness of breath, and LPA was defined as “walking at a slow or leisurely pace.”

PA-related energy expenditure was also calculated in metabolic equivalent (MET) minutes per week by “summing the product of frequency, intensity, and duration,” the investigators noted.

Participants were stratified on the basis of their weekly total PA levels into the following groups:

• Inactive (no LPA beyond basic movements)
• Insufficiently active (less than the recommended target range of 1-499 MET-min/wk)
• Active (meeting the recommended target range of 500-999 MET-min/wk)
• Highly active (exceeding the recommended target range of at least 1,000 MET-min/wk)

Of all participants, 35% were categorized as inactive, 25% were insufficiently active, 24.4% were active, and 15.2% were highly active.
 

Controversy remains

During the total median follow-up of 42 months, 6% of participants had all-cause dementia. After the researchers excluded the first 2 years, incidence of dementia was 21.6 per 1000 person-years during follow-up. 

“The cumulative incidence of dementia was associated with a progressively decreasing trend with increasing physical activity” (P = .001 for trend), the investigators reported.

When using a competing-risk multivariable regression model, they found that higher levels of PA were associated with lower risk for dementia, compared with the inactive group.

Similar findings were obtained after censoring for stroke, and were consistent for all follow-up periods. In subgroup analysis, the association between PA level and dementia risk remained consistent, regardless of age, sex, and comorbidities.

Even a low amount of LPA (1-299 MET-min/wk) was linked to reduced risk for dementia versus total sedentary behavior (adjusted HR, 0.86; 95% CI, 0.74-0.99).

The investigators noted that some “controversy” remains regarding the possibility of reverse causation and, because their study was observational in nature, “it cannot be used to establish causal relationship.”

Nevertheless, the study had important strengths, including the large number of older adults with available data, the assessment of dose-response association between PA and dementia, and the sensitivity analyses they performed, the researchers added.
 

Piece of important evidence

Commenting on the findings, Takashi Tarumi, PhD, senior research investigator, National Institute of Advanced Industrial Science and Technology, Ibaraki, Japan, said previous studies have suggested “an inverse association between physical activity and dementia risk, such that older adults performing a higher dose of exercise may have a greater benefit for reducing the dementia risk.”

Dr. Tarumi, an associate editor at the Journal of Alzheimer’s Disease, added the current study “significantly extends our knowledge by showing that dementia risk can also be reduced by light physical activities when they are performed for longer hours.”

This provides “another piece of important evidence” to support clinicians recommending regular physical activity for the prevention of dementia in later life, said Dr. Tarumi, who was not involved with the research.

Also commenting, Martin Underwood, MD, Warwick Medical School, Coventry, England, described the association between reduced physical inactivity and dementia as well established – and noted the current study “appears to confirm earlier observational data showing this relationship.” 

The current results have “still not been able to fully exclude the possibility of reverse causation,” said Dr. Underwood, who was also not associated with the study.

However, the finding that more physically active individuals are less likely to develop dementia “only becomes of real interest if we can show that increased physical activity prevents the onset, or slows the progression, of dementia,” he noted.

“To my knowledge this has not yet been established” in randomized clinical trials, Dr. Underwood added.

The study was supported by grants from the Patient-Centered Clinical Research Coordinating Center, funded by the Ministry of Health & Welfare, Republic of Korea; and by a research grant from Yonsei University. One coauthor reported serving as a speaker for Bayer, Bristol-Myers Squibb/Pfizer, Medtronic, and Daiichi-Sankyo, and receiving research funds from Medtronic and Abbott. No other author disclosures were reported. Dr. Tarumi and Dr. Underwood have disclosed no relevant financial relationships.

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

Older adults who participate in even light physical activity (LPA) may have a lower risk of developing dementia, new research suggests.

In a retrospective analysis of more than 62,000 individuals aged 65 or older without preexisting dementia, 6% developed dementia.

Compared with inactive individuals, “insufficiently active,” “active,” and “highly active” individuals all had a 10%, 20%, and 28% lower risk for dementia, respectively. And this association was consistent regardless of age, sex, other comorbidities, or after the researchers censored for stroke.

Even the lowest amount of LPA was associated with reduced dementia risk, investigators noted.

“In older adults, an increased physical activity level, including a low amount of LPA, was associated with a reduced risk of dementia,” Minjae Yoon, MD, division of cardiology, Severance Cardiovascular Hospital, Yonsei University, Seoul, South Korea, and colleagues wrote.

“Promotion of LPA might reduce the risk of dementia in older adults,” they added.

The findings were published online in JAMA Network Open.
 

Reverse causation?

Physical activity has been shown previously to be associated with reduced dementia risk. Current World Health Organization guidelines recommend that adults with normal cognition should engage in PA to reduce their risk for cognitive decline.

However, some studies have not yielded this result, “suggesting that previous findings showing a lower risk of dementia in physically active people could be attributed to reverse causation,” the investigators noted. Additionally, previous research regarding exercise intensity has been “inconsistent” concerning the role of LPA in reducing dementia risk.

Many older adults with frailty and comorbidity cannot perform intense or even moderate PA, therefore “these adults would have to gain the benefits of physical activity from LPA,” the researchers noted.

To clarify the potential association between PA and new-onset dementia, they focused specifically on the “dose-response association” between PA and dementia – especially LPA.

Between 2009 and 2012, the investigators enrolled 62,286 older individuals (60.4% women; mean age, 73.2 years) with available health checkup data from the National Health Insurance Service–Senior Database of Korea. All had no history of dementia.

Leisure-time PA was assessed with self-report questionnaires that used a 7-day recall method and included three questions regarding usual frequency (in days per week):

• Vigorous PA (VPA) for at least 20 minutes
• Moderate-intensity PA (MPA) for at least 30 minutes 
• LPA for at least 30 minutes

VPA was defined as “intense exercise that caused severe shortness of breath, MPA was defined as activity causing mild shortness of breath, and LPA was defined as “walking at a slow or leisurely pace.”

PA-related energy expenditure was also calculated in metabolic equivalent (MET) minutes per week by “summing the product of frequency, intensity, and duration,” the investigators noted.

Participants were stratified on the basis of their weekly total PA levels into the following groups:

• Inactive (no LPA beyond basic movements)
• Insufficiently active (less than the recommended target range of 1-499 MET-min/wk)
• Active (meeting the recommended target range of 500-999 MET-min/wk)
• Highly active (exceeding the recommended target range of at least 1,000 MET-min/wk)

Of all participants, 35% were categorized as inactive, 25% were insufficiently active, 24.4% were active, and 15.2% were highly active.
 

Controversy remains

During the total median follow-up of 42 months, 6% of participants had all-cause dementia. After the researchers excluded the first 2 years, incidence of dementia was 21.6 per 1000 person-years during follow-up. 

“The cumulative incidence of dementia was associated with a progressively decreasing trend with increasing physical activity” (P = .001 for trend), the investigators reported.

When using a competing-risk multivariable regression model, they found that higher levels of PA were associated with lower risk for dementia, compared with the inactive group.

Similar findings were obtained after censoring for stroke, and were consistent for all follow-up periods. In subgroup analysis, the association between PA level and dementia risk remained consistent, regardless of age, sex, and comorbidities.

Even a low amount of LPA (1-299 MET-min/wk) was linked to reduced risk for dementia versus total sedentary behavior (adjusted HR, 0.86; 95% CI, 0.74-0.99).

The investigators noted that some “controversy” remains regarding the possibility of reverse causation and, because their study was observational in nature, “it cannot be used to establish causal relationship.”

Nevertheless, the study had important strengths, including the large number of older adults with available data, the assessment of dose-response association between PA and dementia, and the sensitivity analyses they performed, the researchers added.
 

Piece of important evidence

Commenting on the findings, Takashi Tarumi, PhD, senior research investigator, National Institute of Advanced Industrial Science and Technology, Ibaraki, Japan, said previous studies have suggested “an inverse association between physical activity and dementia risk, such that older adults performing a higher dose of exercise may have a greater benefit for reducing the dementia risk.”

Dr. Tarumi, an associate editor at the Journal of Alzheimer’s Disease, added the current study “significantly extends our knowledge by showing that dementia risk can also be reduced by light physical activities when they are performed for longer hours.”

This provides “another piece of important evidence” to support clinicians recommending regular physical activity for the prevention of dementia in later life, said Dr. Tarumi, who was not involved with the research.

Also commenting, Martin Underwood, MD, Warwick Medical School, Coventry, England, described the association between reduced physical inactivity and dementia as well established – and noted the current study “appears to confirm earlier observational data showing this relationship.” 

The current results have “still not been able to fully exclude the possibility of reverse causation,” said Dr. Underwood, who was also not associated with the study.

However, the finding that more physically active individuals are less likely to develop dementia “only becomes of real interest if we can show that increased physical activity prevents the onset, or slows the progression, of dementia,” he noted.

“To my knowledge this has not yet been established” in randomized clinical trials, Dr. Underwood added.

The study was supported by grants from the Patient-Centered Clinical Research Coordinating Center, funded by the Ministry of Health & Welfare, Republic of Korea; and by a research grant from Yonsei University. One coauthor reported serving as a speaker for Bayer, Bristol-Myers Squibb/Pfizer, Medtronic, and Daiichi-Sankyo, and receiving research funds from Medtronic and Abbott. No other author disclosures were reported. Dr. Tarumi and Dr. Underwood have disclosed no relevant financial relationships.

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

Older adults who participate in even light physical activity (LPA) may have a lower risk of developing dementia, new research suggests.

In a retrospective analysis of more than 62,000 individuals aged 65 or older without preexisting dementia, 6% developed dementia.

Compared with inactive individuals, “insufficiently active,” “active,” and “highly active” individuals all had a 10%, 20%, and 28% lower risk for dementia, respectively. And this association was consistent regardless of age, sex, other comorbidities, or after the researchers censored for stroke.

Even the lowest amount of LPA was associated with reduced dementia risk, investigators noted.

“In older adults, an increased physical activity level, including a low amount of LPA, was associated with a reduced risk of dementia,” Minjae Yoon, MD, division of cardiology, Severance Cardiovascular Hospital, Yonsei University, Seoul, South Korea, and colleagues wrote.

“Promotion of LPA might reduce the risk of dementia in older adults,” they added.

The findings were published online in JAMA Network Open.
 

Reverse causation?

Physical activity has been shown previously to be associated with reduced dementia risk. Current World Health Organization guidelines recommend that adults with normal cognition should engage in PA to reduce their risk for cognitive decline.

However, some studies have not yielded this result, “suggesting that previous findings showing a lower risk of dementia in physically active people could be attributed to reverse causation,” the investigators noted. Additionally, previous research regarding exercise intensity has been “inconsistent” concerning the role of LPA in reducing dementia risk.

Many older adults with frailty and comorbidity cannot perform intense or even moderate PA, therefore “these adults would have to gain the benefits of physical activity from LPA,” the researchers noted.

To clarify the potential association between PA and new-onset dementia, they focused specifically on the “dose-response association” between PA and dementia – especially LPA.

Between 2009 and 2012, the investigators enrolled 62,286 older individuals (60.4% women; mean age, 73.2 years) with available health checkup data from the National Health Insurance Service–Senior Database of Korea. All had no history of dementia.

Leisure-time PA was assessed with self-report questionnaires that used a 7-day recall method and included three questions regarding usual frequency (in days per week):

• Vigorous PA (VPA) for at least 20 minutes
• Moderate-intensity PA (MPA) for at least 30 minutes 
• LPA for at least 30 minutes

VPA was defined as “intense exercise that caused severe shortness of breath, MPA was defined as activity causing mild shortness of breath, and LPA was defined as “walking at a slow or leisurely pace.”

PA-related energy expenditure was also calculated in metabolic equivalent (MET) minutes per week by “summing the product of frequency, intensity, and duration,” the investigators noted.

Participants were stratified on the basis of their weekly total PA levels into the following groups:

• Inactive (no LPA beyond basic movements)
• Insufficiently active (less than the recommended target range of 1-499 MET-min/wk)
• Active (meeting the recommended target range of 500-999 MET-min/wk)
• Highly active (exceeding the recommended target range of at least 1,000 MET-min/wk)

Of all participants, 35% were categorized as inactive, 25% were insufficiently active, 24.4% were active, and 15.2% were highly active.
 

Controversy remains

During the total median follow-up of 42 months, 6% of participants had all-cause dementia. After the researchers excluded the first 2 years, incidence of dementia was 21.6 per 1000 person-years during follow-up. 

“The cumulative incidence of dementia was associated with a progressively decreasing trend with increasing physical activity” (P = .001 for trend), the investigators reported.

When using a competing-risk multivariable regression model, they found that higher levels of PA were associated with lower risk for dementia, compared with the inactive group.

Similar findings were obtained after censoring for stroke, and were consistent for all follow-up periods. In subgroup analysis, the association between PA level and dementia risk remained consistent, regardless of age, sex, and comorbidities.

Even a low amount of LPA (1-299 MET-min/wk) was linked to reduced risk for dementia versus total sedentary behavior (adjusted HR, 0.86; 95% CI, 0.74-0.99).

The investigators noted that some “controversy” remains regarding the possibility of reverse causation and, because their study was observational in nature, “it cannot be used to establish causal relationship.”

Nevertheless, the study had important strengths, including the large number of older adults with available data, the assessment of dose-response association between PA and dementia, and the sensitivity analyses they performed, the researchers added.
 

Piece of important evidence

Commenting on the findings, Takashi Tarumi, PhD, senior research investigator, National Institute of Advanced Industrial Science and Technology, Ibaraki, Japan, said previous studies have suggested “an inverse association between physical activity and dementia risk, such that older adults performing a higher dose of exercise may have a greater benefit for reducing the dementia risk.”

Dr. Tarumi, an associate editor at the Journal of Alzheimer’s Disease, added the current study “significantly extends our knowledge by showing that dementia risk can also be reduced by light physical activities when they are performed for longer hours.”

This provides “another piece of important evidence” to support clinicians recommending regular physical activity for the prevention of dementia in later life, said Dr. Tarumi, who was not involved with the research.

Also commenting, Martin Underwood, MD, Warwick Medical School, Coventry, England, described the association between reduced physical inactivity and dementia as well established – and noted the current study “appears to confirm earlier observational data showing this relationship.” 

The current results have “still not been able to fully exclude the possibility of reverse causation,” said Dr. Underwood, who was also not associated with the study.

However, the finding that more physically active individuals are less likely to develop dementia “only becomes of real interest if we can show that increased physical activity prevents the onset, or slows the progression, of dementia,” he noted.

“To my knowledge this has not yet been established” in randomized clinical trials, Dr. Underwood added.

The study was supported by grants from the Patient-Centered Clinical Research Coordinating Center, funded by the Ministry of Health & Welfare, Republic of Korea; and by a research grant from Yonsei University. One coauthor reported serving as a speaker for Bayer, Bristol-Myers Squibb/Pfizer, Medtronic, and Daiichi-Sankyo, and receiving research funds from Medtronic and Abbott. No other author disclosures were reported. Dr. Tarumi and Dr. Underwood have disclosed no relevant financial relationships.

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

A “definitive study” from Johns Hopkins University researchers and others shows that convalescent plasma can cut hospital admissions for COVID-19 by 54% if therapy is administered within 8 days of symptom onset.

In the study of 1,181 adults randomly assigned to high-titer convalescent plasma or placebo, 2.9% of people receiving the therapy were hospitalized, compared with 6.3% who received placebo control plasma.

This translates to a 54% risk reduction for hospitalization with convalescent plasma.

“We have a clear difference,” principal investigator David Sullivan, MD, a professor at Johns Hopkins University, Baltimore, said during a Dec. 21 media briefing.

“This is very good news since we are in the midst of the Omicron surge, which has defeated [some of] our major monocular antibody therapies,” said Arturo Casadevall, MD, chair of the department of molecular microbiology and immunology at Johns Hopkins.

“So we have a new tool to keep people from progressing in their disease and to reduce progression or hospitalization,” Dr. Casadevall said.

The findings were published as a preprint study on Dec. 21, 2021, on medRxiv. The study has not yet been peer reviewed.

Whereas many convalescent plasma studies were done in hospitalized patients, this is one of only a handful performed in outpatients, the researchers noted.

There is a regulatory catch. The Food and Drug Administration restricted emergency use authorization (EUA) for convalescent plasma in February 2021 to include only high-dose titer plasma and to limit the therapy to hospitalized patients with early disease or for immunocompromised people who cannot mount an adequate antibody response.

Dr. Sullivan and colleagues hoped their findings will prompt the FDA to expand the EUA to include outpatients.

“We have shared this data with both the World Health Organization and the FDA,” study coauthor Kelly Gebo, MD, MPH, said during the media briefing.

“We do believe that this could be scaled up quickly,” added Dr. Gebo, professor of medicine at Johns Hopkins University. Convalescent plasma “could be used as a potential treatment as variants continue to evolve, such as we’ve seen with Omicron.”
 

Pre-Omicron results

The study was conducted at Johns Hopkins University and 23 other sites nationwide between June 2020 and October 2021. This means researchers enrolled symptomatic adults during circulation of the SARS-CoV-2 ancestral strain and the Alpha and Delta variants.

However, Dr. Sullivan said, “we think that ... plasma with high levels of antibodies can adapt faster to Omicron, although it will take us longer to get an Omicron-specific supply.”

Because of the timing of the study, 80% of participants were unvaccinated. Mean age was 44 years and 57% were women. Black and Hispanic participants each accounted for more than 12% of the study population.

On average, participants received a transfusion within 6 days of the start of symptoms.

In the study, 37 people out of 589 control group participants were hospitalized, compared with 17 of the 592 who received the convalescent plasma.

“We know antibodies work against SARS-CoV-2. The vaccines have been spectacular – producing antibodies that reduce hospitalizations and prevent transmission,” Dr. Sullivan said. “Convalescent plasma provides much of the same antibodies instantly.”
 

Convalescent and controversial

Convalescent plasma has been one of the controversial treatments for people with COVID-19 – with studies going back and forth on the potential benefits and efficacy. A National Institutes of Health–funded study published in August 2021, for example, showed no significant benefit.

“As you know, convalescent plasma has had a rocky ride,” Dr. Casadevall said.

“It was deployed with great excitement in the terrible, early days of the pandemic. Unfortunately, the early excitement and optimism was dampened with some of the randomized control trials appearing to show no benefit in reducing mortality and hospitalized patients,” he added.

In contrast, the current study shows “where convalescent plasma works using the latest, most rigorous clinical investigation tools available: a double-blinded, randomized, placebo-control trial,” Dr. Casadevall said.
 

Why a preprint, and why now?

The researchers decided to release their data in recognition of the lag time between reporting of COVID-19 cases and hospitalizations, Dr. Sullivan said. “That’s part of the reason we decided to act now with this knowledge – that it does take a couple of weeks – with cases of Omicron going up.”

Furthermore, “we thought this was actionable data for decision-makers,” he added.

A reporter asked why the Johns Hopkins researchers chose to hold a media briefing for a preprint study.

A preprint is “not so unusual given the SARS-CoV-2 pandemic,” said study senior author Daniel Hanley, MD, division director of brain injury outcomes at Johns Hopkins University.

“The data are the data,” Dr. Casadevall added. “This is not going to change from peer review.”

Peer review may change some of the wording of the manuscript, but not the numbers, he added.

“Now with the Omicron crisis and the fact that we have lost some more main monoclonal antibodies, it is essential to get this information out,” Dr. Casadevall said.
 

Plasma therapy nothing new

Donation and transfusion of convalescent plasma is highly regulated with strict criteria, said Evan Bloch, MBChB, associate director of the transfusion medicine division at Johns Hopkins University.

If the FDA opts to expand the EUA based on this or other evidence, administration of convalescent plasma could be rolled out fairly quickly, the researchers noted.

Plasma transfusion takes place in hospitals and at infusion centers every day. The infrastructure is in place in many countries, even low- and middle-resource nations, around the world to provide convalescent plasma therapy. The major difference between traditional plasma and SARS-CoV-2 convalescent plasma is the indication, Dr. Bloch added.

In addition, convalescent plasma has a polyclonal composition – a benefit compared with monoclonal antibodies, he added. “It’s more durable or adaptive [compared with] some of the targeted therapies, such as monoclonal antibodies, where we’ve witnessed this diminished efficacy with viral evolution.”

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

A “definitive study” from Johns Hopkins University researchers and others shows that convalescent plasma can cut hospital admissions for COVID-19 by 54% if therapy is administered within 8 days of symptom onset.

In the study of 1,181 adults randomly assigned to high-titer convalescent plasma or placebo, 2.9% of people receiving the therapy were hospitalized, compared with 6.3% who received placebo control plasma.

This translates to a 54% risk reduction for hospitalization with convalescent plasma.

“We have a clear difference,” principal investigator David Sullivan, MD, a professor at Johns Hopkins University, Baltimore, said during a Dec. 21 media briefing.

“This is very good news since we are in the midst of the Omicron surge, which has defeated [some of] our major monocular antibody therapies,” said Arturo Casadevall, MD, chair of the department of molecular microbiology and immunology at Johns Hopkins.

“So we have a new tool to keep people from progressing in their disease and to reduce progression or hospitalization,” Dr. Casadevall said.

The findings were published as a preprint study on Dec. 21, 2021, on medRxiv. The study has not yet been peer reviewed.

Whereas many convalescent plasma studies were done in hospitalized patients, this is one of only a handful performed in outpatients, the researchers noted.

There is a regulatory catch. The Food and Drug Administration restricted emergency use authorization (EUA) for convalescent plasma in February 2021 to include only high-dose titer plasma and to limit the therapy to hospitalized patients with early disease or for immunocompromised people who cannot mount an adequate antibody response.

Dr. Sullivan and colleagues hoped their findings will prompt the FDA to expand the EUA to include outpatients.

“We have shared this data with both the World Health Organization and the FDA,” study coauthor Kelly Gebo, MD, MPH, said during the media briefing.

“We do believe that this could be scaled up quickly,” added Dr. Gebo, professor of medicine at Johns Hopkins University. Convalescent plasma “could be used as a potential treatment as variants continue to evolve, such as we’ve seen with Omicron.”
 

Pre-Omicron results

The study was conducted at Johns Hopkins University and 23 other sites nationwide between June 2020 and October 2021. This means researchers enrolled symptomatic adults during circulation of the SARS-CoV-2 ancestral strain and the Alpha and Delta variants.

However, Dr. Sullivan said, “we think that ... plasma with high levels of antibodies can adapt faster to Omicron, although it will take us longer to get an Omicron-specific supply.”

Because of the timing of the study, 80% of participants were unvaccinated. Mean age was 44 years and 57% were women. Black and Hispanic participants each accounted for more than 12% of the study population.

On average, participants received a transfusion within 6 days of the start of symptoms.

In the study, 37 people out of 589 control group participants were hospitalized, compared with 17 of the 592 who received the convalescent plasma.

“We know antibodies work against SARS-CoV-2. The vaccines have been spectacular – producing antibodies that reduce hospitalizations and prevent transmission,” Dr. Sullivan said. “Convalescent plasma provides much of the same antibodies instantly.”
 

Convalescent and controversial

Convalescent plasma has been one of the controversial treatments for people with COVID-19 – with studies going back and forth on the potential benefits and efficacy. A National Institutes of Health–funded study published in August 2021, for example, showed no significant benefit.

“As you know, convalescent plasma has had a rocky ride,” Dr. Casadevall said.

“It was deployed with great excitement in the terrible, early days of the pandemic. Unfortunately, the early excitement and optimism was dampened with some of the randomized control trials appearing to show no benefit in reducing mortality and hospitalized patients,” he added.

In contrast, the current study shows “where convalescent plasma works using the latest, most rigorous clinical investigation tools available: a double-blinded, randomized, placebo-control trial,” Dr. Casadevall said.
 

Why a preprint, and why now?

The researchers decided to release their data in recognition of the lag time between reporting of COVID-19 cases and hospitalizations, Dr. Sullivan said. “That’s part of the reason we decided to act now with this knowledge – that it does take a couple of weeks – with cases of Omicron going up.”

Furthermore, “we thought this was actionable data for decision-makers,” he added.

A reporter asked why the Johns Hopkins researchers chose to hold a media briefing for a preprint study.

A preprint is “not so unusual given the SARS-CoV-2 pandemic,” said study senior author Daniel Hanley, MD, division director of brain injury outcomes at Johns Hopkins University.

“The data are the data,” Dr. Casadevall added. “This is not going to change from peer review.”

Peer review may change some of the wording of the manuscript, but not the numbers, he added.

“Now with the Omicron crisis and the fact that we have lost some more main monoclonal antibodies, it is essential to get this information out,” Dr. Casadevall said.
 

Plasma therapy nothing new

Donation and transfusion of convalescent plasma is highly regulated with strict criteria, said Evan Bloch, MBChB, associate director of the transfusion medicine division at Johns Hopkins University.

If the FDA opts to expand the EUA based on this or other evidence, administration of convalescent plasma could be rolled out fairly quickly, the researchers noted.

Plasma transfusion takes place in hospitals and at infusion centers every day. The infrastructure is in place in many countries, even low- and middle-resource nations, around the world to provide convalescent plasma therapy. The major difference between traditional plasma and SARS-CoV-2 convalescent plasma is the indication, Dr. Bloch added.

In addition, convalescent plasma has a polyclonal composition – a benefit compared with monoclonal antibodies, he added. “It’s more durable or adaptive [compared with] some of the targeted therapies, such as monoclonal antibodies, where we’ve witnessed this diminished efficacy with viral evolution.”

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

A “definitive study” from Johns Hopkins University researchers and others shows that convalescent plasma can cut hospital admissions for COVID-19 by 54% if therapy is administered within 8 days of symptom onset.

In the study of 1,181 adults randomly assigned to high-titer convalescent plasma or placebo, 2.9% of people receiving the therapy were hospitalized, compared with 6.3% who received placebo control plasma.

This translates to a 54% risk reduction for hospitalization with convalescent plasma.

“We have a clear difference,” principal investigator David Sullivan, MD, a professor at Johns Hopkins University, Baltimore, said during a Dec. 21 media briefing.

“This is very good news since we are in the midst of the Omicron surge, which has defeated [some of] our major monocular antibody therapies,” said Arturo Casadevall, MD, chair of the department of molecular microbiology and immunology at Johns Hopkins.

“So we have a new tool to keep people from progressing in their disease and to reduce progression or hospitalization,” Dr. Casadevall said.

The findings were published as a preprint study on Dec. 21, 2021, on medRxiv. The study has not yet been peer reviewed.

Whereas many convalescent plasma studies were done in hospitalized patients, this is one of only a handful performed in outpatients, the researchers noted.

There is a regulatory catch. The Food and Drug Administration restricted emergency use authorization (EUA) for convalescent plasma in February 2021 to include only high-dose titer plasma and to limit the therapy to hospitalized patients with early disease or for immunocompromised people who cannot mount an adequate antibody response.

Dr. Sullivan and colleagues hoped their findings will prompt the FDA to expand the EUA to include outpatients.

“We have shared this data with both the World Health Organization and the FDA,” study coauthor Kelly Gebo, MD, MPH, said during the media briefing.

“We do believe that this could be scaled up quickly,” added Dr. Gebo, professor of medicine at Johns Hopkins University. Convalescent plasma “could be used as a potential treatment as variants continue to evolve, such as we’ve seen with Omicron.”
 

Pre-Omicron results

The study was conducted at Johns Hopkins University and 23 other sites nationwide between June 2020 and October 2021. This means researchers enrolled symptomatic adults during circulation of the SARS-CoV-2 ancestral strain and the Alpha and Delta variants.

However, Dr. Sullivan said, “we think that ... plasma with high levels of antibodies can adapt faster to Omicron, although it will take us longer to get an Omicron-specific supply.”

Because of the timing of the study, 80% of participants were unvaccinated. Mean age was 44 years and 57% were women. Black and Hispanic participants each accounted for more than 12% of the study population.

On average, participants received a transfusion within 6 days of the start of symptoms.

In the study, 37 people out of 589 control group participants were hospitalized, compared with 17 of the 592 who received the convalescent plasma.

“We know antibodies work against SARS-CoV-2. The vaccines have been spectacular – producing antibodies that reduce hospitalizations and prevent transmission,” Dr. Sullivan said. “Convalescent plasma provides much of the same antibodies instantly.”
 

Convalescent and controversial

Convalescent plasma has been one of the controversial treatments for people with COVID-19 – with studies going back and forth on the potential benefits and efficacy. A National Institutes of Health–funded study published in August 2021, for example, showed no significant benefit.

“As you know, convalescent plasma has had a rocky ride,” Dr. Casadevall said.

“It was deployed with great excitement in the terrible, early days of the pandemic. Unfortunately, the early excitement and optimism was dampened with some of the randomized control trials appearing to show no benefit in reducing mortality and hospitalized patients,” he added.

In contrast, the current study shows “where convalescent plasma works using the latest, most rigorous clinical investigation tools available: a double-blinded, randomized, placebo-control trial,” Dr. Casadevall said.
 

Why a preprint, and why now?

The researchers decided to release their data in recognition of the lag time between reporting of COVID-19 cases and hospitalizations, Dr. Sullivan said. “That’s part of the reason we decided to act now with this knowledge – that it does take a couple of weeks – with cases of Omicron going up.”

Furthermore, “we thought this was actionable data for decision-makers,” he added.

A reporter asked why the Johns Hopkins researchers chose to hold a media briefing for a preprint study.

A preprint is “not so unusual given the SARS-CoV-2 pandemic,” said study senior author Daniel Hanley, MD, division director of brain injury outcomes at Johns Hopkins University.

“The data are the data,” Dr. Casadevall added. “This is not going to change from peer review.”

Peer review may change some of the wording of the manuscript, but not the numbers, he added.

“Now with the Omicron crisis and the fact that we have lost some more main monoclonal antibodies, it is essential to get this information out,” Dr. Casadevall said.
 

Plasma therapy nothing new

Donation and transfusion of convalescent plasma is highly regulated with strict criteria, said Evan Bloch, MBChB, associate director of the transfusion medicine division at Johns Hopkins University.

If the FDA opts to expand the EUA based on this or other evidence, administration of convalescent plasma could be rolled out fairly quickly, the researchers noted.

Plasma transfusion takes place in hospitals and at infusion centers every day. The infrastructure is in place in many countries, even low- and middle-resource nations, around the world to provide convalescent plasma therapy. The major difference between traditional plasma and SARS-CoV-2 convalescent plasma is the indication, Dr. Bloch added.

In addition, convalescent plasma has a polyclonal composition – a benefit compared with monoclonal antibodies, he added. “It’s more durable or adaptive [compared with] some of the targeted therapies, such as monoclonal antibodies, where we’ve witnessed this diminished efficacy with viral evolution.”

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

The clinical value of bamlanivimab for hospitalized COVID-19 patients depends on whether patients have endogenous neutralizing antibodies at the time of treatment, according to new research.

In the randomized controlled trial, in both the group who received bamlanivimab and the group who received placebo, higher antigen and viral RNA levels were associated with a lower proportion of patients achieving recovery.

Other studies have shown that the use of monoclonal antibodies reduces hospitalization risk in outpatients with early COVID-19, and appears to promote viral load decline in the nasopharynx, wrote Jens D. Lundgren, MD, of the University of Copenhagen and colleagues in their article published in the Annals of Internal Medicine. What had been missing prior to this new research was final results from hospitalized patients, the authors said.

In the new study, the researchers randomized 314 adults hospitalized with COVID-19 but without end-organ failure to receive 7,000 mg bamlanivimab (163 patients) or a placebo (151 patients). All patients received study-supplied remdesivir unless contraindicated. The researchers compared the efficacy of bamlanivimab versus placebo, but considered remdesivir the standard of care in this study.

At baseline, 50% of patients overall had antispike endogenous neutralizing antibodies (nAbs), and 50% had SARS-CoV-2 nucleocapsid plasma antigen levels of at least 1,000 ng/L.

The median time to sustained recovery, 19 days, was not significantly different between the bamlanivimab and placebo groups (subhazard ratio, 0.99).

“As hypothesized, among those who were negative for nAb, the difference between bamlanivimab and placebo was more evident if levels of plasma antigen or nasal-swab viral RNA were above the median entry levels,” with subhazard ratios of 1.48 and 1.89, respectively, the researchers explained.

However, the hazard ratio for death for bamlanivimab vs. placebo was 0.45 for patients negative for nAb vs. 3.53 for those positive for nAb. These differences with respect to nAb status were similar across all 90 elements of a composite safety outcome, the researchers said.

Potential benefits remain unclear

The use of neutralizing monoclonal antibodies has been extensively documented as an effective treatment for COVID-19 among ambulatory patients, corresponding author Dr. Lundgren said in an interview.

“Conversely, among admitted patients with COVID-19 pneumonia, the benefit has been questionable,” he said.

The researchers examined a hypothesis that the null finding in hospitalized patients may stem from differences in underlying mechanisms, “either from uncontrolled viral replication – which would be predicted to occur in particular among those not yet been able to mount an endogenous immune response – or from hyperinflammation among those that have mounted such a response,” Dr. Lundgren said.

 The study findings supported the stated hypothesis, said Dr. Lundgren. “However, it was surprising that not only was the neutralizing antibody without any benefit among those that had mounted an endogenous immune response, but it actually may have been harmful,” he said.

Bamlanivimab was effective against the viral strain that circulated at the time of enrollment in the study, but subsequent viral strains have appeared to be unaffected by the neutralizing activity of the antibody, said Dr. Lundgren.

From a practical standpoint, “the findings would suggest that use of neutralizing monoclonal antibodies for patients admitted to a hospital with COVID pneumonia should be restricted to those that have not yet mounted an endogenous immune response, as determined by lack of detectable neutralizing antibodies at the time of admission,” Dr. Lundgren said.

Looking ahead, studies are currently underway to examine how the findings translate to vaccinated patients, he added. Other questions to be addressed include whether the benefits and harms apply to some or all neutralizing antibody products, he said.

In addition, “our research consortium is currently doing field testing of several point-of-care test candidates to examine their reliability and functionality,” for how quickly they might identify an endogenous neutralizing antibody response in an admitted COVID pneumonia patient,” Dr. Lundgren noted.

Findings show bamlanivimab’s limits

“Based on the findings of the current study, no clear subgroup of patients could be identified who would benefit from bamlanivimab when hospitalized with COVID-19,” said Suman Pal, MD, of the University of New Mexico, Albuquerque, in an interview.

“The study findings also show possible harm of using bamlanivimab in hospitalized COVID-19 patients who were seropositive for neutralizing antibodies prior to receiving therapy,” Dr. Pal emphasized. “Moreover, the study did not include participants with COVID-19 from variant strains, such as delta and omicron, which currently account for a large number of cases.” “Therefore, the results of this study do not support the use of bamlanivimab in the clinical setting until further evidence is available to guide the selection of patients who may benefit from therapy,” he explained.

“The possible benefit of bamlanivimab does not outweigh the risks in patients hospitalized with COVID-19,” he concluded.

Dr. Pal emphasized the need for larger prospective studies to establish whether bamlanivimab may have benefits in a subgroup of patients, but “well-validated point-of-care tests to identify such patients need to be readily available before this therapy can be considered by clinicians at the bedside,” he concluded.

Diligent screening required before use

Monoclonal antibody treatment has been administered to individuals with diagnosis of COVID-19 infection as outpatients as well as for hospitalized inpatients, said Noel Deep, MD, an internist in Antigo, Wisc., in an interview. “This study is important because it helps physicians and health care institutions to evaluate whether continued use of the monoclonal antibodies would be beneficial and, if so, in what patient populations,” he said.

The findings present interesting implications for the care of COVID-19 patients, said Dr. Deep. “This study indicates that bamlanivimab does not provide the benefit that was initially envisioned when the monoclonal antibody infusions were initially initiated in the treatment of COVID-19 infections. “Serological screening of the patients would help to identify that subgroup of individuals who could benefit from this monoclonal antibody rather than administering it to every COVID-19–positive individual,” he explained.

However, “it is important to note that the emergency use authorization (EUA) for single-agent bamlanivimab has been revoked,” Dr. Deep said.

“The potential benefits of bamlanivimab can be realized only if adequate attention is paid to identifying the appropriate candidates based on serological screening, and administering bamlanivimab to those who are already producing endogenous antibodies could lead to increased risk to those individuals,” he said. Dr. Deep added that he would favor administration of bamlanivimab “in those appropriately screened and eligible candidates, and it is my opinion that the benefits outweigh the risks in those individuals.”

Although the EUA for single-agent bamlanivimab has been revoked, “alternative monoclonal antibody therapies remain available under EUA, including REGEN-COV (casirivimab and imdevimab, administered together), and bamlanivimab and etesevimab administered together, for the same uses as previously authorized for bamlanivimab alone,” Dr. Deep said. “The FDA believes that these alternative monoclonal antibody therapies remain appropriate to treat patients with COVID-19, and I would like to see some data about the benefits and risks of these agents,” he noted.

Limitations, funding, and disclosures

The main limitation of the study was the small size and the fact that it was a subgroup analysis of a trial that ended early because of futility, the researchers wrote. However, the Therapeutics for Inpatients With COVID-19 (TICO) platform will proceed with clinical evaluation of additional COVID-19 treatments, they said.

The study was supported primarily by the U.S. government Operation Warp Speed and the National Institute of Allergy and Infectious Diseases. Other funding sources included the Division of Clinical Research and Leidos Biomedical Research for the INSIGHT (International Network for Strategic Initiatives in Global HIV Trials) Network, as well as an agreement between the National Heart, Lung, and Blood Institute and the Research Triangle Institute for the PETAL (Prevention & Early Treatment of Acute Lung Injury) Network and CTSN (Cardiothoracic Surgical Trials Network). Other support came from the U.S. Department of Veterans Affairs and the governments of Denmark (National Research Foundation), Australia (National Health and Medical Research Council), and the United Kingdom (Medical Research Council).

The medications used in the study were donated by Gilead Sciences and Eli Lilly.

The researchers had no financial conflicts do disclose. Dr. Deep and Dr. Pal had no relevant financial conflicts to disclose.

The clinical value of bamlanivimab for hospitalized COVID-19 patients depends on whether patients have endogenous neutralizing antibodies at the time of treatment, according to new research.

In the randomized controlled trial, in both the group who received bamlanivimab and the group who received placebo, higher antigen and viral RNA levels were associated with a lower proportion of patients achieving recovery.

Other studies have shown that the use of monoclonal antibodies reduces hospitalization risk in outpatients with early COVID-19, and appears to promote viral load decline in the nasopharynx, wrote Jens D. Lundgren, MD, of the University of Copenhagen and colleagues in their article published in the Annals of Internal Medicine. What had been missing prior to this new research was final results from hospitalized patients, the authors said.

In the new study, the researchers randomized 314 adults hospitalized with COVID-19 but without end-organ failure to receive 7,000 mg bamlanivimab (163 patients) or a placebo (151 patients). All patients received study-supplied remdesivir unless contraindicated. The researchers compared the efficacy of bamlanivimab versus placebo, but considered remdesivir the standard of care in this study.

At baseline, 50% of patients overall had antispike endogenous neutralizing antibodies (nAbs), and 50% had SARS-CoV-2 nucleocapsid plasma antigen levels of at least 1,000 ng/L.

The median time to sustained recovery, 19 days, was not significantly different between the bamlanivimab and placebo groups (subhazard ratio, 0.99).

“As hypothesized, among those who were negative for nAb, the difference between bamlanivimab and placebo was more evident if levels of plasma antigen or nasal-swab viral RNA were above the median entry levels,” with subhazard ratios of 1.48 and 1.89, respectively, the researchers explained.

However, the hazard ratio for death for bamlanivimab vs. placebo was 0.45 for patients negative for nAb vs. 3.53 for those positive for nAb. These differences with respect to nAb status were similar across all 90 elements of a composite safety outcome, the researchers said.

Potential benefits remain unclear

The use of neutralizing monoclonal antibodies has been extensively documented as an effective treatment for COVID-19 among ambulatory patients, corresponding author Dr. Lundgren said in an interview.

“Conversely, among admitted patients with COVID-19 pneumonia, the benefit has been questionable,” he said.

The researchers examined a hypothesis that the null finding in hospitalized patients may stem from differences in underlying mechanisms, “either from uncontrolled viral replication – which would be predicted to occur in particular among those not yet been able to mount an endogenous immune response – or from hyperinflammation among those that have mounted such a response,” Dr. Lundgren said.

 The study findings supported the stated hypothesis, said Dr. Lundgren. “However, it was surprising that not only was the neutralizing antibody without any benefit among those that had mounted an endogenous immune response, but it actually may have been harmful,” he said.

Bamlanivimab was effective against the viral strain that circulated at the time of enrollment in the study, but subsequent viral strains have appeared to be unaffected by the neutralizing activity of the antibody, said Dr. Lundgren.

From a practical standpoint, “the findings would suggest that use of neutralizing monoclonal antibodies for patients admitted to a hospital with COVID pneumonia should be restricted to those that have not yet mounted an endogenous immune response, as determined by lack of detectable neutralizing antibodies at the time of admission,” Dr. Lundgren said.

Looking ahead, studies are currently underway to examine how the findings translate to vaccinated patients, he added. Other questions to be addressed include whether the benefits and harms apply to some or all neutralizing antibody products, he said.

In addition, “our research consortium is currently doing field testing of several point-of-care test candidates to examine their reliability and functionality,” for how quickly they might identify an endogenous neutralizing antibody response in an admitted COVID pneumonia patient,” Dr. Lundgren noted.

Findings show bamlanivimab’s limits

“Based on the findings of the current study, no clear subgroup of patients could be identified who would benefit from bamlanivimab when hospitalized with COVID-19,” said Suman Pal, MD, of the University of New Mexico, Albuquerque, in an interview.

“The study findings also show possible harm of using bamlanivimab in hospitalized COVID-19 patients who were seropositive for neutralizing antibodies prior to receiving therapy,” Dr. Pal emphasized. “Moreover, the study did not include participants with COVID-19 from variant strains, such as delta and omicron, which currently account for a large number of cases.” “Therefore, the results of this study do not support the use of bamlanivimab in the clinical setting until further evidence is available to guide the selection of patients who may benefit from therapy,” he explained.

“The possible benefit of bamlanivimab does not outweigh the risks in patients hospitalized with COVID-19,” he concluded.

Dr. Pal emphasized the need for larger prospective studies to establish whether bamlanivimab may have benefits in a subgroup of patients, but “well-validated point-of-care tests to identify such patients need to be readily available before this therapy can be considered by clinicians at the bedside,” he concluded.

Diligent screening required before use

Monoclonal antibody treatment has been administered to individuals with diagnosis of COVID-19 infection as outpatients as well as for hospitalized inpatients, said Noel Deep, MD, an internist in Antigo, Wisc., in an interview. “This study is important because it helps physicians and health care institutions to evaluate whether continued use of the monoclonal antibodies would be beneficial and, if so, in what patient populations,” he said.

The findings present interesting implications for the care of COVID-19 patients, said Dr. Deep. “This study indicates that bamlanivimab does not provide the benefit that was initially envisioned when the monoclonal antibody infusions were initially initiated in the treatment of COVID-19 infections. “Serological screening of the patients would help to identify that subgroup of individuals who could benefit from this monoclonal antibody rather than administering it to every COVID-19–positive individual,” he explained.

However, “it is important to note that the emergency use authorization (EUA) for single-agent bamlanivimab has been revoked,” Dr. Deep said.

“The potential benefits of bamlanivimab can be realized only if adequate attention is paid to identifying the appropriate candidates based on serological screening, and administering bamlanivimab to those who are already producing endogenous antibodies could lead to increased risk to those individuals,” he said. Dr. Deep added that he would favor administration of bamlanivimab “in those appropriately screened and eligible candidates, and it is my opinion that the benefits outweigh the risks in those individuals.”

Although the EUA for single-agent bamlanivimab has been revoked, “alternative monoclonal antibody therapies remain available under EUA, including REGEN-COV (casirivimab and imdevimab, administered together), and bamlanivimab and etesevimab administered together, for the same uses as previously authorized for bamlanivimab alone,” Dr. Deep said. “The FDA believes that these alternative monoclonal antibody therapies remain appropriate to treat patients with COVID-19, and I would like to see some data about the benefits and risks of these agents,” he noted.

Limitations, funding, and disclosures

The main limitation of the study was the small size and the fact that it was a subgroup analysis of a trial that ended early because of futility, the researchers wrote. However, the Therapeutics for Inpatients With COVID-19 (TICO) platform will proceed with clinical evaluation of additional COVID-19 treatments, they said.

The study was supported primarily by the U.S. government Operation Warp Speed and the National Institute of Allergy and Infectious Diseases. Other funding sources included the Division of Clinical Research and Leidos Biomedical Research for the INSIGHT (International Network for Strategic Initiatives in Global HIV Trials) Network, as well as an agreement between the National Heart, Lung, and Blood Institute and the Research Triangle Institute for the PETAL (Prevention & Early Treatment of Acute Lung Injury) Network and CTSN (Cardiothoracic Surgical Trials Network). Other support came from the U.S. Department of Veterans Affairs and the governments of Denmark (National Research Foundation), Australia (National Health and Medical Research Council), and the United Kingdom (Medical Research Council).

The medications used in the study were donated by Gilead Sciences and Eli Lilly.

The researchers had no financial conflicts do disclose. Dr. Deep and Dr. Pal had no relevant financial conflicts to disclose.

The clinical value of bamlanivimab for hospitalized COVID-19 patients depends on whether patients have endogenous neutralizing antibodies at the time of treatment, according to new research.

In the randomized controlled trial, in both the group who received bamlanivimab and the group who received placebo, higher antigen and viral RNA levels were associated with a lower proportion of patients achieving recovery.

Other studies have shown that the use of monoclonal antibodies reduces hospitalization risk in outpatients with early COVID-19, and appears to promote viral load decline in the nasopharynx, wrote Jens D. Lundgren, MD, of the University of Copenhagen and colleagues in their article published in the Annals of Internal Medicine. What had been missing prior to this new research was final results from hospitalized patients, the authors said.

In the new study, the researchers randomized 314 adults hospitalized with COVID-19 but without end-organ failure to receive 7,000 mg bamlanivimab (163 patients) or a placebo (151 patients). All patients received study-supplied remdesivir unless contraindicated. The researchers compared the efficacy of bamlanivimab versus placebo, but considered remdesivir the standard of care in this study.

At baseline, 50% of patients overall had antispike endogenous neutralizing antibodies (nAbs), and 50% had SARS-CoV-2 nucleocapsid plasma antigen levels of at least 1,000 ng/L.

The median time to sustained recovery, 19 days, was not significantly different between the bamlanivimab and placebo groups (subhazard ratio, 0.99).

“As hypothesized, among those who were negative for nAb, the difference between bamlanivimab and placebo was more evident if levels of plasma antigen or nasal-swab viral RNA were above the median entry levels,” with subhazard ratios of 1.48 and 1.89, respectively, the researchers explained.

However, the hazard ratio for death for bamlanivimab vs. placebo was 0.45 for patients negative for nAb vs. 3.53 for those positive for nAb. These differences with respect to nAb status were similar across all 90 elements of a composite safety outcome, the researchers said.

Potential benefits remain unclear

The use of neutralizing monoclonal antibodies has been extensively documented as an effective treatment for COVID-19 among ambulatory patients, corresponding author Dr. Lundgren said in an interview.

“Conversely, among admitted patients with COVID-19 pneumonia, the benefit has been questionable,” he said.

The researchers examined a hypothesis that the null finding in hospitalized patients may stem from differences in underlying mechanisms, “either from uncontrolled viral replication – which would be predicted to occur in particular among those not yet been able to mount an endogenous immune response – or from hyperinflammation among those that have mounted such a response,” Dr. Lundgren said.

 The study findings supported the stated hypothesis, said Dr. Lundgren. “However, it was surprising that not only was the neutralizing antibody without any benefit among those that had mounted an endogenous immune response, but it actually may have been harmful,” he said.

Bamlanivimab was effective against the viral strain that circulated at the time of enrollment in the study, but subsequent viral strains have appeared to be unaffected by the neutralizing activity of the antibody, said Dr. Lundgren.

From a practical standpoint, “the findings would suggest that use of neutralizing monoclonal antibodies for patients admitted to a hospital with COVID pneumonia should be restricted to those that have not yet mounted an endogenous immune response, as determined by lack of detectable neutralizing antibodies at the time of admission,” Dr. Lundgren said.

Looking ahead, studies are currently underway to examine how the findings translate to vaccinated patients, he added. Other questions to be addressed include whether the benefits and harms apply to some or all neutralizing antibody products, he said.

In addition, “our research consortium is currently doing field testing of several point-of-care test candidates to examine their reliability and functionality,” for how quickly they might identify an endogenous neutralizing antibody response in an admitted COVID pneumonia patient,” Dr. Lundgren noted.

Findings show bamlanivimab’s limits

“Based on the findings of the current study, no clear subgroup of patients could be identified who would benefit from bamlanivimab when hospitalized with COVID-19,” said Suman Pal, MD, of the University of New Mexico, Albuquerque, in an interview.

“The study findings also show possible harm of using bamlanivimab in hospitalized COVID-19 patients who were seropositive for neutralizing antibodies prior to receiving therapy,” Dr. Pal emphasized. “Moreover, the study did not include participants with COVID-19 from variant strains, such as delta and omicron, which currently account for a large number of cases.” “Therefore, the results of this study do not support the use of bamlanivimab in the clinical setting until further evidence is available to guide the selection of patients who may benefit from therapy,” he explained.

“The possible benefit of bamlanivimab does not outweigh the risks in patients hospitalized with COVID-19,” he concluded.

Dr. Pal emphasized the need for larger prospective studies to establish whether bamlanivimab may have benefits in a subgroup of patients, but “well-validated point-of-care tests to identify such patients need to be readily available before this therapy can be considered by clinicians at the bedside,” he concluded.

Diligent screening required before use

Monoclonal antibody treatment has been administered to individuals with diagnosis of COVID-19 infection as outpatients as well as for hospitalized inpatients, said Noel Deep, MD, an internist in Antigo, Wisc., in an interview. “This study is important because it helps physicians and health care institutions to evaluate whether continued use of the monoclonal antibodies would be beneficial and, if so, in what patient populations,” he said.

The findings present interesting implications for the care of COVID-19 patients, said Dr. Deep. “This study indicates that bamlanivimab does not provide the benefit that was initially envisioned when the monoclonal antibody infusions were initially initiated in the treatment of COVID-19 infections. “Serological screening of the patients would help to identify that subgroup of individuals who could benefit from this monoclonal antibody rather than administering it to every COVID-19–positive individual,” he explained.

However, “it is important to note that the emergency use authorization (EUA) for single-agent bamlanivimab has been revoked,” Dr. Deep said.

“The potential benefits of bamlanivimab can be realized only if adequate attention is paid to identifying the appropriate candidates based on serological screening, and administering bamlanivimab to those who are already producing endogenous antibodies could lead to increased risk to those individuals,” he said. Dr. Deep added that he would favor administration of bamlanivimab “in those appropriately screened and eligible candidates, and it is my opinion that the benefits outweigh the risks in those individuals.”

Although the EUA for single-agent bamlanivimab has been revoked, “alternative monoclonal antibody therapies remain available under EUA, including REGEN-COV (casirivimab and imdevimab, administered together), and bamlanivimab and etesevimab administered together, for the same uses as previously authorized for bamlanivimab alone,” Dr. Deep said. “The FDA believes that these alternative monoclonal antibody therapies remain appropriate to treat patients with COVID-19, and I would like to see some data about the benefits and risks of these agents,” he noted.

Limitations, funding, and disclosures

The main limitation of the study was the small size and the fact that it was a subgroup analysis of a trial that ended early because of futility, the researchers wrote. However, the Therapeutics for Inpatients With COVID-19 (TICO) platform will proceed with clinical evaluation of additional COVID-19 treatments, they said.

The study was supported primarily by the U.S. government Operation Warp Speed and the National Institute of Allergy and Infectious Diseases. Other funding sources included the Division of Clinical Research and Leidos Biomedical Research for the INSIGHT (International Network for Strategic Initiatives in Global HIV Trials) Network, as well as an agreement between the National Heart, Lung, and Blood Institute and the Research Triangle Institute for the PETAL (Prevention & Early Treatment of Acute Lung Injury) Network and CTSN (Cardiothoracic Surgical Trials Network). Other support came from the U.S. Department of Veterans Affairs and the governments of Denmark (National Research Foundation), Australia (National Health and Medical Research Council), and the United Kingdom (Medical Research Council).

The medications used in the study were donated by Gilead Sciences and Eli Lilly.

The researchers had no financial conflicts do disclose. Dr. Deep and Dr. Pal had no relevant financial conflicts to disclose.

Fish oil supplementation does not help prevent depression or boost mood, new research suggests.

The VITAL-DEP study included more than 18,000 participants. Among adults aged 50 years or older free of clinically relevant depressive symptoms at baseline, long-term use of marine omega-3 fatty acid (omega-3) supplements did not reduce risk for depression or clinically relevant depressive symptoms — or make a difference in the quality of mood.

In fact, there was a small increase found in risk for depression or depressive symptoms with omega-3 supplements.

“While a small increase in risk of depression was inside the statistical margin of significance, there was no harmful or beneficial effect of omega-3 on the overall course of mood during the roughly 5 to 7 years of follow-up,” lead author Olivia I. Okereke, MD, Massachusetts General Hospital and Harvard Medical School, Boston, told Medscape Medical News.

“The takeaway from our study is that there is no net benefit of long-term use of daily omega-3 fish oil supplements for preventing depression or boosting mood,” Okereke said.

The findings were published online Dec. 21 in JAMA.
 

Assessing general population risk

For many years, experts have recommended omega-3 supplements for reduction in depression recurrence in some high-risk patients, Okereke noted.

“However, there are no guidelines related to the use of omega-3 supplements for preventing depression in the general population. Therefore, we undertook this study to provide clarity in the issue,” she said.

The VITAL-DEP study enrolled 18,353 older adults (mean age, 67.5 years; 49% women). Of these, 16,657 were at risk for incident depression, defined as having no previous history of depression; and 1696 were at risk for recurrent depression, defined as having a history of depression but not having undergone treatment for depression within the past 2 years.

Roughly half the participants were randomly assigned to receive marine omega-3 fatty acids (1 g/d of fish oil, including 465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]) and the other half to matching placebo for an average of 5.3 years.

“Because of the large sample size and long follow-up, we were able to test the effects of daily omega-3 fish oil supplements on universal prevention of depression in the adult population,” Okereke said.
 

No significant benefit

Results showed risk for depression or clinically relevant depressive symptoms (total of incident and recurrent cases) was not significantly different between the omega-3 group and the placebo group.

The omega-3 group had 651 depression or clinically relevant depressive symptom events (13.9 per 1000 person-years), and the placebo group had 583 depression or clinically relevant depressive symptom events (12.3 per 1000 person-years). The hazard ratio was 1.13 (95% CI, 1.01 - 1.26; P = .03).

There were also no significant between-group differences in longitudinal mood scores. The mean difference in change in 8-item Patient Health Questionnaire (PHQ-8) score was 0.03 points (95% CI, −0.01 to 0.07; P = .19).

“Patients, physicians, and other clinicians should understand that there are still many reasons for some people, under the guidance of their health care providers, to take omega-3 fish oil supplements,” Okereke noted.

“These supplements increasingly have been found to have benefits for cardiac disease prevention and treatment of inflammatory conditions, in addition to being used for management of existing depressive disorders in some high-risk patients,” she said.

“However, the results of our study indicate there is no reason for adults in the general population to be taking daily omega-3 fish oil supplements solely for the purpose of preventing depression or for maintaining a positive mood,” she added.

Okereke noted, however, that the VITAL-DEP study used 1 g/day of omega-3 fatty acids and there may be a greater benefit from taking higher doses, such as 4 g/day.
 

Cautionary notes

Commenting on the study for Medscape Medical News, Kuan-Pin Su, MD, PhD, chief of the Department of General Psychiatry, China Medical University, Taichung, Taiwan, highlighted some of the limitations cited by the investigators.

First, depression or depressive symptoms were defined using self-rating scales, which are “convenient to screen for depressive disorders, but a high score obtained on a self-rating scale does not necessarily indicate the presence of depressive psychopathology,” said Su, who was not involved with the research.

He also noted that use of 465 mg of EPA and 375 mg of DHA in VITAL-DEP “might be too low” to have an impact.

Finally, Su said it is “very important to also address the potential for type I error, which makes the secondary and subgroup analyses less reliable.”

VITAL-DEP was supported by a grant from the National Institute of Mental Health. Pronova BioPharma donated the fish oil and matching placebo. Okereke reported receiving royalties from Springer Publishing. Su is a founding committee member of the International Society for Nutritional Psychiatry Research, the board director of the International Society for the Study of Fatty Acids, and an associate editor of the journal Brain, Behavior, and Immunity.

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

Fish oil supplementation does not help prevent depression or boost mood, new research suggests.

The VITAL-DEP study included more than 18,000 participants. Among adults aged 50 years or older free of clinically relevant depressive symptoms at baseline, long-term use of marine omega-3 fatty acid (omega-3) supplements did not reduce risk for depression or clinically relevant depressive symptoms — or make a difference in the quality of mood.

In fact, there was a small increase found in risk for depression or depressive symptoms with omega-3 supplements.

“While a small increase in risk of depression was inside the statistical margin of significance, there was no harmful or beneficial effect of omega-3 on the overall course of mood during the roughly 5 to 7 years of follow-up,” lead author Olivia I. Okereke, MD, Massachusetts General Hospital and Harvard Medical School, Boston, told Medscape Medical News.

“The takeaway from our study is that there is no net benefit of long-term use of daily omega-3 fish oil supplements for preventing depression or boosting mood,” Okereke said.

The findings were published online Dec. 21 in JAMA.
 

Assessing general population risk

For many years, experts have recommended omega-3 supplements for reduction in depression recurrence in some high-risk patients, Okereke noted.

“However, there are no guidelines related to the use of omega-3 supplements for preventing depression in the general population. Therefore, we undertook this study to provide clarity in the issue,” she said.

The VITAL-DEP study enrolled 18,353 older adults (mean age, 67.5 years; 49% women). Of these, 16,657 were at risk for incident depression, defined as having no previous history of depression; and 1696 were at risk for recurrent depression, defined as having a history of depression but not having undergone treatment for depression within the past 2 years.

Roughly half the participants were randomly assigned to receive marine omega-3 fatty acids (1 g/d of fish oil, including 465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]) and the other half to matching placebo for an average of 5.3 years.

“Because of the large sample size and long follow-up, we were able to test the effects of daily omega-3 fish oil supplements on universal prevention of depression in the adult population,” Okereke said.
 

No significant benefit

Results showed risk for depression or clinically relevant depressive symptoms (total of incident and recurrent cases) was not significantly different between the omega-3 group and the placebo group.

The omega-3 group had 651 depression or clinically relevant depressive symptom events (13.9 per 1000 person-years), and the placebo group had 583 depression or clinically relevant depressive symptom events (12.3 per 1000 person-years). The hazard ratio was 1.13 (95% CI, 1.01 - 1.26; P = .03).

There were also no significant between-group differences in longitudinal mood scores. The mean difference in change in 8-item Patient Health Questionnaire (PHQ-8) score was 0.03 points (95% CI, −0.01 to 0.07; P = .19).

“Patients, physicians, and other clinicians should understand that there are still many reasons for some people, under the guidance of their health care providers, to take omega-3 fish oil supplements,” Okereke noted.

“These supplements increasingly have been found to have benefits for cardiac disease prevention and treatment of inflammatory conditions, in addition to being used for management of existing depressive disorders in some high-risk patients,” she said.

“However, the results of our study indicate there is no reason for adults in the general population to be taking daily omega-3 fish oil supplements solely for the purpose of preventing depression or for maintaining a positive mood,” she added.

Okereke noted, however, that the VITAL-DEP study used 1 g/day of omega-3 fatty acids and there may be a greater benefit from taking higher doses, such as 4 g/day.
 

Cautionary notes

Commenting on the study for Medscape Medical News, Kuan-Pin Su, MD, PhD, chief of the Department of General Psychiatry, China Medical University, Taichung, Taiwan, highlighted some of the limitations cited by the investigators.

First, depression or depressive symptoms were defined using self-rating scales, which are “convenient to screen for depressive disorders, but a high score obtained on a self-rating scale does not necessarily indicate the presence of depressive psychopathology,” said Su, who was not involved with the research.

He also noted that use of 465 mg of EPA and 375 mg of DHA in VITAL-DEP “might be too low” to have an impact.

Finally, Su said it is “very important to also address the potential for type I error, which makes the secondary and subgroup analyses less reliable.”

VITAL-DEP was supported by a grant from the National Institute of Mental Health. Pronova BioPharma donated the fish oil and matching placebo. Okereke reported receiving royalties from Springer Publishing. Su is a founding committee member of the International Society for Nutritional Psychiatry Research, the board director of the International Society for the Study of Fatty Acids, and an associate editor of the journal Brain, Behavior, and Immunity.

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

Fish oil supplementation does not help prevent depression or boost mood, new research suggests.

The VITAL-DEP study included more than 18,000 participants. Among adults aged 50 years or older free of clinically relevant depressive symptoms at baseline, long-term use of marine omega-3 fatty acid (omega-3) supplements did not reduce risk for depression or clinically relevant depressive symptoms — or make a difference in the quality of mood.

In fact, there was a small increase found in risk for depression or depressive symptoms with omega-3 supplements.

“While a small increase in risk of depression was inside the statistical margin of significance, there was no harmful or beneficial effect of omega-3 on the overall course of mood during the roughly 5 to 7 years of follow-up,” lead author Olivia I. Okereke, MD, Massachusetts General Hospital and Harvard Medical School, Boston, told Medscape Medical News.

“The takeaway from our study is that there is no net benefit of long-term use of daily omega-3 fish oil supplements for preventing depression or boosting mood,” Okereke said.

The findings were published online Dec. 21 in JAMA.
 

Assessing general population risk

For many years, experts have recommended omega-3 supplements for reduction in depression recurrence in some high-risk patients, Okereke noted.

“However, there are no guidelines related to the use of omega-3 supplements for preventing depression in the general population. Therefore, we undertook this study to provide clarity in the issue,” she said.

The VITAL-DEP study enrolled 18,353 older adults (mean age, 67.5 years; 49% women). Of these, 16,657 were at risk for incident depression, defined as having no previous history of depression; and 1696 were at risk for recurrent depression, defined as having a history of depression but not having undergone treatment for depression within the past 2 years.

Roughly half the participants were randomly assigned to receive marine omega-3 fatty acids (1 g/d of fish oil, including 465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]) and the other half to matching placebo for an average of 5.3 years.

“Because of the large sample size and long follow-up, we were able to test the effects of daily omega-3 fish oil supplements on universal prevention of depression in the adult population,” Okereke said.
 

No significant benefit

Results showed risk for depression or clinically relevant depressive symptoms (total of incident and recurrent cases) was not significantly different between the omega-3 group and the placebo group.

The omega-3 group had 651 depression or clinically relevant depressive symptom events (13.9 per 1000 person-years), and the placebo group had 583 depression or clinically relevant depressive symptom events (12.3 per 1000 person-years). The hazard ratio was 1.13 (95% CI, 1.01 - 1.26; P = .03).

There were also no significant between-group differences in longitudinal mood scores. The mean difference in change in 8-item Patient Health Questionnaire (PHQ-8) score was 0.03 points (95% CI, −0.01 to 0.07; P = .19).

“Patients, physicians, and other clinicians should understand that there are still many reasons for some people, under the guidance of their health care providers, to take omega-3 fish oil supplements,” Okereke noted.

“These supplements increasingly have been found to have benefits for cardiac disease prevention and treatment of inflammatory conditions, in addition to being used for management of existing depressive disorders in some high-risk patients,” she said.

“However, the results of our study indicate there is no reason for adults in the general population to be taking daily omega-3 fish oil supplements solely for the purpose of preventing depression or for maintaining a positive mood,” she added.

Okereke noted, however, that the VITAL-DEP study used 1 g/day of omega-3 fatty acids and there may be a greater benefit from taking higher doses, such as 4 g/day.
 

Cautionary notes

Commenting on the study for Medscape Medical News, Kuan-Pin Su, MD, PhD, chief of the Department of General Psychiatry, China Medical University, Taichung, Taiwan, highlighted some of the limitations cited by the investigators.

First, depression or depressive symptoms were defined using self-rating scales, which are “convenient to screen for depressive disorders, but a high score obtained on a self-rating scale does not necessarily indicate the presence of depressive psychopathology,” said Su, who was not involved with the research.

He also noted that use of 465 mg of EPA and 375 mg of DHA in VITAL-DEP “might be too low” to have an impact.

Finally, Su said it is “very important to also address the potential for type I error, which makes the secondary and subgroup analyses less reliable.”

VITAL-DEP was supported by a grant from the National Institute of Mental Health. Pronova BioPharma donated the fish oil and matching placebo. Okereke reported receiving royalties from Springer Publishing. Su is a founding committee member of the International Society for Nutritional Psychiatry Research, the board director of the International Society for the Study of Fatty Acids, and an associate editor of the journal Brain, Behavior, and Immunity.

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

Editors at the BMJ have released an urgent request to Facebook’s Mark Zuckerberg and parent company Meta regarding a recent “fact-check” on the medical trade journal’s article about questionable Pfizer vaccine trial practices.

According to an open letter written by outgoing BMJ editor-in-chief Fiona Godlee, MD, and incoming editor-in-chief Kamran Abbasi, MD, Facebook hired a third-party contractor to evaluate the article’s findings. This resulted in “inaccurate, incompetent, and irresponsible” conclusions that “should be of concern to anyone who values and relies on sources such as the BMJ for reliable medical information.”

The article in question investigated data integrity concerns at Pfizer vaccine clinical trial sites. In September 2020, the letter states, a former employee of the research group involved in Pfizer’s main vaccine trials, Ventavia, reached out to the BMJ and “began providing ... dozens of internal company documents, photos, audio recordings, and emails.” According to the company’s website, Ventavia “played a significant part in [COVID-19 clinical trial] recruitment” and “has received recognition by Pfizer for their contribution to vaccine trials.”

It was previously reported that the whistle-blower is a former regional director who was involved in Pfizer’s vaccine trials in Texas during the fall of 2020. She alleges “the company falsified data, unblinded patients, employed inadequately trained vaccinators, and was slow to follow up on adverse events reported in Pfizer’s pivotal phase 3 trial.”

The images provided to the BMJ “showed needles discarded in a plastic biohazard bag instead of a sharps container box” and another displayed “vaccine packaging materials with trial participants’ identification numbers written on them left out in the open, potentially unblinding participants.”

Despite informing Ventavia, the director’s concerns went unaddressed. She then filed a complaint with the Food and Drug Administration and was subsequently fired the same day. The FDA did not investigate the director’s allegations, said Dr. Godlee and Dr. Abbasi, even though the evidence “revealed a host of poor clinical trial research practices occurring at Ventavia that could impact data integrity and patient safety.”
 

Article labeled as ‘hoax,’ without pointing out errors

The BMJ hired an investigative reporter to follow up on the clinical trial claims. The findings were published in an article on Nov. 2, 2021, after the article “went through ... the usual high-level legal and editorial oversight and peer review,” according to the journal.

However, by Nov. 10, the journal began receiving complaints from readers unable to share the article on social media. Others had their posts flagged with warnings, such as “missing context ... independent fact-checkers say this information could mislead people.” Administrators of various Facebook groups were notified that posts containing the article were “partly false.”

Readers were informed that Facebook contractor Lead Stories performed the article’s “fact check.” Lead Stories is “an award-winning innovative fact checking and debunking website” and “an active part of Facebook’s partnership with third-party fact checkers” – with the latter granting them “access to listings of content that has been flagged as potentially false by Facebook’s systems or its users.” The company said they “decide independently if we want to fact check it or not.”

Lead Stories stated that they “can enter our fact checks into a tool provided by Facebook and Facebook then uses our data to help slow down the spread of false information on its platform.” Although the contractor is compensated, Lead Stories claims they have “no say or influence over what we fact check or what our conclusions are.”

Both editors question the validity of the fact check performed by Lead Stories, as it failed to provide any “assertions of fact” as to what the BMJ got wrong. Moreover, the editors take issue with Lead Stories referring to the journal as a “news blog” and using the phrase “hoax-alert” in the URL when publishing the story on its site.

The BMJ has reached out to Lead Stories and Facebook, said the letter, but Lead Stories refuses to “change anything about their article or actions that have led to Facebook flagging our article.” Requests for Facebook to remove the “fact-checking” label and allow “readers to freely share the article on [Facebook’s] platform” have been unfruitful.

Dr. Godlee and Dr. Abbasi expressed concern that other “high quality information provider[s] have been affected by the incompetence of Meta’s fact checking regime.” In November, Instagram censored Cochrane, an international provider of independent systematic medical reviews. Instagram, also owned by Meta, prohibited users from tagging Cochrane because the organization “repeatedly posted ... false content about COVID-19 or vaccines.” Cochrane refuted the allegations.

While “fact checking has been a staple of good journalism for decades,” said the editors, Meta has “apparently delegated responsibility to people incompetent in carrying out this crucial task.” They urged the company to reconsider its fact-checking strategy and review the issues that contributed to the error.

This news organization reached out to Meta for comment but did not receive a response at press time.

Lead Stories has posted a reply (Lead Stories’ Response To BMJ Open Letter Objecting To A Lead Stories Fact Check) to the BMJ’s complaint on its website.

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

Editors at the BMJ have released an urgent request to Facebook’s Mark Zuckerberg and parent company Meta regarding a recent “fact-check” on the medical trade journal’s article about questionable Pfizer vaccine trial practices.

According to an open letter written by outgoing BMJ editor-in-chief Fiona Godlee, MD, and incoming editor-in-chief Kamran Abbasi, MD, Facebook hired a third-party contractor to evaluate the article’s findings. This resulted in “inaccurate, incompetent, and irresponsible” conclusions that “should be of concern to anyone who values and relies on sources such as the BMJ for reliable medical information.”

The article in question investigated data integrity concerns at Pfizer vaccine clinical trial sites. In September 2020, the letter states, a former employee of the research group involved in Pfizer’s main vaccine trials, Ventavia, reached out to the BMJ and “began providing ... dozens of internal company documents, photos, audio recordings, and emails.” According to the company’s website, Ventavia “played a significant part in [COVID-19 clinical trial] recruitment” and “has received recognition by Pfizer for their contribution to vaccine trials.”

It was previously reported that the whistle-blower is a former regional director who was involved in Pfizer’s vaccine trials in Texas during the fall of 2020. She alleges “the company falsified data, unblinded patients, employed inadequately trained vaccinators, and was slow to follow up on adverse events reported in Pfizer’s pivotal phase 3 trial.”

The images provided to the BMJ “showed needles discarded in a plastic biohazard bag instead of a sharps container box” and another displayed “vaccine packaging materials with trial participants’ identification numbers written on them left out in the open, potentially unblinding participants.”

Despite informing Ventavia, the director’s concerns went unaddressed. She then filed a complaint with the Food and Drug Administration and was subsequently fired the same day. The FDA did not investigate the director’s allegations, said Dr. Godlee and Dr. Abbasi, even though the evidence “revealed a host of poor clinical trial research practices occurring at Ventavia that could impact data integrity and patient safety.”
 

Article labeled as ‘hoax,’ without pointing out errors

The BMJ hired an investigative reporter to follow up on the clinical trial claims. The findings were published in an article on Nov. 2, 2021, after the article “went through ... the usual high-level legal and editorial oversight and peer review,” according to the journal.

However, by Nov. 10, the journal began receiving complaints from readers unable to share the article on social media. Others had their posts flagged with warnings, such as “missing context ... independent fact-checkers say this information could mislead people.” Administrators of various Facebook groups were notified that posts containing the article were “partly false.”

Readers were informed that Facebook contractor Lead Stories performed the article’s “fact check.” Lead Stories is “an award-winning innovative fact checking and debunking website” and “an active part of Facebook’s partnership with third-party fact checkers” – with the latter granting them “access to listings of content that has been flagged as potentially false by Facebook’s systems or its users.” The company said they “decide independently if we want to fact check it or not.”

Lead Stories stated that they “can enter our fact checks into a tool provided by Facebook and Facebook then uses our data to help slow down the spread of false information on its platform.” Although the contractor is compensated, Lead Stories claims they have “no say or influence over what we fact check or what our conclusions are.”

Both editors question the validity of the fact check performed by Lead Stories, as it failed to provide any “assertions of fact” as to what the BMJ got wrong. Moreover, the editors take issue with Lead Stories referring to the journal as a “news blog” and using the phrase “hoax-alert” in the URL when publishing the story on its site.

The BMJ has reached out to Lead Stories and Facebook, said the letter, but Lead Stories refuses to “change anything about their article or actions that have led to Facebook flagging our article.” Requests for Facebook to remove the “fact-checking” label and allow “readers to freely share the article on [Facebook’s] platform” have been unfruitful.

Dr. Godlee and Dr. Abbasi expressed concern that other “high quality information provider[s] have been affected by the incompetence of Meta’s fact checking regime.” In November, Instagram censored Cochrane, an international provider of independent systematic medical reviews. Instagram, also owned by Meta, prohibited users from tagging Cochrane because the organization “repeatedly posted ... false content about COVID-19 or vaccines.” Cochrane refuted the allegations.

While “fact checking has been a staple of good journalism for decades,” said the editors, Meta has “apparently delegated responsibility to people incompetent in carrying out this crucial task.” They urged the company to reconsider its fact-checking strategy and review the issues that contributed to the error.

This news organization reached out to Meta for comment but did not receive a response at press time.

Lead Stories has posted a reply (Lead Stories’ Response To BMJ Open Letter Objecting To A Lead Stories Fact Check) to the BMJ’s complaint on its website.

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

Editors at the BMJ have released an urgent request to Facebook’s Mark Zuckerberg and parent company Meta regarding a recent “fact-check” on the medical trade journal’s article about questionable Pfizer vaccine trial practices.

According to an open letter written by outgoing BMJ editor-in-chief Fiona Godlee, MD, and incoming editor-in-chief Kamran Abbasi, MD, Facebook hired a third-party contractor to evaluate the article’s findings. This resulted in “inaccurate, incompetent, and irresponsible” conclusions that “should be of concern to anyone who values and relies on sources such as the BMJ for reliable medical information.”

The article in question investigated data integrity concerns at Pfizer vaccine clinical trial sites. In September 2020, the letter states, a former employee of the research group involved in Pfizer’s main vaccine trials, Ventavia, reached out to the BMJ and “began providing ... dozens of internal company documents, photos, audio recordings, and emails.” According to the company’s website, Ventavia “played a significant part in [COVID-19 clinical trial] recruitment” and “has received recognition by Pfizer for their contribution to vaccine trials.”

It was previously reported that the whistle-blower is a former regional director who was involved in Pfizer’s vaccine trials in Texas during the fall of 2020. She alleges “the company falsified data, unblinded patients, employed inadequately trained vaccinators, and was slow to follow up on adverse events reported in Pfizer’s pivotal phase 3 trial.”

The images provided to the BMJ “showed needles discarded in a plastic biohazard bag instead of a sharps container box” and another displayed “vaccine packaging materials with trial participants’ identification numbers written on them left out in the open, potentially unblinding participants.”

Despite informing Ventavia, the director’s concerns went unaddressed. She then filed a complaint with the Food and Drug Administration and was subsequently fired the same day. The FDA did not investigate the director’s allegations, said Dr. Godlee and Dr. Abbasi, even though the evidence “revealed a host of poor clinical trial research practices occurring at Ventavia that could impact data integrity and patient safety.”
 

Article labeled as ‘hoax,’ without pointing out errors

The BMJ hired an investigative reporter to follow up on the clinical trial claims. The findings were published in an article on Nov. 2, 2021, after the article “went through ... the usual high-level legal and editorial oversight and peer review,” according to the journal.

However, by Nov. 10, the journal began receiving complaints from readers unable to share the article on social media. Others had their posts flagged with warnings, such as “missing context ... independent fact-checkers say this information could mislead people.” Administrators of various Facebook groups were notified that posts containing the article were “partly false.”

Readers were informed that Facebook contractor Lead Stories performed the article’s “fact check.” Lead Stories is “an award-winning innovative fact checking and debunking website” and “an active part of Facebook’s partnership with third-party fact checkers” – with the latter granting them “access to listings of content that has been flagged as potentially false by Facebook’s systems or its users.” The company said they “decide independently if we want to fact check it or not.”

Lead Stories stated that they “can enter our fact checks into a tool provided by Facebook and Facebook then uses our data to help slow down the spread of false information on its platform.” Although the contractor is compensated, Lead Stories claims they have “no say or influence over what we fact check or what our conclusions are.”

Both editors question the validity of the fact check performed by Lead Stories, as it failed to provide any “assertions of fact” as to what the BMJ got wrong. Moreover, the editors take issue with Lead Stories referring to the journal as a “news blog” and using the phrase “hoax-alert” in the URL when publishing the story on its site.

The BMJ has reached out to Lead Stories and Facebook, said the letter, but Lead Stories refuses to “change anything about their article or actions that have led to Facebook flagging our article.” Requests for Facebook to remove the “fact-checking” label and allow “readers to freely share the article on [Facebook’s] platform” have been unfruitful.

Dr. Godlee and Dr. Abbasi expressed concern that other “high quality information provider[s] have been affected by the incompetence of Meta’s fact checking regime.” In November, Instagram censored Cochrane, an international provider of independent systematic medical reviews. Instagram, also owned by Meta, prohibited users from tagging Cochrane because the organization “repeatedly posted ... false content about COVID-19 or vaccines.” Cochrane refuted the allegations.

While “fact checking has been a staple of good journalism for decades,” said the editors, Meta has “apparently delegated responsibility to people incompetent in carrying out this crucial task.” They urged the company to reconsider its fact-checking strategy and review the issues that contributed to the error.

This news organization reached out to Meta for comment but did not receive a response at press time.

Lead Stories has posted a reply (Lead Stories’ Response To BMJ Open Letter Objecting To A Lead Stories Fact Check) to the BMJ’s complaint on its website.

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

The amount of fat surrounding abdominal organs may help clinicians identify cardiovascular risk in young people with obesity, researchers have found.

Severely overweight children and young adults showed a subtle association between visceral fat and arterial stiffness independent of body mass index (BMI). The association was not present in those of healthy weight, possibly because their visceral fat stores are too small to have a detectable effect on cardiovascular health, according to the researchers, who reported their findings in the latest issue of Pediatric Obesity.

“Those kids with greater visceral fat had stiffer arteries, which can overtax and overstress the system and lead to unfortunate consequences in terms of cardiovascular health down the line,” senior author Joseph M. Kindler, PhD, an assistant professor of nutritional sciences at the University of Georgia, Athens, told this news organization.

The data came from cross-sectional measurements in 605 youth (67% female, 56% non-Black) aged 10-23 years at Cincinnati Children’s Hospital Medical Center. The sample included 236 individuals of healthy weight, 224 with obesity, and 145 with type 2 diabetes.    

Visceral fat was assessed with dual-energy x-ray absorptiometry (DXA), a widely used test of bone mineral density screening to assess fracture risk. Carotid-femoral pulse wave velocity (PWV) was used to gauge arterial stiffness, a subclinical sign of cardiovascular disease.

Visceral fat was associated with PWV in all three groups of study subjects (P < .05), the researchers found, whereas the amount of subcutaneous fat was linked to arterial stiffness in obese youth and those with obesity but not those whose weight was considered healthy.

The amount of fat was associated with an additional 1.6% of the variability in arterial stiffness in youth with obesity after accounting for BMI. Subcutaneous fat, meanwhile, did not appear to affect PWV, the researchers found. “In youth with healthy weight, visceral fat, subcutaneous fat, BMI, and waist circumference were not significantly associated with PWV in any analyses,” they write.

The researchers cited a paucity of data on the relationship between visceral fat and cardiovascular disease in children with obesity. Although BMI is a reliable and readily available indicator of risk for disease, DXA “might give us a little more information,” Dr. Kindler, a nutritionist and bone biologist, said. As for clinical use to supplement BMI and waist circumference, he said, “maybe there’s room for visceral fat, but we do need a lot more science to back those decisions down the line.”

For example, what normal visceral fat accumulation during childhood looks like is unknown, he said.

Rigorous longitudinal studies are needed to establish cause and effect, but the new findings offer “a potential connection between visceral fat and cardiovascular disease risk in youth in a relatively large sample,” Wei Shen, MD, MPH, the associate director of the body composition unit at the New York Obesity Nutrition Research Center at Columbia University, New York, said.

Ideally, said Dr. Shen, who was not involved in the latest study, it would be “more credible to use the most accurate measure of visceral fat, the volumetric measurement of visceral fat using MRI” to establish a causal relationship with cardiovascular risk. However, MRI is more expensive and less accessible than DXA. To assess visceral fat in the clinic, “waist circumference may still be a good choice, as it is so convenient to use,” she added.

Dr. Kindler and his colleagues highlighted the need to examine the effect of excess visceral fat as well as intrahepatic fat on youth with type 2 diabetes, who experience cardiovascular complications independent of whether they are obese. In the new study, the positive association between visceral fat and arterial stiffness did not differ between youth with obesity and normal glucose control and those with obesity and type 2 diabetes.

Funding came from the Endocrine Fellows Foundation, the National Institutes of Health, and the University of Georgia Obesity Initiative. Dr. Kindler and Dr. Shen have disclosed no relevant financial relationships.

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

The amount of fat surrounding abdominal organs may help clinicians identify cardiovascular risk in young people with obesity, researchers have found.

Severely overweight children and young adults showed a subtle association between visceral fat and arterial stiffness independent of body mass index (BMI). The association was not present in those of healthy weight, possibly because their visceral fat stores are too small to have a detectable effect on cardiovascular health, according to the researchers, who reported their findings in the latest issue of Pediatric Obesity.

“Those kids with greater visceral fat had stiffer arteries, which can overtax and overstress the system and lead to unfortunate consequences in terms of cardiovascular health down the line,” senior author Joseph M. Kindler, PhD, an assistant professor of nutritional sciences at the University of Georgia, Athens, told this news organization.

The data came from cross-sectional measurements in 605 youth (67% female, 56% non-Black) aged 10-23 years at Cincinnati Children’s Hospital Medical Center. The sample included 236 individuals of healthy weight, 224 with obesity, and 145 with type 2 diabetes.    

Visceral fat was assessed with dual-energy x-ray absorptiometry (DXA), a widely used test of bone mineral density screening to assess fracture risk. Carotid-femoral pulse wave velocity (PWV) was used to gauge arterial stiffness, a subclinical sign of cardiovascular disease.

Visceral fat was associated with PWV in all three groups of study subjects (P < .05), the researchers found, whereas the amount of subcutaneous fat was linked to arterial stiffness in obese youth and those with obesity but not those whose weight was considered healthy.

The amount of fat was associated with an additional 1.6% of the variability in arterial stiffness in youth with obesity after accounting for BMI. Subcutaneous fat, meanwhile, did not appear to affect PWV, the researchers found. “In youth with healthy weight, visceral fat, subcutaneous fat, BMI, and waist circumference were not significantly associated with PWV in any analyses,” they write.

The researchers cited a paucity of data on the relationship between visceral fat and cardiovascular disease in children with obesity. Although BMI is a reliable and readily available indicator of risk for disease, DXA “might give us a little more information,” Dr. Kindler, a nutritionist and bone biologist, said. As for clinical use to supplement BMI and waist circumference, he said, “maybe there’s room for visceral fat, but we do need a lot more science to back those decisions down the line.”

For example, what normal visceral fat accumulation during childhood looks like is unknown, he said.

Rigorous longitudinal studies are needed to establish cause and effect, but the new findings offer “a potential connection between visceral fat and cardiovascular disease risk in youth in a relatively large sample,” Wei Shen, MD, MPH, the associate director of the body composition unit at the New York Obesity Nutrition Research Center at Columbia University, New York, said.

Ideally, said Dr. Shen, who was not involved in the latest study, it would be “more credible to use the most accurate measure of visceral fat, the volumetric measurement of visceral fat using MRI” to establish a causal relationship with cardiovascular risk. However, MRI is more expensive and less accessible than DXA. To assess visceral fat in the clinic, “waist circumference may still be a good choice, as it is so convenient to use,” she added.

Dr. Kindler and his colleagues highlighted the need to examine the effect of excess visceral fat as well as intrahepatic fat on youth with type 2 diabetes, who experience cardiovascular complications independent of whether they are obese. In the new study, the positive association between visceral fat and arterial stiffness did not differ between youth with obesity and normal glucose control and those with obesity and type 2 diabetes.

Funding came from the Endocrine Fellows Foundation, the National Institutes of Health, and the University of Georgia Obesity Initiative. Dr. Kindler and Dr. Shen have disclosed no relevant financial relationships.

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

The amount of fat surrounding abdominal organs may help clinicians identify cardiovascular risk in young people with obesity, researchers have found.

Severely overweight children and young adults showed a subtle association between visceral fat and arterial stiffness independent of body mass index (BMI). The association was not present in those of healthy weight, possibly because their visceral fat stores are too small to have a detectable effect on cardiovascular health, according to the researchers, who reported their findings in the latest issue of Pediatric Obesity.

“Those kids with greater visceral fat had stiffer arteries, which can overtax and overstress the system and lead to unfortunate consequences in terms of cardiovascular health down the line,” senior author Joseph M. Kindler, PhD, an assistant professor of nutritional sciences at the University of Georgia, Athens, told this news organization.

The data came from cross-sectional measurements in 605 youth (67% female, 56% non-Black) aged 10-23 years at Cincinnati Children’s Hospital Medical Center. The sample included 236 individuals of healthy weight, 224 with obesity, and 145 with type 2 diabetes.    

Visceral fat was assessed with dual-energy x-ray absorptiometry (DXA), a widely used test of bone mineral density screening to assess fracture risk. Carotid-femoral pulse wave velocity (PWV) was used to gauge arterial stiffness, a subclinical sign of cardiovascular disease.

Visceral fat was associated with PWV in all three groups of study subjects (P < .05), the researchers found, whereas the amount of subcutaneous fat was linked to arterial stiffness in obese youth and those with obesity but not those whose weight was considered healthy.

The amount of fat was associated with an additional 1.6% of the variability in arterial stiffness in youth with obesity after accounting for BMI. Subcutaneous fat, meanwhile, did not appear to affect PWV, the researchers found. “In youth with healthy weight, visceral fat, subcutaneous fat, BMI, and waist circumference were not significantly associated with PWV in any analyses,” they write.

The researchers cited a paucity of data on the relationship between visceral fat and cardiovascular disease in children with obesity. Although BMI is a reliable and readily available indicator of risk for disease, DXA “might give us a little more information,” Dr. Kindler, a nutritionist and bone biologist, said. As for clinical use to supplement BMI and waist circumference, he said, “maybe there’s room for visceral fat, but we do need a lot more science to back those decisions down the line.”

For example, what normal visceral fat accumulation during childhood looks like is unknown, he said.

Rigorous longitudinal studies are needed to establish cause and effect, but the new findings offer “a potential connection between visceral fat and cardiovascular disease risk in youth in a relatively large sample,” Wei Shen, MD, MPH, the associate director of the body composition unit at the New York Obesity Nutrition Research Center at Columbia University, New York, said.

Ideally, said Dr. Shen, who was not involved in the latest study, it would be “more credible to use the most accurate measure of visceral fat, the volumetric measurement of visceral fat using MRI” to establish a causal relationship with cardiovascular risk. However, MRI is more expensive and less accessible than DXA. To assess visceral fat in the clinic, “waist circumference may still be a good choice, as it is so convenient to use,” she added.

Dr. Kindler and his colleagues highlighted the need to examine the effect of excess visceral fat as well as intrahepatic fat on youth with type 2 diabetes, who experience cardiovascular complications independent of whether they are obese. In the new study, the positive association between visceral fat and arterial stiffness did not differ between youth with obesity and normal glucose control and those with obesity and type 2 diabetes.

Funding came from the Endocrine Fellows Foundation, the National Institutes of Health, and the University of Georgia Obesity Initiative. Dr. Kindler and Dr. Shen have disclosed no relevant financial relationships.

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

Patients with obesity and type 2 diabetes who underwent bariatric surgery and had 10-year durable diabetes remission had a 60% lower risk of incident cancer than patients who had usual obesity care.

And women who had bariatric surgery had a 42% lower risk of having cancer during a median 21-year follow-up, compared with women who had usual obesity care.

These findings from 701 patients in the Swedish Obese Subjects (SOS) study who had type 2 diabetes were recently published in Diabetes Care.

The results illustrate the “connection between glucose control and cancer prevention” and suggest that “among patients with type 2 diabetes, many cancer cases are preventable,” lead author Kajsa Sjöholm, PhD, associate professor of molecular medicine at Sahlgrenska Academy, University of Gothenburg (Sweden), said in a press release from the university.

“The global epidemic of both obesity and diabetes leads to an increased risk of cancer, as well as an increased risk of premature death,” added senior author Magdalena Taube, PhD, associate professor of molecular medicine in the same academy.

“It has been estimated that, over the next 10-15 years, obesity may cause more cancer cases than smoking in several countries,” she noted. Therefore, “strategies are needed to prevent this development, and our results can provide vital guidance for prevention of cancer in patients with obesity and type 2 diabetes.”
 

Durable diabetes remission seems key

Two-thirds of the patients in the bariatric surgery group had vertical banded gastroplasty (65%), and the rest had adjustable or nonadjustable gastric banding (18%) or gastric bypass (17%).

Each type of bariatric surgery was associated with higher diabetes remission rates, compared with usual care, in a previous study by these researchers, Dr. Taube said in an interview.

“In our present study,” she added, “we observed a nonsignificant trend, where patients with obesity and type 2 diabetes in the highest weight loss tertile (average weight loss, –44.8 kg) had somewhat lower risk of cancer compared to the lowest tertile [average weight loss, –14.9 kg].”

This might suggest, Dr. Taube continued, that with respect to cancer risk, surgery techniques resulting in greater weight loss (for example, Roux-en-Y gastric bypass and sleeve gastrectomy) should be recommended in patients with obesity and diabetes.

“However, it should also be noted that long-term diabetes remission seems imperative for cancer risk reduction,” she said, “and in a recent meta-analysis by McTigue et al., published in JAMA Surgery, it was shown that patients who had Roux-en-Y gastric bypass had greater weight loss, a slightly higher type 2 diabetes remission rate, less type 2 diabetes relapse, and better long-term glycemic control, compared with those who had sleeve gastrectomy.

“The observed cancer reduction in women with obesity and type 2 diabetes is in line with previous findings showing that cancer risk reduction following bariatric surgery in patients with obesity is more marked among women than men,” Dr. Taube noted. This may be because cancer rates are higher in women with diabetes than in men with diabetes, and common cancer types associated with obesity are female specific.

The main cancers in women were breast cancer, followed by endometrial and colorectal cancer. In men, the main cancers were colorectal, prostate, and urothelial/malignant skin cancer.
 

Study design and findings

It is well established that obesity is a risk factor for 13 types of cancer, and some of these cancers (liver, pancreatic, endometrial, colon and rectal, breast, and bladder) may be related to type 2 diabetes. And bariatric surgery has been shown to reduce cancer risk in patients with obesity.

However, it is not clear how bariatric surgery may affect cancer risk in patients with obesity and type 2 diabetes.

To study this, the researchers examined data from 393 patients who underwent bariatric surgery and 308 patients who received usual obesity treatment, who were part of the SOS study.

The SOS study enrolled men with a body mass index of at least 34 kg/m², and women with a BMI of at least 38 kg/m² who were aged 37-60 years between 1987 and 2001.

The current study outcome – cancer incidence in patients with obesity and type 2 diabetes – was not a prespecified outcome

The intervention groups were matched on 18 variables, including age, sex, serum insulin, alcohol, education, and smoking.

At baseline, the patients had a mean age of about 49 and 60% were women. They had a mean BMI of about 42 and a mean hemoglobin A1c of 7.8%.

On average, patients in the surgery group had lost 27.5 kg and 22.7 kg, and patients in the usual care group had lost 3.2 kg and 4.8 kg, at 2 years and 10 years, respectively.

During a median follow-up of 21 years, there were 74 incident cancers in the control group and 68 cancers in the bariatric surgery group.

The risk of cancer during follow-up was 37% lower in the surgery group than in the usual care group, after multivariable adjustment (adjusted hazard ratio, 0.63; 95% confidence interval, 0.44-0.89; P = .008).

A deeper dive showed that there were 86 incident cancers in women and 56 cancers in men. The risk of cancer was significantly lower in women who had bariatric surgery, compared with those who had usual care (aHR, 0.58; 95% CI 0.38-0.90, P = .016). However, the risk of cancer was not significantly lower in men who had bariatric surgery versus those who had usual care (aHR 0.79, 95% CI, 0.46-1.38; P = .413).

Diabetes remission at 10 years was associated with a 60% reduced cancer incidence (aHR, 0.40; 95% CI, 0.22-0.74, P = .003).

The study was funded by the Swedish state (under an agreement between the Swedish government and the county councils), the Swedish Research Council, the Novo Nordisk Foundation, the Swedish Heart-Lung Foundation, and the Swedish Diabetes Foundation. One author received consulting fees from Johnson & Johnson. The other authors had no relevant financial disclosures.

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

Patients with obesity and type 2 diabetes who underwent bariatric surgery and had 10-year durable diabetes remission had a 60% lower risk of incident cancer than patients who had usual obesity care.

And women who had bariatric surgery had a 42% lower risk of having cancer during a median 21-year follow-up, compared with women who had usual obesity care.

These findings from 701 patients in the Swedish Obese Subjects (SOS) study who had type 2 diabetes were recently published in Diabetes Care.

The results illustrate the “connection between glucose control and cancer prevention” and suggest that “among patients with type 2 diabetes, many cancer cases are preventable,” lead author Kajsa Sjöholm, PhD, associate professor of molecular medicine at Sahlgrenska Academy, University of Gothenburg (Sweden), said in a press release from the university.

“The global epidemic of both obesity and diabetes leads to an increased risk of cancer, as well as an increased risk of premature death,” added senior author Magdalena Taube, PhD, associate professor of molecular medicine in the same academy.

“It has been estimated that, over the next 10-15 years, obesity may cause more cancer cases than smoking in several countries,” she noted. Therefore, “strategies are needed to prevent this development, and our results can provide vital guidance for prevention of cancer in patients with obesity and type 2 diabetes.”
 

Durable diabetes remission seems key

Two-thirds of the patients in the bariatric surgery group had vertical banded gastroplasty (65%), and the rest had adjustable or nonadjustable gastric banding (18%) or gastric bypass (17%).

Each type of bariatric surgery was associated with higher diabetes remission rates, compared with usual care, in a previous study by these researchers, Dr. Taube said in an interview.

“In our present study,” she added, “we observed a nonsignificant trend, where patients with obesity and type 2 diabetes in the highest weight loss tertile (average weight loss, –44.8 kg) had somewhat lower risk of cancer compared to the lowest tertile [average weight loss, –14.9 kg].”

This might suggest, Dr. Taube continued, that with respect to cancer risk, surgery techniques resulting in greater weight loss (for example, Roux-en-Y gastric bypass and sleeve gastrectomy) should be recommended in patients with obesity and diabetes.

“However, it should also be noted that long-term diabetes remission seems imperative for cancer risk reduction,” she said, “and in a recent meta-analysis by McTigue et al., published in JAMA Surgery, it was shown that patients who had Roux-en-Y gastric bypass had greater weight loss, a slightly higher type 2 diabetes remission rate, less type 2 diabetes relapse, and better long-term glycemic control, compared with those who had sleeve gastrectomy.

“The observed cancer reduction in women with obesity and type 2 diabetes is in line with previous findings showing that cancer risk reduction following bariatric surgery in patients with obesity is more marked among women than men,” Dr. Taube noted. This may be because cancer rates are higher in women with diabetes than in men with diabetes, and common cancer types associated with obesity are female specific.

The main cancers in women were breast cancer, followed by endometrial and colorectal cancer. In men, the main cancers were colorectal, prostate, and urothelial/malignant skin cancer.
 

Study design and findings

It is well established that obesity is a risk factor for 13 types of cancer, and some of these cancers (liver, pancreatic, endometrial, colon and rectal, breast, and bladder) may be related to type 2 diabetes. And bariatric surgery has been shown to reduce cancer risk in patients with obesity.

However, it is not clear how bariatric surgery may affect cancer risk in patients with obesity and type 2 diabetes.

To study this, the researchers examined data from 393 patients who underwent bariatric surgery and 308 patients who received usual obesity treatment, who were part of the SOS study.

The SOS study enrolled men with a body mass index of at least 34 kg/m², and women with a BMI of at least 38 kg/m² who were aged 37-60 years between 1987 and 2001.

The current study outcome – cancer incidence in patients with obesity and type 2 diabetes – was not a prespecified outcome

The intervention groups were matched on 18 variables, including age, sex, serum insulin, alcohol, education, and smoking.

At baseline, the patients had a mean age of about 49 and 60% were women. They had a mean BMI of about 42 and a mean hemoglobin A1c of 7.8%.

On average, patients in the surgery group had lost 27.5 kg and 22.7 kg, and patients in the usual care group had lost 3.2 kg and 4.8 kg, at 2 years and 10 years, respectively.

During a median follow-up of 21 years, there were 74 incident cancers in the control group and 68 cancers in the bariatric surgery group.

The risk of cancer during follow-up was 37% lower in the surgery group than in the usual care group, after multivariable adjustment (adjusted hazard ratio, 0.63; 95% confidence interval, 0.44-0.89; P = .008).

A deeper dive showed that there were 86 incident cancers in women and 56 cancers in men. The risk of cancer was significantly lower in women who had bariatric surgery, compared with those who had usual care (aHR, 0.58; 95% CI 0.38-0.90, P = .016). However, the risk of cancer was not significantly lower in men who had bariatric surgery versus those who had usual care (aHR 0.79, 95% CI, 0.46-1.38; P = .413).

Diabetes remission at 10 years was associated with a 60% reduced cancer incidence (aHR, 0.40; 95% CI, 0.22-0.74, P = .003).

The study was funded by the Swedish state (under an agreement between the Swedish government and the county councils), the Swedish Research Council, the Novo Nordisk Foundation, the Swedish Heart-Lung Foundation, and the Swedish Diabetes Foundation. One author received consulting fees from Johnson & Johnson. The other authors had no relevant financial disclosures.

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

Patients with obesity and type 2 diabetes who underwent bariatric surgery and had 10-year durable diabetes remission had a 60% lower risk of incident cancer than patients who had usual obesity care.

And women who had bariatric surgery had a 42% lower risk of having cancer during a median 21-year follow-up, compared with women who had usual obesity care.

These findings from 701 patients in the Swedish Obese Subjects (SOS) study who had type 2 diabetes were recently published in Diabetes Care.

The results illustrate the “connection between glucose control and cancer prevention” and suggest that “among patients with type 2 diabetes, many cancer cases are preventable,” lead author Kajsa Sjöholm, PhD, associate professor of molecular medicine at Sahlgrenska Academy, University of Gothenburg (Sweden), said in a press release from the university.

“The global epidemic of both obesity and diabetes leads to an increased risk of cancer, as well as an increased risk of premature death,” added senior author Magdalena Taube, PhD, associate professor of molecular medicine in the same academy.

“It has been estimated that, over the next 10-15 years, obesity may cause more cancer cases than smoking in several countries,” she noted. Therefore, “strategies are needed to prevent this development, and our results can provide vital guidance for prevention of cancer in patients with obesity and type 2 diabetes.”
 

Durable diabetes remission seems key

Two-thirds of the patients in the bariatric surgery group had vertical banded gastroplasty (65%), and the rest had adjustable or nonadjustable gastric banding (18%) or gastric bypass (17%).

Each type of bariatric surgery was associated with higher diabetes remission rates, compared with usual care, in a previous study by these researchers, Dr. Taube said in an interview.

“In our present study,” she added, “we observed a nonsignificant trend, where patients with obesity and type 2 diabetes in the highest weight loss tertile (average weight loss, –44.8 kg) had somewhat lower risk of cancer compared to the lowest tertile [average weight loss, –14.9 kg].”

This might suggest, Dr. Taube continued, that with respect to cancer risk, surgery techniques resulting in greater weight loss (for example, Roux-en-Y gastric bypass and sleeve gastrectomy) should be recommended in patients with obesity and diabetes.

“However, it should also be noted that long-term diabetes remission seems imperative for cancer risk reduction,” she said, “and in a recent meta-analysis by McTigue et al., published in JAMA Surgery, it was shown that patients who had Roux-en-Y gastric bypass had greater weight loss, a slightly higher type 2 diabetes remission rate, less type 2 diabetes relapse, and better long-term glycemic control, compared with those who had sleeve gastrectomy.

“The observed cancer reduction in women with obesity and type 2 diabetes is in line with previous findings showing that cancer risk reduction following bariatric surgery in patients with obesity is more marked among women than men,” Dr. Taube noted. This may be because cancer rates are higher in women with diabetes than in men with diabetes, and common cancer types associated with obesity are female specific.

The main cancers in women were breast cancer, followed by endometrial and colorectal cancer. In men, the main cancers were colorectal, prostate, and urothelial/malignant skin cancer.
 

Study design and findings

It is well established that obesity is a risk factor for 13 types of cancer, and some of these cancers (liver, pancreatic, endometrial, colon and rectal, breast, and bladder) may be related to type 2 diabetes. And bariatric surgery has been shown to reduce cancer risk in patients with obesity.

However, it is not clear how bariatric surgery may affect cancer risk in patients with obesity and type 2 diabetes.

To study this, the researchers examined data from 393 patients who underwent bariatric surgery and 308 patients who received usual obesity treatment, who were part of the SOS study.

The SOS study enrolled men with a body mass index of at least 34 kg/m², and women with a BMI of at least 38 kg/m² who were aged 37-60 years between 1987 and 2001.

The current study outcome – cancer incidence in patients with obesity and type 2 diabetes – was not a prespecified outcome

The intervention groups were matched on 18 variables, including age, sex, serum insulin, alcohol, education, and smoking.

At baseline, the patients had a mean age of about 49 and 60% were women. They had a mean BMI of about 42 and a mean hemoglobin A1c of 7.8%.

On average, patients in the surgery group had lost 27.5 kg and 22.7 kg, and patients in the usual care group had lost 3.2 kg and 4.8 kg, at 2 years and 10 years, respectively.

During a median follow-up of 21 years, there were 74 incident cancers in the control group and 68 cancers in the bariatric surgery group.

The risk of cancer during follow-up was 37% lower in the surgery group than in the usual care group, after multivariable adjustment (adjusted hazard ratio, 0.63; 95% confidence interval, 0.44-0.89; P = .008).

A deeper dive showed that there were 86 incident cancers in women and 56 cancers in men. The risk of cancer was significantly lower in women who had bariatric surgery, compared with those who had usual care (aHR, 0.58; 95% CI 0.38-0.90, P = .016). However, the risk of cancer was not significantly lower in men who had bariatric surgery versus those who had usual care (aHR 0.79, 95% CI, 0.46-1.38; P = .413).

Diabetes remission at 10 years was associated with a 60% reduced cancer incidence (aHR, 0.40; 95% CI, 0.22-0.74, P = .003).

The study was funded by the Swedish state (under an agreement between the Swedish government and the county councils), the Swedish Research Council, the Novo Nordisk Foundation, the Swedish Heart-Lung Foundation, and the Swedish Diabetes Foundation. One author received consulting fees from Johnson & Johnson. The other authors had no relevant financial disclosures.

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

A feasibility study has found that coronary artery calcium scanning has the potential to better target patients who truly need statin therapy, reduce unnecessary statin prescriptions, and improve medication adherence than the current standard of using pooled cohort equations to determine atherosclerotic cardiovascular disease risk.

Researchers at the University of Utah, Salt Lake City, and Intermountain Healthcare, a network of 25 hospitals in Utah, reported that the rate of statin usage in patients evaluated with coronary artery calcium (CAC) was 25% lower than in those whose treatment decisions were based on pooled cohort equations (PCE). None of the patients were on statin therapy when they enrolled in the study, published online in JACC: Cardiovascular Imaging.

“This study demonstrates that doing a large outcomes trial is feasible and has a reasonable likelihood of perhaps being a positive trial for the use of CAC,” lead author Joseph B. Muhlestein, MD, said in an interview. Dr. Muhlestein is codirector of cardiovascular research at Intermountain Healthcare and a professor at the University of Utah.

The findings address the 2018 American College of Cardiology/American Heart Association guideline that states PCE is the “single most robust tool for estimating 10-year risk in U.S. adults 40-75 years of age”. However, the guideline also bases statin determination on shared decision-making between the patient and physician, and recommends CAC for patients for whom a decision about statin treatment is uncertain and those at intermediate risk to fine-tune the need for statins.

The results also have spurred a larger randomized trial known as CorCal, which aims to enroll 5,500 patients and compare CAC and PCE, Dr. Muhlestein said. So far 3,000 patients have been enrolled.
 

Results of CAC vs. PCE

The feasibility study enrolled 601 patients randomized to CAC (302) or PCE (299), 504 of whom were included in the final analysis. In the CAC group, 35.9% went on statin therapy, compared with 47.9% of the PCE patients (P = .005). Participating physicians accepted the study-dictated recommendation to start a statin in 88.1% of patients in the CAC arm versus 75.0% in the PCE arm.

Dr. Muhlestein noted that the feasibility study did not evaluate key outcomes, such as stroke or heart attack, but they will be a key endpoint of the larger randomized trial. “We found in this feasibility study that the recommendations that come from the CAC arm, compared with the PCE arm are significantly different enough that there may be a different outcome,” he said.

“There were cases in which the PCE did not recommend a statin but the patient had a lot of coronary calcium, so we recommended the statin in that patient,” he said. “At the same time, there were also even more patients in which the PCE said they ought to take a statin but they had zero coronary calcium, so we didn’t recommend that they get a statin.”

Compared with PCE-based recommendations, CAC patients were taken off statins in 36% of cases and put on statins in 5.6% of cases. “We think that PCE gives statins to a lot of patients who don’t really need them,” Dr. Muhlestein said.

The feasibility study also found patients were more adherent to therapy if they had CAC than PCE – 63.3% versus 45.6% at a year (P = .03). “Patients and physicians are more likely to be concerned enough to begin preventative therapy when they know that they are not just at risk for the disease, but they actually have the disease; that’s what the CAC score tells them,” Dr. Muhlestein said.

He noted that, while observational evidence has embraced CAC, insurers have been hesitant to cover it. “That is one of the major motivations for us to do this study,” Dr. Muhlestein said. “CAC is not very expensive; it costs less than $100, which is about what it costs to get a lipid panel, but insurance won’t pay for it because we haven’t proved that CAC actually changes outcomes, and that’s a legitimate complaint. But, of course, there’s never been a randomized trial that proves that a PCE changes outcomes either.”

The findings validate the 2018 ACC/AHA guideline “and opens a way to broader use for CAC for statin assessment,” said Neil J. Stone, MD, chair of the ACC/AHA 2013 guideline-writing committee and vice chair of the 2018 committee. “The study confirms a large body of information that a deterministic approach, i.e., calcium score, outperforms a probabilistic approach on an individual patient level.” Dr. Stone is the Bonow Professor of Medicine at Northwestern University and medical director of the Vascular Center of the Bluhm Cardiovascular Institute of Northwestern Memorial Hospital, both in Chicago.

“I applaud the investigators for using this as a hypothesis-generating study and planning a larger, more definitive trial,” he said. “This study would encourage regulators and insurance companies to support the use of calcium scores as recommended by the 2018 guideline.”

Intermountain Healthcare is the sole source of funding for the CorCal feasibility study. Dr. Muhlestein and Dr. Stone have no relevant relationships to disclose.
 

A feasibility study has found that coronary artery calcium scanning has the potential to better target patients who truly need statin therapy, reduce unnecessary statin prescriptions, and improve medication adherence than the current standard of using pooled cohort equations to determine atherosclerotic cardiovascular disease risk.

Researchers at the University of Utah, Salt Lake City, and Intermountain Healthcare, a network of 25 hospitals in Utah, reported that the rate of statin usage in patients evaluated with coronary artery calcium (CAC) was 25% lower than in those whose treatment decisions were based on pooled cohort equations (PCE). None of the patients were on statin therapy when they enrolled in the study, published online in JACC: Cardiovascular Imaging.

“This study demonstrates that doing a large outcomes trial is feasible and has a reasonable likelihood of perhaps being a positive trial for the use of CAC,” lead author Joseph B. Muhlestein, MD, said in an interview. Dr. Muhlestein is codirector of cardiovascular research at Intermountain Healthcare and a professor at the University of Utah.

The findings address the 2018 American College of Cardiology/American Heart Association guideline that states PCE is the “single most robust tool for estimating 10-year risk in U.S. adults 40-75 years of age”. However, the guideline also bases statin determination on shared decision-making between the patient and physician, and recommends CAC for patients for whom a decision about statin treatment is uncertain and those at intermediate risk to fine-tune the need for statins.

The results also have spurred a larger randomized trial known as CorCal, which aims to enroll 5,500 patients and compare CAC and PCE, Dr. Muhlestein said. So far 3,000 patients have been enrolled.
 

Results of CAC vs. PCE

The feasibility study enrolled 601 patients randomized to CAC (302) or PCE (299), 504 of whom were included in the final analysis. In the CAC group, 35.9% went on statin therapy, compared with 47.9% of the PCE patients (P = .005). Participating physicians accepted the study-dictated recommendation to start a statin in 88.1% of patients in the CAC arm versus 75.0% in the PCE arm.

Dr. Muhlestein noted that the feasibility study did not evaluate key outcomes, such as stroke or heart attack, but they will be a key endpoint of the larger randomized trial. “We found in this feasibility study that the recommendations that come from the CAC arm, compared with the PCE arm are significantly different enough that there may be a different outcome,” he said.

“There were cases in which the PCE did not recommend a statin but the patient had a lot of coronary calcium, so we recommended the statin in that patient,” he said. “At the same time, there were also even more patients in which the PCE said they ought to take a statin but they had zero coronary calcium, so we didn’t recommend that they get a statin.”

Compared with PCE-based recommendations, CAC patients were taken off statins in 36% of cases and put on statins in 5.6% of cases. “We think that PCE gives statins to a lot of patients who don’t really need them,” Dr. Muhlestein said.

The feasibility study also found patients were more adherent to therapy if they had CAC than PCE – 63.3% versus 45.6% at a year (P = .03). “Patients and physicians are more likely to be concerned enough to begin preventative therapy when they know that they are not just at risk for the disease, but they actually have the disease; that’s what the CAC score tells them,” Dr. Muhlestein said.

He noted that, while observational evidence has embraced CAC, insurers have been hesitant to cover it. “That is one of the major motivations for us to do this study,” Dr. Muhlestein said. “CAC is not very expensive; it costs less than $100, which is about what it costs to get a lipid panel, but insurance won’t pay for it because we haven’t proved that CAC actually changes outcomes, and that’s a legitimate complaint. But, of course, there’s never been a randomized trial that proves that a PCE changes outcomes either.”

The findings validate the 2018 ACC/AHA guideline “and opens a way to broader use for CAC for statin assessment,” said Neil J. Stone, MD, chair of the ACC/AHA 2013 guideline-writing committee and vice chair of the 2018 committee. “The study confirms a large body of information that a deterministic approach, i.e., calcium score, outperforms a probabilistic approach on an individual patient level.” Dr. Stone is the Bonow Professor of Medicine at Northwestern University and medical director of the Vascular Center of the Bluhm Cardiovascular Institute of Northwestern Memorial Hospital, both in Chicago.

“I applaud the investigators for using this as a hypothesis-generating study and planning a larger, more definitive trial,” he said. “This study would encourage regulators and insurance companies to support the use of calcium scores as recommended by the 2018 guideline.”

Intermountain Healthcare is the sole source of funding for the CorCal feasibility study. Dr. Muhlestein and Dr. Stone have no relevant relationships to disclose.
 

A feasibility study has found that coronary artery calcium scanning has the potential to better target patients who truly need statin therapy, reduce unnecessary statin prescriptions, and improve medication adherence than the current standard of using pooled cohort equations to determine atherosclerotic cardiovascular disease risk.

Researchers at the University of Utah, Salt Lake City, and Intermountain Healthcare, a network of 25 hospitals in Utah, reported that the rate of statin usage in patients evaluated with coronary artery calcium (CAC) was 25% lower than in those whose treatment decisions were based on pooled cohort equations (PCE). None of the patients were on statin therapy when they enrolled in the study, published online in JACC: Cardiovascular Imaging.

“This study demonstrates that doing a large outcomes trial is feasible and has a reasonable likelihood of perhaps being a positive trial for the use of CAC,” lead author Joseph B. Muhlestein, MD, said in an interview. Dr. Muhlestein is codirector of cardiovascular research at Intermountain Healthcare and a professor at the University of Utah.

The findings address the 2018 American College of Cardiology/American Heart Association guideline that states PCE is the “single most robust tool for estimating 10-year risk in U.S. adults 40-75 years of age”. However, the guideline also bases statin determination on shared decision-making between the patient and physician, and recommends CAC for patients for whom a decision about statin treatment is uncertain and those at intermediate risk to fine-tune the need for statins.

The results also have spurred a larger randomized trial known as CorCal, which aims to enroll 5,500 patients and compare CAC and PCE, Dr. Muhlestein said. So far 3,000 patients have been enrolled.
 

Results of CAC vs. PCE

The feasibility study enrolled 601 patients randomized to CAC (302) or PCE (299), 504 of whom were included in the final analysis. In the CAC group, 35.9% went on statin therapy, compared with 47.9% of the PCE patients (P = .005). Participating physicians accepted the study-dictated recommendation to start a statin in 88.1% of patients in the CAC arm versus 75.0% in the PCE arm.

Dr. Muhlestein noted that the feasibility study did not evaluate key outcomes, such as stroke or heart attack, but they will be a key endpoint of the larger randomized trial. “We found in this feasibility study that the recommendations that come from the CAC arm, compared with the PCE arm are significantly different enough that there may be a different outcome,” he said.

“There were cases in which the PCE did not recommend a statin but the patient had a lot of coronary calcium, so we recommended the statin in that patient,” he said. “At the same time, there were also even more patients in which the PCE said they ought to take a statin but they had zero coronary calcium, so we didn’t recommend that they get a statin.”

Compared with PCE-based recommendations, CAC patients were taken off statins in 36% of cases and put on statins in 5.6% of cases. “We think that PCE gives statins to a lot of patients who don’t really need them,” Dr. Muhlestein said.

The feasibility study also found patients were more adherent to therapy if they had CAC than PCE – 63.3% versus 45.6% at a year (P = .03). “Patients and physicians are more likely to be concerned enough to begin preventative therapy when they know that they are not just at risk for the disease, but they actually have the disease; that’s what the CAC score tells them,” Dr. Muhlestein said.

He noted that, while observational evidence has embraced CAC, insurers have been hesitant to cover it. “That is one of the major motivations for us to do this study,” Dr. Muhlestein said. “CAC is not very expensive; it costs less than $100, which is about what it costs to get a lipid panel, but insurance won’t pay for it because we haven’t proved that CAC actually changes outcomes, and that’s a legitimate complaint. But, of course, there’s never been a randomized trial that proves that a PCE changes outcomes either.”

The findings validate the 2018 ACC/AHA guideline “and opens a way to broader use for CAC for statin assessment,” said Neil J. Stone, MD, chair of the ACC/AHA 2013 guideline-writing committee and vice chair of the 2018 committee. “The study confirms a large body of information that a deterministic approach, i.e., calcium score, outperforms a probabilistic approach on an individual patient level.” Dr. Stone is the Bonow Professor of Medicine at Northwestern University and medical director of the Vascular Center of the Bluhm Cardiovascular Institute of Northwestern Memorial Hospital, both in Chicago.

“I applaud the investigators for using this as a hypothesis-generating study and planning a larger, more definitive trial,” he said. “This study would encourage regulators and insurance companies to support the use of calcium scores as recommended by the 2018 guideline.”

Intermountain Healthcare is the sole source of funding for the CorCal feasibility study. Dr. Muhlestein and Dr. Stone have no relevant relationships to disclose.
 

With emergency departments straining to keep up with the latest COVID surge, the American College of Emergency Physicians (ACEP) issued a plea this week for a “collaborative effort” to solve the nursing shortage.

The organization said that it is “very concerned that nursing shortages in emergency departments can complicate patient access to care and add to incredible levels of stress already on physician-led care teams,” according to a press release.

ACEP President Gillian Schmitz, MD, told this news organization, “The situation is dire in many emergency departments around the country. Emergency physicians are seeing more patients with fewer resources and less staff.

“Emergency physicians in the hardest hit communities are scrambling to locate available experts, exhausting federal support, and doing all they can to adapt to the demands of the current surge – everyone is being stretched to their limit.”

The Emergency Nurses Association (ENA) agrees with ACEP’s call for a team approach to stemming the shortage.

ENA President Ron Kraus, MSN, RN, said in an interview, “The pandemic has only amplified several long-standing issues impacting emergency nurses, such as workplace violence, a healthy work environment, and concerns about staffing shortages and the pipeline of new nurses. That said, we can’t lose focus on what’s most important in these challenging moments – ensuring every patient receives the high quality of care.”

The responsibility falls on the “collaborative effort” of the emergency department with emergency nurses playing a pivotal role, he said. But the stress, fatigue, and burnout driving nurses away from their jobs “should not be viewed as added inconvenience to anyone during a pandemic, but as a long-term threat to our health care system.”

ACEP’s press release stated that with fewer nurses available in the emergency department, team members are clocking extra hours, caring for more patients, and stretched to take on additional clinical and nonclinical duties.

“I am hearing from colleagues from Washington state to Michigan to New York that this is the worst they have seen since the beginning of the pandemic,” Dr. Schmitz said. “Everyone available is filling gaps as best they can, but the current path for many frontline workers is not sustainable,” she said in the release.

Meanwhile, ACEP is also tackling violence in the emergency department and has initiatives to protect the mental health of those working on the front lines, the release states.

“Emergency physicians will continue to do everything necessary to treat patients,” Dr. Schmitz said in the release, “but it will take a collaborative effort with legislators, policymakers and health system leaders to strengthen care teams, improve access and address capacity concerns with solutions that can save lives right now and in the months ahead.”

Dr. Schmitz stated that in Washington state, ICUs are at 97% to 100% capacity and less than 30 pediatric inpatient beds are available in the western part of the state.

“In Michigan and New York, several emergency departments are overflowing, and doctors are being called in to triage people in the waiting room because all of the emergency department beds are holding admissions. There are scenarios where entire hospitals are backing up into the emergency department and waiting room and we are physically running out of space and nursing staff.”

ACEP represents its 40,000 emergency physician members.

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

With emergency departments straining to keep up with the latest COVID surge, the American College of Emergency Physicians (ACEP) issued a plea this week for a “collaborative effort” to solve the nursing shortage.

The organization said that it is “very concerned that nursing shortages in emergency departments can complicate patient access to care and add to incredible levels of stress already on physician-led care teams,” according to a press release.

ACEP President Gillian Schmitz, MD, told this news organization, “The situation is dire in many emergency departments around the country. Emergency physicians are seeing more patients with fewer resources and less staff.

“Emergency physicians in the hardest hit communities are scrambling to locate available experts, exhausting federal support, and doing all they can to adapt to the demands of the current surge – everyone is being stretched to their limit.”

The Emergency Nurses Association (ENA) agrees with ACEP’s call for a team approach to stemming the shortage.

ENA President Ron Kraus, MSN, RN, said in an interview, “The pandemic has only amplified several long-standing issues impacting emergency nurses, such as workplace violence, a healthy work environment, and concerns about staffing shortages and the pipeline of new nurses. That said, we can’t lose focus on what’s most important in these challenging moments – ensuring every patient receives the high quality of care.”

The responsibility falls on the “collaborative effort” of the emergency department with emergency nurses playing a pivotal role, he said. But the stress, fatigue, and burnout driving nurses away from their jobs “should not be viewed as added inconvenience to anyone during a pandemic, but as a long-term threat to our health care system.”

ACEP’s press release stated that with fewer nurses available in the emergency department, team members are clocking extra hours, caring for more patients, and stretched to take on additional clinical and nonclinical duties.

“I am hearing from colleagues from Washington state to Michigan to New York that this is the worst they have seen since the beginning of the pandemic,” Dr. Schmitz said. “Everyone available is filling gaps as best they can, but the current path for many frontline workers is not sustainable,” she said in the release.

Meanwhile, ACEP is also tackling violence in the emergency department and has initiatives to protect the mental health of those working on the front lines, the release states.

“Emergency physicians will continue to do everything necessary to treat patients,” Dr. Schmitz said in the release, “but it will take a collaborative effort with legislators, policymakers and health system leaders to strengthen care teams, improve access and address capacity concerns with solutions that can save lives right now and in the months ahead.”

Dr. Schmitz stated that in Washington state, ICUs are at 97% to 100% capacity and less than 30 pediatric inpatient beds are available in the western part of the state.

“In Michigan and New York, several emergency departments are overflowing, and doctors are being called in to triage people in the waiting room because all of the emergency department beds are holding admissions. There are scenarios where entire hospitals are backing up into the emergency department and waiting room and we are physically running out of space and nursing staff.”

ACEP represents its 40,000 emergency physician members.

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

With emergency departments straining to keep up with the latest COVID surge, the American College of Emergency Physicians (ACEP) issued a plea this week for a “collaborative effort” to solve the nursing shortage.

The organization said that it is “very concerned that nursing shortages in emergency departments can complicate patient access to care and add to incredible levels of stress already on physician-led care teams,” according to a press release.

ACEP President Gillian Schmitz, MD, told this news organization, “The situation is dire in many emergency departments around the country. Emergency physicians are seeing more patients with fewer resources and less staff.

“Emergency physicians in the hardest hit communities are scrambling to locate available experts, exhausting federal support, and doing all they can to adapt to the demands of the current surge – everyone is being stretched to their limit.”

The Emergency Nurses Association (ENA) agrees with ACEP’s call for a team approach to stemming the shortage.

ENA President Ron Kraus, MSN, RN, said in an interview, “The pandemic has only amplified several long-standing issues impacting emergency nurses, such as workplace violence, a healthy work environment, and concerns about staffing shortages and the pipeline of new nurses. That said, we can’t lose focus on what’s most important in these challenging moments – ensuring every patient receives the high quality of care.”

The responsibility falls on the “collaborative effort” of the emergency department with emergency nurses playing a pivotal role, he said. But the stress, fatigue, and burnout driving nurses away from their jobs “should not be viewed as added inconvenience to anyone during a pandemic, but as a long-term threat to our health care system.”

ACEP’s press release stated that with fewer nurses available in the emergency department, team members are clocking extra hours, caring for more patients, and stretched to take on additional clinical and nonclinical duties.

“I am hearing from colleagues from Washington state to Michigan to New York that this is the worst they have seen since the beginning of the pandemic,” Dr. Schmitz said. “Everyone available is filling gaps as best they can, but the current path for many frontline workers is not sustainable,” she said in the release.

Meanwhile, ACEP is also tackling violence in the emergency department and has initiatives to protect the mental health of those working on the front lines, the release states.

“Emergency physicians will continue to do everything necessary to treat patients,” Dr. Schmitz said in the release, “but it will take a collaborative effort with legislators, policymakers and health system leaders to strengthen care teams, improve access and address capacity concerns with solutions that can save lives right now and in the months ahead.”

Dr. Schmitz stated that in Washington state, ICUs are at 97% to 100% capacity and less than 30 pediatric inpatient beds are available in the western part of the state.

“In Michigan and New York, several emergency departments are overflowing, and doctors are being called in to triage people in the waiting room because all of the emergency department beds are holding admissions. There are scenarios where entire hospitals are backing up into the emergency department and waiting room and we are physically running out of space and nursing staff.”

ACEP represents its 40,000 emergency physician members.

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