Feature

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.

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.

Axilla swelling, one of the side effects of the initial COVID-19 vaccine series in women, has also materialized with the boosters.

This inflammation is caused by the enlargement of lymph nodes and can show up as an abnormal finding on mammograms and other types of chest scans, causing concern and even the need for additional imaging and follow up, wrote Constance D. Lehman, MD, PhD, and colleagues in an article published in Journal of the American College of Radiology.

Lymph node swelling is a normal immune system reaction to vaccination, and “COVID-19 vaccinations in the arm are a well-documented cause of inflammatory unilateral axillary adenopathy,” noted Dr. Lehman, in an interview. The side effect will occur on the side of the body where the patient received a vaccine, and it is not always noticeable to the woman experiencing it, she said.

“We’re finding that the patients’ bodies are responding to the booster in many ways that are similar to the initial COVID vaccines, with lymph node swelling, muscle aches and pains, headaches, and so on,” said Dr. Lehman, who is chief of breast imaging at the Massachusetts General Hospital, Boston. There have been no real differences in reactions between the Moderna and Pfizer vaccines, she added.

Because axillary lymph node swelling can obscure mammogram results, staff of at least a few imaging centers, including Penn State Breast Center in Hershey, Pa., and Providence Women’s Imaging Center in Torrance, Calif., told this news organization that they are asking women to delay mammogram imaging either 6 weeks or 4-6 weeks after getting a COVID-19 booster.
 

Experts’ suggestions on mammograms, boosters timing

Other experts, including Jessica Leung, MD, acknowledged that vaccine-related reactive adenopathy is seen after the booster dose and provided recommendations for the timing of getting mammograms and the booster with this in mind.

“I would recommend getting the screening mammogram first, which can be followed immediately by vaccination, even on the same day,” said Jessica Leung, MD, a professor of diagnostic radiology at the University of Texas MD Anderson Cancer Center in Houston, Tex.

“If this is not possible from the scheduling perspective, then the patient should consult her health care provider regarding whether it is okay to wait a bit after receiving the vaccine before getting her screening mammogram.”

The answer to that question will likely depend on the time interval since the prior mammogram and the patient’s personal risk factors for developing breast cancer. Dr. Leung noted. “This is all predicated on the assumption that the patient is asymptomatic. If she has any symptoms, for example a palpable breast lump, then she should seek medical attention regardless of timing of vaccination.”

The same holds true for boosters, she said.

She emphasized that careful consideration should be given before delaying the mammogram. “The medical community has a great deal more knowledge at this time than in the early days of COVID-19 vaccination, so we are often able to identify reactive adenopathy related to vaccination. If patients were to delay the mammogram, any reactive adenopathy may persist, on average, for 4-6 weeks.”

Debra Patt, MD, PhD, MBA, executive vice president at Texas Oncology, professor at the University of Texas at Austin, provided a specific example of when a patient should not delay the diagnostic imaging, which is “in the event that there is an abnormal mass in the breast that requires evaluation.”

Providers are now prepared to address these issues, she added.
 

Dr. Lehman’s nuanced recommendations

“It’s easy to get both a mammogram and booster, and just a matter of timing them – so that the reaction doesn’t interfere with the mammography results,” Dr. Lehman said.

But she emphasized that women should not be choosing between their mammograms or a booster. “We are now saying the same thing that we did with the initial vaccine,” said Dr. Lehman. “We don’t want patients delaying their mammograms, and we don’t want them delaying their boosters – both are critical to staying healthy.”

In her center, a model was developed to navigate vaccine-associated adenopathy. While this approach was developed for the primary vaccine series, the same applies for the booster, which is essentially a third dose of the same vaccine, explained Dr. Lehman.

When patients present for mammography, ultrasound, or MRI, the technologist will document their COVID-19 vaccination status (first or second dose or booster), the date it was given, and the location. Adding vaccination documentation to intake forms helps to support appropriate management of patients who undergo imaging after COVID-19 vaccination. Six weeks is used as the cutoff point for defining “recent” vaccination.

For patients who are getting a screening mammography or MRI, and who have no symptoms beyond unilateral axillary adenopathy on the same side of the body where they received the COVID-19 vaccination (given in the arm) within a 6-week period, the following is included in the screening mammography or screening MRI report: “In the specific setting of a patient with documented recent (within the past 6 weeks) COVID-19 vaccination in the ipsilateral arm, axillary adenopathy is a benign imaging finding. No further imaging is indicated at this time. If there is clinical concern that persists more than 6 weeks after the patient received the final vaccine dose, axillary ultrasound is recommended.”

The experts interviewed reported no conflicts of interest.

Axilla swelling, one of the side effects of the initial COVID-19 vaccine series in women, has also materialized with the boosters.

This inflammation is caused by the enlargement of lymph nodes and can show up as an abnormal finding on mammograms and other types of chest scans, causing concern and even the need for additional imaging and follow up, wrote Constance D. Lehman, MD, PhD, and colleagues in an article published in Journal of the American College of Radiology.

Lymph node swelling is a normal immune system reaction to vaccination, and “COVID-19 vaccinations in the arm are a well-documented cause of inflammatory unilateral axillary adenopathy,” noted Dr. Lehman, in an interview. The side effect will occur on the side of the body where the patient received a vaccine, and it is not always noticeable to the woman experiencing it, she said.

“We’re finding that the patients’ bodies are responding to the booster in many ways that are similar to the initial COVID vaccines, with lymph node swelling, muscle aches and pains, headaches, and so on,” said Dr. Lehman, who is chief of breast imaging at the Massachusetts General Hospital, Boston. There have been no real differences in reactions between the Moderna and Pfizer vaccines, she added.

Because axillary lymph node swelling can obscure mammogram results, staff of at least a few imaging centers, including Penn State Breast Center in Hershey, Pa., and Providence Women’s Imaging Center in Torrance, Calif., told this news organization that they are asking women to delay mammogram imaging either 6 weeks or 4-6 weeks after getting a COVID-19 booster.
 

Experts’ suggestions on mammograms, boosters timing

Other experts, including Jessica Leung, MD, acknowledged that vaccine-related reactive adenopathy is seen after the booster dose and provided recommendations for the timing of getting mammograms and the booster with this in mind.

“I would recommend getting the screening mammogram first, which can be followed immediately by vaccination, even on the same day,” said Jessica Leung, MD, a professor of diagnostic radiology at the University of Texas MD Anderson Cancer Center in Houston, Tex.

“If this is not possible from the scheduling perspective, then the patient should consult her health care provider regarding whether it is okay to wait a bit after receiving the vaccine before getting her screening mammogram.”

The answer to that question will likely depend on the time interval since the prior mammogram and the patient’s personal risk factors for developing breast cancer. Dr. Leung noted. “This is all predicated on the assumption that the patient is asymptomatic. If she has any symptoms, for example a palpable breast lump, then she should seek medical attention regardless of timing of vaccination.”

The same holds true for boosters, she said.

She emphasized that careful consideration should be given before delaying the mammogram. “The medical community has a great deal more knowledge at this time than in the early days of COVID-19 vaccination, so we are often able to identify reactive adenopathy related to vaccination. If patients were to delay the mammogram, any reactive adenopathy may persist, on average, for 4-6 weeks.”

Debra Patt, MD, PhD, MBA, executive vice president at Texas Oncology, professor at the University of Texas at Austin, provided a specific example of when a patient should not delay the diagnostic imaging, which is “in the event that there is an abnormal mass in the breast that requires evaluation.”

Providers are now prepared to address these issues, she added.
 

Dr. Lehman’s nuanced recommendations

“It’s easy to get both a mammogram and booster, and just a matter of timing them – so that the reaction doesn’t interfere with the mammography results,” Dr. Lehman said.

But she emphasized that women should not be choosing between their mammograms or a booster. “We are now saying the same thing that we did with the initial vaccine,” said Dr. Lehman. “We don’t want patients delaying their mammograms, and we don’t want them delaying their boosters – both are critical to staying healthy.”

In her center, a model was developed to navigate vaccine-associated adenopathy. While this approach was developed for the primary vaccine series, the same applies for the booster, which is essentially a third dose of the same vaccine, explained Dr. Lehman.

When patients present for mammography, ultrasound, or MRI, the technologist will document their COVID-19 vaccination status (first or second dose or booster), the date it was given, and the location. Adding vaccination documentation to intake forms helps to support appropriate management of patients who undergo imaging after COVID-19 vaccination. Six weeks is used as the cutoff point for defining “recent” vaccination.

For patients who are getting a screening mammography or MRI, and who have no symptoms beyond unilateral axillary adenopathy on the same side of the body where they received the COVID-19 vaccination (given in the arm) within a 6-week period, the following is included in the screening mammography or screening MRI report: “In the specific setting of a patient with documented recent (within the past 6 weeks) COVID-19 vaccination in the ipsilateral arm, axillary adenopathy is a benign imaging finding. No further imaging is indicated at this time. If there is clinical concern that persists more than 6 weeks after the patient received the final vaccine dose, axillary ultrasound is recommended.”

The experts interviewed reported no conflicts of interest.

Axilla swelling, one of the side effects of the initial COVID-19 vaccine series in women, has also materialized with the boosters.

This inflammation is caused by the enlargement of lymph nodes and can show up as an abnormal finding on mammograms and other types of chest scans, causing concern and even the need for additional imaging and follow up, wrote Constance D. Lehman, MD, PhD, and colleagues in an article published in Journal of the American College of Radiology.

Lymph node swelling is a normal immune system reaction to vaccination, and “COVID-19 vaccinations in the arm are a well-documented cause of inflammatory unilateral axillary adenopathy,” noted Dr. Lehman, in an interview. The side effect will occur on the side of the body where the patient received a vaccine, and it is not always noticeable to the woman experiencing it, she said.

“We’re finding that the patients’ bodies are responding to the booster in many ways that are similar to the initial COVID vaccines, with lymph node swelling, muscle aches and pains, headaches, and so on,” said Dr. Lehman, who is chief of breast imaging at the Massachusetts General Hospital, Boston. There have been no real differences in reactions between the Moderna and Pfizer vaccines, she added.

Because axillary lymph node swelling can obscure mammogram results, staff of at least a few imaging centers, including Penn State Breast Center in Hershey, Pa., and Providence Women’s Imaging Center in Torrance, Calif., told this news organization that they are asking women to delay mammogram imaging either 6 weeks or 4-6 weeks after getting a COVID-19 booster.
 

Experts’ suggestions on mammograms, boosters timing

Other experts, including Jessica Leung, MD, acknowledged that vaccine-related reactive adenopathy is seen after the booster dose and provided recommendations for the timing of getting mammograms and the booster with this in mind.

“I would recommend getting the screening mammogram first, which can be followed immediately by vaccination, even on the same day,” said Jessica Leung, MD, a professor of diagnostic radiology at the University of Texas MD Anderson Cancer Center in Houston, Tex.

“If this is not possible from the scheduling perspective, then the patient should consult her health care provider regarding whether it is okay to wait a bit after receiving the vaccine before getting her screening mammogram.”

The answer to that question will likely depend on the time interval since the prior mammogram and the patient’s personal risk factors for developing breast cancer. Dr. Leung noted. “This is all predicated on the assumption that the patient is asymptomatic. If she has any symptoms, for example a palpable breast lump, then she should seek medical attention regardless of timing of vaccination.”

The same holds true for boosters, she said.

She emphasized that careful consideration should be given before delaying the mammogram. “The medical community has a great deal more knowledge at this time than in the early days of COVID-19 vaccination, so we are often able to identify reactive adenopathy related to vaccination. If patients were to delay the mammogram, any reactive adenopathy may persist, on average, for 4-6 weeks.”

Debra Patt, MD, PhD, MBA, executive vice president at Texas Oncology, professor at the University of Texas at Austin, provided a specific example of when a patient should not delay the diagnostic imaging, which is “in the event that there is an abnormal mass in the breast that requires evaluation.”

Providers are now prepared to address these issues, she added.
 

Dr. Lehman’s nuanced recommendations

“It’s easy to get both a mammogram and booster, and just a matter of timing them – so that the reaction doesn’t interfere with the mammography results,” Dr. Lehman said.

But she emphasized that women should not be choosing between their mammograms or a booster. “We are now saying the same thing that we did with the initial vaccine,” said Dr. Lehman. “We don’t want patients delaying their mammograms, and we don’t want them delaying their boosters – both are critical to staying healthy.”

In her center, a model was developed to navigate vaccine-associated adenopathy. While this approach was developed for the primary vaccine series, the same applies for the booster, which is essentially a third dose of the same vaccine, explained Dr. Lehman.

When patients present for mammography, ultrasound, or MRI, the technologist will document their COVID-19 vaccination status (first or second dose or booster), the date it was given, and the location. Adding vaccination documentation to intake forms helps to support appropriate management of patients who undergo imaging after COVID-19 vaccination. Six weeks is used as the cutoff point for defining “recent” vaccination.

For patients who are getting a screening mammography or MRI, and who have no symptoms beyond unilateral axillary adenopathy on the same side of the body where they received the COVID-19 vaccination (given in the arm) within a 6-week period, the following is included in the screening mammography or screening MRI report: “In the specific setting of a patient with documented recent (within the past 6 weeks) COVID-19 vaccination in the ipsilateral arm, axillary adenopathy is a benign imaging finding. No further imaging is indicated at this time. If there is clinical concern that persists more than 6 weeks after the patient received the final vaccine dose, axillary ultrasound is recommended.”

The experts interviewed reported no conflicts of interest.

The Food and Drug Administration has announced that women no longer will have to pick up the abortion pill mifepristone (Mifeprex) in person at certain certified sites and can get a prescription via an online consultation and delivery through the mail.

In April 2021, the FDA lifted the in-person dispensing requirement for mifepristone for the duration of the COVID-19 pandemic and in December the agency made that decision permanent.

As this news organization reported on April 12, 2021, acting commissioner of food and drugs, Janet Woodcock, MD, stated that the FDA would “permit the dispensing of mifepristone through the mail when done by or under the supervision of a certified prescriber; or through a mail-order pharmacy under the supervision of a certified prescriber.”

That decision came after suspension of the in-person dispensing requirement in response to COVID-19 safety concerns for patients as well as providers associated with in-person clinic visits.
 

Decision comes amid Supreme Court debate

The FDA decision comes as the Supreme Court nears a decision on whether to overturn its 1973 ruling on Roe v. Wade.

Additionally, the Supreme Court on returned a lawsuit over Texas’ ban on abortions after 6 weeks to a federal appeals court that has twice allowed the law to stay in effect, rather than to a district judge who wanted it blocked.

Alexis McGill Johnson, president and CEO, of the Planned Parenthood Federation of America, said in a statement, “Abortion is time sensitive, essential health care, and this decision will remove a sometimes insurmountable barrier for patients seeking an abortion. With abortion rights at risk like never before, the FDA’s decision is a long overdue step toward expanding people’s access to safe medication abortion.”

Georgeanne Usova, senior legislative counsel at the American Civil Liberties Union told CNBC News: “The FDA’s decision will come as a tremendous relief for countless abortion and miscarriage patients.”

Catherine D. Cansino, MD, MPH, associate clinical professor in the department of obstetrics and gynecology at the University of California, Davis, and member of the editorial advisory board for ObGyn News said in an interview: “I think that this change is a long time coming and speaks to the fact that science matters and medicine prevails over politics. We need to protect health rights first!”

Others expressed doubt or outrage.

Fidelma Rigby, MD, a professor in the department of obstetrics and gynecology, division of maternal fetal medicine, Virginia Commonwealth University Medical Center, Richmond, said in an interview: “My concern is that what if there is an ectopic pregnancy? I’m not as enthusiastic as some of my partners would be about this announcement.”

“The FDA’s decision today places women at risk,” said Carol Tobias, president of the National Right to Life Committee. “These changes do not make this abortion process safer for women. What these changes do is make the process easier for the abortion industry.”

The antiabortion groups Charlotte Lozier Institute and the Susan B. Anthony List were among other organizations issuing statements against Dec. 16’s FDA ruling.

The FDA stated that mifepristone prescribers will still need to earn certification and training. Additionally, the agency said dispensing pharmacies will have to be certified.

The FDA said in updated guidance on its website that after conducting a review of the Risk Evaluation and Mitigation Strategy for mifepristone, it “determined that the data support modification of the REMS to reduce burden on patient access and the health care delivery system and to ensure the benefits of the product outweigh the risks.”

The modifications include:

• “Removing the requirement that mifepristone be dispensed only in certain health care settings, specifically clinics, medical offices, and hospitals (referred to as the ‘in-person dispensing requirement’).”
• Adding a requirement that pharmacies must be certified to dispense the drug.

The FDA said removing the in-person dispensing rule will allow delivery of mifepristone by mail via certified prescribers or pharmacies, in addition to in-person dispensing in clinics, medical offices, and hospitals.

In 2018, an expert National Academies of Science, Engineering, and Medicine panel concluded that requiring that medication abortion be provided at only certain facilities, solely by a physician or in the physical presence of certain providers, did not improve safety or quality of care.

Mifepristone is used, together with misoprostol, to end an early pregnancy. The FDA first approved Mifeprex in 2000 for use through 10 weeks’ gestation. According to the FDA, mifepristone is approved in more than 60 other countries.
 

Many states bar mailing of abortion pills

However, according to the Guttmacher Institute, 19 U.S. states have laws that bar telehealth consultations or mailing of abortion pills.

Reuters reported that women in those states would not be able to make use of the rule change get the drug delivered to their home but could potentially travel to other states to obtain medication abortion.

“States such as California and New York that have sought to strengthen access to abortion may make the drug available to women from other states,” Reuters reported.

Jessica Arons, senior advocacy and policy counsel for reproductive freedom at the ACLU, told CBS News, “Medication abortion is one more lens through which we see that we are witnessing a tale of two countries. Half the states are protecting access to abortion and half are trying every single way they can to eliminate access to abortion care.”
 

Positive results when Canada lifted restrictions

As this news organization has reported, a study found positive results when Canada lifted restrictions on access to the abortion pills and a good safety profile for mifepristone.

A study in the New England Journal of Medicine found abortion rates remained stable and adverse events were rare after mifepristone prescribing restrictions were lifted in Canada.

Senior author Wendy V. Norman, MD, professor in the department of family practice at the University of British Columbia, Vancouver, said in a statement, “Our study is a signal to other countries that restrictions are not necessary to ensure patient safety.”

Another recent study in JAMA Network Open (2021 Aug 24. doi: 10.1001/jamanetworkopen.2021.22320) found that abortion via telehealth prescriptions may be just as safe and effective as in-person care.

The study investigators said that, “of the 110 women from whom researchers collected remote abortion outcome data, 95% had a complete abortion without additional medical interventions, such as aspiration or surgery, and none experienced adverse events. Researchers said this efficacy rate is similar to in-person visits.”

The Food and Drug Administration has announced that women no longer will have to pick up the abortion pill mifepristone (Mifeprex) in person at certain certified sites and can get a prescription via an online consultation and delivery through the mail.

In April 2021, the FDA lifted the in-person dispensing requirement for mifepristone for the duration of the COVID-19 pandemic and in December the agency made that decision permanent.

As this news organization reported on April 12, 2021, acting commissioner of food and drugs, Janet Woodcock, MD, stated that the FDA would “permit the dispensing of mifepristone through the mail when done by or under the supervision of a certified prescriber; or through a mail-order pharmacy under the supervision of a certified prescriber.”

That decision came after suspension of the in-person dispensing requirement in response to COVID-19 safety concerns for patients as well as providers associated with in-person clinic visits.
 

Decision comes amid Supreme Court debate

The FDA decision comes as the Supreme Court nears a decision on whether to overturn its 1973 ruling on Roe v. Wade.

Additionally, the Supreme Court on returned a lawsuit over Texas’ ban on abortions after 6 weeks to a federal appeals court that has twice allowed the law to stay in effect, rather than to a district judge who wanted it blocked.

Alexis McGill Johnson, president and CEO, of the Planned Parenthood Federation of America, said in a statement, “Abortion is time sensitive, essential health care, and this decision will remove a sometimes insurmountable barrier for patients seeking an abortion. With abortion rights at risk like never before, the FDA’s decision is a long overdue step toward expanding people’s access to safe medication abortion.”

Georgeanne Usova, senior legislative counsel at the American Civil Liberties Union told CNBC News: “The FDA’s decision will come as a tremendous relief for countless abortion and miscarriage patients.”

Catherine D. Cansino, MD, MPH, associate clinical professor in the department of obstetrics and gynecology at the University of California, Davis, and member of the editorial advisory board for ObGyn News said in an interview: “I think that this change is a long time coming and speaks to the fact that science matters and medicine prevails over politics. We need to protect health rights first!”

Others expressed doubt or outrage.

Fidelma Rigby, MD, a professor in the department of obstetrics and gynecology, division of maternal fetal medicine, Virginia Commonwealth University Medical Center, Richmond, said in an interview: “My concern is that what if there is an ectopic pregnancy? I’m not as enthusiastic as some of my partners would be about this announcement.”

“The FDA’s decision today places women at risk,” said Carol Tobias, president of the National Right to Life Committee. “These changes do not make this abortion process safer for women. What these changes do is make the process easier for the abortion industry.”

The antiabortion groups Charlotte Lozier Institute and the Susan B. Anthony List were among other organizations issuing statements against Dec. 16’s FDA ruling.

The FDA stated that mifepristone prescribers will still need to earn certification and training. Additionally, the agency said dispensing pharmacies will have to be certified.

The FDA said in updated guidance on its website that after conducting a review of the Risk Evaluation and Mitigation Strategy for mifepristone, it “determined that the data support modification of the REMS to reduce burden on patient access and the health care delivery system and to ensure the benefits of the product outweigh the risks.”

The modifications include:

• “Removing the requirement that mifepristone be dispensed only in certain health care settings, specifically clinics, medical offices, and hospitals (referred to as the ‘in-person dispensing requirement’).”
• Adding a requirement that pharmacies must be certified to dispense the drug.

The FDA said removing the in-person dispensing rule will allow delivery of mifepristone by mail via certified prescribers or pharmacies, in addition to in-person dispensing in clinics, medical offices, and hospitals.

In 2018, an expert National Academies of Science, Engineering, and Medicine panel concluded that requiring that medication abortion be provided at only certain facilities, solely by a physician or in the physical presence of certain providers, did not improve safety or quality of care.

Mifepristone is used, together with misoprostol, to end an early pregnancy. The FDA first approved Mifeprex in 2000 for use through 10 weeks’ gestation. According to the FDA, mifepristone is approved in more than 60 other countries.
 

Many states bar mailing of abortion pills

However, according to the Guttmacher Institute, 19 U.S. states have laws that bar telehealth consultations or mailing of abortion pills.

Reuters reported that women in those states would not be able to make use of the rule change get the drug delivered to their home but could potentially travel to other states to obtain medication abortion.

“States such as California and New York that have sought to strengthen access to abortion may make the drug available to women from other states,” Reuters reported.

Jessica Arons, senior advocacy and policy counsel for reproductive freedom at the ACLU, told CBS News, “Medication abortion is one more lens through which we see that we are witnessing a tale of two countries. Half the states are protecting access to abortion and half are trying every single way they can to eliminate access to abortion care.”
 

Positive results when Canada lifted restrictions

As this news organization has reported, a study found positive results when Canada lifted restrictions on access to the abortion pills and a good safety profile for mifepristone.

A study in the New England Journal of Medicine found abortion rates remained stable and adverse events were rare after mifepristone prescribing restrictions were lifted in Canada.

Senior author Wendy V. Norman, MD, professor in the department of family practice at the University of British Columbia, Vancouver, said in a statement, “Our study is a signal to other countries that restrictions are not necessary to ensure patient safety.”

Another recent study in JAMA Network Open (2021 Aug 24. doi: 10.1001/jamanetworkopen.2021.22320) found that abortion via telehealth prescriptions may be just as safe and effective as in-person care.

The study investigators said that, “of the 110 women from whom researchers collected remote abortion outcome data, 95% had a complete abortion without additional medical interventions, such as aspiration or surgery, and none experienced adverse events. Researchers said this efficacy rate is similar to in-person visits.”

The Food and Drug Administration has announced that women no longer will have to pick up the abortion pill mifepristone (Mifeprex) in person at certain certified sites and can get a prescription via an online consultation and delivery through the mail.

In April 2021, the FDA lifted the in-person dispensing requirement for mifepristone for the duration of the COVID-19 pandemic and in December the agency made that decision permanent.

As this news organization reported on April 12, 2021, acting commissioner of food and drugs, Janet Woodcock, MD, stated that the FDA would “permit the dispensing of mifepristone through the mail when done by or under the supervision of a certified prescriber; or through a mail-order pharmacy under the supervision of a certified prescriber.”

That decision came after suspension of the in-person dispensing requirement in response to COVID-19 safety concerns for patients as well as providers associated with in-person clinic visits.
 

Decision comes amid Supreme Court debate

The FDA decision comes as the Supreme Court nears a decision on whether to overturn its 1973 ruling on Roe v. Wade.

Additionally, the Supreme Court on returned a lawsuit over Texas’ ban on abortions after 6 weeks to a federal appeals court that has twice allowed the law to stay in effect, rather than to a district judge who wanted it blocked.

Alexis McGill Johnson, president and CEO, of the Planned Parenthood Federation of America, said in a statement, “Abortion is time sensitive, essential health care, and this decision will remove a sometimes insurmountable barrier for patients seeking an abortion. With abortion rights at risk like never before, the FDA’s decision is a long overdue step toward expanding people’s access to safe medication abortion.”

Georgeanne Usova, senior legislative counsel at the American Civil Liberties Union told CNBC News: “The FDA’s decision will come as a tremendous relief for countless abortion and miscarriage patients.”

Catherine D. Cansino, MD, MPH, associate clinical professor in the department of obstetrics and gynecology at the University of California, Davis, and member of the editorial advisory board for ObGyn News said in an interview: “I think that this change is a long time coming and speaks to the fact that science matters and medicine prevails over politics. We need to protect health rights first!”

Others expressed doubt or outrage.

Fidelma Rigby, MD, a professor in the department of obstetrics and gynecology, division of maternal fetal medicine, Virginia Commonwealth University Medical Center, Richmond, said in an interview: “My concern is that what if there is an ectopic pregnancy? I’m not as enthusiastic as some of my partners would be about this announcement.”

“The FDA’s decision today places women at risk,” said Carol Tobias, president of the National Right to Life Committee. “These changes do not make this abortion process safer for women. What these changes do is make the process easier for the abortion industry.”

The antiabortion groups Charlotte Lozier Institute and the Susan B. Anthony List were among other organizations issuing statements against Dec. 16’s FDA ruling.

The FDA stated that mifepristone prescribers will still need to earn certification and training. Additionally, the agency said dispensing pharmacies will have to be certified.

The FDA said in updated guidance on its website that after conducting a review of the Risk Evaluation and Mitigation Strategy for mifepristone, it “determined that the data support modification of the REMS to reduce burden on patient access and the health care delivery system and to ensure the benefits of the product outweigh the risks.”

The modifications include:

• “Removing the requirement that mifepristone be dispensed only in certain health care settings, specifically clinics, medical offices, and hospitals (referred to as the ‘in-person dispensing requirement’).”
• Adding a requirement that pharmacies must be certified to dispense the drug.

The FDA said removing the in-person dispensing rule will allow delivery of mifepristone by mail via certified prescribers or pharmacies, in addition to in-person dispensing in clinics, medical offices, and hospitals.

In 2018, an expert National Academies of Science, Engineering, and Medicine panel concluded that requiring that medication abortion be provided at only certain facilities, solely by a physician or in the physical presence of certain providers, did not improve safety or quality of care.

Mifepristone is used, together with misoprostol, to end an early pregnancy. The FDA first approved Mifeprex in 2000 for use through 10 weeks’ gestation. According to the FDA, mifepristone is approved in more than 60 other countries.
 

Many states bar mailing of abortion pills

However, according to the Guttmacher Institute, 19 U.S. states have laws that bar telehealth consultations or mailing of abortion pills.

Reuters reported that women in those states would not be able to make use of the rule change get the drug delivered to their home but could potentially travel to other states to obtain medication abortion.

“States such as California and New York that have sought to strengthen access to abortion may make the drug available to women from other states,” Reuters reported.

Jessica Arons, senior advocacy and policy counsel for reproductive freedom at the ACLU, told CBS News, “Medication abortion is one more lens through which we see that we are witnessing a tale of two countries. Half the states are protecting access to abortion and half are trying every single way they can to eliminate access to abortion care.”
 

Positive results when Canada lifted restrictions

As this news organization has reported, a study found positive results when Canada lifted restrictions on access to the abortion pills and a good safety profile for mifepristone.

A study in the New England Journal of Medicine found abortion rates remained stable and adverse events were rare after mifepristone prescribing restrictions were lifted in Canada.

Senior author Wendy V. Norman, MD, professor in the department of family practice at the University of British Columbia, Vancouver, said in a statement, “Our study is a signal to other countries that restrictions are not necessary to ensure patient safety.”

Another recent study in JAMA Network Open (2021 Aug 24. doi: 10.1001/jamanetworkopen.2021.22320) found that abortion via telehealth prescriptions may be just as safe and effective as in-person care.

The study investigators said that, “of the 110 women from whom researchers collected remote abortion outcome data, 95% had a complete abortion without additional medical interventions, such as aspiration or surgery, and none experienced adverse events. Researchers said this efficacy rate is similar to in-person visits.”

Advances in technology and genomics have given rise to many issues, such as the extent to which genetic and lifestyle factors contribute to the individual-level risk for coronary artery disease, and the extent one’s genetic risk can be offset by a healthy lifestyle.

Mount Sinai Heart/CCA 3.0

Over the years, Valentin Fuster, MD, PhD, director of Mount Sinai Heart and physician-in-chief at the Mount Sinai Hospital, both in New York, has focused much of his research on this topic. At the virtual ACC Latin America 2021 conference, the cardiologist spoke about his hypotheses and findings during his opening plenary on imaging genomics, an emerging field that is rapidly identifying genes that influence the brain, cognition, and risk for disease.

Dr. Fuster discussed his research (J Am Coll Cardiol. 2021;77:2777-91; J Am Coll Cardiol. 2020;75:1617-27; J Am Coll Cardiol. 2019;73:1371-82; J Am Coll Cardiol. 2017;70:2979-91; Circulation. 2015;131:2104-13) and spoke about his innovative program that looks at cardiovascular health in people from young children to senior citizens. The work has been a process of learning and discovery. “We’re beginning to understand how the disease can develop earlier and how we can prevent it from getting worse. There’s nothing more beneficial than beginning to see how the disease starts in the arteries – something that we’re able to do with imaging technologies that, in the next 2 years, will be available worldwide.” And “by using imaging biomarkers in conjunction with genomic biomarkers, we’re beginning to get an idea earlier on as to whether the person is at risk.”

We need to be talking more about health and healthy arteries and trying to come up with epistemologies that are more modern, Dr. Fuster said. “To be able to see who we actually are is fascinating, and all of this is completely new” with imaging genomics.

Developing cardiovascular disease can be identified in people aged 40-60 years when seven risk factors – obesity, metabolic syndrome, blood pressure, diabetes, smoking, sedentary lifestyle, and poor nutrition” – are grouped together, he explained. In their 2015 study, Dr. Fuster and colleagues explored, using high-quality three-dimensional ultrasonography, five areas of the body – right and left carotids, aorta, and right and left iliofemorals – in more than 4,000 people with no history of cardiovascular disease.

“The first thing I want to point out is that the disease originates in a territory that is not commonly evaluated. And we had no idea. We only learned about this development through imaging tests, assessing plaques. The disease starts in the femoral artery and, in fact, it starts with an inflammatory process – seen at autopsy – that can lead to fibrosis and, in later years, can form lipid-rich vulnerable plaque,” he said.

His work has shown an increase in disease progression in groups of people who have been monitored for 20 years. What is most interesting is the way lesions are silent and evolve as the years go by.

“Atherosclerosis appears as a silent phenomenon initially and worsens in the presence of risk factors that trigger its progression,” he said.

But can subclinical disease be identified in people who have few or no risk factors? “What we call normal is not, in fact, normal,” said Dr. Fuster. To not have subclinical disease, LDL cholesterol needs to be 70 mg/dL and hemoglobin A1c needs to be 5%-6%, according to a 2020 study by Dr. Fuster and colleagues.

“The fact that we’re seeing people with no apparent risk factors develop atherosclerosis is the reason what we consider normal is not,” he said. It is necessary to take into account what happened in the first 40 years of these individuals’ lives, he added.

Dr. Fuster presented findings on 6,000 people aged 60-100 years underwent three-dimensional ultrasonography and were monitored for 12 years. The data have yet to be published, but they indicate that, with this disease, more than just risk factors are at play; atherosclerosis is related to what happens early on in one’s life.

In their 2016 study of more than 55,000 participants, Dr. Fuster and associates quantified the genetic risk for coronary artery disease with a polygenic risk score derived from an analysis of up to 50 genetic polymorphisms that had been associated with coronary artery disease in previous studies. On the basis of this score, the participants were divided into subgroups by genetic risk: low, intermediate, and high. Genetic and lifestyle factors were independently associated with susceptibility to coronary artery disease. For participants at high genetic risk, a favorable lifestyle was associated with a relative risk for coronary artery disease nearly 50% lower than an unfavorable lifestyle.

The risk factors cause the bone marrow to be activated and, when this happens, an inflammatory process occurs in the arteries. This activation is a defense mechanism designed to help monocytes heal the arteries. “When we’re dealing with a disease in the arteries, inflammation starts in the bone marrow, where cholesterol is deposited, and there are macrophages that, because there’s too much to clean up and they can’t keep up, will actually kill themselves. When that happens, they will release substances that will damage the arteries,” Dr. Fuster reported.

In elderly people, risk factors have an impact not only on the great vessels, they can also lead to cerebral small vessel disease.

“The problem is that, before, we didn’t have the technology to make this observation. And this is something critical with respect to late-onset dementia,” he said, citing a 2016 study on Alzheimer’s disease. Even if risk factors are increasing, the person will not necessarily develop the disease, but there is a greater chance that they will.
 

Education

Playful activities have a major impact in childhood. With this in mind, Dr. Fuster instituted a 6-month, 60-hour educational program for children aged 3-6 years. The approach was aimed at teaching children about healthy eating habits and how the human body works. “Children are able to absorb everything we say, but then at age 10, it all goes away,” he said. With another intervention that involved the same children, he showed that the benefits were greater than those seen in the first intervention.

“Our hypothesis is that, regardless of age, any program that has to do with prevention needs to be repeated,” Dr. Fuster said. “Repetition will bring more benefits every x years. That’s what we’re learning.

“We learned that when these children go home, they tell their parents what to do. The program had a greater impact on the children than their parents. So we need to use repetition in prevention efforts directed at young children. And we need to remember that the later we start this kind of work, the less impact it will have. The sooner things start, the greater the benefit and the lower the cost,” he concluded.

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

Advances in technology and genomics have given rise to many issues, such as the extent to which genetic and lifestyle factors contribute to the individual-level risk for coronary artery disease, and the extent one’s genetic risk can be offset by a healthy lifestyle.

Mount Sinai Heart/CCA 3.0

Over the years, Valentin Fuster, MD, PhD, director of Mount Sinai Heart and physician-in-chief at the Mount Sinai Hospital, both in New York, has focused much of his research on this topic. At the virtual ACC Latin America 2021 conference, the cardiologist spoke about his hypotheses and findings during his opening plenary on imaging genomics, an emerging field that is rapidly identifying genes that influence the brain, cognition, and risk for disease.

Dr. Fuster discussed his research (J Am Coll Cardiol. 2021;77:2777-91; J Am Coll Cardiol. 2020;75:1617-27; J Am Coll Cardiol. 2019;73:1371-82; J Am Coll Cardiol. 2017;70:2979-91; Circulation. 2015;131:2104-13) and spoke about his innovative program that looks at cardiovascular health in people from young children to senior citizens. The work has been a process of learning and discovery. “We’re beginning to understand how the disease can develop earlier and how we can prevent it from getting worse. There’s nothing more beneficial than beginning to see how the disease starts in the arteries – something that we’re able to do with imaging technologies that, in the next 2 years, will be available worldwide.” And “by using imaging biomarkers in conjunction with genomic biomarkers, we’re beginning to get an idea earlier on as to whether the person is at risk.”

We need to be talking more about health and healthy arteries and trying to come up with epistemologies that are more modern, Dr. Fuster said. “To be able to see who we actually are is fascinating, and all of this is completely new” with imaging genomics.

Developing cardiovascular disease can be identified in people aged 40-60 years when seven risk factors – obesity, metabolic syndrome, blood pressure, diabetes, smoking, sedentary lifestyle, and poor nutrition” – are grouped together, he explained. In their 2015 study, Dr. Fuster and colleagues explored, using high-quality three-dimensional ultrasonography, five areas of the body – right and left carotids, aorta, and right and left iliofemorals – in more than 4,000 people with no history of cardiovascular disease.

“The first thing I want to point out is that the disease originates in a territory that is not commonly evaluated. And we had no idea. We only learned about this development through imaging tests, assessing plaques. The disease starts in the femoral artery and, in fact, it starts with an inflammatory process – seen at autopsy – that can lead to fibrosis and, in later years, can form lipid-rich vulnerable plaque,” he said.

His work has shown an increase in disease progression in groups of people who have been monitored for 20 years. What is most interesting is the way lesions are silent and evolve as the years go by.

“Atherosclerosis appears as a silent phenomenon initially and worsens in the presence of risk factors that trigger its progression,” he said.

But can subclinical disease be identified in people who have few or no risk factors? “What we call normal is not, in fact, normal,” said Dr. Fuster. To not have subclinical disease, LDL cholesterol needs to be 70 mg/dL and hemoglobin A1c needs to be 5%-6%, according to a 2020 study by Dr. Fuster and colleagues.

“The fact that we’re seeing people with no apparent risk factors develop atherosclerosis is the reason what we consider normal is not,” he said. It is necessary to take into account what happened in the first 40 years of these individuals’ lives, he added.

Dr. Fuster presented findings on 6,000 people aged 60-100 years underwent three-dimensional ultrasonography and were monitored for 12 years. The data have yet to be published, but they indicate that, with this disease, more than just risk factors are at play; atherosclerosis is related to what happens early on in one’s life.

In their 2016 study of more than 55,000 participants, Dr. Fuster and associates quantified the genetic risk for coronary artery disease with a polygenic risk score derived from an analysis of up to 50 genetic polymorphisms that had been associated with coronary artery disease in previous studies. On the basis of this score, the participants were divided into subgroups by genetic risk: low, intermediate, and high. Genetic and lifestyle factors were independently associated with susceptibility to coronary artery disease. For participants at high genetic risk, a favorable lifestyle was associated with a relative risk for coronary artery disease nearly 50% lower than an unfavorable lifestyle.

The risk factors cause the bone marrow to be activated and, when this happens, an inflammatory process occurs in the arteries. This activation is a defense mechanism designed to help monocytes heal the arteries. “When we’re dealing with a disease in the arteries, inflammation starts in the bone marrow, where cholesterol is deposited, and there are macrophages that, because there’s too much to clean up and they can’t keep up, will actually kill themselves. When that happens, they will release substances that will damage the arteries,” Dr. Fuster reported.

In elderly people, risk factors have an impact not only on the great vessels, they can also lead to cerebral small vessel disease.

“The problem is that, before, we didn’t have the technology to make this observation. And this is something critical with respect to late-onset dementia,” he said, citing a 2016 study on Alzheimer’s disease. Even if risk factors are increasing, the person will not necessarily develop the disease, but there is a greater chance that they will.
 

Education

Playful activities have a major impact in childhood. With this in mind, Dr. Fuster instituted a 6-month, 60-hour educational program for children aged 3-6 years. The approach was aimed at teaching children about healthy eating habits and how the human body works. “Children are able to absorb everything we say, but then at age 10, it all goes away,” he said. With another intervention that involved the same children, he showed that the benefits were greater than those seen in the first intervention.

“Our hypothesis is that, regardless of age, any program that has to do with prevention needs to be repeated,” Dr. Fuster said. “Repetition will bring more benefits every x years. That’s what we’re learning.

“We learned that when these children go home, they tell their parents what to do. The program had a greater impact on the children than their parents. So we need to use repetition in prevention efforts directed at young children. And we need to remember that the later we start this kind of work, the less impact it will have. The sooner things start, the greater the benefit and the lower the cost,” he concluded.

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

Advances in technology and genomics have given rise to many issues, such as the extent to which genetic and lifestyle factors contribute to the individual-level risk for coronary artery disease, and the extent one’s genetic risk can be offset by a healthy lifestyle.

Mount Sinai Heart/CCA 3.0

Over the years, Valentin Fuster, MD, PhD, director of Mount Sinai Heart and physician-in-chief at the Mount Sinai Hospital, both in New York, has focused much of his research on this topic. At the virtual ACC Latin America 2021 conference, the cardiologist spoke about his hypotheses and findings during his opening plenary on imaging genomics, an emerging field that is rapidly identifying genes that influence the brain, cognition, and risk for disease.

Dr. Fuster discussed his research (J Am Coll Cardiol. 2021;77:2777-91; J Am Coll Cardiol. 2020;75:1617-27; J Am Coll Cardiol. 2019;73:1371-82; J Am Coll Cardiol. 2017;70:2979-91; Circulation. 2015;131:2104-13) and spoke about his innovative program that looks at cardiovascular health in people from young children to senior citizens. The work has been a process of learning and discovery. “We’re beginning to understand how the disease can develop earlier and how we can prevent it from getting worse. There’s nothing more beneficial than beginning to see how the disease starts in the arteries – something that we’re able to do with imaging technologies that, in the next 2 years, will be available worldwide.” And “by using imaging biomarkers in conjunction with genomic biomarkers, we’re beginning to get an idea earlier on as to whether the person is at risk.”

We need to be talking more about health and healthy arteries and trying to come up with epistemologies that are more modern, Dr. Fuster said. “To be able to see who we actually are is fascinating, and all of this is completely new” with imaging genomics.

Developing cardiovascular disease can be identified in people aged 40-60 years when seven risk factors – obesity, metabolic syndrome, blood pressure, diabetes, smoking, sedentary lifestyle, and poor nutrition” – are grouped together, he explained. In their 2015 study, Dr. Fuster and colleagues explored, using high-quality three-dimensional ultrasonography, five areas of the body – right and left carotids, aorta, and right and left iliofemorals – in more than 4,000 people with no history of cardiovascular disease.

“The first thing I want to point out is that the disease originates in a territory that is not commonly evaluated. And we had no idea. We only learned about this development through imaging tests, assessing plaques. The disease starts in the femoral artery and, in fact, it starts with an inflammatory process – seen at autopsy – that can lead to fibrosis and, in later years, can form lipid-rich vulnerable plaque,” he said.

His work has shown an increase in disease progression in groups of people who have been monitored for 20 years. What is most interesting is the way lesions are silent and evolve as the years go by.

“Atherosclerosis appears as a silent phenomenon initially and worsens in the presence of risk factors that trigger its progression,” he said.

But can subclinical disease be identified in people who have few or no risk factors? “What we call normal is not, in fact, normal,” said Dr. Fuster. To not have subclinical disease, LDL cholesterol needs to be 70 mg/dL and hemoglobin A1c needs to be 5%-6%, according to a 2020 study by Dr. Fuster and colleagues.

“The fact that we’re seeing people with no apparent risk factors develop atherosclerosis is the reason what we consider normal is not,” he said. It is necessary to take into account what happened in the first 40 years of these individuals’ lives, he added.

Dr. Fuster presented findings on 6,000 people aged 60-100 years underwent three-dimensional ultrasonography and were monitored for 12 years. The data have yet to be published, but they indicate that, with this disease, more than just risk factors are at play; atherosclerosis is related to what happens early on in one’s life.

In their 2016 study of more than 55,000 participants, Dr. Fuster and associates quantified the genetic risk for coronary artery disease with a polygenic risk score derived from an analysis of up to 50 genetic polymorphisms that had been associated with coronary artery disease in previous studies. On the basis of this score, the participants were divided into subgroups by genetic risk: low, intermediate, and high. Genetic and lifestyle factors were independently associated with susceptibility to coronary artery disease. For participants at high genetic risk, a favorable lifestyle was associated with a relative risk for coronary artery disease nearly 50% lower than an unfavorable lifestyle.

The risk factors cause the bone marrow to be activated and, when this happens, an inflammatory process occurs in the arteries. This activation is a defense mechanism designed to help monocytes heal the arteries. “When we’re dealing with a disease in the arteries, inflammation starts in the bone marrow, where cholesterol is deposited, and there are macrophages that, because there’s too much to clean up and they can’t keep up, will actually kill themselves. When that happens, they will release substances that will damage the arteries,” Dr. Fuster reported.

In elderly people, risk factors have an impact not only on the great vessels, they can also lead to cerebral small vessel disease.

“The problem is that, before, we didn’t have the technology to make this observation. And this is something critical with respect to late-onset dementia,” he said, citing a 2016 study on Alzheimer’s disease. Even if risk factors are increasing, the person will not necessarily develop the disease, but there is a greater chance that they will.
 

Education

Playful activities have a major impact in childhood. With this in mind, Dr. Fuster instituted a 6-month, 60-hour educational program for children aged 3-6 years. The approach was aimed at teaching children about healthy eating habits and how the human body works. “Children are able to absorb everything we say, but then at age 10, it all goes away,” he said. With another intervention that involved the same children, he showed that the benefits were greater than those seen in the first intervention.

“Our hypothesis is that, regardless of age, any program that has to do with prevention needs to be repeated,” Dr. Fuster said. “Repetition will bring more benefits every x years. That’s what we’re learning.

“We learned that when these children go home, they tell their parents what to do. The program had a greater impact on the children than their parents. So we need to use repetition in prevention efforts directed at young children. And we need to remember that the later we start this kind of work, the less impact it will have. The sooner things start, the greater the benefit and the lower the cost,” he concluded.

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

New draft guidance from the World Professional Association for Transgender Health (WPATH) is raising serious concerns among professionals caring for people with gender dysphoria, prompting claims that WPATH is an organization “captured by activists.”

LemonTreeImages/Thinkstock

Experts in adolescent and child psychology, as well as pediatric health, have expressed dismay that the WPATH Standards of Care (SOC) 8 appear to miss some of the most urgent issues in the field of transgender medicine and are considered to express a radical and unreserved leaning towards “gender-affirmation.”

The WPATH SOC 8 document is available for view and comment until Dec. 16 until 11.59 PM EST, after which time revisions will be made and the final version published. 

Despite repeated attempts by this news organization to seek clarification on certain aspects of the guidance from members of the WPATH SOC 8 committee, requests were declined “until the guidance is finalized.”

According to the WPATH website, the SOC 8 aims to provide “clinical guidance for health professionals to assist transgender and gender diverse people with safe and effective pathways” to manage their gender dysphoria and potentially transition.

Such pathways may relate to primary care, gynecologic and urologic care, reproductive options, voice and communication therapy, mental health services, and hormonal or surgical treatments, among others.

WPATH adds that it was felt necessary to revise the existing SOC 7 (published in 2012) because of recent “globally unprecedented increase and visibility of transgender and gender-diverse people seeking support and gender-affirming medical treatment.”

Gender-affirming medical treatment means different things at different ages. In the case of kids with gender dysphoria who have not yet entered puberty associated with their birth sex, this might include prescribing so-called “puberty blockers” to delay natural puberty – gonadotrophin-releasing hormone analogs that are licensed for use in precocious puberty in children. Such agents have not been licensed for use in children with gender dysphoria, however, so any use for this purpose is off-label.

Following puberty blockade – or in cases where adolescents have already undergone natural puberty – the next step is to begin cross-sex hormones. So, for a female patient who wants to transition to male (FTM), that would be lifelong testosterone, and for a male who wants to be female (MTF), it involves lifelong estrogen. Again, use of such hormones in transgender individuals is entirely off-label.

Just last month, two of America’s leading experts on transgender medicine, both psychologists – including one who is transgender – told this news organization they were concerned that the quality of the evaluations of youth with gender dysphoria are being stifled by activists who are worried that open discussions will further stigmatize trans individuals.

They subsequently wrote an op-ed on the topic entitled, “The mental health establishment is failing trans kids,” which was finally published in the Washington Post on Nov. 24, after numerous other mainstream U.S. media outlets had rejected it.
 

New SOC 8 ‘is not evidence based,’ should not be new ‘gold standard’

One expert says the draft SOC 8 lacks balance and does not address certain issues, while paying undue attention to others that detract from real questions facing the field of transgender medicine, both in the United States and around the world.

Julia Mason, MD, is a pediatrician based in Gresham, Oregon, with a special interest in children and adolescents experiencing gender dysphoria. “The SOC 8 shows us that WPATH remains captured by activists,” she asserts. 

Dr. Mason questions the integrity of WPATH based on what she has read in the draft SOC 8.

“We need a serious organization to take a sober look at the evidence, and that is why we have established the Society for Evidence-Based Gender Medicine [SEGM],” she noted. “This is what we do – we are looking at all of the evidence.”

Dr. Mason is a clinical advisor to SEGM, an organization set-up to evaluate current interventions and evidence on gender dysphoria.

The pediatrician has particular concerns regarding the child and adolescent chapters in the draft SOC 8. The adolescent chapter states: “Guidelines are meant to provide a gold standard based on the available evidence at this moment of time.”

Dr. Mason disputes this assertion. “This document should not be the new gold standard going forward, primarily because it is not evidence based.”

In an interview, Dr. Mason explained that WPATH say they used the “Delphi consensus process” to determine their recommendations, but “this process is designed for use with a panel of experts when evidence is lacking. I would say they didn’t have a panel of experts. They largely had a panel of activists, with a few experts.”

There is no mention, for example, of England’s National Institute for Health and Care Excellence (NICE) evidence reviews on puberty blockers and cross-sex hormones from earlier this year. These reviews determined that no studies have compared cross-sex hormones or puberty blockers with a control group and all follow-up periods for cross-sex hormones were relatively short.

This disappoints Dr. Mason: “These are significant; they are important documents.”

And much of the evidence quoted comes from the well-known and often-quoted “Dutch-protocol” study of 2011, in which the children studied were much younger at the time of their gender dysphoria, compared with the many adolescents who make up the current surge in presentation at gender clinics worldwide, she adds.
 

Rapid-onset GD: adolescents presenting late with little history

Dr. Mason also stresses that the SOC 8 does not address the most urgent issues in transgender medicine today, mainly because it does not address rapid-onset gender dysphoria (ROGD): “This is the dilemma of the 21st century; it’s new.”

ROGD – a term first coined in 2018 by researcher Lisa Littman, MD, MPH, now president of the Institute for Comprehensive Gender Dysphoria Research (ICGDR) – refers to the phenomena of adolescents expressing a desire to transition from their birth sex after little or no apparent previous indication.

However, the SOC 8 does make reference to aspects of adolescent development that might impact their decision-making processes around gender identity during teen years. The chapter on adolescents reads: “... adolescence is also often associated with increased risk-taking behaviors. Along with these notable changes ... individuation from parents ... [there is] often a heightened focus on peer relationships, which can be both positive and detrimental.” 

The guidance goes on to point out that “it is critical to understand how all of these aspects of development may impact the decision-making for a given young person within their specific cultural context.” 
 

Desistance and detransitioning not adequately addressed

Dr. Mason also says there is little mention “about detransitioning in this SOC [8], and ‘gender dysphoria’ and ‘trans’ are terms that are not defined.” 

Likewise, there is no mention of desistance, she highlights, which is when individuals naturally resolve their dysphoria around their birth sex as they grow older.

The most recent published data seen by this news organization relates to a study from March 2021 that showed nearly 88% of boys who struggled with gender identity in childhood (approximate mean age 8 years and follow-up at approximate mean age 20 years) desisted. It reads: “Of the 139 participants, 17 (12.2%) were classified as ‘persisters’ and the remaining 122 (87.8%) were classified as desisters.”

“Most children with gender dysphoria will desist and lose their concept of themselves as being the opposite gender,” Dr. Mason explains. “This is the safest path for a child – desistance.”

“Transition can turn a healthy young person into a lifelong medical patient and has significant health risks,” she emphasizes, stressing that transition has not been shown to decrease the probability of suicide, or attempts at suicide, despite myriad claims saying otherwise. 

“Before we were routinely transitioning kids at school, the vast majority of children grew out of their gender dysphoria. This history is not recognized at all in these SOC [8],” she maintains.

Ken Zucker, PhD, CPsych, an author of the study of desistance in boys, says the terms desistence and persistence of gender dysphoria have caused some consternation in certain circles.

An editor of the Archives of Sexual Behavior and professor in the department of psychiatry, University of Toronto, Dr. Zucker has published widely on the topic.

He told this news organization: “The terms persistence and desistance have become verboten among the WPATH cognoscenti. Perhaps the contributors to SOC 8 have come up with alternative descriptors.”  

“The term ‘desistance’ is particularly annoying to some of the gender-affirming clinicians, because they don’t believe that desistance is bona fide,” Dr. Zucker points out.

“The desistance resisters are like anti-vaxxers – nothing one can provide as evidence for the efficacy of vaccines is sufficient. There will always be a new objection.” 

Other mental health issues, in particular ADHD and autism

It is also widely acknowledged that there is a higher rate of neurodevelopmental and psychiatric diagnoses in individuals with gender dysphoria. For example, one 2020 study found that transgender people were three to six times as likely to be autistic as cisgender people (those whose gender is aligned with their birth sex). 

Statement one in the chapter on adolescents in draft WPATH SOC 8 does give a nod to this, pointing out that health professionals working with gender diverse adolescents “should receive training and develop expertise in autism spectrum disorders and other neurodiversity conditions.”

It also notes that in some cases “a more extended assessment process may be useful, such as for youth with more complex presentations (e.g., complicated mental health histories, co-occurring autism spectrum characteristics in particular) and an absence of experienced childhood gender incongruence.”

However, Dr. Mason stresses that underlying mental health issues are central to addressing how to manage a significant number of these patients.

“If a young person has ADHD or autism, they are not ready to make decisions about the rest of their life at age 18. Even a neurotypical young person is still developing their frontal cortex in their early 20s, and it takes longer for those with ADHD or on the autism spectrum.”

She firmly believes that the guidance does not give sufficient consideration to comorbidities in people over the age of 18.

According to their [SOC 8] guidelines, “once someone is 18 they are ready for anything,” says Dr. Mason.  

Offering some explanation for the increased prevalence of ADHD and autism in those with gender dysphoria, Dr. Mason notes that children can have “hyperfocus” and those with autism will fixate on a particular area of interest. “If a child is unhappy in their life, and this can be more likely if someone is neuro-atypical, then it is likely that the individual might go online and find this one solution [for example, a transgender identity] that seems to fix everything.” 

Perceptions of femininity and masculinity can also be extra challenging for a child with autism, Dr. Mason says. “It is relatively easy for an autistic girl to feel like she should be a boy because the rules of femininity are composed of nonverbal, subtle behaviors that can be difficult to pick up on,” she points out. “An autistic child who isn’t particularly good at nonverbal communication might not pick up on these and thus feel they are not very ‘female.’” 

“There’s a whole lot of grass-is-greener-type thinking. Girls think boys have an easier life, and boys think girls have an easier life. I know some detransitioners who have spoken eloquently about realizing their mistake on this,” she adds.

Other parts of the SOC 8 that Dr. Mason disagrees with include the recommendation in the adolescent chapter that 14-year-olds are mature enough to start cross-sex hormones, that is, giving testosterone to a female who wants to transition to male or estrogen to a male who wishes to transition to female. “I think that’s far too young,” she asserts.

And she points out that the document states 17-year-olds are ready for genital reassignment surgery. Again, she believes this is far too young.

“Also, the SOC 8 document does not clarify who is appropriate for surgery. Whenever surgery is discussed, it becomes very vague,” she said. 

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

New draft guidance from the World Professional Association for Transgender Health (WPATH) is raising serious concerns among professionals caring for people with gender dysphoria, prompting claims that WPATH is an organization “captured by activists.”

LemonTreeImages/Thinkstock

Experts in adolescent and child psychology, as well as pediatric health, have expressed dismay that the WPATH Standards of Care (SOC) 8 appear to miss some of the most urgent issues in the field of transgender medicine and are considered to express a radical and unreserved leaning towards “gender-affirmation.”

The WPATH SOC 8 document is available for view and comment until Dec. 16 until 11.59 PM EST, after which time revisions will be made and the final version published. 

Despite repeated attempts by this news organization to seek clarification on certain aspects of the guidance from members of the WPATH SOC 8 committee, requests were declined “until the guidance is finalized.”

According to the WPATH website, the SOC 8 aims to provide “clinical guidance for health professionals to assist transgender and gender diverse people with safe and effective pathways” to manage their gender dysphoria and potentially transition.

Such pathways may relate to primary care, gynecologic and urologic care, reproductive options, voice and communication therapy, mental health services, and hormonal or surgical treatments, among others.

WPATH adds that it was felt necessary to revise the existing SOC 7 (published in 2012) because of recent “globally unprecedented increase and visibility of transgender and gender-diverse people seeking support and gender-affirming medical treatment.”

Gender-affirming medical treatment means different things at different ages. In the case of kids with gender dysphoria who have not yet entered puberty associated with their birth sex, this might include prescribing so-called “puberty blockers” to delay natural puberty – gonadotrophin-releasing hormone analogs that are licensed for use in precocious puberty in children. Such agents have not been licensed for use in children with gender dysphoria, however, so any use for this purpose is off-label.

Following puberty blockade – or in cases where adolescents have already undergone natural puberty – the next step is to begin cross-sex hormones. So, for a female patient who wants to transition to male (FTM), that would be lifelong testosterone, and for a male who wants to be female (MTF), it involves lifelong estrogen. Again, use of such hormones in transgender individuals is entirely off-label.

Just last month, two of America’s leading experts on transgender medicine, both psychologists – including one who is transgender – told this news organization they were concerned that the quality of the evaluations of youth with gender dysphoria are being stifled by activists who are worried that open discussions will further stigmatize trans individuals.

They subsequently wrote an op-ed on the topic entitled, “The mental health establishment is failing trans kids,” which was finally published in the Washington Post on Nov. 24, after numerous other mainstream U.S. media outlets had rejected it.
 

New SOC 8 ‘is not evidence based,’ should not be new ‘gold standard’

One expert says the draft SOC 8 lacks balance and does not address certain issues, while paying undue attention to others that detract from real questions facing the field of transgender medicine, both in the United States and around the world.

Julia Mason, MD, is a pediatrician based in Gresham, Oregon, with a special interest in children and adolescents experiencing gender dysphoria. “The SOC 8 shows us that WPATH remains captured by activists,” she asserts. 

Dr. Mason questions the integrity of WPATH based on what she has read in the draft SOC 8.

“We need a serious organization to take a sober look at the evidence, and that is why we have established the Society for Evidence-Based Gender Medicine [SEGM],” she noted. “This is what we do – we are looking at all of the evidence.”

Dr. Mason is a clinical advisor to SEGM, an organization set-up to evaluate current interventions and evidence on gender dysphoria.

The pediatrician has particular concerns regarding the child and adolescent chapters in the draft SOC 8. The adolescent chapter states: “Guidelines are meant to provide a gold standard based on the available evidence at this moment of time.”

Dr. Mason disputes this assertion. “This document should not be the new gold standard going forward, primarily because it is not evidence based.”

In an interview, Dr. Mason explained that WPATH say they used the “Delphi consensus process” to determine their recommendations, but “this process is designed for use with a panel of experts when evidence is lacking. I would say they didn’t have a panel of experts. They largely had a panel of activists, with a few experts.”

There is no mention, for example, of England’s National Institute for Health and Care Excellence (NICE) evidence reviews on puberty blockers and cross-sex hormones from earlier this year. These reviews determined that no studies have compared cross-sex hormones or puberty blockers with a control group and all follow-up periods for cross-sex hormones were relatively short.

This disappoints Dr. Mason: “These are significant; they are important documents.”

And much of the evidence quoted comes from the well-known and often-quoted “Dutch-protocol” study of 2011, in which the children studied were much younger at the time of their gender dysphoria, compared with the many adolescents who make up the current surge in presentation at gender clinics worldwide, she adds.
 

Rapid-onset GD: adolescents presenting late with little history

Dr. Mason also stresses that the SOC 8 does not address the most urgent issues in transgender medicine today, mainly because it does not address rapid-onset gender dysphoria (ROGD): “This is the dilemma of the 21st century; it’s new.”

ROGD – a term first coined in 2018 by researcher Lisa Littman, MD, MPH, now president of the Institute for Comprehensive Gender Dysphoria Research (ICGDR) – refers to the phenomena of adolescents expressing a desire to transition from their birth sex after little or no apparent previous indication.

However, the SOC 8 does make reference to aspects of adolescent development that might impact their decision-making processes around gender identity during teen years. The chapter on adolescents reads: “... adolescence is also often associated with increased risk-taking behaviors. Along with these notable changes ... individuation from parents ... [there is] often a heightened focus on peer relationships, which can be both positive and detrimental.” 

The guidance goes on to point out that “it is critical to understand how all of these aspects of development may impact the decision-making for a given young person within their specific cultural context.” 
 

Desistance and detransitioning not adequately addressed

Dr. Mason also says there is little mention “about detransitioning in this SOC [8], and ‘gender dysphoria’ and ‘trans’ are terms that are not defined.” 

Likewise, there is no mention of desistance, she highlights, which is when individuals naturally resolve their dysphoria around their birth sex as they grow older.

The most recent published data seen by this news organization relates to a study from March 2021 that showed nearly 88% of boys who struggled with gender identity in childhood (approximate mean age 8 years and follow-up at approximate mean age 20 years) desisted. It reads: “Of the 139 participants, 17 (12.2%) were classified as ‘persisters’ and the remaining 122 (87.8%) were classified as desisters.”

“Most children with gender dysphoria will desist and lose their concept of themselves as being the opposite gender,” Dr. Mason explains. “This is the safest path for a child – desistance.”

“Transition can turn a healthy young person into a lifelong medical patient and has significant health risks,” she emphasizes, stressing that transition has not been shown to decrease the probability of suicide, or attempts at suicide, despite myriad claims saying otherwise. 

“Before we were routinely transitioning kids at school, the vast majority of children grew out of their gender dysphoria. This history is not recognized at all in these SOC [8],” she maintains.

Ken Zucker, PhD, CPsych, an author of the study of desistance in boys, says the terms desistence and persistence of gender dysphoria have caused some consternation in certain circles.

An editor of the Archives of Sexual Behavior and professor in the department of psychiatry, University of Toronto, Dr. Zucker has published widely on the topic.

He told this news organization: “The terms persistence and desistance have become verboten among the WPATH cognoscenti. Perhaps the contributors to SOC 8 have come up with alternative descriptors.”  

“The term ‘desistance’ is particularly annoying to some of the gender-affirming clinicians, because they don’t believe that desistance is bona fide,” Dr. Zucker points out.

“The desistance resisters are like anti-vaxxers – nothing one can provide as evidence for the efficacy of vaccines is sufficient. There will always be a new objection.” 

Other mental health issues, in particular ADHD and autism

It is also widely acknowledged that there is a higher rate of neurodevelopmental and psychiatric diagnoses in individuals with gender dysphoria. For example, one 2020 study found that transgender people were three to six times as likely to be autistic as cisgender people (those whose gender is aligned with their birth sex). 

Statement one in the chapter on adolescents in draft WPATH SOC 8 does give a nod to this, pointing out that health professionals working with gender diverse adolescents “should receive training and develop expertise in autism spectrum disorders and other neurodiversity conditions.”

It also notes that in some cases “a more extended assessment process may be useful, such as for youth with more complex presentations (e.g., complicated mental health histories, co-occurring autism spectrum characteristics in particular) and an absence of experienced childhood gender incongruence.”

However, Dr. Mason stresses that underlying mental health issues are central to addressing how to manage a significant number of these patients.

“If a young person has ADHD or autism, they are not ready to make decisions about the rest of their life at age 18. Even a neurotypical young person is still developing their frontal cortex in their early 20s, and it takes longer for those with ADHD or on the autism spectrum.”

She firmly believes that the guidance does not give sufficient consideration to comorbidities in people over the age of 18.

According to their [SOC 8] guidelines, “once someone is 18 they are ready for anything,” says Dr. Mason.  

Offering some explanation for the increased prevalence of ADHD and autism in those with gender dysphoria, Dr. Mason notes that children can have “hyperfocus” and those with autism will fixate on a particular area of interest. “If a child is unhappy in their life, and this can be more likely if someone is neuro-atypical, then it is likely that the individual might go online and find this one solution [for example, a transgender identity] that seems to fix everything.” 

Perceptions of femininity and masculinity can also be extra challenging for a child with autism, Dr. Mason says. “It is relatively easy for an autistic girl to feel like she should be a boy because the rules of femininity are composed of nonverbal, subtle behaviors that can be difficult to pick up on,” she points out. “An autistic child who isn’t particularly good at nonverbal communication might not pick up on these and thus feel they are not very ‘female.’” 

“There’s a whole lot of grass-is-greener-type thinking. Girls think boys have an easier life, and boys think girls have an easier life. I know some detransitioners who have spoken eloquently about realizing their mistake on this,” she adds.

Other parts of the SOC 8 that Dr. Mason disagrees with include the recommendation in the adolescent chapter that 14-year-olds are mature enough to start cross-sex hormones, that is, giving testosterone to a female who wants to transition to male or estrogen to a male who wishes to transition to female. “I think that’s far too young,” she asserts.

And she points out that the document states 17-year-olds are ready for genital reassignment surgery. Again, she believes this is far too young.

“Also, the SOC 8 document does not clarify who is appropriate for surgery. Whenever surgery is discussed, it becomes very vague,” she said. 

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

New draft guidance from the World Professional Association for Transgender Health (WPATH) is raising serious concerns among professionals caring for people with gender dysphoria, prompting claims that WPATH is an organization “captured by activists.”

LemonTreeImages/Thinkstock

Experts in adolescent and child psychology, as well as pediatric health, have expressed dismay that the WPATH Standards of Care (SOC) 8 appear to miss some of the most urgent issues in the field of transgender medicine and are considered to express a radical and unreserved leaning towards “gender-affirmation.”

The WPATH SOC 8 document is available for view and comment until Dec. 16 until 11.59 PM EST, after which time revisions will be made and the final version published. 

Despite repeated attempts by this news organization to seek clarification on certain aspects of the guidance from members of the WPATH SOC 8 committee, requests were declined “until the guidance is finalized.”

According to the WPATH website, the SOC 8 aims to provide “clinical guidance for health professionals to assist transgender and gender diverse people with safe and effective pathways” to manage their gender dysphoria and potentially transition.

Such pathways may relate to primary care, gynecologic and urologic care, reproductive options, voice and communication therapy, mental health services, and hormonal or surgical treatments, among others.

WPATH adds that it was felt necessary to revise the existing SOC 7 (published in 2012) because of recent “globally unprecedented increase and visibility of transgender and gender-diverse people seeking support and gender-affirming medical treatment.”

Gender-affirming medical treatment means different things at different ages. In the case of kids with gender dysphoria who have not yet entered puberty associated with their birth sex, this might include prescribing so-called “puberty blockers” to delay natural puberty – gonadotrophin-releasing hormone analogs that are licensed for use in precocious puberty in children. Such agents have not been licensed for use in children with gender dysphoria, however, so any use for this purpose is off-label.

Following puberty blockade – or in cases where adolescents have already undergone natural puberty – the next step is to begin cross-sex hormones. So, for a female patient who wants to transition to male (FTM), that would be lifelong testosterone, and for a male who wants to be female (MTF), it involves lifelong estrogen. Again, use of such hormones in transgender individuals is entirely off-label.

Just last month, two of America’s leading experts on transgender medicine, both psychologists – including one who is transgender – told this news organization they were concerned that the quality of the evaluations of youth with gender dysphoria are being stifled by activists who are worried that open discussions will further stigmatize trans individuals.

They subsequently wrote an op-ed on the topic entitled, “The mental health establishment is failing trans kids,” which was finally published in the Washington Post on Nov. 24, after numerous other mainstream U.S. media outlets had rejected it.
 

New SOC 8 ‘is not evidence based,’ should not be new ‘gold standard’

One expert says the draft SOC 8 lacks balance and does not address certain issues, while paying undue attention to others that detract from real questions facing the field of transgender medicine, both in the United States and around the world.

Julia Mason, MD, is a pediatrician based in Gresham, Oregon, with a special interest in children and adolescents experiencing gender dysphoria. “The SOC 8 shows us that WPATH remains captured by activists,” she asserts. 

Dr. Mason questions the integrity of WPATH based on what she has read in the draft SOC 8.

“We need a serious organization to take a sober look at the evidence, and that is why we have established the Society for Evidence-Based Gender Medicine [SEGM],” she noted. “This is what we do – we are looking at all of the evidence.”

Dr. Mason is a clinical advisor to SEGM, an organization set-up to evaluate current interventions and evidence on gender dysphoria.

The pediatrician has particular concerns regarding the child and adolescent chapters in the draft SOC 8. The adolescent chapter states: “Guidelines are meant to provide a gold standard based on the available evidence at this moment of time.”

Dr. Mason disputes this assertion. “This document should not be the new gold standard going forward, primarily because it is not evidence based.”

In an interview, Dr. Mason explained that WPATH say they used the “Delphi consensus process” to determine their recommendations, but “this process is designed for use with a panel of experts when evidence is lacking. I would say they didn’t have a panel of experts. They largely had a panel of activists, with a few experts.”

There is no mention, for example, of England’s National Institute for Health and Care Excellence (NICE) evidence reviews on puberty blockers and cross-sex hormones from earlier this year. These reviews determined that no studies have compared cross-sex hormones or puberty blockers with a control group and all follow-up periods for cross-sex hormones were relatively short.

This disappoints Dr. Mason: “These are significant; they are important documents.”

And much of the evidence quoted comes from the well-known and often-quoted “Dutch-protocol” study of 2011, in which the children studied were much younger at the time of their gender dysphoria, compared with the many adolescents who make up the current surge in presentation at gender clinics worldwide, she adds.
 

Rapid-onset GD: adolescents presenting late with little history

Dr. Mason also stresses that the SOC 8 does not address the most urgent issues in transgender medicine today, mainly because it does not address rapid-onset gender dysphoria (ROGD): “This is the dilemma of the 21st century; it’s new.”

ROGD – a term first coined in 2018 by researcher Lisa Littman, MD, MPH, now president of the Institute for Comprehensive Gender Dysphoria Research (ICGDR) – refers to the phenomena of adolescents expressing a desire to transition from their birth sex after little or no apparent previous indication.

However, the SOC 8 does make reference to aspects of adolescent development that might impact their decision-making processes around gender identity during teen years. The chapter on adolescents reads: “... adolescence is also often associated with increased risk-taking behaviors. Along with these notable changes ... individuation from parents ... [there is] often a heightened focus on peer relationships, which can be both positive and detrimental.” 

The guidance goes on to point out that “it is critical to understand how all of these aspects of development may impact the decision-making for a given young person within their specific cultural context.” 
 

Desistance and detransitioning not adequately addressed

Dr. Mason also says there is little mention “about detransitioning in this SOC [8], and ‘gender dysphoria’ and ‘trans’ are terms that are not defined.” 

Likewise, there is no mention of desistance, she highlights, which is when individuals naturally resolve their dysphoria around their birth sex as they grow older.

The most recent published data seen by this news organization relates to a study from March 2021 that showed nearly 88% of boys who struggled with gender identity in childhood (approximate mean age 8 years and follow-up at approximate mean age 20 years) desisted. It reads: “Of the 139 participants, 17 (12.2%) were classified as ‘persisters’ and the remaining 122 (87.8%) were classified as desisters.”

“Most children with gender dysphoria will desist and lose their concept of themselves as being the opposite gender,” Dr. Mason explains. “This is the safest path for a child – desistance.”

“Transition can turn a healthy young person into a lifelong medical patient and has significant health risks,” she emphasizes, stressing that transition has not been shown to decrease the probability of suicide, or attempts at suicide, despite myriad claims saying otherwise. 

“Before we were routinely transitioning kids at school, the vast majority of children grew out of their gender dysphoria. This history is not recognized at all in these SOC [8],” she maintains.

Ken Zucker, PhD, CPsych, an author of the study of desistance in boys, says the terms desistence and persistence of gender dysphoria have caused some consternation in certain circles.

An editor of the Archives of Sexual Behavior and professor in the department of psychiatry, University of Toronto, Dr. Zucker has published widely on the topic.

He told this news organization: “The terms persistence and desistance have become verboten among the WPATH cognoscenti. Perhaps the contributors to SOC 8 have come up with alternative descriptors.”  

“The term ‘desistance’ is particularly annoying to some of the gender-affirming clinicians, because they don’t believe that desistance is bona fide,” Dr. Zucker points out.

“The desistance resisters are like anti-vaxxers – nothing one can provide as evidence for the efficacy of vaccines is sufficient. There will always be a new objection.” 

Other mental health issues, in particular ADHD and autism

It is also widely acknowledged that there is a higher rate of neurodevelopmental and psychiatric diagnoses in individuals with gender dysphoria. For example, one 2020 study found that transgender people were three to six times as likely to be autistic as cisgender people (those whose gender is aligned with their birth sex). 

Statement one in the chapter on adolescents in draft WPATH SOC 8 does give a nod to this, pointing out that health professionals working with gender diverse adolescents “should receive training and develop expertise in autism spectrum disorders and other neurodiversity conditions.”

It also notes that in some cases “a more extended assessment process may be useful, such as for youth with more complex presentations (e.g., complicated mental health histories, co-occurring autism spectrum characteristics in particular) and an absence of experienced childhood gender incongruence.”

However, Dr. Mason stresses that underlying mental health issues are central to addressing how to manage a significant number of these patients.

“If a young person has ADHD or autism, they are not ready to make decisions about the rest of their life at age 18. Even a neurotypical young person is still developing their frontal cortex in their early 20s, and it takes longer for those with ADHD or on the autism spectrum.”

She firmly believes that the guidance does not give sufficient consideration to comorbidities in people over the age of 18.

According to their [SOC 8] guidelines, “once someone is 18 they are ready for anything,” says Dr. Mason.  

Offering some explanation for the increased prevalence of ADHD and autism in those with gender dysphoria, Dr. Mason notes that children can have “hyperfocus” and those with autism will fixate on a particular area of interest. “If a child is unhappy in their life, and this can be more likely if someone is neuro-atypical, then it is likely that the individual might go online and find this one solution [for example, a transgender identity] that seems to fix everything.” 

Perceptions of femininity and masculinity can also be extra challenging for a child with autism, Dr. Mason says. “It is relatively easy for an autistic girl to feel like she should be a boy because the rules of femininity are composed of nonverbal, subtle behaviors that can be difficult to pick up on,” she points out. “An autistic child who isn’t particularly good at nonverbal communication might not pick up on these and thus feel they are not very ‘female.’” 

“There’s a whole lot of grass-is-greener-type thinking. Girls think boys have an easier life, and boys think girls have an easier life. I know some detransitioners who have spoken eloquently about realizing their mistake on this,” she adds.

Other parts of the SOC 8 that Dr. Mason disagrees with include the recommendation in the adolescent chapter that 14-year-olds are mature enough to start cross-sex hormones, that is, giving testosterone to a female who wants to transition to male or estrogen to a male who wishes to transition to female. “I think that’s far too young,” she asserts.

And she points out that the document states 17-year-olds are ready for genital reassignment surgery. Again, she believes this is far too young.

“Also, the SOC 8 document does not clarify who is appropriate for surgery. Whenever surgery is discussed, it becomes very vague,” she said. 

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

A young woman is having her lip swabbed with an unknown substance, smiling, on the TikTok video. Seconds later, another young woman, wearing gloves, pushes a hyaluron pen against the first woman’s lips, who, in the next cut, is smiling, happy. “My first syringe down and already 1,000x more confident,” the caption reads.

That video is one of thousands showing hyaluron pen use on TikTok. The pens are sold online and are unapproved – which led to a Food and Drug Administration warning in October 2021 that use could cause bleeding, infection, blood vessel occlusion that could result in blindness or stroke, allergic reactions, and other injuries.

The warning has not stopped many TikTokkers, who also use the medium to promote all sorts of skin and aesthetic products and procedures, a large number unproven, unapproved, or ill advised. As TikTok has become one of the most widely used social media platforms, millions of mostly teenagers regularly log on for skin care advice, which, more often than not, comes from “skinfluencers,” aestheticians, and other laypeople, not board-certified dermatologists.

The suggested “hacks” can be harmless or ineffective, but they also can be misleading, fraudulent, or even dangerous.
 

Skinfluencers take the lead

TikTok has a reported 1 billion monthly users. Two-thirds are aged 10-29 years, according to data reported in February 2021 in the Journal of the American Academy of Dermatology by David X. Zheng, BA, and colleagues at Case Western Reserve University, Cleveland, and the department of dermatology, Johns Hopkins University, Baltimore.

Visitors consume information in video bits that run from 15 seconds to up to 3 minutes and can follow their favorite TikTokkers, browse for people or hashtags with a search function, or click on content recommended by the platform, which uses algorithms based on the user’s viewing habits to determine what might be of interest.

Some of the biggest “skinfluencers” have millions of followers: Hyram Yarbro, (@skincarebyhyram) for instance, has 6.6 million followers and his own line of skin care products at Sephora. Mr. Yarbro is seen as a no-nonsense debunker of skin care myths, as is British influencer James Welsh, who has 124,000 followers.

“The reason why people trust your average influencer person who’s not a doctor is because they’re relatable,” said Muneeb Shah, MD, a dermatology resident at Atlantic Dermatology in Wilmington, N.C. – known to his 11.4 million TikTok followers as @dermdoctor.

To Sandra Lee, MD, the popularity of nonprofessionals is easy to explain. “You have to think about the fact that a lot of people can’t see dermatologists – they don’t have the money, they don’t have the time to travel there, they don’t have health insurance, or they’re scared of doctors, so they’re willing to try to find an answer, and one of the easiest ways, one of the more entertaining ways to get information, is on social media.”

Dr. Lee is in private practice in Upland, Calif., but is better known as “Dr. Pimple Popper,” through her television show of the same name and her social media accounts, including on TikTok, where she has 14.4 million followers after having started in 2020.

“We’re all looking for that no-down-time, no-expense, no-lines, no-wrinkles, stay-young-forever magic bullet,” said Dr. Lee.

Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, agreed that people are looking for a quick fix. They don’t want to wait 12 weeks for an acne medication or 16 weeks for a biologic to work. “They want something simple, easy, do-it-yourself,” and “natural,” he said.

Laypeople are still the dominant producers – and have the most views – of dermatology content.

Morgan Nguyen, BA, at Northwestern University, Chicago, and colleagues looked at hashtags for the top 10 dermatologic diagnoses and procedures and analyzed the content of the first 40 TikTok videos in each category. About half the videos were produced by an individual, and 39% by a health care provider, according to the study, published in the International Journal of Women’s Dermatology. About 40% of the videos were educational, focusing on skin care, procedures, and disease treatment.

Viewership was highest for videos by laypeople, followed by those produced by business or industry accounts. Those produced by health care providers received only 18% of the views.

The most popular videos were about dermatologic diagnoses, with 2.5 billion views, followed by dermatologic procedures, with 708 million views.

Ms. Nguyen noted in the study that the most liked and most viewed posts were related to #skincare but that board-certified dermatologists produced only 2.5% of the #skincare videos.


 

Dermatologists take to TikTok

Some dermatologists have started their own TikTok accounts, seeking both to counteract misinformation and provide education.

Dr. Shah has become one of the top influencers on the platform. In a year-end wrap, TikTok put Dr. Shah at No. 7 on its top creators list for 2021.

MDedge

Doris Day, MD, who goes by @drdorisday on TikTok, agreed with Dr. Lee. “There are so many creative ways you can convey information with it that’s different than what you have on Instagram,” said Dr. Day, who is in private practice in New York. And, she added, “it does really lend itself to getting points out super-fast.”

Dermatologists on TikTok also said they like the “duets” and the “stitch” features, which allow users to add on to an existing video, essentially chiming in or responding to what might have already been posted, in a side-by-side format.

Dr. Shah said he often duets videos that have questionable content. “It allows me to directly respond to people. A lot of times, if something is going really viral and it’s not accurate, you’ll have a response from me or one of the other doctors” within hours or days.

Dr. Shah’s duets are labeled with “DermDoctor Reacts” or “DermDoctor Explains.” In one duet, with more than 2.8 million views, the upper half of the video is someone squeezing a blackhead, while Dr. Shah, in the bottom half, in green scrubs, opines over some hip-hop music: “This is just a blackhead. But once it gets to this point, they do need to be extracted because topical treatments won’t help.”

TikTok trends gone bad

And some people are being hurt by emulating what they see on TikTok.

Dr. Friedman had a patient with extreme irritant contact dermatitis, “almost like chemical burns to her underarms,” he said. He determined that she saw a video “hack” that recommended using baking soda to stop hyperhidrosis. The patient used so much that it burned her skin.

In 2020, do-it-yourself freckles – with henna or sewing needles impregnated with ink – went viral. Tilly Whitfeld, a 21-year-old reality TV star on Australia’s Big Brother show, told the New York Times that she tried it at home after seeing a TikTok video. She ordered brown tattoo ink online and later found out that it was contaminated with lead, according to the Times. Ms. Whitfeld developed an infection and temporary vision loss and has permanent scarring.

She has since put out a cautionary TikTok video that’s been viewed some 300,000 times.

TikTokkers have also flocked to the idea of using sunscreen to “contour” the face. Selected areas are left without sunscreen to burn or tan. In a duet, a plastic surgeon shakes his head as a young woman explains that “it works.”

Scalp-popping – in which the hair is yanked so hard that it pulls the galea off the skull – has been mostly shut down by TikTok. A search of “scalp popping” brings up the message: “Learn how to recognize harmful challenges and hoaxes.” At-home mole and skin tag removal, pimple-popping, and supposed acne cures such as drinking chlorophyll are all avidly documented and shared on TikTok.

Dr. Shah had a back-and-forth video dialog with someone who had stubbed a toe and then drilled a hole into the nail to drain the hematoma. In a reaction video, Dr. Shah said it was likely to turn into an infection. When it did, the man revealed the infection in a video where he tagged Dr. Shah and later posted a video at the podiatrist’s office having his nail removed, again tagging Dr. Shah.

“I think that pretty much no procedure for skin is good to do at home,” said Dr. Shah, who repeatedly admonishes against mole removal by a nonphysician. He tells followers that “it’s extremely dangerous – not only is it going to cause scarring, but you are potentially discarding a cancerous lesion.”

Unfortunately, most will not follow the advice, said Dr. Shah. That’s especially true of pimple-popping. Aiming for the least harm, he suggests in some TikTok videos that poppers keep the area clean, wear gloves, and consult a physician to get an antibiotic prescription. “You might as well at least guide them in the right direction,” he added.

Dr. Lee believes that lack of access to physicians, insurance, or money may play into how TikTok trends evolve. “Probably those people who injected their lips with this air gun thing, maybe they didn’t have the money necessarily to get filler,” she said.

Also, she noted, while TikTok may try to police its content, creators are incentivized to be outrageous. “The more inflammatory your post is, the more engagement you get.”

Dr. Shah thinks TikTok is self-correcting. “If you’re not being ethical or contradicting yourself, putting out information that’s not accurate, people are going to catch on very quickly,” he said. “The only value, the only currency you have on social media is the trust that you build with people that follow you.”
 

What it takes to be a TikTokker

For dermatologists, conveying their credentials and experience is one way to build that currency. Dr. Lee advised fellow doctors on TikTok to “showcase your training and how many years it took to become a dermatologist.”

Plunging into TikTok is not for everyone, though. It’s time consuming, said Dr. Lee, who now devotes most of her nonclinical time to TikTok. She creates her own content, leaving others to manage her Instagram account.

Many of those in the medical field who have dived into TikTok are residents, like Dr. Shah. “They are attuned to it and understand it more,” said Dr. Lee. “It’s harder for a lot of us who are older, who really weren’t involved that much in social media at all. It’s very hard to jump in.” There’s a learning curve, and it takes hours to create a single video. “You have to enjoy it and it has to be a part of your life,” she said.

Dr. Shah started experimenting with TikTok at the beginning of the pandemic in 2020 and has never turned back. Fast-talking, curious, and with an infectious sense of fun, he shares tidbits about his personal life – putting his wife in some of his videos – and always seems upbeat.

He said that, as his following grew, users began to see him as an authority figure and started “tagging” him more often, seeking his opinion on other videos. Although still a resident, he believes he has specialized knowledge to share. “Even if you’re not the world’s leading expert in a particular topic, you’re still adding value for the person who doesn’t know much.”

Dr. Shah also occasionally does promotional TikToks, identified as sponsored content. He said he only works with companies that he believes have legitimate products. “You do have to monetize at some point,” he said, noting that many dermatologists, himself included, are trading clinic time for TikTok. “There’s no universe where they can do this for free.”

Product endorsements are likely more rewarding for influencers and other users like Dr. Shah than the remuneration from TikTok, the company. The platform pays user accounts $20 per 1 million views, Dr. Shah said. “Financially, it’s not a big winner for a practicing dermatologist, but the educational outreach is worthwhile.”

To be successful also means understanding what drives viewership.

Using “trending” sounds has “been shown to increase the likelihood of a video amassing millions of views” and may increase engagement with dermatologists’ TikTok videos, wrote Bina Kassamali, BA, and colleagues at the Brigham and Women’s Hospital in Boston and the Ponce Health Science University School of Medicine in Ponce, Puerto Rico, in a letter published in the Journal of the American Academy of Dermatology in July 2021.

Certain content is more likely to engage viewers. In their analysis of top trending dermatologic hashtags, acne-related content was viewed 6.7 billion times, followed by alopecia, with 1.1 billion views. Psoriasis content had 84 million views, putting it eighth on the list of topics.

Dermatologists are still cracking TikTok. They are accumulating more followers on TikTok than on Instagram but have greater engagement on Instagram reels, wrote Mindy D. Szeto, MS, and colleagues at the University of Colorado at Denver, Aurora, and Rocky Vista University in Parker, Colo., in the Journal of the American Academy of Dermatology in April 2021.

Dr. Lee and Dr. Shah had the highest engagement rate on TikTok, according to Ms. Szeto. The engagement rate is calculated as (likes + comments per post)/(total followers) x 100.

“TikTok may currently be the leading avenue for audience education by dermatologist influencers,” they wrote, urging dermatologists to use the platform to answer the call as more of the public “continues to turn to social media for medical advice.”

Dr. Day said she will keep trying to build her TikTok audience. She has just 239 followers, compared with her 44,500 on Instagram. “The more I do TikTok, the more I do any of these mediums, the better I get at it,” she said. “We just have to put a little time and effort into it and try to get more followers and just keep sharing the information.”

Dr. Friedman sees it as a positive that some dermatologists have taken to TikTok to dispel myths and put “good information out there in small bites.” But to be more effective, they need more followers.

“The truth is that 14-year-old is probably going to listen more to a Hyram than a dermatologist,” he said. “Maybe we need to work with these other individuals who know how to take these messages and convert them to a language that can be digested by a 14-year-old, by a 12-year-old, by a 23-year-old. We need to come to the table together and not fight.”

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

A young woman is having her lip swabbed with an unknown substance, smiling, on the TikTok video. Seconds later, another young woman, wearing gloves, pushes a hyaluron pen against the first woman’s lips, who, in the next cut, is smiling, happy. “My first syringe down and already 1,000x more confident,” the caption reads.

That video is one of thousands showing hyaluron pen use on TikTok. The pens are sold online and are unapproved – which led to a Food and Drug Administration warning in October 2021 that use could cause bleeding, infection, blood vessel occlusion that could result in blindness or stroke, allergic reactions, and other injuries.

The warning has not stopped many TikTokkers, who also use the medium to promote all sorts of skin and aesthetic products and procedures, a large number unproven, unapproved, or ill advised. As TikTok has become one of the most widely used social media platforms, millions of mostly teenagers regularly log on for skin care advice, which, more often than not, comes from “skinfluencers,” aestheticians, and other laypeople, not board-certified dermatologists.

The suggested “hacks” can be harmless or ineffective, but they also can be misleading, fraudulent, or even dangerous.
 

Skinfluencers take the lead

TikTok has a reported 1 billion monthly users. Two-thirds are aged 10-29 years, according to data reported in February 2021 in the Journal of the American Academy of Dermatology by David X. Zheng, BA, and colleagues at Case Western Reserve University, Cleveland, and the department of dermatology, Johns Hopkins University, Baltimore.

Visitors consume information in video bits that run from 15 seconds to up to 3 minutes and can follow their favorite TikTokkers, browse for people or hashtags with a search function, or click on content recommended by the platform, which uses algorithms based on the user’s viewing habits to determine what might be of interest.

Some of the biggest “skinfluencers” have millions of followers: Hyram Yarbro, (@skincarebyhyram) for instance, has 6.6 million followers and his own line of skin care products at Sephora. Mr. Yarbro is seen as a no-nonsense debunker of skin care myths, as is British influencer James Welsh, who has 124,000 followers.

“The reason why people trust your average influencer person who’s not a doctor is because they’re relatable,” said Muneeb Shah, MD, a dermatology resident at Atlantic Dermatology in Wilmington, N.C. – known to his 11.4 million TikTok followers as @dermdoctor.

To Sandra Lee, MD, the popularity of nonprofessionals is easy to explain. “You have to think about the fact that a lot of people can’t see dermatologists – they don’t have the money, they don’t have the time to travel there, they don’t have health insurance, or they’re scared of doctors, so they’re willing to try to find an answer, and one of the easiest ways, one of the more entertaining ways to get information, is on social media.”

Dr. Lee is in private practice in Upland, Calif., but is better known as “Dr. Pimple Popper,” through her television show of the same name and her social media accounts, including on TikTok, where she has 14.4 million followers after having started in 2020.

“We’re all looking for that no-down-time, no-expense, no-lines, no-wrinkles, stay-young-forever magic bullet,” said Dr. Lee.

Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, agreed that people are looking for a quick fix. They don’t want to wait 12 weeks for an acne medication or 16 weeks for a biologic to work. “They want something simple, easy, do-it-yourself,” and “natural,” he said.

Laypeople are still the dominant producers – and have the most views – of dermatology content.

Morgan Nguyen, BA, at Northwestern University, Chicago, and colleagues looked at hashtags for the top 10 dermatologic diagnoses and procedures and analyzed the content of the first 40 TikTok videos in each category. About half the videos were produced by an individual, and 39% by a health care provider, according to the study, published in the International Journal of Women’s Dermatology. About 40% of the videos were educational, focusing on skin care, procedures, and disease treatment.

Viewership was highest for videos by laypeople, followed by those produced by business or industry accounts. Those produced by health care providers received only 18% of the views.

The most popular videos were about dermatologic diagnoses, with 2.5 billion views, followed by dermatologic procedures, with 708 million views.

Ms. Nguyen noted in the study that the most liked and most viewed posts were related to #skincare but that board-certified dermatologists produced only 2.5% of the #skincare videos.


 

Dermatologists take to TikTok

Some dermatologists have started their own TikTok accounts, seeking both to counteract misinformation and provide education.

Dr. Shah has become one of the top influencers on the platform. In a year-end wrap, TikTok put Dr. Shah at No. 7 on its top creators list for 2021.

MDedge

Doris Day, MD, who goes by @drdorisday on TikTok, agreed with Dr. Lee. “There are so many creative ways you can convey information with it that’s different than what you have on Instagram,” said Dr. Day, who is in private practice in New York. And, she added, “it does really lend itself to getting points out super-fast.”

Dermatologists on TikTok also said they like the “duets” and the “stitch” features, which allow users to add on to an existing video, essentially chiming in or responding to what might have already been posted, in a side-by-side format.

Dr. Shah said he often duets videos that have questionable content. “It allows me to directly respond to people. A lot of times, if something is going really viral and it’s not accurate, you’ll have a response from me or one of the other doctors” within hours or days.

Dr. Shah’s duets are labeled with “DermDoctor Reacts” or “DermDoctor Explains.” In one duet, with more than 2.8 million views, the upper half of the video is someone squeezing a blackhead, while Dr. Shah, in the bottom half, in green scrubs, opines over some hip-hop music: “This is just a blackhead. But once it gets to this point, they do need to be extracted because topical treatments won’t help.”

TikTok trends gone bad

And some people are being hurt by emulating what they see on TikTok.

Dr. Friedman had a patient with extreme irritant contact dermatitis, “almost like chemical burns to her underarms,” he said. He determined that she saw a video “hack” that recommended using baking soda to stop hyperhidrosis. The patient used so much that it burned her skin.

In 2020, do-it-yourself freckles – with henna or sewing needles impregnated with ink – went viral. Tilly Whitfeld, a 21-year-old reality TV star on Australia’s Big Brother show, told the New York Times that she tried it at home after seeing a TikTok video. She ordered brown tattoo ink online and later found out that it was contaminated with lead, according to the Times. Ms. Whitfeld developed an infection and temporary vision loss and has permanent scarring.

She has since put out a cautionary TikTok video that’s been viewed some 300,000 times.

TikTokkers have also flocked to the idea of using sunscreen to “contour” the face. Selected areas are left without sunscreen to burn or tan. In a duet, a plastic surgeon shakes his head as a young woman explains that “it works.”

Scalp-popping – in which the hair is yanked so hard that it pulls the galea off the skull – has been mostly shut down by TikTok. A search of “scalp popping” brings up the message: “Learn how to recognize harmful challenges and hoaxes.” At-home mole and skin tag removal, pimple-popping, and supposed acne cures such as drinking chlorophyll are all avidly documented and shared on TikTok.

Dr. Shah had a back-and-forth video dialog with someone who had stubbed a toe and then drilled a hole into the nail to drain the hematoma. In a reaction video, Dr. Shah said it was likely to turn into an infection. When it did, the man revealed the infection in a video where he tagged Dr. Shah and later posted a video at the podiatrist’s office having his nail removed, again tagging Dr. Shah.

“I think that pretty much no procedure for skin is good to do at home,” said Dr. Shah, who repeatedly admonishes against mole removal by a nonphysician. He tells followers that “it’s extremely dangerous – not only is it going to cause scarring, but you are potentially discarding a cancerous lesion.”

Unfortunately, most will not follow the advice, said Dr. Shah. That’s especially true of pimple-popping. Aiming for the least harm, he suggests in some TikTok videos that poppers keep the area clean, wear gloves, and consult a physician to get an antibiotic prescription. “You might as well at least guide them in the right direction,” he added.

Dr. Lee believes that lack of access to physicians, insurance, or money may play into how TikTok trends evolve. “Probably those people who injected their lips with this air gun thing, maybe they didn’t have the money necessarily to get filler,” she said.

Also, she noted, while TikTok may try to police its content, creators are incentivized to be outrageous. “The more inflammatory your post is, the more engagement you get.”

Dr. Shah thinks TikTok is self-correcting. “If you’re not being ethical or contradicting yourself, putting out information that’s not accurate, people are going to catch on very quickly,” he said. “The only value, the only currency you have on social media is the trust that you build with people that follow you.”
 

What it takes to be a TikTokker

For dermatologists, conveying their credentials and experience is one way to build that currency. Dr. Lee advised fellow doctors on TikTok to “showcase your training and how many years it took to become a dermatologist.”

Plunging into TikTok is not for everyone, though. It’s time consuming, said Dr. Lee, who now devotes most of her nonclinical time to TikTok. She creates her own content, leaving others to manage her Instagram account.

Many of those in the medical field who have dived into TikTok are residents, like Dr. Shah. “They are attuned to it and understand it more,” said Dr. Lee. “It’s harder for a lot of us who are older, who really weren’t involved that much in social media at all. It’s very hard to jump in.” There’s a learning curve, and it takes hours to create a single video. “You have to enjoy it and it has to be a part of your life,” she said.

Dr. Shah started experimenting with TikTok at the beginning of the pandemic in 2020 and has never turned back. Fast-talking, curious, and with an infectious sense of fun, he shares tidbits about his personal life – putting his wife in some of his videos – and always seems upbeat.

He said that, as his following grew, users began to see him as an authority figure and started “tagging” him more often, seeking his opinion on other videos. Although still a resident, he believes he has specialized knowledge to share. “Even if you’re not the world’s leading expert in a particular topic, you’re still adding value for the person who doesn’t know much.”

Dr. Shah also occasionally does promotional TikToks, identified as sponsored content. He said he only works with companies that he believes have legitimate products. “You do have to monetize at some point,” he said, noting that many dermatologists, himself included, are trading clinic time for TikTok. “There’s no universe where they can do this for free.”

Product endorsements are likely more rewarding for influencers and other users like Dr. Shah than the remuneration from TikTok, the company. The platform pays user accounts $20 per 1 million views, Dr. Shah said. “Financially, it’s not a big winner for a practicing dermatologist, but the educational outreach is worthwhile.”

To be successful also means understanding what drives viewership.

Using “trending” sounds has “been shown to increase the likelihood of a video amassing millions of views” and may increase engagement with dermatologists’ TikTok videos, wrote Bina Kassamali, BA, and colleagues at the Brigham and Women’s Hospital in Boston and the Ponce Health Science University School of Medicine in Ponce, Puerto Rico, in a letter published in the Journal of the American Academy of Dermatology in July 2021.

Certain content is more likely to engage viewers. In their analysis of top trending dermatologic hashtags, acne-related content was viewed 6.7 billion times, followed by alopecia, with 1.1 billion views. Psoriasis content had 84 million views, putting it eighth on the list of topics.

Dermatologists are still cracking TikTok. They are accumulating more followers on TikTok than on Instagram but have greater engagement on Instagram reels, wrote Mindy D. Szeto, MS, and colleagues at the University of Colorado at Denver, Aurora, and Rocky Vista University in Parker, Colo., in the Journal of the American Academy of Dermatology in April 2021.

Dr. Lee and Dr. Shah had the highest engagement rate on TikTok, according to Ms. Szeto. The engagement rate is calculated as (likes + comments per post)/(total followers) x 100.

“TikTok may currently be the leading avenue for audience education by dermatologist influencers,” they wrote, urging dermatologists to use the platform to answer the call as more of the public “continues to turn to social media for medical advice.”

Dr. Day said she will keep trying to build her TikTok audience. She has just 239 followers, compared with her 44,500 on Instagram. “The more I do TikTok, the more I do any of these mediums, the better I get at it,” she said. “We just have to put a little time and effort into it and try to get more followers and just keep sharing the information.”

Dr. Friedman sees it as a positive that some dermatologists have taken to TikTok to dispel myths and put “good information out there in small bites.” But to be more effective, they need more followers.

“The truth is that 14-year-old is probably going to listen more to a Hyram than a dermatologist,” he said. “Maybe we need to work with these other individuals who know how to take these messages and convert them to a language that can be digested by a 14-year-old, by a 12-year-old, by a 23-year-old. We need to come to the table together and not fight.”

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

A young woman is having her lip swabbed with an unknown substance, smiling, on the TikTok video. Seconds later, another young woman, wearing gloves, pushes a hyaluron pen against the first woman’s lips, who, in the next cut, is smiling, happy. “My first syringe down and already 1,000x more confident,” the caption reads.

That video is one of thousands showing hyaluron pen use on TikTok. The pens are sold online and are unapproved – which led to a Food and Drug Administration warning in October 2021 that use could cause bleeding, infection, blood vessel occlusion that could result in blindness or stroke, allergic reactions, and other injuries.

The warning has not stopped many TikTokkers, who also use the medium to promote all sorts of skin and aesthetic products and procedures, a large number unproven, unapproved, or ill advised. As TikTok has become one of the most widely used social media platforms, millions of mostly teenagers regularly log on for skin care advice, which, more often than not, comes from “skinfluencers,” aestheticians, and other laypeople, not board-certified dermatologists.

The suggested “hacks” can be harmless or ineffective, but they also can be misleading, fraudulent, or even dangerous.
 

Skinfluencers take the lead

TikTok has a reported 1 billion monthly users. Two-thirds are aged 10-29 years, according to data reported in February 2021 in the Journal of the American Academy of Dermatology by David X. Zheng, BA, and colleagues at Case Western Reserve University, Cleveland, and the department of dermatology, Johns Hopkins University, Baltimore.

Visitors consume information in video bits that run from 15 seconds to up to 3 minutes and can follow their favorite TikTokkers, browse for people or hashtags with a search function, or click on content recommended by the platform, which uses algorithms based on the user’s viewing habits to determine what might be of interest.

Some of the biggest “skinfluencers” have millions of followers: Hyram Yarbro, (@skincarebyhyram) for instance, has 6.6 million followers and his own line of skin care products at Sephora. Mr. Yarbro is seen as a no-nonsense debunker of skin care myths, as is British influencer James Welsh, who has 124,000 followers.

“The reason why people trust your average influencer person who’s not a doctor is because they’re relatable,” said Muneeb Shah, MD, a dermatology resident at Atlantic Dermatology in Wilmington, N.C. – known to his 11.4 million TikTok followers as @dermdoctor.

To Sandra Lee, MD, the popularity of nonprofessionals is easy to explain. “You have to think about the fact that a lot of people can’t see dermatologists – they don’t have the money, they don’t have the time to travel there, they don’t have health insurance, or they’re scared of doctors, so they’re willing to try to find an answer, and one of the easiest ways, one of the more entertaining ways to get information, is on social media.”

Dr. Lee is in private practice in Upland, Calif., but is better known as “Dr. Pimple Popper,” through her television show of the same name and her social media accounts, including on TikTok, where she has 14.4 million followers after having started in 2020.

“We’re all looking for that no-down-time, no-expense, no-lines, no-wrinkles, stay-young-forever magic bullet,” said Dr. Lee.

Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, agreed that people are looking for a quick fix. They don’t want to wait 12 weeks for an acne medication or 16 weeks for a biologic to work. “They want something simple, easy, do-it-yourself,” and “natural,” he said.

Laypeople are still the dominant producers – and have the most views – of dermatology content.

Morgan Nguyen, BA, at Northwestern University, Chicago, and colleagues looked at hashtags for the top 10 dermatologic diagnoses and procedures and analyzed the content of the first 40 TikTok videos in each category. About half the videos were produced by an individual, and 39% by a health care provider, according to the study, published in the International Journal of Women’s Dermatology. About 40% of the videos were educational, focusing on skin care, procedures, and disease treatment.

Viewership was highest for videos by laypeople, followed by those produced by business or industry accounts. Those produced by health care providers received only 18% of the views.

The most popular videos were about dermatologic diagnoses, with 2.5 billion views, followed by dermatologic procedures, with 708 million views.

Ms. Nguyen noted in the study that the most liked and most viewed posts were related to #skincare but that board-certified dermatologists produced only 2.5% of the #skincare videos.


 

Dermatologists take to TikTok

Some dermatologists have started their own TikTok accounts, seeking both to counteract misinformation and provide education.

Dr. Shah has become one of the top influencers on the platform. In a year-end wrap, TikTok put Dr. Shah at No. 7 on its top creators list for 2021.

MDedge

Doris Day, MD, who goes by @drdorisday on TikTok, agreed with Dr. Lee. “There are so many creative ways you can convey information with it that’s different than what you have on Instagram,” said Dr. Day, who is in private practice in New York. And, she added, “it does really lend itself to getting points out super-fast.”

Dermatologists on TikTok also said they like the “duets” and the “stitch” features, which allow users to add on to an existing video, essentially chiming in or responding to what might have already been posted, in a side-by-side format.

Dr. Shah said he often duets videos that have questionable content. “It allows me to directly respond to people. A lot of times, if something is going really viral and it’s not accurate, you’ll have a response from me or one of the other doctors” within hours or days.

Dr. Shah’s duets are labeled with “DermDoctor Reacts” or “DermDoctor Explains.” In one duet, with more than 2.8 million views, the upper half of the video is someone squeezing a blackhead, while Dr. Shah, in the bottom half, in green scrubs, opines over some hip-hop music: “This is just a blackhead. But once it gets to this point, they do need to be extracted because topical treatments won’t help.”

TikTok trends gone bad

And some people are being hurt by emulating what they see on TikTok.

Dr. Friedman had a patient with extreme irritant contact dermatitis, “almost like chemical burns to her underarms,” he said. He determined that she saw a video “hack” that recommended using baking soda to stop hyperhidrosis. The patient used so much that it burned her skin.

In 2020, do-it-yourself freckles – with henna or sewing needles impregnated with ink – went viral. Tilly Whitfeld, a 21-year-old reality TV star on Australia’s Big Brother show, told the New York Times that she tried it at home after seeing a TikTok video. She ordered brown tattoo ink online and later found out that it was contaminated with lead, according to the Times. Ms. Whitfeld developed an infection and temporary vision loss and has permanent scarring.

She has since put out a cautionary TikTok video that’s been viewed some 300,000 times.

TikTokkers have also flocked to the idea of using sunscreen to “contour” the face. Selected areas are left without sunscreen to burn or tan. In a duet, a plastic surgeon shakes his head as a young woman explains that “it works.”

Scalp-popping – in which the hair is yanked so hard that it pulls the galea off the skull – has been mostly shut down by TikTok. A search of “scalp popping” brings up the message: “Learn how to recognize harmful challenges and hoaxes.” At-home mole and skin tag removal, pimple-popping, and supposed acne cures such as drinking chlorophyll are all avidly documented and shared on TikTok.

Dr. Shah had a back-and-forth video dialog with someone who had stubbed a toe and then drilled a hole into the nail to drain the hematoma. In a reaction video, Dr. Shah said it was likely to turn into an infection. When it did, the man revealed the infection in a video where he tagged Dr. Shah and later posted a video at the podiatrist’s office having his nail removed, again tagging Dr. Shah.

“I think that pretty much no procedure for skin is good to do at home,” said Dr. Shah, who repeatedly admonishes against mole removal by a nonphysician. He tells followers that “it’s extremely dangerous – not only is it going to cause scarring, but you are potentially discarding a cancerous lesion.”

Unfortunately, most will not follow the advice, said Dr. Shah. That’s especially true of pimple-popping. Aiming for the least harm, he suggests in some TikTok videos that poppers keep the area clean, wear gloves, and consult a physician to get an antibiotic prescription. “You might as well at least guide them in the right direction,” he added.

Dr. Lee believes that lack of access to physicians, insurance, or money may play into how TikTok trends evolve. “Probably those people who injected their lips with this air gun thing, maybe they didn’t have the money necessarily to get filler,” she said.

Also, she noted, while TikTok may try to police its content, creators are incentivized to be outrageous. “The more inflammatory your post is, the more engagement you get.”

Dr. Shah thinks TikTok is self-correcting. “If you’re not being ethical or contradicting yourself, putting out information that’s not accurate, people are going to catch on very quickly,” he said. “The only value, the only currency you have on social media is the trust that you build with people that follow you.”
 

What it takes to be a TikTokker

For dermatologists, conveying their credentials and experience is one way to build that currency. Dr. Lee advised fellow doctors on TikTok to “showcase your training and how many years it took to become a dermatologist.”

Plunging into TikTok is not for everyone, though. It’s time consuming, said Dr. Lee, who now devotes most of her nonclinical time to TikTok. She creates her own content, leaving others to manage her Instagram account.

Many of those in the medical field who have dived into TikTok are residents, like Dr. Shah. “They are attuned to it and understand it more,” said Dr. Lee. “It’s harder for a lot of us who are older, who really weren’t involved that much in social media at all. It’s very hard to jump in.” There’s a learning curve, and it takes hours to create a single video. “You have to enjoy it and it has to be a part of your life,” she said.

Dr. Shah started experimenting with TikTok at the beginning of the pandemic in 2020 and has never turned back. Fast-talking, curious, and with an infectious sense of fun, he shares tidbits about his personal life – putting his wife in some of his videos – and always seems upbeat.

He said that, as his following grew, users began to see him as an authority figure and started “tagging” him more often, seeking his opinion on other videos. Although still a resident, he believes he has specialized knowledge to share. “Even if you’re not the world’s leading expert in a particular topic, you’re still adding value for the person who doesn’t know much.”

Dr. Shah also occasionally does promotional TikToks, identified as sponsored content. He said he only works with companies that he believes have legitimate products. “You do have to monetize at some point,” he said, noting that many dermatologists, himself included, are trading clinic time for TikTok. “There’s no universe where they can do this for free.”

Product endorsements are likely more rewarding for influencers and other users like Dr. Shah than the remuneration from TikTok, the company. The platform pays user accounts $20 per 1 million views, Dr. Shah said. “Financially, it’s not a big winner for a practicing dermatologist, but the educational outreach is worthwhile.”

To be successful also means understanding what drives viewership.

Using “trending” sounds has “been shown to increase the likelihood of a video amassing millions of views” and may increase engagement with dermatologists’ TikTok videos, wrote Bina Kassamali, BA, and colleagues at the Brigham and Women’s Hospital in Boston and the Ponce Health Science University School of Medicine in Ponce, Puerto Rico, in a letter published in the Journal of the American Academy of Dermatology in July 2021.

Certain content is more likely to engage viewers. In their analysis of top trending dermatologic hashtags, acne-related content was viewed 6.7 billion times, followed by alopecia, with 1.1 billion views. Psoriasis content had 84 million views, putting it eighth on the list of topics.

Dermatologists are still cracking TikTok. They are accumulating more followers on TikTok than on Instagram but have greater engagement on Instagram reels, wrote Mindy D. Szeto, MS, and colleagues at the University of Colorado at Denver, Aurora, and Rocky Vista University in Parker, Colo., in the Journal of the American Academy of Dermatology in April 2021.

Dr. Lee and Dr. Shah had the highest engagement rate on TikTok, according to Ms. Szeto. The engagement rate is calculated as (likes + comments per post)/(total followers) x 100.

“TikTok may currently be the leading avenue for audience education by dermatologist influencers,” they wrote, urging dermatologists to use the platform to answer the call as more of the public “continues to turn to social media for medical advice.”

Dr. Day said she will keep trying to build her TikTok audience. She has just 239 followers, compared with her 44,500 on Instagram. “The more I do TikTok, the more I do any of these mediums, the better I get at it,” she said. “We just have to put a little time and effort into it and try to get more followers and just keep sharing the information.”

Dr. Friedman sees it as a positive that some dermatologists have taken to TikTok to dispel myths and put “good information out there in small bites.” But to be more effective, they need more followers.

“The truth is that 14-year-old is probably going to listen more to a Hyram than a dermatologist,” he said. “Maybe we need to work with these other individuals who know how to take these messages and convert them to a language that can be digested by a 14-year-old, by a 12-year-old, by a 23-year-old. We need to come to the table together and not fight.”

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

The advisory on youth mental health from Surgeon General Vivek Murthy, MD, casts a necessary spotlight on the crisis, clinical psychiatrists say. But some think it could have produced more specifics about funding and payment parity for reimbursement.

The 53-page advisory says that about one in five U.S. children and adolescents aged 3-17 suffer from a mental, emotional, developmental, or behavioral disorder. In the decade before COVID, feelings of sadness and hopelessness, as well as suicidal behaviors, were on the rise. The pandemic has exacerbated symptoms of anxiety, depression, and other mental health issues in young people. Compared with 2019, ED visits in early 2021 for suspected suicide attempts rose 51% in adolescent girls and 4% in boys. “Depressive and anxiety symptoms doubled during the pandemic,” the advisory said.
 

Scope of the advisory

The advisory, released Dec. 7, covers all sectors and considers all social and policy factors that might be contributing to this crisis, said Jessica (Jessi) Gold, MD, MS, an assistant professor in the department of psychiatry at Washington University, St. Louis.

“It is always possible to reimagine health care to be more patient centered and mental health forward.” But changes of this magnitude take time, Dr. Gold, also director of wellness, engagement, and outreach at the university, said in an interview.

She has seen the impact of the pandemic firsthand in her clinic among students and frontline health care workers aged 18-30. People in that age group “feel everything deeply,” Dr. Gold said. Emotions tied to COVID-19 are just a part of it. Confounding factors, such as climate change, racism, and school shootings all contribute to their overall mental health.

Some children and adolescents with social anxiety have fared better during the pandemic, but those who are part of demographic groups such as racial and ethnic minorities, LGBTQ individuals, low-income youth, and those involved in juvenile justice or welfare systems face a higher risk of mental health challenges, the pandemic notwithstanding.

In her work with schools, Denese Shervington, MD, MPH, has witnessed more mental health challenges related to isolation and separation. “There’s an overall worry about the loss of what used to be, the seeming predictability and certainty of prepandemic life,” said Dr. Shervington, clinical professor of psychiatry at Tulane University, and president and CEO of the Institute for Women and Ethnic Studies, both in New Orleans.
 

A systems of care plan

The advisory lists actionable items for health care and 10 other industry sectors to improve mental health of children and young adults.

Health care organizations and professionals were advised to take the following six steps:

• Implement trauma-informed care principles and other prevention strategies. This may involve referring patients to resources such as economic and legal supports, school enrichment programs, and educating families on healthy child development in the clinic.
• Routinely screen children for mental health challenges and risk factors such as adverse childhood experiences during primary care well-visits or annual physicals, or at schools or EDs. Primary care physicians should use principles of trauma-informed care to conduct these screenings.
• Screen parents, caregivers, and other family members for depression, intimate partner violence, substance use, and other challenges. These can be done in tandem with broader assessments of social determinants of health such as food or housing insecurity.
• Combine efforts of clinical staff with trusted community partners and child welfare and juvenile justice. Hospital-based violence intervention programs, for example, identify patients at risk of repeat violent injury and refer them to hospital- and community-based resources.
• Build multidisciplinary teams, enlisting children and families to develop services that are tailored to their needs for screening and treatment. Such services should reflect cultural diversity and offered in multiple languages.
• Support the well-being of mental health workers and community leaders to foster their ability to help youth and their families.

Dr. Murthy is talking about a “systems of care” approach, in which all sectors that touch children and youth – not just health care – must work together and do their jobs effectively but collaboratively to address this public health crisis, said Aradhana (Bela) Sood MD, MSHA, FAACAP, senior professor of child mental health policy at Virginia Commonwealth University, Richmond. “An investment in infrastructure support of positive mental health in early childhood, be it in schools, communities, or family well-being will lead to a future where illness is not the result of major preventable societal factors, such as a lack of social supports and trauma.”
 

Changes will ‘take a lot of buy-in’

The recommendations are actionable in the real world – but there are a lot of them, said Dr. Gold. Dr. Murthy doesn’t specify what the plan is to accomplish these metrics or fund them, she added. He “has money and funders like foundations as steps, but foundations have also suffered in the pandemic, so it is not that simple.” Many of these changes are wide in scope and will take a lot of buy-in.

Dr. Shervington would like to have seen more of a focus on educator well-being, given that young people spend a lot of time in educational settings.

“My organization just completed a study in New Orleans that showed teachers having elevated levels of trauma-based conditions since the pandemic,” she said. Schools are indeed a key place to support holistic mental health by focusing on school climate, Dr. Sood added. “If school administrators became uniformly consistent with recognizing the importance of psychological wellness as a prerequisite of good learning, they will create environments where teachers are keenly aware of a child’s mental wellness and make reduction of bullying, wellness check-ins, [and] school-based mental health clinics a priority.

“These are ways nonmedical, community-based supports can enhance student well-being, and reduce depression and other mental health conditions,” Dr. Sood added.
 

Child psychiatrists stretched ‘even thinner’

Despite mental health parity rules, health plans have not been held accountable. That failure, combined with excessive demands for prior authorization for mental health treatments “have led to dangerous shortages of psychiatrists able to accept insurance,” said Paul S. Nestadt, MD, an assistant professor and public mental health researcher at Johns Hopkins University, Baltimore.

“This is particularly true for child psychiatrists, who are stretched even thinner than those of us in general practice,” Dr. Nestadt said.

While he doesn’t address it head on, Dr. Murthy uses classic parity language when he states that “mental health is no less important than physical health,” said Dr. Nestadt, who consulted with the surgeon general on developing this advisory. “While many of us would have liked to see parity highlighted more directly, this advisory was designed to be an overview.”
 

Highlighting social media, gun violence

Dr. Nestadt said he was pleased that the advisory emphasized the importance of restricting access to lethal means in preventing youth suicide.

“With youth suicide rates rising faster than in other age groups, and suicide mortality tied so closely to method availability, the surgeon general made the right choice in highlighting the role of guns in suicide,” he said.

The advisory also discussed the role of media and social media companies in addressing the crisis, which is important, said Dr. Gold.

“I believe very strongly that the way we talk about and portray mental health in the media matters,” she said. “I have seen it matter in the clinic with patients. They’ll wonder if someone will think they are now violent if they are diagnosed with a mental illness. Stories change the narrative.”

While the advisory isn’t perfect, the state of youth mental health “will only get worse if we don’t do something,” noted Dr. Gold. “It is critical that this is validated and discussed at the highest level and messages like Dr. Murthy’s get heard.”

Dr. Gold, Dr. Shervington, and Dr. Sood had no disclosures. Dr. Nestadt disclosed serving as a consultant to the surgeon general advisory.

The advisory on youth mental health from Surgeon General Vivek Murthy, MD, casts a necessary spotlight on the crisis, clinical psychiatrists say. But some think it could have produced more specifics about funding and payment parity for reimbursement.

The 53-page advisory says that about one in five U.S. children and adolescents aged 3-17 suffer from a mental, emotional, developmental, or behavioral disorder. In the decade before COVID, feelings of sadness and hopelessness, as well as suicidal behaviors, were on the rise. The pandemic has exacerbated symptoms of anxiety, depression, and other mental health issues in young people. Compared with 2019, ED visits in early 2021 for suspected suicide attempts rose 51% in adolescent girls and 4% in boys. “Depressive and anxiety symptoms doubled during the pandemic,” the advisory said.
 

Scope of the advisory

The advisory, released Dec. 7, covers all sectors and considers all social and policy factors that might be contributing to this crisis, said Jessica (Jessi) Gold, MD, MS, an assistant professor in the department of psychiatry at Washington University, St. Louis.

“It is always possible to reimagine health care to be more patient centered and mental health forward.” But changes of this magnitude take time, Dr. Gold, also director of wellness, engagement, and outreach at the university, said in an interview.

She has seen the impact of the pandemic firsthand in her clinic among students and frontline health care workers aged 18-30. People in that age group “feel everything deeply,” Dr. Gold said. Emotions tied to COVID-19 are just a part of it. Confounding factors, such as climate change, racism, and school shootings all contribute to their overall mental health.

Some children and adolescents with social anxiety have fared better during the pandemic, but those who are part of demographic groups such as racial and ethnic minorities, LGBTQ individuals, low-income youth, and those involved in juvenile justice or welfare systems face a higher risk of mental health challenges, the pandemic notwithstanding.

In her work with schools, Denese Shervington, MD, MPH, has witnessed more mental health challenges related to isolation and separation. “There’s an overall worry about the loss of what used to be, the seeming predictability and certainty of prepandemic life,” said Dr. Shervington, clinical professor of psychiatry at Tulane University, and president and CEO of the Institute for Women and Ethnic Studies, both in New Orleans.
 

A systems of care plan

The advisory lists actionable items for health care and 10 other industry sectors to improve mental health of children and young adults.

Health care organizations and professionals were advised to take the following six steps:

• Implement trauma-informed care principles and other prevention strategies. This may involve referring patients to resources such as economic and legal supports, school enrichment programs, and educating families on healthy child development in the clinic.
• Routinely screen children for mental health challenges and risk factors such as adverse childhood experiences during primary care well-visits or annual physicals, or at schools or EDs. Primary care physicians should use principles of trauma-informed care to conduct these screenings.
• Screen parents, caregivers, and other family members for depression, intimate partner violence, substance use, and other challenges. These can be done in tandem with broader assessments of social determinants of health such as food or housing insecurity.
• Combine efforts of clinical staff with trusted community partners and child welfare and juvenile justice. Hospital-based violence intervention programs, for example, identify patients at risk of repeat violent injury and refer them to hospital- and community-based resources.
• Build multidisciplinary teams, enlisting children and families to develop services that are tailored to their needs for screening and treatment. Such services should reflect cultural diversity and offered in multiple languages.
• Support the well-being of mental health workers and community leaders to foster their ability to help youth and their families.

Dr. Murthy is talking about a “systems of care” approach, in which all sectors that touch children and youth – not just health care – must work together and do their jobs effectively but collaboratively to address this public health crisis, said Aradhana (Bela) Sood MD, MSHA, FAACAP, senior professor of child mental health policy at Virginia Commonwealth University, Richmond. “An investment in infrastructure support of positive mental health in early childhood, be it in schools, communities, or family well-being will lead to a future where illness is not the result of major preventable societal factors, such as a lack of social supports and trauma.”
 

Changes will ‘take a lot of buy-in’

The recommendations are actionable in the real world – but there are a lot of them, said Dr. Gold. Dr. Murthy doesn’t specify what the plan is to accomplish these metrics or fund them, she added. He “has money and funders like foundations as steps, but foundations have also suffered in the pandemic, so it is not that simple.” Many of these changes are wide in scope and will take a lot of buy-in.

Dr. Shervington would like to have seen more of a focus on educator well-being, given that young people spend a lot of time in educational settings.

“My organization just completed a study in New Orleans that showed teachers having elevated levels of trauma-based conditions since the pandemic,” she said. Schools are indeed a key place to support holistic mental health by focusing on school climate, Dr. Sood added. “If school administrators became uniformly consistent with recognizing the importance of psychological wellness as a prerequisite of good learning, they will create environments where teachers are keenly aware of a child’s mental wellness and make reduction of bullying, wellness check-ins, [and] school-based mental health clinics a priority.

“These are ways nonmedical, community-based supports can enhance student well-being, and reduce depression and other mental health conditions,” Dr. Sood added.
 

Child psychiatrists stretched ‘even thinner’

Despite mental health parity rules, health plans have not been held accountable. That failure, combined with excessive demands for prior authorization for mental health treatments “have led to dangerous shortages of psychiatrists able to accept insurance,” said Paul S. Nestadt, MD, an assistant professor and public mental health researcher at Johns Hopkins University, Baltimore.

“This is particularly true for child psychiatrists, who are stretched even thinner than those of us in general practice,” Dr. Nestadt said.

While he doesn’t address it head on, Dr. Murthy uses classic parity language when he states that “mental health is no less important than physical health,” said Dr. Nestadt, who consulted with the surgeon general on developing this advisory. “While many of us would have liked to see parity highlighted more directly, this advisory was designed to be an overview.”
 

Highlighting social media, gun violence

Dr. Nestadt said he was pleased that the advisory emphasized the importance of restricting access to lethal means in preventing youth suicide.

“With youth suicide rates rising faster than in other age groups, and suicide mortality tied so closely to method availability, the surgeon general made the right choice in highlighting the role of guns in suicide,” he said.

The advisory also discussed the role of media and social media companies in addressing the crisis, which is important, said Dr. Gold.

“I believe very strongly that the way we talk about and portray mental health in the media matters,” she said. “I have seen it matter in the clinic with patients. They’ll wonder if someone will think they are now violent if they are diagnosed with a mental illness. Stories change the narrative.”

While the advisory isn’t perfect, the state of youth mental health “will only get worse if we don’t do something,” noted Dr. Gold. “It is critical that this is validated and discussed at the highest level and messages like Dr. Murthy’s get heard.”

Dr. Gold, Dr. Shervington, and Dr. Sood had no disclosures. Dr. Nestadt disclosed serving as a consultant to the surgeon general advisory.

The advisory on youth mental health from Surgeon General Vivek Murthy, MD, casts a necessary spotlight on the crisis, clinical psychiatrists say. But some think it could have produced more specifics about funding and payment parity for reimbursement.

The 53-page advisory says that about one in five U.S. children and adolescents aged 3-17 suffer from a mental, emotional, developmental, or behavioral disorder. In the decade before COVID, feelings of sadness and hopelessness, as well as suicidal behaviors, were on the rise. The pandemic has exacerbated symptoms of anxiety, depression, and other mental health issues in young people. Compared with 2019, ED visits in early 2021 for suspected suicide attempts rose 51% in adolescent girls and 4% in boys. “Depressive and anxiety symptoms doubled during the pandemic,” the advisory said.
 

Scope of the advisory

The advisory, released Dec. 7, covers all sectors and considers all social and policy factors that might be contributing to this crisis, said Jessica (Jessi) Gold, MD, MS, an assistant professor in the department of psychiatry at Washington University, St. Louis.

“It is always possible to reimagine health care to be more patient centered and mental health forward.” But changes of this magnitude take time, Dr. Gold, also director of wellness, engagement, and outreach at the university, said in an interview.

She has seen the impact of the pandemic firsthand in her clinic among students and frontline health care workers aged 18-30. People in that age group “feel everything deeply,” Dr. Gold said. Emotions tied to COVID-19 are just a part of it. Confounding factors, such as climate change, racism, and school shootings all contribute to their overall mental health.

Some children and adolescents with social anxiety have fared better during the pandemic, but those who are part of demographic groups such as racial and ethnic minorities, LGBTQ individuals, low-income youth, and those involved in juvenile justice or welfare systems face a higher risk of mental health challenges, the pandemic notwithstanding.

In her work with schools, Denese Shervington, MD, MPH, has witnessed more mental health challenges related to isolation and separation. “There’s an overall worry about the loss of what used to be, the seeming predictability and certainty of prepandemic life,” said Dr. Shervington, clinical professor of psychiatry at Tulane University, and president and CEO of the Institute for Women and Ethnic Studies, both in New Orleans.
 

A systems of care plan

The advisory lists actionable items for health care and 10 other industry sectors to improve mental health of children and young adults.

Health care organizations and professionals were advised to take the following six steps:

• Implement trauma-informed care principles and other prevention strategies. This may involve referring patients to resources such as economic and legal supports, school enrichment programs, and educating families on healthy child development in the clinic.
• Routinely screen children for mental health challenges and risk factors such as adverse childhood experiences during primary care well-visits or annual physicals, or at schools or EDs. Primary care physicians should use principles of trauma-informed care to conduct these screenings.
• Screen parents, caregivers, and other family members for depression, intimate partner violence, substance use, and other challenges. These can be done in tandem with broader assessments of social determinants of health such as food or housing insecurity.
• Combine efforts of clinical staff with trusted community partners and child welfare and juvenile justice. Hospital-based violence intervention programs, for example, identify patients at risk of repeat violent injury and refer them to hospital- and community-based resources.
• Build multidisciplinary teams, enlisting children and families to develop services that are tailored to their needs for screening and treatment. Such services should reflect cultural diversity and offered in multiple languages.
• Support the well-being of mental health workers and community leaders to foster their ability to help youth and their families.

Dr. Murthy is talking about a “systems of care” approach, in which all sectors that touch children and youth – not just health care – must work together and do their jobs effectively but collaboratively to address this public health crisis, said Aradhana (Bela) Sood MD, MSHA, FAACAP, senior professor of child mental health policy at Virginia Commonwealth University, Richmond. “An investment in infrastructure support of positive mental health in early childhood, be it in schools, communities, or family well-being will lead to a future where illness is not the result of major preventable societal factors, such as a lack of social supports and trauma.”
 

Changes will ‘take a lot of buy-in’

The recommendations are actionable in the real world – but there are a lot of them, said Dr. Gold. Dr. Murthy doesn’t specify what the plan is to accomplish these metrics or fund them, she added. He “has money and funders like foundations as steps, but foundations have also suffered in the pandemic, so it is not that simple.” Many of these changes are wide in scope and will take a lot of buy-in.

Dr. Shervington would like to have seen more of a focus on educator well-being, given that young people spend a lot of time in educational settings.

“My organization just completed a study in New Orleans that showed teachers having elevated levels of trauma-based conditions since the pandemic,” she said. Schools are indeed a key place to support holistic mental health by focusing on school climate, Dr. Sood added. “If school administrators became uniformly consistent with recognizing the importance of psychological wellness as a prerequisite of good learning, they will create environments where teachers are keenly aware of a child’s mental wellness and make reduction of bullying, wellness check-ins, [and] school-based mental health clinics a priority.

“These are ways nonmedical, community-based supports can enhance student well-being, and reduce depression and other mental health conditions,” Dr. Sood added.
 

Child psychiatrists stretched ‘even thinner’

Despite mental health parity rules, health plans have not been held accountable. That failure, combined with excessive demands for prior authorization for mental health treatments “have led to dangerous shortages of psychiatrists able to accept insurance,” said Paul S. Nestadt, MD, an assistant professor and public mental health researcher at Johns Hopkins University, Baltimore.

“This is particularly true for child psychiatrists, who are stretched even thinner than those of us in general practice,” Dr. Nestadt said.

While he doesn’t address it head on, Dr. Murthy uses classic parity language when he states that “mental health is no less important than physical health,” said Dr. Nestadt, who consulted with the surgeon general on developing this advisory. “While many of us would have liked to see parity highlighted more directly, this advisory was designed to be an overview.”
 

Highlighting social media, gun violence

Dr. Nestadt said he was pleased that the advisory emphasized the importance of restricting access to lethal means in preventing youth suicide.

“With youth suicide rates rising faster than in other age groups, and suicide mortality tied so closely to method availability, the surgeon general made the right choice in highlighting the role of guns in suicide,” he said.

The advisory also discussed the role of media and social media companies in addressing the crisis, which is important, said Dr. Gold.

“I believe very strongly that the way we talk about and portray mental health in the media matters,” she said. “I have seen it matter in the clinic with patients. They’ll wonder if someone will think they are now violent if they are diagnosed with a mental illness. Stories change the narrative.”

While the advisory isn’t perfect, the state of youth mental health “will only get worse if we don’t do something,” noted Dr. Gold. “It is critical that this is validated and discussed at the highest level and messages like Dr. Murthy’s get heard.”

Dr. Gold, Dr. Shervington, and Dr. Sood had no disclosures. Dr. Nestadt disclosed serving as a consultant to the surgeon general advisory.

Robert M. Califf, MD, plans to take a close look at federal policies on opioid prescriptions in his expected second turn as the top U.S. regulator of medical products, as well as keep closer tabs on the performance of drugs cleared with accelerated approvals.

Catherine Hackett/Frontline Medical News

Dr. Califf on Tuesday fielded questions at a Senate hearing about his nomination by President Joe Biden to serve as administrator of the U.S. Food and Drug Administration, a role in which he served in the Obama administration. He also spoke about the need to bolster the nation’s ability to maintain an adequate supply of key medical products, including drugs.

Members of the Senate Health, Education, Labor and Pensions Committee, which is handling Dr. Califf’s nomination, were largely cordial and supportive during the hearing. Sen. Patty Murray (D-Wash.), the committee chair, and the panel’s top Republican, Sen. Richard Burr of North Carolina, addressed Dr. Califf during the hearing as if he would soon serve again as the FDA’s leader. Both were among the senators who voted 89-4 to confirm Dr. Califf in a February 2016 vote.

Dr. Califf “was previously confirmed to lead FDA in an overwhelming bipartisan vote, and I look forward to working with him again to ensure FDA continues to protect families across the country, uphold the gold standard of safety and effectiveness, and put science and data first,” Sen. Murray said.

Less enthusiastic about Dr. Califf was Sen. Bernie Sanders (I-VT), who was among the seven senators who did not vote on Dr. Califf’s nomination in 2016.

Sen. Sanders objected in 2016 to Dr. Califf’s ties to the pharmaceutical industry, and he did so again Tuesday. A noted leader in conducting clinical trials, Dr. Califf has worked with many drugmakers. But at the hearing, Dr. Califf said he concurs with Sen. Sanders on an idea strongly opposed by the pharmaceutical industry.

In response to Sen. Sanders’ question, Dr. Califf said he already is “on record as being in favor of Medicare negotiating with the industry on prices.”

The FDA would not take direct part in negotiations, as this work would be handled by the Centers for Medicare & Medicaid Services. Democrats want to give Medicare some negotiating authority through their sweeping Build Back Better Act.

People in the United States are dismayed over both the cost of prescription drugs and the widespread distribution of prescription painkillers that helped fuel the current opioid epidemic, Sen. Sanders told Dr. Califf. Many people will be concerned about an FDA commissioner who has benefited from close ties to the industry, Sen. Sanders said.

“How are they going to believe that you’re going to be an independent and strong voice against this enormously powerful, special interest?” Sen. Sanders asked.

“I’m totally with you on the concept that the price of pharmaceuticals is way too high in this country,” Dr. Califf said in reply.

Dr. Califf was paid $2.7 million in salary and bonus by Verily Life Sciences, the biomedical research organization operated by Alphabet, parent company of Google, according to his federal financial disclosure. He also reported holding board positions with pharmaceutical companies AmyriAD and Centessa Pharmaceuticals.

Bloomberg Government reported that Dr. Califf has ties to about 16 other research organizations and biotech companies. Bloomberg Government also said that, in his earlier FDA service, Dr. Califf kept a whiteboard in his office that listed all the activities and projects that required his recusal, citing as a source Howard Sklamberg, who was a deputy commissioner under Dr. Califf.

“He was very, very, very careful,” Mr. Sklamberg, who’s now an attorney at Arnold & Porter LLP, told Bloomberg Government.
 

‘Work to do’ on opioids

Senators looped back repeatedly to the topic of opioids during Dr. Califf’s hearing, reflecting deep concerns about the FDA’s efforts to warn of the risks of prescription painkillers.

There were an estimated 100,306 drug overdose deaths in the United States in the 12 months ending in April, an increase of 28.5% from the 78,056 deaths during the same period the year before, according to the Centers for Disease Control and Prevention.

Dr. Califf said he plans to focus on what information the FDA conveys to the public about the risks of prescription painkillers, including a look at what the labels for these products say.

“I am committed to do a comprehensive review of the status of opioids, early in my tenure,” Dr. Califf said.

Dr. Califf indicated that physicians are still too quick to provide excess doses of these medicines, despite years of efforts to restrain their use. He said he knows relatives who were given 30-day prescriptions for opioids after minor surgery.

“So I know we have work to do,” Dr. Califf said.

Concerns about the FDA’s previous work in managing opioids has led to protests from a few Democratic senators about the prospect of President Biden nominating the acting FDA commissioner, Janet Woodcock, MD, for the permanent post.

At the hearing, Sen. Ben Ray Luján (D-NM) raised the case of the FDA’s approval of the powerful Zohydro painkiller. The agency approved that drug despite an 11-2 vote against it by the FDA’s Anesthetic and Analgesic Drug Products Advisory Committee.

Sen. Luján asked Dr. Califf what he would do if an FDA advisory committee voted “overwhelmingly” against recommending approval of a medicine, as happened in the Zohydro case.

While not mentioned by Sen. Luján in this exchange during the hearing with Dr. Califf, the FDA staff’s rejection of recommendations of advisory committees has been a growing concern among researchers.

The agency last year approved aducanumab (Aduhelm, Biogen), a drug for Alzheimer’s disease, dismissing the advice of its Peripheral and Central Nervous System Drugs Advisory Committee. That decision triggered the resignation of several members of the panel. The FDA staff also earlier rejected the conclusion the majority of members of the same advisory committee offered in 2016 on eteplirsen (Exondys 51, Sarepta), a drug for Duchenne muscular dystrophy.

Dr. Califf told Sen. Luján he had done recent research into how often the FDA staff does not concur with the recommendations of an advisory committee. He said the FDA takes a different course of action in about 25% of cases. In about three-quarters of those cases, the FDA staff opts for a “more stringent” approach regarding allowing the public access to the drug, as opposed to a more generous one as seen in the Zohydro, Aduhelm, and Exondys 51 cases.

Still, Dr. Califf said that when there’s an 11-2 advisory committee vote against recommendation of a product, “the leaders at FDA really need to take a close look” at what’s happening.

Question on accelerated approvals

The FDA’s approval of aducanumab drew attention to a debate already underway about conditional clearances known as accelerated approvals.

The FDA has used this path since the 1990s to speed access to drugs for serious conditions. The trade-off for early access is that the agency sometimes makes the wrong call based on initial findings, and clears a medicine later found not to benefit patients as expected.

The FDA’s cancer division is in the midst of public efforts to address cases where drugmakers have not been able to deliver studies that support accelerated approvals of their oncology drugs. In addition, the Office of Inspector General of the U.S. Department of Health & Human Services announced in August that it is reviewing the FDA’s handling of the accelerated approval process.

At Tuesday’s hearing, Sen. Burr grilled Dr. Califf about how he would respond to calls to change how the FDA handles the accelerated-approval process.

“Can you commit to me and to patients who may rely on cutting-edge treatments that you will not support efforts to narrow this pathway or raise the bar for drugs to be approved under those pathways?” Burr asked Califf.

Dr. Califf responded by saying he was “a fan of accelerated approval – for the right conditions.”

Earlier, in his opening statement, Dr. Califf had said his mother benefited directly from the accelerated approval of new drugs for multiple myeloma. Dr. Califf told Sen. Burr that he had spent “countless hours with patient groups” and understands the need to speed the approval of medicines for serious diseases.

But the FDA also has to make sure it holds up its end of the bargain struck with accelerated approvals. This involves checking on how these medicines work once they are marketed.

“We’re accepting that there’s more uncertainty,” Dr. Califf said. “That means we’ve got to have a better system to evaluate these products as they’re used on the market. And I think there are ways that we can do that now. Technology is making this possible in ways that it just was not possible before.”
 

Worries about the medical supply chain

Sen. Susan Collins (R-Maine) asked Dr. Califf about the vulnerability of the U.S. medical system to disruptions of the supply chain. She raised concerns about China’s dominance in antibiotic manufacturing as an example. She asked if Congress could do more to encourage domestic manufacturing of medical supplies, such as by offering tax incentives.

Dr. Califf told Sen. Collins he shared her concern about the U.S. manufacturing of ingredients used in both branded and generic drugs. He said he recently has served on a committee of the National Academy of Medicine that is examining supply chain issues.

This committee will soon release a report with specific recommendations, Dr. Califf said.

“We don’t have enough competitive entities in what’s become sort of a commodity business” of drug manufacturing, Dr. Califf said. “So we need a number of steps to make the system more resilient.”

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

Robert M. Califf, MD, plans to take a close look at federal policies on opioid prescriptions in his expected second turn as the top U.S. regulator of medical products, as well as keep closer tabs on the performance of drugs cleared with accelerated approvals.

Catherine Hackett/Frontline Medical News

Dr. Califf on Tuesday fielded questions at a Senate hearing about his nomination by President Joe Biden to serve as administrator of the U.S. Food and Drug Administration, a role in which he served in the Obama administration. He also spoke about the need to bolster the nation’s ability to maintain an adequate supply of key medical products, including drugs.

Members of the Senate Health, Education, Labor and Pensions Committee, which is handling Dr. Califf’s nomination, were largely cordial and supportive during the hearing. Sen. Patty Murray (D-Wash.), the committee chair, and the panel’s top Republican, Sen. Richard Burr of North Carolina, addressed Dr. Califf during the hearing as if he would soon serve again as the FDA’s leader. Both were among the senators who voted 89-4 to confirm Dr. Califf in a February 2016 vote.

Dr. Califf “was previously confirmed to lead FDA in an overwhelming bipartisan vote, and I look forward to working with him again to ensure FDA continues to protect families across the country, uphold the gold standard of safety and effectiveness, and put science and data first,” Sen. Murray said.

Less enthusiastic about Dr. Califf was Sen. Bernie Sanders (I-VT), who was among the seven senators who did not vote on Dr. Califf’s nomination in 2016.

Sen. Sanders objected in 2016 to Dr. Califf’s ties to the pharmaceutical industry, and he did so again Tuesday. A noted leader in conducting clinical trials, Dr. Califf has worked with many drugmakers. But at the hearing, Dr. Califf said he concurs with Sen. Sanders on an idea strongly opposed by the pharmaceutical industry.

In response to Sen. Sanders’ question, Dr. Califf said he already is “on record as being in favor of Medicare negotiating with the industry on prices.”

The FDA would not take direct part in negotiations, as this work would be handled by the Centers for Medicare & Medicaid Services. Democrats want to give Medicare some negotiating authority through their sweeping Build Back Better Act.

People in the United States are dismayed over both the cost of prescription drugs and the widespread distribution of prescription painkillers that helped fuel the current opioid epidemic, Sen. Sanders told Dr. Califf. Many people will be concerned about an FDA commissioner who has benefited from close ties to the industry, Sen. Sanders said.

“How are they going to believe that you’re going to be an independent and strong voice against this enormously powerful, special interest?” Sen. Sanders asked.

“I’m totally with you on the concept that the price of pharmaceuticals is way too high in this country,” Dr. Califf said in reply.

Dr. Califf was paid $2.7 million in salary and bonus by Verily Life Sciences, the biomedical research organization operated by Alphabet, parent company of Google, according to his federal financial disclosure. He also reported holding board positions with pharmaceutical companies AmyriAD and Centessa Pharmaceuticals.

Bloomberg Government reported that Dr. Califf has ties to about 16 other research organizations and biotech companies. Bloomberg Government also said that, in his earlier FDA service, Dr. Califf kept a whiteboard in his office that listed all the activities and projects that required his recusal, citing as a source Howard Sklamberg, who was a deputy commissioner under Dr. Califf.

“He was very, very, very careful,” Mr. Sklamberg, who’s now an attorney at Arnold & Porter LLP, told Bloomberg Government.
 

‘Work to do’ on opioids

Senators looped back repeatedly to the topic of opioids during Dr. Califf’s hearing, reflecting deep concerns about the FDA’s efforts to warn of the risks of prescription painkillers.

There were an estimated 100,306 drug overdose deaths in the United States in the 12 months ending in April, an increase of 28.5% from the 78,056 deaths during the same period the year before, according to the Centers for Disease Control and Prevention.

Dr. Califf said he plans to focus on what information the FDA conveys to the public about the risks of prescription painkillers, including a look at what the labels for these products say.

“I am committed to do a comprehensive review of the status of opioids, early in my tenure,” Dr. Califf said.

Dr. Califf indicated that physicians are still too quick to provide excess doses of these medicines, despite years of efforts to restrain their use. He said he knows relatives who were given 30-day prescriptions for opioids after minor surgery.

“So I know we have work to do,” Dr. Califf said.

Concerns about the FDA’s previous work in managing opioids has led to protests from a few Democratic senators about the prospect of President Biden nominating the acting FDA commissioner, Janet Woodcock, MD, for the permanent post.

At the hearing, Sen. Ben Ray Luján (D-NM) raised the case of the FDA’s approval of the powerful Zohydro painkiller. The agency approved that drug despite an 11-2 vote against it by the FDA’s Anesthetic and Analgesic Drug Products Advisory Committee.

Sen. Luján asked Dr. Califf what he would do if an FDA advisory committee voted “overwhelmingly” against recommending approval of a medicine, as happened in the Zohydro case.

While not mentioned by Sen. Luján in this exchange during the hearing with Dr. Califf, the FDA staff’s rejection of recommendations of advisory committees has been a growing concern among researchers.

The agency last year approved aducanumab (Aduhelm, Biogen), a drug for Alzheimer’s disease, dismissing the advice of its Peripheral and Central Nervous System Drugs Advisory Committee. That decision triggered the resignation of several members of the panel. The FDA staff also earlier rejected the conclusion the majority of members of the same advisory committee offered in 2016 on eteplirsen (Exondys 51, Sarepta), a drug for Duchenne muscular dystrophy.

Dr. Califf told Sen. Luján he had done recent research into how often the FDA staff does not concur with the recommendations of an advisory committee. He said the FDA takes a different course of action in about 25% of cases. In about three-quarters of those cases, the FDA staff opts for a “more stringent” approach regarding allowing the public access to the drug, as opposed to a more generous one as seen in the Zohydro, Aduhelm, and Exondys 51 cases.

Still, Dr. Califf said that when there’s an 11-2 advisory committee vote against recommendation of a product, “the leaders at FDA really need to take a close look” at what’s happening.

Question on accelerated approvals

The FDA’s approval of aducanumab drew attention to a debate already underway about conditional clearances known as accelerated approvals.

The FDA has used this path since the 1990s to speed access to drugs for serious conditions. The trade-off for early access is that the agency sometimes makes the wrong call based on initial findings, and clears a medicine later found not to benefit patients as expected.

The FDA’s cancer division is in the midst of public efforts to address cases where drugmakers have not been able to deliver studies that support accelerated approvals of their oncology drugs. In addition, the Office of Inspector General of the U.S. Department of Health & Human Services announced in August that it is reviewing the FDA’s handling of the accelerated approval process.

At Tuesday’s hearing, Sen. Burr grilled Dr. Califf about how he would respond to calls to change how the FDA handles the accelerated-approval process.

“Can you commit to me and to patients who may rely on cutting-edge treatments that you will not support efforts to narrow this pathway or raise the bar for drugs to be approved under those pathways?” Burr asked Califf.

Dr. Califf responded by saying he was “a fan of accelerated approval – for the right conditions.”

Earlier, in his opening statement, Dr. Califf had said his mother benefited directly from the accelerated approval of new drugs for multiple myeloma. Dr. Califf told Sen. Burr that he had spent “countless hours with patient groups” and understands the need to speed the approval of medicines for serious diseases.

But the FDA also has to make sure it holds up its end of the bargain struck with accelerated approvals. This involves checking on how these medicines work once they are marketed.

“We’re accepting that there’s more uncertainty,” Dr. Califf said. “That means we’ve got to have a better system to evaluate these products as they’re used on the market. And I think there are ways that we can do that now. Technology is making this possible in ways that it just was not possible before.”
 

Worries about the medical supply chain

Sen. Susan Collins (R-Maine) asked Dr. Califf about the vulnerability of the U.S. medical system to disruptions of the supply chain. She raised concerns about China’s dominance in antibiotic manufacturing as an example. She asked if Congress could do more to encourage domestic manufacturing of medical supplies, such as by offering tax incentives.

Dr. Califf told Sen. Collins he shared her concern about the U.S. manufacturing of ingredients used in both branded and generic drugs. He said he recently has served on a committee of the National Academy of Medicine that is examining supply chain issues.

This committee will soon release a report with specific recommendations, Dr. Califf said.

“We don’t have enough competitive entities in what’s become sort of a commodity business” of drug manufacturing, Dr. Califf said. “So we need a number of steps to make the system more resilient.”

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

Robert M. Califf, MD, plans to take a close look at federal policies on opioid prescriptions in his expected second turn as the top U.S. regulator of medical products, as well as keep closer tabs on the performance of drugs cleared with accelerated approvals.

Catherine Hackett/Frontline Medical News

Dr. Califf on Tuesday fielded questions at a Senate hearing about his nomination by President Joe Biden to serve as administrator of the U.S. Food and Drug Administration, a role in which he served in the Obama administration. He also spoke about the need to bolster the nation’s ability to maintain an adequate supply of key medical products, including drugs.

Members of the Senate Health, Education, Labor and Pensions Committee, which is handling Dr. Califf’s nomination, were largely cordial and supportive during the hearing. Sen. Patty Murray (D-Wash.), the committee chair, and the panel’s top Republican, Sen. Richard Burr of North Carolina, addressed Dr. Califf during the hearing as if he would soon serve again as the FDA’s leader. Both were among the senators who voted 89-4 to confirm Dr. Califf in a February 2016 vote.

Dr. Califf “was previously confirmed to lead FDA in an overwhelming bipartisan vote, and I look forward to working with him again to ensure FDA continues to protect families across the country, uphold the gold standard of safety and effectiveness, and put science and data first,” Sen. Murray said.

Less enthusiastic about Dr. Califf was Sen. Bernie Sanders (I-VT), who was among the seven senators who did not vote on Dr. Califf’s nomination in 2016.

Sen. Sanders objected in 2016 to Dr. Califf’s ties to the pharmaceutical industry, and he did so again Tuesday. A noted leader in conducting clinical trials, Dr. Califf has worked with many drugmakers. But at the hearing, Dr. Califf said he concurs with Sen. Sanders on an idea strongly opposed by the pharmaceutical industry.

In response to Sen. Sanders’ question, Dr. Califf said he already is “on record as being in favor of Medicare negotiating with the industry on prices.”

The FDA would not take direct part in negotiations, as this work would be handled by the Centers for Medicare & Medicaid Services. Democrats want to give Medicare some negotiating authority through their sweeping Build Back Better Act.

People in the United States are dismayed over both the cost of prescription drugs and the widespread distribution of prescription painkillers that helped fuel the current opioid epidemic, Sen. Sanders told Dr. Califf. Many people will be concerned about an FDA commissioner who has benefited from close ties to the industry, Sen. Sanders said.

“How are they going to believe that you’re going to be an independent and strong voice against this enormously powerful, special interest?” Sen. Sanders asked.

“I’m totally with you on the concept that the price of pharmaceuticals is way too high in this country,” Dr. Califf said in reply.

Dr. Califf was paid $2.7 million in salary and bonus by Verily Life Sciences, the biomedical research organization operated by Alphabet, parent company of Google, according to his federal financial disclosure. He also reported holding board positions with pharmaceutical companies AmyriAD and Centessa Pharmaceuticals.

Bloomberg Government reported that Dr. Califf has ties to about 16 other research organizations and biotech companies. Bloomberg Government also said that, in his earlier FDA service, Dr. Califf kept a whiteboard in his office that listed all the activities and projects that required his recusal, citing as a source Howard Sklamberg, who was a deputy commissioner under Dr. Califf.

“He was very, very, very careful,” Mr. Sklamberg, who’s now an attorney at Arnold & Porter LLP, told Bloomberg Government.
 

‘Work to do’ on opioids

Senators looped back repeatedly to the topic of opioids during Dr. Califf’s hearing, reflecting deep concerns about the FDA’s efforts to warn of the risks of prescription painkillers.

There were an estimated 100,306 drug overdose deaths in the United States in the 12 months ending in April, an increase of 28.5% from the 78,056 deaths during the same period the year before, according to the Centers for Disease Control and Prevention.

Dr. Califf said he plans to focus on what information the FDA conveys to the public about the risks of prescription painkillers, including a look at what the labels for these products say.

“I am committed to do a comprehensive review of the status of opioids, early in my tenure,” Dr. Califf said.

Dr. Califf indicated that physicians are still too quick to provide excess doses of these medicines, despite years of efforts to restrain their use. He said he knows relatives who were given 30-day prescriptions for opioids after minor surgery.

“So I know we have work to do,” Dr. Califf said.

Concerns about the FDA’s previous work in managing opioids has led to protests from a few Democratic senators about the prospect of President Biden nominating the acting FDA commissioner, Janet Woodcock, MD, for the permanent post.

At the hearing, Sen. Ben Ray Luján (D-NM) raised the case of the FDA’s approval of the powerful Zohydro painkiller. The agency approved that drug despite an 11-2 vote against it by the FDA’s Anesthetic and Analgesic Drug Products Advisory Committee.

Sen. Luján asked Dr. Califf what he would do if an FDA advisory committee voted “overwhelmingly” against recommending approval of a medicine, as happened in the Zohydro case.

While not mentioned by Sen. Luján in this exchange during the hearing with Dr. Califf, the FDA staff’s rejection of recommendations of advisory committees has been a growing concern among researchers.

The agency last year approved aducanumab (Aduhelm, Biogen), a drug for Alzheimer’s disease, dismissing the advice of its Peripheral and Central Nervous System Drugs Advisory Committee. That decision triggered the resignation of several members of the panel. The FDA staff also earlier rejected the conclusion the majority of members of the same advisory committee offered in 2016 on eteplirsen (Exondys 51, Sarepta), a drug for Duchenne muscular dystrophy.

Dr. Califf told Sen. Luján he had done recent research into how often the FDA staff does not concur with the recommendations of an advisory committee. He said the FDA takes a different course of action in about 25% of cases. In about three-quarters of those cases, the FDA staff opts for a “more stringent” approach regarding allowing the public access to the drug, as opposed to a more generous one as seen in the Zohydro, Aduhelm, and Exondys 51 cases.

Still, Dr. Califf said that when there’s an 11-2 advisory committee vote against recommendation of a product, “the leaders at FDA really need to take a close look” at what’s happening.

Question on accelerated approvals

The FDA’s approval of aducanumab drew attention to a debate already underway about conditional clearances known as accelerated approvals.

The FDA has used this path since the 1990s to speed access to drugs for serious conditions. The trade-off for early access is that the agency sometimes makes the wrong call based on initial findings, and clears a medicine later found not to benefit patients as expected.

The FDA’s cancer division is in the midst of public efforts to address cases where drugmakers have not been able to deliver studies that support accelerated approvals of their oncology drugs. In addition, the Office of Inspector General of the U.S. Department of Health & Human Services announced in August that it is reviewing the FDA’s handling of the accelerated approval process.

At Tuesday’s hearing, Sen. Burr grilled Dr. Califf about how he would respond to calls to change how the FDA handles the accelerated-approval process.

“Can you commit to me and to patients who may rely on cutting-edge treatments that you will not support efforts to narrow this pathway or raise the bar for drugs to be approved under those pathways?” Burr asked Califf.

Dr. Califf responded by saying he was “a fan of accelerated approval – for the right conditions.”

Earlier, in his opening statement, Dr. Califf had said his mother benefited directly from the accelerated approval of new drugs for multiple myeloma. Dr. Califf told Sen. Burr that he had spent “countless hours with patient groups” and understands the need to speed the approval of medicines for serious diseases.

But the FDA also has to make sure it holds up its end of the bargain struck with accelerated approvals. This involves checking on how these medicines work once they are marketed.

“We’re accepting that there’s more uncertainty,” Dr. Califf said. “That means we’ve got to have a better system to evaluate these products as they’re used on the market. And I think there are ways that we can do that now. Technology is making this possible in ways that it just was not possible before.”
 

Worries about the medical supply chain

Sen. Susan Collins (R-Maine) asked Dr. Califf about the vulnerability of the U.S. medical system to disruptions of the supply chain. She raised concerns about China’s dominance in antibiotic manufacturing as an example. She asked if Congress could do more to encourage domestic manufacturing of medical supplies, such as by offering tax incentives.

Dr. Califf told Sen. Collins he shared her concern about the U.S. manufacturing of ingredients used in both branded and generic drugs. He said he recently has served on a committee of the National Academy of Medicine that is examining supply chain issues.

This committee will soon release a report with specific recommendations, Dr. Califf said.

“We don’t have enough competitive entities in what’s become sort of a commodity business” of drug manufacturing, Dr. Califf said. “So we need a number of steps to make the system more resilient.”

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

In a shocking, yet low-key, announcement, the sodium-glucose transporter 2 (SGLT2) inhibitor dapagliflozin (Forxiga, AstraZeneca) has been withdrawn from the market in all EU countries for the indication of type 1 diabetes.

Courtesy AstraZeneca

This includes withdrawal in the U.K., which was part of the EU when dapagliflozin was approved for type 1 diabetes in 2019, but following Brexit, is no longer.

AstraZeneca said the decision is not motivated by safety concerns but points nevertheless to an increased risk of diabetic ketoacidosis (DKA) associated with SGLT2 inhibitors in those with type 1 diabetes, which it said might cause “confusion” among physicians using the drug to treat numerous other indications for which this agent is now approved.

DKA is a potentially dangerous side effect resulting from acid build-up in the blood and is normally accompanied by very high glucose levels. DKA is flagged as a potential side effect in type 2 diabetes but is more common in those with type 1 diabetes. It can also occur as “euglycemic” DKA, which is ketosis but with relatively normal glucose levels (and therefore harder for patients to detect). Euglycemic DKA is thought to be more of a risk in those with type 1 diabetes than in those with type 2 diabetes.

One charity believes concerns around safety are the underlying factor for the withdrawal of dapagliflozin for type 1 diabetes in Europe, suggesting that AstraZeneca might not want to risk income from more lucrative indications – such as type 2 diabetes with much larger patient populations – because of potential concerns from doctors, who may be deterred from prescribing the drug due to concerns about DKA.

JDRF International, a leading global type 1 diabetes charity, called on AstraZeneca in a statement “to explain to people affected by type 1 diabetes why the drug has been withdrawn.”

It added that dapagliflozin is the “only other drug besides insulin” to be licensed in Europe for the treatment of type 1 diabetes and represents a “major advancement since the discovery of insulin 100 years ago.”

Karen Addington, U.K. Chief Executive of JDRF, said it is “appalling” that the drug has been withdrawn, as “many people with type 1 are finding it an effective and useful tool to help manage their glucose levels.”
 

SGLT2 inhibitors never approved for type 1 diabetes in U.S.

Dapagliflozin and other drugs from the SGLT2 inhibitor class had already been approved for the treatment of type 2 diabetes for a number of years when dapagliflozin was approved in early 2019 for the treatment of adults with type 1 diabetes meeting certain criteria by the European Medicines Agency (EMA), which at that time included the U.K. in its remit, based on data from the DEPICT series of phase 3 trials.

SGLT2 inhibitors have also recently shown benefit in other indications, such as heart failure and chronic kidney disease – even in the absence of diabetes – leaving some to label them a new class of wonder drugs.

Following the 2019 EU approval for type 1 diabetes, dapagliflozin was subsequently recommended for this use on the National Health Service (NHS) in England and Wales and was accompanied by guidance from the National Institute for Health and Care Excellence (NICE), which has now had to be withdrawn.

Of note, dapagliflozin was never approved for use in type 1 diabetes in the United States (where it is known as Farxiga), with the U.S. Food and Drug Administration turning it down in July 2019.

An advisory panel for the FDA also later turned down another SGLT2 inhibitor for type 1 diabetes, empagliflozin (Jardiance, Boehringer Ingelheim) in Nov. 2019, as reported by this news organization.
 

Discontinuation ‘not due to safety concerns,’ says AZ

The announcement to discontinue dapagliflozin for the indication of type 1 diabetes in certain adults just two and a half years after its approval in the EU comes as a big surprise, especially as it was made with little fanfare just last month.

In the U.K., AstraZeneca sent a letter to health care professionals on Nov. 2 stating that, from Oct. 25, dapagliflozin 5 mg was “no longer authorized” for the treatment of type 1 diabetes and “should no longer be used” in this patient population.

However, it underlined that other indications for dapagliflozin 5 mg and 10 mg were “not affected by this licensing change,” and it remains available for adults with type 2 diabetes, as well as for the management of symptomatic chronic heart feature with reduced ejection fraction (HFrEF) and chronic kidney disease (CKD).

In the letter, sent by Tom Keith-Roach, country president of AstraZeneca UK, the company asserts that the removal of the type 1 diabetes indication from dapagliflozin is “not due to any safety concern” with the drug “in any indication, including type 1 diabetes.”

It nevertheless goes on to highlight that DKA is a known common side effect of dapagliflozin in type 1 diabetes and, following the announcement, “additional risk minimization measures ... will no longer be available.”

In a separate statement, AstraZeneca said that the decision to remove the indication was made “voluntarily” and had been “agreed” with the Medicines and Healthcare products Regulatory Agency (MHRA) in Great Britain and the equivalent body in Northern Ireland.

“It follows discussions regarding product information changes needed post-approval for dapagliflozin 5 mg specific to type 1 diabetes,” the company said, “which might cause confusion” among physicians treating patients with type 2 diabetes, chronic heart feature with reduced ejection fraction, or CKD.

AstraZeneca told this news organization that similar communications about the withdrawal were issued to health care agencies and health care professionals in all countries of the EU.
 

‘Appalling, devastating, disappointing’ for patients

The announcement has been met with disappointment in some quarters and outrage in others, and questions have been raised as to the explanation given by AstraZeneca for the drug’s withdrawal.

“Although only a small number of people with type 1 diabetes have been using dapagliflozin, we know that those who have been using it will have been benefitting from tighter control of their condition,” Simon O’Neill, director of health intelligence and professional liaison at Diabetes UK, told this news organization.

“It’s disappointing that these people will now need to go back to the drawing board and will have to work with their clinical team to find other ways of better managing their condition.”

Mr. O’Neill said it was “disappointing that AstraZeneca and the MHRA were unable to find a workable solution to allow people living with type 1 diabetes to continue using the drug safely without leading to confusion for clinicians or people living with type 2 diabetes, who also use it.”

Sanjoy Dutta, JDRF International vice president of research, added that the news is “devastating.”

“The impending negative impact of removing a drug like dapagliflozin from any market can be detrimental in the potential for other national medical ruling boards to have confidence in approving it for their citizens,” he added.

“We stand with our type 1 diabetes communities across the globe in demanding an explanation to clarify this removal.”
 

Why not an educational campaign about DKA risk?

In an interview, Hilary Nathan, policy & communications director at JDRF International, explained that the charity has its theories as to why dapagliflozin has been withdrawn for type 1 diabetes.

What AstraZeneca is saying, “and what we don’t agree with them on,” is that the “black triangle” warning that has to be put onto the drug due to the increased risk of DKA in type 1 diabetes is “misunderstood by health care practitioners” outside of that specialty and that “by having that black triangle, it will inhibit take-up in those other markets.”

In other words, “there will be less desire to prescribe it,” ventured Ms. Nathan.

She continued: “For us, we feel that if a medicine is deemed safe and efficacious, it should not be withdrawn because of other patient constituencies.”

“We asked: ‘Why can’t you do an educational awareness campaign about the black triangle?’ And the might of AstraZeneca said it would be too big a task.”

Ms. Nathan was also surprised at how the drug could be withdrawn without any warning or real explanation.

“How is it possible that, when a drug is approved there are multiple stakeholders that are involved in putting forward views and experiences – both from the clinical and patient advocacy communities, as well as obviously the pharmaceutical community – yet [a drug] can be withdrawn by a ... company that may well have conflicts of interest around commercial take-up.”

She added: “I feel that there are potentially motives around the withdrawal that AstraZeneca are still not being clear about.”

Perhaps a further clue as to the real motives behind the withdrawal can be found in an announcement, just last week, by the British MHRA.

“The decision by the marketing authorization holder to voluntarily withdraw the indication in type 1 diabetes followed commercial considerations due to a specific European-wide regulatory requirement for this authorization,” it said.

“The decision was not driven by any new safety concerns, such as the already known increased risk of DKA in type 1 diabetes compared with type 2 diabetes.”

Separately, a new in-depth investigation into when Johnson & Johnson, which markets another SGLT2 inhibitor, canagliflozin (Invokana), first knew that its agent was associated with DKA has revealed multiple discrepancies in staff accounts. Some claim the company knew as early as 2010 that canagliflozin – first approved for type 2 diabetes in the United States in 2013 – could increase the risk of DKA. It was not until May 2015 that the FDA first issued a warning about the potential risk of DKA associated with use of SGLT2 inhibitors, with the EMA following suit a month later. In Dec. 2015, the FDA updated the labels for all SGLT2 inhibitors approved in the United States at that time – canagliflozin, empagliflozin, and dapagliflozin – to include the risks for ketoacidosis (and urinary tract infections).

Forxiga (dapagliflozin) is manufactured by AstraZeneca. No relevant financial relationships declared.

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

In a shocking, yet low-key, announcement, the sodium-glucose transporter 2 (SGLT2) inhibitor dapagliflozin (Forxiga, AstraZeneca) has been withdrawn from the market in all EU countries for the indication of type 1 diabetes.

Courtesy AstraZeneca

This includes withdrawal in the U.K., which was part of the EU when dapagliflozin was approved for type 1 diabetes in 2019, but following Brexit, is no longer.

AstraZeneca said the decision is not motivated by safety concerns but points nevertheless to an increased risk of diabetic ketoacidosis (DKA) associated with SGLT2 inhibitors in those with type 1 diabetes, which it said might cause “confusion” among physicians using the drug to treat numerous other indications for which this agent is now approved.

DKA is a potentially dangerous side effect resulting from acid build-up in the blood and is normally accompanied by very high glucose levels. DKA is flagged as a potential side effect in type 2 diabetes but is more common in those with type 1 diabetes. It can also occur as “euglycemic” DKA, which is ketosis but with relatively normal glucose levels (and therefore harder for patients to detect). Euglycemic DKA is thought to be more of a risk in those with type 1 diabetes than in those with type 2 diabetes.

One charity believes concerns around safety are the underlying factor for the withdrawal of dapagliflozin for type 1 diabetes in Europe, suggesting that AstraZeneca might not want to risk income from more lucrative indications – such as type 2 diabetes with much larger patient populations – because of potential concerns from doctors, who may be deterred from prescribing the drug due to concerns about DKA.

JDRF International, a leading global type 1 diabetes charity, called on AstraZeneca in a statement “to explain to people affected by type 1 diabetes why the drug has been withdrawn.”

It added that dapagliflozin is the “only other drug besides insulin” to be licensed in Europe for the treatment of type 1 diabetes and represents a “major advancement since the discovery of insulin 100 years ago.”

Karen Addington, U.K. Chief Executive of JDRF, said it is “appalling” that the drug has been withdrawn, as “many people with type 1 are finding it an effective and useful tool to help manage their glucose levels.”
 

SGLT2 inhibitors never approved for type 1 diabetes in U.S.

Dapagliflozin and other drugs from the SGLT2 inhibitor class had already been approved for the treatment of type 2 diabetes for a number of years when dapagliflozin was approved in early 2019 for the treatment of adults with type 1 diabetes meeting certain criteria by the European Medicines Agency (EMA), which at that time included the U.K. in its remit, based on data from the DEPICT series of phase 3 trials.

SGLT2 inhibitors have also recently shown benefit in other indications, such as heart failure and chronic kidney disease – even in the absence of diabetes – leaving some to label them a new class of wonder drugs.

Following the 2019 EU approval for type 1 diabetes, dapagliflozin was subsequently recommended for this use on the National Health Service (NHS) in England and Wales and was accompanied by guidance from the National Institute for Health and Care Excellence (NICE), which has now had to be withdrawn.

Of note, dapagliflozin was never approved for use in type 1 diabetes in the United States (where it is known as Farxiga), with the U.S. Food and Drug Administration turning it down in July 2019.

An advisory panel for the FDA also later turned down another SGLT2 inhibitor for type 1 diabetes, empagliflozin (Jardiance, Boehringer Ingelheim) in Nov. 2019, as reported by this news organization.
 

Discontinuation ‘not due to safety concerns,’ says AZ

The announcement to discontinue dapagliflozin for the indication of type 1 diabetes in certain adults just two and a half years after its approval in the EU comes as a big surprise, especially as it was made with little fanfare just last month.

In the U.K., AstraZeneca sent a letter to health care professionals on Nov. 2 stating that, from Oct. 25, dapagliflozin 5 mg was “no longer authorized” for the treatment of type 1 diabetes and “should no longer be used” in this patient population.

However, it underlined that other indications for dapagliflozin 5 mg and 10 mg were “not affected by this licensing change,” and it remains available for adults with type 2 diabetes, as well as for the management of symptomatic chronic heart feature with reduced ejection fraction (HFrEF) and chronic kidney disease (CKD).

In the letter, sent by Tom Keith-Roach, country president of AstraZeneca UK, the company asserts that the removal of the type 1 diabetes indication from dapagliflozin is “not due to any safety concern” with the drug “in any indication, including type 1 diabetes.”

It nevertheless goes on to highlight that DKA is a known common side effect of dapagliflozin in type 1 diabetes and, following the announcement, “additional risk minimization measures ... will no longer be available.”

In a separate statement, AstraZeneca said that the decision to remove the indication was made “voluntarily” and had been “agreed” with the Medicines and Healthcare products Regulatory Agency (MHRA) in Great Britain and the equivalent body in Northern Ireland.

“It follows discussions regarding product information changes needed post-approval for dapagliflozin 5 mg specific to type 1 diabetes,” the company said, “which might cause confusion” among physicians treating patients with type 2 diabetes, chronic heart feature with reduced ejection fraction, or CKD.

AstraZeneca told this news organization that similar communications about the withdrawal were issued to health care agencies and health care professionals in all countries of the EU.
 

‘Appalling, devastating, disappointing’ for patients

The announcement has been met with disappointment in some quarters and outrage in others, and questions have been raised as to the explanation given by AstraZeneca for the drug’s withdrawal.

“Although only a small number of people with type 1 diabetes have been using dapagliflozin, we know that those who have been using it will have been benefitting from tighter control of their condition,” Simon O’Neill, director of health intelligence and professional liaison at Diabetes UK, told this news organization.

“It’s disappointing that these people will now need to go back to the drawing board and will have to work with their clinical team to find other ways of better managing their condition.”

Mr. O’Neill said it was “disappointing that AstraZeneca and the MHRA were unable to find a workable solution to allow people living with type 1 diabetes to continue using the drug safely without leading to confusion for clinicians or people living with type 2 diabetes, who also use it.”

Sanjoy Dutta, JDRF International vice president of research, added that the news is “devastating.”

“The impending negative impact of removing a drug like dapagliflozin from any market can be detrimental in the potential for other national medical ruling boards to have confidence in approving it for their citizens,” he added.

“We stand with our type 1 diabetes communities across the globe in demanding an explanation to clarify this removal.”
 

Why not an educational campaign about DKA risk?

In an interview, Hilary Nathan, policy & communications director at JDRF International, explained that the charity has its theories as to why dapagliflozin has been withdrawn for type 1 diabetes.

What AstraZeneca is saying, “and what we don’t agree with them on,” is that the “black triangle” warning that has to be put onto the drug due to the increased risk of DKA in type 1 diabetes is “misunderstood by health care practitioners” outside of that specialty and that “by having that black triangle, it will inhibit take-up in those other markets.”

In other words, “there will be less desire to prescribe it,” ventured Ms. Nathan.

She continued: “For us, we feel that if a medicine is deemed safe and efficacious, it should not be withdrawn because of other patient constituencies.”

“We asked: ‘Why can’t you do an educational awareness campaign about the black triangle?’ And the might of AstraZeneca said it would be too big a task.”

Ms. Nathan was also surprised at how the drug could be withdrawn without any warning or real explanation.

“How is it possible that, when a drug is approved there are multiple stakeholders that are involved in putting forward views and experiences – both from the clinical and patient advocacy communities, as well as obviously the pharmaceutical community – yet [a drug] can be withdrawn by a ... company that may well have conflicts of interest around commercial take-up.”

She added: “I feel that there are potentially motives around the withdrawal that AstraZeneca are still not being clear about.”

Perhaps a further clue as to the real motives behind the withdrawal can be found in an announcement, just last week, by the British MHRA.

“The decision by the marketing authorization holder to voluntarily withdraw the indication in type 1 diabetes followed commercial considerations due to a specific European-wide regulatory requirement for this authorization,” it said.

“The decision was not driven by any new safety concerns, such as the already known increased risk of DKA in type 1 diabetes compared with type 2 diabetes.”

Separately, a new in-depth investigation into when Johnson & Johnson, which markets another SGLT2 inhibitor, canagliflozin (Invokana), first knew that its agent was associated with DKA has revealed multiple discrepancies in staff accounts. Some claim the company knew as early as 2010 that canagliflozin – first approved for type 2 diabetes in the United States in 2013 – could increase the risk of DKA. It was not until May 2015 that the FDA first issued a warning about the potential risk of DKA associated with use of SGLT2 inhibitors, with the EMA following suit a month later. In Dec. 2015, the FDA updated the labels for all SGLT2 inhibitors approved in the United States at that time – canagliflozin, empagliflozin, and dapagliflozin – to include the risks for ketoacidosis (and urinary tract infections).

Forxiga (dapagliflozin) is manufactured by AstraZeneca. No relevant financial relationships declared.

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

In a shocking, yet low-key, announcement, the sodium-glucose transporter 2 (SGLT2) inhibitor dapagliflozin (Forxiga, AstraZeneca) has been withdrawn from the market in all EU countries for the indication of type 1 diabetes.

Courtesy AstraZeneca

This includes withdrawal in the U.K., which was part of the EU when dapagliflozin was approved for type 1 diabetes in 2019, but following Brexit, is no longer.

AstraZeneca said the decision is not motivated by safety concerns but points nevertheless to an increased risk of diabetic ketoacidosis (DKA) associated with SGLT2 inhibitors in those with type 1 diabetes, which it said might cause “confusion” among physicians using the drug to treat numerous other indications for which this agent is now approved.

DKA is a potentially dangerous side effect resulting from acid build-up in the blood and is normally accompanied by very high glucose levels. DKA is flagged as a potential side effect in type 2 diabetes but is more common in those with type 1 diabetes. It can also occur as “euglycemic” DKA, which is ketosis but with relatively normal glucose levels (and therefore harder for patients to detect). Euglycemic DKA is thought to be more of a risk in those with type 1 diabetes than in those with type 2 diabetes.

One charity believes concerns around safety are the underlying factor for the withdrawal of dapagliflozin for type 1 diabetes in Europe, suggesting that AstraZeneca might not want to risk income from more lucrative indications – such as type 2 diabetes with much larger patient populations – because of potential concerns from doctors, who may be deterred from prescribing the drug due to concerns about DKA.

JDRF International, a leading global type 1 diabetes charity, called on AstraZeneca in a statement “to explain to people affected by type 1 diabetes why the drug has been withdrawn.”

It added that dapagliflozin is the “only other drug besides insulin” to be licensed in Europe for the treatment of type 1 diabetes and represents a “major advancement since the discovery of insulin 100 years ago.”

Karen Addington, U.K. Chief Executive of JDRF, said it is “appalling” that the drug has been withdrawn, as “many people with type 1 are finding it an effective and useful tool to help manage their glucose levels.”
 

SGLT2 inhibitors never approved for type 1 diabetes in U.S.

Dapagliflozin and other drugs from the SGLT2 inhibitor class had already been approved for the treatment of type 2 diabetes for a number of years when dapagliflozin was approved in early 2019 for the treatment of adults with type 1 diabetes meeting certain criteria by the European Medicines Agency (EMA), which at that time included the U.K. in its remit, based on data from the DEPICT series of phase 3 trials.

SGLT2 inhibitors have also recently shown benefit in other indications, such as heart failure and chronic kidney disease – even in the absence of diabetes – leaving some to label them a new class of wonder drugs.

Following the 2019 EU approval for type 1 diabetes, dapagliflozin was subsequently recommended for this use on the National Health Service (NHS) in England and Wales and was accompanied by guidance from the National Institute for Health and Care Excellence (NICE), which has now had to be withdrawn.

Of note, dapagliflozin was never approved for use in type 1 diabetes in the United States (where it is known as Farxiga), with the U.S. Food and Drug Administration turning it down in July 2019.

An advisory panel for the FDA also later turned down another SGLT2 inhibitor for type 1 diabetes, empagliflozin (Jardiance, Boehringer Ingelheim) in Nov. 2019, as reported by this news organization.
 

Discontinuation ‘not due to safety concerns,’ says AZ

The announcement to discontinue dapagliflozin for the indication of type 1 diabetes in certain adults just two and a half years after its approval in the EU comes as a big surprise, especially as it was made with little fanfare just last month.

In the U.K., AstraZeneca sent a letter to health care professionals on Nov. 2 stating that, from Oct. 25, dapagliflozin 5 mg was “no longer authorized” for the treatment of type 1 diabetes and “should no longer be used” in this patient population.

However, it underlined that other indications for dapagliflozin 5 mg and 10 mg were “not affected by this licensing change,” and it remains available for adults with type 2 diabetes, as well as for the management of symptomatic chronic heart feature with reduced ejection fraction (HFrEF) and chronic kidney disease (CKD).

In the letter, sent by Tom Keith-Roach, country president of AstraZeneca UK, the company asserts that the removal of the type 1 diabetes indication from dapagliflozin is “not due to any safety concern” with the drug “in any indication, including type 1 diabetes.”

It nevertheless goes on to highlight that DKA is a known common side effect of dapagliflozin in type 1 diabetes and, following the announcement, “additional risk minimization measures ... will no longer be available.”

In a separate statement, AstraZeneca said that the decision to remove the indication was made “voluntarily” and had been “agreed” with the Medicines and Healthcare products Regulatory Agency (MHRA) in Great Britain and the equivalent body in Northern Ireland.

“It follows discussions regarding product information changes needed post-approval for dapagliflozin 5 mg specific to type 1 diabetes,” the company said, “which might cause confusion” among physicians treating patients with type 2 diabetes, chronic heart feature with reduced ejection fraction, or CKD.

AstraZeneca told this news organization that similar communications about the withdrawal were issued to health care agencies and health care professionals in all countries of the EU.
 

‘Appalling, devastating, disappointing’ for patients

The announcement has been met with disappointment in some quarters and outrage in others, and questions have been raised as to the explanation given by AstraZeneca for the drug’s withdrawal.

“Although only a small number of people with type 1 diabetes have been using dapagliflozin, we know that those who have been using it will have been benefitting from tighter control of their condition,” Simon O’Neill, director of health intelligence and professional liaison at Diabetes UK, told this news organization.

“It’s disappointing that these people will now need to go back to the drawing board and will have to work with their clinical team to find other ways of better managing their condition.”

Mr. O’Neill said it was “disappointing that AstraZeneca and the MHRA were unable to find a workable solution to allow people living with type 1 diabetes to continue using the drug safely without leading to confusion for clinicians or people living with type 2 diabetes, who also use it.”

Sanjoy Dutta, JDRF International vice president of research, added that the news is “devastating.”

“The impending negative impact of removing a drug like dapagliflozin from any market can be detrimental in the potential for other national medical ruling boards to have confidence in approving it for their citizens,” he added.

“We stand with our type 1 diabetes communities across the globe in demanding an explanation to clarify this removal.”
 

Why not an educational campaign about DKA risk?

In an interview, Hilary Nathan, policy & communications director at JDRF International, explained that the charity has its theories as to why dapagliflozin has been withdrawn for type 1 diabetes.

What AstraZeneca is saying, “and what we don’t agree with them on,” is that the “black triangle” warning that has to be put onto the drug due to the increased risk of DKA in type 1 diabetes is “misunderstood by health care practitioners” outside of that specialty and that “by having that black triangle, it will inhibit take-up in those other markets.”

In other words, “there will be less desire to prescribe it,” ventured Ms. Nathan.

She continued: “For us, we feel that if a medicine is deemed safe and efficacious, it should not be withdrawn because of other patient constituencies.”

“We asked: ‘Why can’t you do an educational awareness campaign about the black triangle?’ And the might of AstraZeneca said it would be too big a task.”

Ms. Nathan was also surprised at how the drug could be withdrawn without any warning or real explanation.

“How is it possible that, when a drug is approved there are multiple stakeholders that are involved in putting forward views and experiences – both from the clinical and patient advocacy communities, as well as obviously the pharmaceutical community – yet [a drug] can be withdrawn by a ... company that may well have conflicts of interest around commercial take-up.”

She added: “I feel that there are potentially motives around the withdrawal that AstraZeneca are still not being clear about.”

Perhaps a further clue as to the real motives behind the withdrawal can be found in an announcement, just last week, by the British MHRA.

“The decision by the marketing authorization holder to voluntarily withdraw the indication in type 1 diabetes followed commercial considerations due to a specific European-wide regulatory requirement for this authorization,” it said.

“The decision was not driven by any new safety concerns, such as the already known increased risk of DKA in type 1 diabetes compared with type 2 diabetes.”

Separately, a new in-depth investigation into when Johnson & Johnson, which markets another SGLT2 inhibitor, canagliflozin (Invokana), first knew that its agent was associated with DKA has revealed multiple discrepancies in staff accounts. Some claim the company knew as early as 2010 that canagliflozin – first approved for type 2 diabetes in the United States in 2013 – could increase the risk of DKA. It was not until May 2015 that the FDA first issued a warning about the potential risk of DKA associated with use of SGLT2 inhibitors, with the EMA following suit a month later. In Dec. 2015, the FDA updated the labels for all SGLT2 inhibitors approved in the United States at that time – canagliflozin, empagliflozin, and dapagliflozin – to include the risks for ketoacidosis (and urinary tract infections).

Forxiga (dapagliflozin) is manufactured by AstraZeneca. No relevant financial relationships declared.

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