Pediatric News

Teens are identifying as transgender in record numbers. In 2017, 3-4 in 100 teens in the United States reported that they are or may be transgender. A more recent 2021 study suggests that the rate of transgender identification among America’s youth may be as high as 9 in 100. All of the major gender centers in the world have reported a several-thousand-percent increase in youth presenting with gender distress.

Origovisualis/Getty Images

How do we reconcile these numbers with 2013 data reporting the prevalence of adult gender dysphoria to be a rare 2-14 in 100,000? Reflection is warranted because many U.S. medical societies support providing youth who have transgender identification (over 1 million children and adolescents, using the latest estimates) with access to powerful endocrine interventions.

GnRH analogues (colloquially known as “puberty blockers”) are now available at Tanner stage 2 of puberty – a threshold crossed by females as young as 8-9 years old. Cross-sex hormones and surgeries follow, and mastectomies are now available to children as young as 13. Genital-altering surgeries, as well as the removal of the ovaries, uterus, and testes, can be obtained as soon as a patient turns 18.

What’s driving this massive increase in trans-identified youth? What are the risks, benefits, and uncertainties associated with hormonal and surgical interventions? Do such interventions improve the long-term psychological health of gender-dysphoric youth? How many will regret the irreversible changes made to their bodies during what may have been a temporary phase in their development?

We don’t know the answers to these questions, but we need to figure them out before offering such interventions. Frontline clinicians – especially those working with youth – will not be able to remain on the sidelines of this issue for much longer. Each clinician considering writing a prescription for puberty blockers or cross-sex hormones, or generating a referral for surgery, will need to answer for themselves: Just because I can, does it mean I should?

What’s contributing to the rapid rise of gender-dysphoric youth?

The etiology of the rapid rise of transgender identifications in young people is vigorously debated. Proponents of hormonal and surgical interventions for youth argue that the several-thousand-percent increase in the numbers of youth seeking gender reassignment is a reflection of more social acceptance of transgender identities, allowing more young people to “come out.” But closer examination of this claim reveals several inconsistencies.

Because adolescent and young adult females now account for 6-8 in 10 of the presenting cases (previously, prepubertal males were more common), one would expect a commensurate increase in the rate of transgender identification in older females. This has not occurred. In addition, more than three-quarters of currently presenting cases have significant mental health problems or suffer from neurocognitive comorbidities such as autism spectrum disorder or attention-deficit/hyperactivity disorder – a much higher burden of mental health comorbidities than the historical cohort with gender dysphoria.

There is legitimate concern that these comorbid mental health conditions, as well as the influence of social groups and online immersion into transgender topics, may be playing a role in the rapidly growing rate of transgender identification among these particularly vulnerable youth.

The initial study positing the theory that social influence is playing a role in the increased incidence of “late” or adolescent-onset (vs. childhood-onset) transgender-identified youth was harshly attacked by proponents of medical transitioning of youth, despite the fact that the study utilized methods similar to those used in other areas of health research. The study underwent an unprecedented second peer review and emerged with largely unchanged conclusions.

Since the study’s publication, a number of mental health clinicians working directly with gender-distressed youth have corroborated a rapid onset of transgender identification among teens with previously gender-normative childhoods.

Pioneers in gender dysphoria treatment are changing course

Several European countries that were pioneers in pediatric medical transition are now reversing course toward far more caution after their own evidence evaluations failed to show that medically transitioning gender-distressed youth improves mental health outcomes. In Sweden, following Karolinska Hospital’s announcement that it will no longer transition people under 18 outside of strictly regulated clinical trials, a number of other pediatric gender clinics followed suit and made the same decision.

In the United Kingdom, Keira Bell – a young woman who was treated with “affirmative” hormonal and surgical interventions before detransitioning – brought a challenge against the national gender clinic. Her landmark case and the UK High Court’s original judgement against the clinic have highlighted the urgency to reassess treatment approaches for the increasingly varied presentations of gender dysphoria in young people. As this article went to press, the UK’s national gender clinic won its appeal against Keira Bell, meaning that doctors there will once again be able to decide whether their patients under 16 can properly consent to puberty blockers. Keira Bell said she is disappointed with this decision and will be seeking permission to appeal to the Supreme Court. She said the medical service had become “politicized,” and added: “A global conversation has begun and has been shaped by this case. It has shone a light into the dark corners of a medical scandal that is harming children and harmed me. There is more to be done.”

And the UK National Health Service (NHS) has already commissioned an independent systematic review of data, which concluded that the evidence of benefit of hormonal interventions in gender dysphoric youth is of very low certainty and must be carefully weighed against the risks. An independent taskforce has also been convened to reassess the country’s approach to treating gender dysphoric youth.

Finland has arguably undertaken the biggest change of all. An early adopter of pediatric medical transition, researchers there noticed that adolescents who had mental health struggles at baseline failed to improve after transition. The Finnish national Gender Identity Development services issued new treatment guidelines in 2020 stating that psychotherapy, rather than gender reassignment, should be the first line of treatment for gender-dysphoric youth.

Leaders of America’s medical societies have been slower to respond. Recently, the Society for Evidence-Based Gender Medicine applied to share information about youth gender transitions at the yearly meeting of the American Academy of Pediatrics (AAP). The application was denied without explanation, despite the fact that 80% of rank-and-file pediatricians who voted on AAP resolutions days earlier endorsed a resolution calling for a reassessment of the evidence and more caution regarding gender transitions of minors.

The AAP leadership apparently ignored the resounding support for this resolution, but the clear message from that vote is that frontline pediatricians do not agree with the “one size fits all” approach of automatically affirming gender-distressed youth as transgender and proceeding to gender reassignment.

What we know and don’t know


There is now growing evidence that the “gender-affirming” model, based on the unproven assumption that gender reassignment is the best way to help gender-distressed youth, is not living up to its promise. This should not be surprising. Despite more than 50 years of experience with mature adult gender transitions, there is a lack of convincing evidence that transitions improve the psychological functioning of those with gender dysphoria, and studies on regret have been plagued by high dropout rates that prevent meaningful conclusions for practitioners and patients alike. Pediatric transitions are a much more recent phenomenon, with little to no quality data to guide decision-making.

We are witnessing a growing number of vocal regretters who underwent gender reassignment as teens and young adults under “gender-affirming” care protocols in recent years. A review of stories on the subreddit r/detrans, which counts over 20,000 members (not all are detransitioners, as the forum is open to those fully detransitioned, partially detransitioned, desisted [those who identified as transgender for a period of time in their youth but no longer do], and questioning their transition) is flush with first-hand accounts of regret and should be mandatory reading for any clinician who is considering becoming a prescriber of gender-affirmative care.  

Here is a brief outline of what we know – and more importantly, what we don’t know – about the practice of medically transitioning minors.

Most cases of early childhood-onset gender dysphoria self-resolve. Eleven out of 11 studies that followed the trajectory of gender-variant youth show that the most common outcome is natural resolution of gender dysphoria around or after puberty. Among those diagnosed as having gender identity disorder, 67% no longer met the diagnostic criteria as adults; among those subthreshold for diagnosis, 93% were not gender dysphoric as adults. Gender dysphoria in childhood is a far better predictor of future homosexuality than of future trans identity.

The future trajectory of people whose transgender identity emerged during or after puberty is entirely unknown. No one has studied future trajectories of patients whose transgender identity emerged for the first time after the onset of puberty – a previously rare but now increasingly common presentation. Growing numbers of young detransitioners and desisters are precisely from this demographic, suggesting that a transgender identity that emerges in adolescence may not be durable.

Social transition does not improve mental health outcomes. Recent studies show that while socially transitioned children can thrive in the short term, they do not fare any better than their non–socially transitioned dysphoric peers. It appears that peer relations, not the social transition status, predict mental health in gender-dysphoric children. We don’t yet know the long-term trajectories of socially transitioned minors, but emerging evidence suggests that they may be more likely to persist with gender-related distress rather than outgrow it, as previously observed. This in turn necessitates decades of invasive and risky medical interventions. In fact, the Dutch researchers who pioneered the protocol used to medically transition minors explicitly and strongly discouraged social transition of children and early adolescents.

Nearly 100% of children who begin puberty blockers will proceed to cross-sex hormones and surgeries. The two main studies that have evaluated the effects of puberty blockers on mental health found no improvements or improvements of marginal clinical significance. Both studies are also at critical risk of bias due to the absence of control groups.

Four additional studies looking at the mental health effects of puberty blockers were plagued by design limitations and also failed to show any convincing positive effects on psychological health. However, one effect of puberty blockers has been consistently replicated: At least four studies show that virtually all of the children who start puberty blockers proceed to cross-sex hormones. This suggests that rather than being a pause button, puberty blockers may serve as the “gas pedal” for gender transition.

Most of the long-term health risks are largely unknown. No long-term studies exist of patients who underwent medical transition as teens or young adults. Therefore, our ability to assess risks vs. benefits is limited. Puberty blockers have been demonstrated to significantly impair bone health, and it is not clear whether this will result in future osteoporosis. Cross-sex hormones are associated with roughly 3-5 times the risk for heart attacks and strokes, though long-term studies are of insufficient quality for accurate risk assessments. Other risks associated with these endocrine interventions will come to light as the practice continues to scale and as young people spend years and decades on these interventions. The risks to fertility are largely unknown, but it is almost certain that if puberty blockers are given at the early stages of puberty and followed by cross-sex hormones, sterility will result.

The medical pathway of “affirmative care” rests on a single Dutch study that is not applicable to the current populations of gender-dysphoric youth. Most of the youth presenting for care today would have been explicitly disqualified by the original Dutch protocol, as most have significant mental health comorbidities and post-puberty onset of trans identities. This fact has been recognized by the principal investigators of the Dutch protocol itself, who have recently begun to sound the alarm about the potential misapplication of their protocol and who suggest that psychotherapy – rather than gender reassignment – is more appropriate for many of the currently presenting cases.

On suicidality

The urgency to put gender-dysphoric youth through gender reassignment despite the dearth of evidence appears to stem from the notion that if we don’t intervene medically and in short order, these youth will commit suicide. However, studies using quality data reveal a markedly different reality.

While gender-dysphoric youth do have elevated rates of suicidality, it’s not uniquely high. In fact, it’s roughly similar to the rate of suicidality found in populations of youth referred for other mental health conditions. Quality long-term studies that explored whether transition leads to reduced suicidality have not been able to demonstrate a reduction.

Medicine has a pattern of enthusiastically embracing unproven medical interventions, only to find out years or decades later that the harms from those interventions outweigh the benefits. We owe it to our patients to be transparent about the limits of our knowledge and the fact that the “affirmative care” pathway is largely irreversible.

When the benefits of an intervention have not been shown to outweigh the risks, medical ethics dictate that such interventions should not occur outside of clinical trials. We must not conflate medical care for gender-dysphoric youth with experimental and risky interventions that are based on low-quality evidence. It’s time to hit pause on gender transitions for youth.

A brief history of the Dutch protocol

Before the mid-1990s, medical transition was primarily reserved for mature adults. However, noting the “never-disappearing masculine appearance” of many adult male transitioners, a team of Dutch researchers hypothesized that it might be appropriate to provide early intervention to a carefully selected group of adolescents before the irreversible physical changes of puberty occur.

To differentiate the majority of gender-dysphoric children who would outgrow their cross-sex identification by adulthood from the few who would probably not have resolution and would wish to transition later in life, the Dutch gender clinic designed a rigorous screening protocol, with multidisciplinary teams closely following prospective candidates for several years.

To qualify for early intervention, the adolescents had to have had persistent and severe cross-sex identification from early childhood (cases of adolescent-onset trans identity were disqualified); the distress had to worsen during puberty; and the adolescents had to be free from any other significant mental health conditions. For qualifying adolescents, puberty blockers were initiated no earlier than 12 years of age, cross-sex hormones at 16, and surgeries upon turning 18. Ongoing psychotherapy was provided through the entire assessment and intervention period.

The Dutch team published the final results of their research in 2014. The authors reported that at the average age of 21 (approximately 1.5 years post surgery), the young people were free from gender dysphoria and functioning well. Despite a postsurgical death from infection, several new diagnoses of metabolic illness, and multiple dropouts, the Western world enthusiastically embraced the early-intervention model. Concerningly, the only attempt to replicate the Dutch protocol outside of the Netherlands failed to show any psychological improvements, and to date, no long-term outcome data are available for the cohort of the 55 treated Dutch adolescents.

These progressively irreversible interventions form the basis of the “Dutch Protocol.” Currently, this protocol is being scaled in ways it was never designed for. For example, it strongly discouraged childhood social transition and did not transition adolescents with postpubertal onset of transgender identity or those with significant mental health comorbidities. Yet, treating such cases with the interventions outlined in the Dutch protocol is now common, and the age of eligibility for hormonal and surgical interventions has progressively lowered, with children as young as 8 now eligible to begin puberty blockers.

William Malone, MD, is an assistant professor of endocrinology practicing in Southern Idaho and an adviser to the Society for Evidence-Based Gender Medicine. A version of this article first appeared on Medscape.com.

Teens are identifying as transgender in record numbers. In 2017, 3-4 in 100 teens in the United States reported that they are or may be transgender. A more recent 2021 study suggests that the rate of transgender identification among America’s youth may be as high as 9 in 100. All of the major gender centers in the world have reported a several-thousand-percent increase in youth presenting with gender distress.

Origovisualis/Getty Images

How do we reconcile these numbers with 2013 data reporting the prevalence of adult gender dysphoria to be a rare 2-14 in 100,000? Reflection is warranted because many U.S. medical societies support providing youth who have transgender identification (over 1 million children and adolescents, using the latest estimates) with access to powerful endocrine interventions.

GnRH analogues (colloquially known as “puberty blockers”) are now available at Tanner stage 2 of puberty – a threshold crossed by females as young as 8-9 years old. Cross-sex hormones and surgeries follow, and mastectomies are now available to children as young as 13. Genital-altering surgeries, as well as the removal of the ovaries, uterus, and testes, can be obtained as soon as a patient turns 18.

What’s driving this massive increase in trans-identified youth? What are the risks, benefits, and uncertainties associated with hormonal and surgical interventions? Do such interventions improve the long-term psychological health of gender-dysphoric youth? How many will regret the irreversible changes made to their bodies during what may have been a temporary phase in their development?

We don’t know the answers to these questions, but we need to figure them out before offering such interventions. Frontline clinicians – especially those working with youth – will not be able to remain on the sidelines of this issue for much longer. Each clinician considering writing a prescription for puberty blockers or cross-sex hormones, or generating a referral for surgery, will need to answer for themselves: Just because I can, does it mean I should?

What’s contributing to the rapid rise of gender-dysphoric youth?

The etiology of the rapid rise of transgender identifications in young people is vigorously debated. Proponents of hormonal and surgical interventions for youth argue that the several-thousand-percent increase in the numbers of youth seeking gender reassignment is a reflection of more social acceptance of transgender identities, allowing more young people to “come out.” But closer examination of this claim reveals several inconsistencies.

Because adolescent and young adult females now account for 6-8 in 10 of the presenting cases (previously, prepubertal males were more common), one would expect a commensurate increase in the rate of transgender identification in older females. This has not occurred. In addition, more than three-quarters of currently presenting cases have significant mental health problems or suffer from neurocognitive comorbidities such as autism spectrum disorder or attention-deficit/hyperactivity disorder – a much higher burden of mental health comorbidities than the historical cohort with gender dysphoria.

There is legitimate concern that these comorbid mental health conditions, as well as the influence of social groups and online immersion into transgender topics, may be playing a role in the rapidly growing rate of transgender identification among these particularly vulnerable youth.

The initial study positing the theory that social influence is playing a role in the increased incidence of “late” or adolescent-onset (vs. childhood-onset) transgender-identified youth was harshly attacked by proponents of medical transitioning of youth, despite the fact that the study utilized methods similar to those used in other areas of health research. The study underwent an unprecedented second peer review and emerged with largely unchanged conclusions.

Since the study’s publication, a number of mental health clinicians working directly with gender-distressed youth have corroborated a rapid onset of transgender identification among teens with previously gender-normative childhoods.

Pioneers in gender dysphoria treatment are changing course

Several European countries that were pioneers in pediatric medical transition are now reversing course toward far more caution after their own evidence evaluations failed to show that medically transitioning gender-distressed youth improves mental health outcomes. In Sweden, following Karolinska Hospital’s announcement that it will no longer transition people under 18 outside of strictly regulated clinical trials, a number of other pediatric gender clinics followed suit and made the same decision.

In the United Kingdom, Keira Bell – a young woman who was treated with “affirmative” hormonal and surgical interventions before detransitioning – brought a challenge against the national gender clinic. Her landmark case and the UK High Court’s original judgement against the clinic have highlighted the urgency to reassess treatment approaches for the increasingly varied presentations of gender dysphoria in young people. As this article went to press, the UK’s national gender clinic won its appeal against Keira Bell, meaning that doctors there will once again be able to decide whether their patients under 16 can properly consent to puberty blockers. Keira Bell said she is disappointed with this decision and will be seeking permission to appeal to the Supreme Court. She said the medical service had become “politicized,” and added: “A global conversation has begun and has been shaped by this case. It has shone a light into the dark corners of a medical scandal that is harming children and harmed me. There is more to be done.”

And the UK National Health Service (NHS) has already commissioned an independent systematic review of data, which concluded that the evidence of benefit of hormonal interventions in gender dysphoric youth is of very low certainty and must be carefully weighed against the risks. An independent taskforce has also been convened to reassess the country’s approach to treating gender dysphoric youth.

Finland has arguably undertaken the biggest change of all. An early adopter of pediatric medical transition, researchers there noticed that adolescents who had mental health struggles at baseline failed to improve after transition. The Finnish national Gender Identity Development services issued new treatment guidelines in 2020 stating that psychotherapy, rather than gender reassignment, should be the first line of treatment for gender-dysphoric youth.

Leaders of America’s medical societies have been slower to respond. Recently, the Society for Evidence-Based Gender Medicine applied to share information about youth gender transitions at the yearly meeting of the American Academy of Pediatrics (AAP). The application was denied without explanation, despite the fact that 80% of rank-and-file pediatricians who voted on AAP resolutions days earlier endorsed a resolution calling for a reassessment of the evidence and more caution regarding gender transitions of minors.

The AAP leadership apparently ignored the resounding support for this resolution, but the clear message from that vote is that frontline pediatricians do not agree with the “one size fits all” approach of automatically affirming gender-distressed youth as transgender and proceeding to gender reassignment.

What we know and don’t know


There is now growing evidence that the “gender-affirming” model, based on the unproven assumption that gender reassignment is the best way to help gender-distressed youth, is not living up to its promise. This should not be surprising. Despite more than 50 years of experience with mature adult gender transitions, there is a lack of convincing evidence that transitions improve the psychological functioning of those with gender dysphoria, and studies on regret have been plagued by high dropout rates that prevent meaningful conclusions for practitioners and patients alike. Pediatric transitions are a much more recent phenomenon, with little to no quality data to guide decision-making.

We are witnessing a growing number of vocal regretters who underwent gender reassignment as teens and young adults under “gender-affirming” care protocols in recent years. A review of stories on the subreddit r/detrans, which counts over 20,000 members (not all are detransitioners, as the forum is open to those fully detransitioned, partially detransitioned, desisted [those who identified as transgender for a period of time in their youth but no longer do], and questioning their transition) is flush with first-hand accounts of regret and should be mandatory reading for any clinician who is considering becoming a prescriber of gender-affirmative care.  

Here is a brief outline of what we know – and more importantly, what we don’t know – about the practice of medically transitioning minors.

Most cases of early childhood-onset gender dysphoria self-resolve. Eleven out of 11 studies that followed the trajectory of gender-variant youth show that the most common outcome is natural resolution of gender dysphoria around or after puberty. Among those diagnosed as having gender identity disorder, 67% no longer met the diagnostic criteria as adults; among those subthreshold for diagnosis, 93% were not gender dysphoric as adults. Gender dysphoria in childhood is a far better predictor of future homosexuality than of future trans identity.

The future trajectory of people whose transgender identity emerged during or after puberty is entirely unknown. No one has studied future trajectories of patients whose transgender identity emerged for the first time after the onset of puberty – a previously rare but now increasingly common presentation. Growing numbers of young detransitioners and desisters are precisely from this demographic, suggesting that a transgender identity that emerges in adolescence may not be durable.

Social transition does not improve mental health outcomes. Recent studies show that while socially transitioned children can thrive in the short term, they do not fare any better than their non–socially transitioned dysphoric peers. It appears that peer relations, not the social transition status, predict mental health in gender-dysphoric children. We don’t yet know the long-term trajectories of socially transitioned minors, but emerging evidence suggests that they may be more likely to persist with gender-related distress rather than outgrow it, as previously observed. This in turn necessitates decades of invasive and risky medical interventions. In fact, the Dutch researchers who pioneered the protocol used to medically transition minors explicitly and strongly discouraged social transition of children and early adolescents.

Nearly 100% of children who begin puberty blockers will proceed to cross-sex hormones and surgeries. The two main studies that have evaluated the effects of puberty blockers on mental health found no improvements or improvements of marginal clinical significance. Both studies are also at critical risk of bias due to the absence of control groups.

Four additional studies looking at the mental health effects of puberty blockers were plagued by design limitations and also failed to show any convincing positive effects on psychological health. However, one effect of puberty blockers has been consistently replicated: At least four studies show that virtually all of the children who start puberty blockers proceed to cross-sex hormones. This suggests that rather than being a pause button, puberty blockers may serve as the “gas pedal” for gender transition.

Most of the long-term health risks are largely unknown. No long-term studies exist of patients who underwent medical transition as teens or young adults. Therefore, our ability to assess risks vs. benefits is limited. Puberty blockers have been demonstrated to significantly impair bone health, and it is not clear whether this will result in future osteoporosis. Cross-sex hormones are associated with roughly 3-5 times the risk for heart attacks and strokes, though long-term studies are of insufficient quality for accurate risk assessments. Other risks associated with these endocrine interventions will come to light as the practice continues to scale and as young people spend years and decades on these interventions. The risks to fertility are largely unknown, but it is almost certain that if puberty blockers are given at the early stages of puberty and followed by cross-sex hormones, sterility will result.

The medical pathway of “affirmative care” rests on a single Dutch study that is not applicable to the current populations of gender-dysphoric youth. Most of the youth presenting for care today would have been explicitly disqualified by the original Dutch protocol, as most have significant mental health comorbidities and post-puberty onset of trans identities. This fact has been recognized by the principal investigators of the Dutch protocol itself, who have recently begun to sound the alarm about the potential misapplication of their protocol and who suggest that psychotherapy – rather than gender reassignment – is more appropriate for many of the currently presenting cases.

On suicidality

The urgency to put gender-dysphoric youth through gender reassignment despite the dearth of evidence appears to stem from the notion that if we don’t intervene medically and in short order, these youth will commit suicide. However, studies using quality data reveal a markedly different reality.

While gender-dysphoric youth do have elevated rates of suicidality, it’s not uniquely high. In fact, it’s roughly similar to the rate of suicidality found in populations of youth referred for other mental health conditions. Quality long-term studies that explored whether transition leads to reduced suicidality have not been able to demonstrate a reduction.

Medicine has a pattern of enthusiastically embracing unproven medical interventions, only to find out years or decades later that the harms from those interventions outweigh the benefits. We owe it to our patients to be transparent about the limits of our knowledge and the fact that the “affirmative care” pathway is largely irreversible.

When the benefits of an intervention have not been shown to outweigh the risks, medical ethics dictate that such interventions should not occur outside of clinical trials. We must not conflate medical care for gender-dysphoric youth with experimental and risky interventions that are based on low-quality evidence. It’s time to hit pause on gender transitions for youth.

A brief history of the Dutch protocol

Before the mid-1990s, medical transition was primarily reserved for mature adults. However, noting the “never-disappearing masculine appearance” of many adult male transitioners, a team of Dutch researchers hypothesized that it might be appropriate to provide early intervention to a carefully selected group of adolescents before the irreversible physical changes of puberty occur.

To differentiate the majority of gender-dysphoric children who would outgrow their cross-sex identification by adulthood from the few who would probably not have resolution and would wish to transition later in life, the Dutch gender clinic designed a rigorous screening protocol, with multidisciplinary teams closely following prospective candidates for several years.

To qualify for early intervention, the adolescents had to have had persistent and severe cross-sex identification from early childhood (cases of adolescent-onset trans identity were disqualified); the distress had to worsen during puberty; and the adolescents had to be free from any other significant mental health conditions. For qualifying adolescents, puberty blockers were initiated no earlier than 12 years of age, cross-sex hormones at 16, and surgeries upon turning 18. Ongoing psychotherapy was provided through the entire assessment and intervention period.

The Dutch team published the final results of their research in 2014. The authors reported that at the average age of 21 (approximately 1.5 years post surgery), the young people were free from gender dysphoria and functioning well. Despite a postsurgical death from infection, several new diagnoses of metabolic illness, and multiple dropouts, the Western world enthusiastically embraced the early-intervention model. Concerningly, the only attempt to replicate the Dutch protocol outside of the Netherlands failed to show any psychological improvements, and to date, no long-term outcome data are available for the cohort of the 55 treated Dutch adolescents.

These progressively irreversible interventions form the basis of the “Dutch Protocol.” Currently, this protocol is being scaled in ways it was never designed for. For example, it strongly discouraged childhood social transition and did not transition adolescents with postpubertal onset of transgender identity or those with significant mental health comorbidities. Yet, treating such cases with the interventions outlined in the Dutch protocol is now common, and the age of eligibility for hormonal and surgical interventions has progressively lowered, with children as young as 8 now eligible to begin puberty blockers.

William Malone, MD, is an assistant professor of endocrinology practicing in Southern Idaho and an adviser to the Society for Evidence-Based Gender Medicine. A version of this article first appeared on Medscape.com.

Teens are identifying as transgender in record numbers. In 2017, 3-4 in 100 teens in the United States reported that they are or may be transgender. A more recent 2021 study suggests that the rate of transgender identification among America’s youth may be as high as 9 in 100. All of the major gender centers in the world have reported a several-thousand-percent increase in youth presenting with gender distress.

Origovisualis/Getty Images

How do we reconcile these numbers with 2013 data reporting the prevalence of adult gender dysphoria to be a rare 2-14 in 100,000? Reflection is warranted because many U.S. medical societies support providing youth who have transgender identification (over 1 million children and adolescents, using the latest estimates) with access to powerful endocrine interventions.

GnRH analogues (colloquially known as “puberty blockers”) are now available at Tanner stage 2 of puberty – a threshold crossed by females as young as 8-9 years old. Cross-sex hormones and surgeries follow, and mastectomies are now available to children as young as 13. Genital-altering surgeries, as well as the removal of the ovaries, uterus, and testes, can be obtained as soon as a patient turns 18.

What’s driving this massive increase in trans-identified youth? What are the risks, benefits, and uncertainties associated with hormonal and surgical interventions? Do such interventions improve the long-term psychological health of gender-dysphoric youth? How many will regret the irreversible changes made to their bodies during what may have been a temporary phase in their development?

We don’t know the answers to these questions, but we need to figure them out before offering such interventions. Frontline clinicians – especially those working with youth – will not be able to remain on the sidelines of this issue for much longer. Each clinician considering writing a prescription for puberty blockers or cross-sex hormones, or generating a referral for surgery, will need to answer for themselves: Just because I can, does it mean I should?

What’s contributing to the rapid rise of gender-dysphoric youth?

The etiology of the rapid rise of transgender identifications in young people is vigorously debated. Proponents of hormonal and surgical interventions for youth argue that the several-thousand-percent increase in the numbers of youth seeking gender reassignment is a reflection of more social acceptance of transgender identities, allowing more young people to “come out.” But closer examination of this claim reveals several inconsistencies.

Because adolescent and young adult females now account for 6-8 in 10 of the presenting cases (previously, prepubertal males were more common), one would expect a commensurate increase in the rate of transgender identification in older females. This has not occurred. In addition, more than three-quarters of currently presenting cases have significant mental health problems or suffer from neurocognitive comorbidities such as autism spectrum disorder or attention-deficit/hyperactivity disorder – a much higher burden of mental health comorbidities than the historical cohort with gender dysphoria.

There is legitimate concern that these comorbid mental health conditions, as well as the influence of social groups and online immersion into transgender topics, may be playing a role in the rapidly growing rate of transgender identification among these particularly vulnerable youth.

The initial study positing the theory that social influence is playing a role in the increased incidence of “late” or adolescent-onset (vs. childhood-onset) transgender-identified youth was harshly attacked by proponents of medical transitioning of youth, despite the fact that the study utilized methods similar to those used in other areas of health research. The study underwent an unprecedented second peer review and emerged with largely unchanged conclusions.

Since the study’s publication, a number of mental health clinicians working directly with gender-distressed youth have corroborated a rapid onset of transgender identification among teens with previously gender-normative childhoods.

Pioneers in gender dysphoria treatment are changing course

Several European countries that were pioneers in pediatric medical transition are now reversing course toward far more caution after their own evidence evaluations failed to show that medically transitioning gender-distressed youth improves mental health outcomes. In Sweden, following Karolinska Hospital’s announcement that it will no longer transition people under 18 outside of strictly regulated clinical trials, a number of other pediatric gender clinics followed suit and made the same decision.

In the United Kingdom, Keira Bell – a young woman who was treated with “affirmative” hormonal and surgical interventions before detransitioning – brought a challenge against the national gender clinic. Her landmark case and the UK High Court’s original judgement against the clinic have highlighted the urgency to reassess treatment approaches for the increasingly varied presentations of gender dysphoria in young people. As this article went to press, the UK’s national gender clinic won its appeal against Keira Bell, meaning that doctors there will once again be able to decide whether their patients under 16 can properly consent to puberty blockers. Keira Bell said she is disappointed with this decision and will be seeking permission to appeal to the Supreme Court. She said the medical service had become “politicized,” and added: “A global conversation has begun and has been shaped by this case. It has shone a light into the dark corners of a medical scandal that is harming children and harmed me. There is more to be done.”

And the UK National Health Service (NHS) has already commissioned an independent systematic review of data, which concluded that the evidence of benefit of hormonal interventions in gender dysphoric youth is of very low certainty and must be carefully weighed against the risks. An independent taskforce has also been convened to reassess the country’s approach to treating gender dysphoric youth.

Finland has arguably undertaken the biggest change of all. An early adopter of pediatric medical transition, researchers there noticed that adolescents who had mental health struggles at baseline failed to improve after transition. The Finnish national Gender Identity Development services issued new treatment guidelines in 2020 stating that psychotherapy, rather than gender reassignment, should be the first line of treatment for gender-dysphoric youth.

Leaders of America’s medical societies have been slower to respond. Recently, the Society for Evidence-Based Gender Medicine applied to share information about youth gender transitions at the yearly meeting of the American Academy of Pediatrics (AAP). The application was denied without explanation, despite the fact that 80% of rank-and-file pediatricians who voted on AAP resolutions days earlier endorsed a resolution calling for a reassessment of the evidence and more caution regarding gender transitions of minors.

The AAP leadership apparently ignored the resounding support for this resolution, but the clear message from that vote is that frontline pediatricians do not agree with the “one size fits all” approach of automatically affirming gender-distressed youth as transgender and proceeding to gender reassignment.

What we know and don’t know


There is now growing evidence that the “gender-affirming” model, based on the unproven assumption that gender reassignment is the best way to help gender-distressed youth, is not living up to its promise. This should not be surprising. Despite more than 50 years of experience with mature adult gender transitions, there is a lack of convincing evidence that transitions improve the psychological functioning of those with gender dysphoria, and studies on regret have been plagued by high dropout rates that prevent meaningful conclusions for practitioners and patients alike. Pediatric transitions are a much more recent phenomenon, with little to no quality data to guide decision-making.

We are witnessing a growing number of vocal regretters who underwent gender reassignment as teens and young adults under “gender-affirming” care protocols in recent years. A review of stories on the subreddit r/detrans, which counts over 20,000 members (not all are detransitioners, as the forum is open to those fully detransitioned, partially detransitioned, desisted [those who identified as transgender for a period of time in their youth but no longer do], and questioning their transition) is flush with first-hand accounts of regret and should be mandatory reading for any clinician who is considering becoming a prescriber of gender-affirmative care.  

Here is a brief outline of what we know – and more importantly, what we don’t know – about the practice of medically transitioning minors.

Most cases of early childhood-onset gender dysphoria self-resolve. Eleven out of 11 studies that followed the trajectory of gender-variant youth show that the most common outcome is natural resolution of gender dysphoria around or after puberty. Among those diagnosed as having gender identity disorder, 67% no longer met the diagnostic criteria as adults; among those subthreshold for diagnosis, 93% were not gender dysphoric as adults. Gender dysphoria in childhood is a far better predictor of future homosexuality than of future trans identity.

The future trajectory of people whose transgender identity emerged during or after puberty is entirely unknown. No one has studied future trajectories of patients whose transgender identity emerged for the first time after the onset of puberty – a previously rare but now increasingly common presentation. Growing numbers of young detransitioners and desisters are precisely from this demographic, suggesting that a transgender identity that emerges in adolescence may not be durable.

Social transition does not improve mental health outcomes. Recent studies show that while socially transitioned children can thrive in the short term, they do not fare any better than their non–socially transitioned dysphoric peers. It appears that peer relations, not the social transition status, predict mental health in gender-dysphoric children. We don’t yet know the long-term trajectories of socially transitioned minors, but emerging evidence suggests that they may be more likely to persist with gender-related distress rather than outgrow it, as previously observed. This in turn necessitates decades of invasive and risky medical interventions. In fact, the Dutch researchers who pioneered the protocol used to medically transition minors explicitly and strongly discouraged social transition of children and early adolescents.

Nearly 100% of children who begin puberty blockers will proceed to cross-sex hormones and surgeries. The two main studies that have evaluated the effects of puberty blockers on mental health found no improvements or improvements of marginal clinical significance. Both studies are also at critical risk of bias due to the absence of control groups.

Four additional studies looking at the mental health effects of puberty blockers were plagued by design limitations and also failed to show any convincing positive effects on psychological health. However, one effect of puberty blockers has been consistently replicated: At least four studies show that virtually all of the children who start puberty blockers proceed to cross-sex hormones. This suggests that rather than being a pause button, puberty blockers may serve as the “gas pedal” for gender transition.

Most of the long-term health risks are largely unknown. No long-term studies exist of patients who underwent medical transition as teens or young adults. Therefore, our ability to assess risks vs. benefits is limited. Puberty blockers have been demonstrated to significantly impair bone health, and it is not clear whether this will result in future osteoporosis. Cross-sex hormones are associated with roughly 3-5 times the risk for heart attacks and strokes, though long-term studies are of insufficient quality for accurate risk assessments. Other risks associated with these endocrine interventions will come to light as the practice continues to scale and as young people spend years and decades on these interventions. The risks to fertility are largely unknown, but it is almost certain that if puberty blockers are given at the early stages of puberty and followed by cross-sex hormones, sterility will result.

The medical pathway of “affirmative care” rests on a single Dutch study that is not applicable to the current populations of gender-dysphoric youth. Most of the youth presenting for care today would have been explicitly disqualified by the original Dutch protocol, as most have significant mental health comorbidities and post-puberty onset of trans identities. This fact has been recognized by the principal investigators of the Dutch protocol itself, who have recently begun to sound the alarm about the potential misapplication of their protocol and who suggest that psychotherapy – rather than gender reassignment – is more appropriate for many of the currently presenting cases.

On suicidality

The urgency to put gender-dysphoric youth through gender reassignment despite the dearth of evidence appears to stem from the notion that if we don’t intervene medically and in short order, these youth will commit suicide. However, studies using quality data reveal a markedly different reality.

While gender-dysphoric youth do have elevated rates of suicidality, it’s not uniquely high. In fact, it’s roughly similar to the rate of suicidality found in populations of youth referred for other mental health conditions. Quality long-term studies that explored whether transition leads to reduced suicidality have not been able to demonstrate a reduction.

Medicine has a pattern of enthusiastically embracing unproven medical interventions, only to find out years or decades later that the harms from those interventions outweigh the benefits. We owe it to our patients to be transparent about the limits of our knowledge and the fact that the “affirmative care” pathway is largely irreversible.

When the benefits of an intervention have not been shown to outweigh the risks, medical ethics dictate that such interventions should not occur outside of clinical trials. We must not conflate medical care for gender-dysphoric youth with experimental and risky interventions that are based on low-quality evidence. It’s time to hit pause on gender transitions for youth.

A brief history of the Dutch protocol

Before the mid-1990s, medical transition was primarily reserved for mature adults. However, noting the “never-disappearing masculine appearance” of many adult male transitioners, a team of Dutch researchers hypothesized that it might be appropriate to provide early intervention to a carefully selected group of adolescents before the irreversible physical changes of puberty occur.

To differentiate the majority of gender-dysphoric children who would outgrow their cross-sex identification by adulthood from the few who would probably not have resolution and would wish to transition later in life, the Dutch gender clinic designed a rigorous screening protocol, with multidisciplinary teams closely following prospective candidates for several years.

To qualify for early intervention, the adolescents had to have had persistent and severe cross-sex identification from early childhood (cases of adolescent-onset trans identity were disqualified); the distress had to worsen during puberty; and the adolescents had to be free from any other significant mental health conditions. For qualifying adolescents, puberty blockers were initiated no earlier than 12 years of age, cross-sex hormones at 16, and surgeries upon turning 18. Ongoing psychotherapy was provided through the entire assessment and intervention period.

The Dutch team published the final results of their research in 2014. The authors reported that at the average age of 21 (approximately 1.5 years post surgery), the young people were free from gender dysphoria and functioning well. Despite a postsurgical death from infection, several new diagnoses of metabolic illness, and multiple dropouts, the Western world enthusiastically embraced the early-intervention model. Concerningly, the only attempt to replicate the Dutch protocol outside of the Netherlands failed to show any psychological improvements, and to date, no long-term outcome data are available for the cohort of the 55 treated Dutch adolescents.

These progressively irreversible interventions form the basis of the “Dutch Protocol.” Currently, this protocol is being scaled in ways it was never designed for. For example, it strongly discouraged childhood social transition and did not transition adolescents with postpubertal onset of transgender identity or those with significant mental health comorbidities. Yet, treating such cases with the interventions outlined in the Dutch protocol is now common, and the age of eligibility for hormonal and surgical interventions has progressively lowered, with children as young as 8 now eligible to begin puberty blockers.

William Malone, MD, is an assistant professor of endocrinology practicing in Southern Idaho and an adviser to the Society for Evidence-Based Gender Medicine. A version of this article first appeared on Medscape.com.

Pregnant women should use paracetamol/acetaminophen only with a medical indication and at the lowest effective dose for the shortest possible time, according to an international consensus statement published online Sept. 23 in Nature Reviews Endocrinology.

With global rates of use high and risks considered negligible, the expert panel of 13 U.S. and European authors call for focused research into how this analgesic and febrifuge may impair fetal development and lead to adverse outcomes in children. They outline several precautionary measures to be taken in the meantime.

According to first author and epidemiologist Ann Z. Bauer, ScD, a postdoctoral research fellow at the University of Massachusetts in Lowell, and colleagues, this drug is used by an estimated 65% of pregnant women in the United States, and more than 50% worldwide. It is currently the active ingredient in more than 600 prescription and nonprescription medications, including Tylenol, which historically has been deemed safe in all trimesters of pregnancy.

But a growing body of experimental and epidemiological evidence suggests prenatal exposure to paracetamol (N-acetyl-p-aminophenol, or APAP) might alter fetal development and elevate the risks of neurodevelopmental, reproductive and urogenital disorders in both sexes. Exposure in utero has been linked, for example, to potential behavioral problems in children.

The new recommendations are based on a review of experimental animal and cell-based research as well as human epidemiological data published from January 1995 to October 2020. The authors include clinicians, epidemiologists, and scientists specializing in toxicology, endocrinology, reproductive medicine and neurodevelopment.
 

Recommendations

Although the new guidance does not differ markedly from current advice, the authors believe stronger communication and greater awareness of risks are needed. In addition to restricting use of this medication to low doses for short periods when medically necessary, expectant mothers should receive counseling before conception or early in pregnancy. If uncertain about its use, they should consult their physicians or pharmacists.

In other recommendations, the panel said:

• The 2015 FDA Drug Safety Communication recommendations should be updated based on evaluation of all available scientific evidence.
• The European Medicines Agency Pharmacovigilance Risk Assessment Committee should review the most recent epidemiologic and experimental research and issue an updated Drug Safety Communication.
• Obstetric and gynecological associations should update their guidance after reviewing all available research.
• The Acetaminophen Awareness Coalition (“Know Your Dose” Campaign) should add standardized warnings and specifically advise pregnant women to forgo APAP unless it’s medically indicated.
• All sales of APAP-containing medications should be accompanied by recommendations specifically for use in pregnancy. This information should include warning labels on packaging, and if possible, APAP should be sold only in pharmacies (as in France).

Mechanism of action

APAP is an endocrine disruptor (Neuroscientist. 2020 Sep 11. doi: 10.1177/1073858420952046). “Chemicals that disrupt the endocrine system are concerning because they can interfere with the activity of endogenous hormones that are essential for healthy neurological, urogenital, and reproductive development,” researchers wrote.

“The precise mechanism is not clear but its toxicity is thought to be due mainly to hormone disruption,” Dr. Bauer said in an interview.

Moreover, APAP readily crosses the placenta and blood–brain barrier, and changes in APAP metabolism during pregnancy might make women and their fetuses more vulnerable to its toxic effects. For instance, the molar dose fraction of APAP converted to the oxidative metabolite N-acetyl-p-benzoquinone imine increases during pregnancy. In addition to its hepatotoxicity, this poisonous byproduct is thought to be a genotoxin that increases DNA cleavage by acting on the enzyme topoisomerase II.

Asked for her perspective on the statement, Kjersti Aagaard, MD, PhD, a professor of obstetrics and gynecology at Baylor College of Medicine and Texas Children’s Hospital in Houston, called the expert panel’s statement thoughtful and comprehensive, but she urged caution in interpreting the role of acetaminophen.

The challenge in linking any commonly used medication to adverse effects and congenital defects, she said, is “teasing out an association from causation. Given the commonality of the use of acetaminophen with the relative rarity of the outcomes, it is clear that not all cases of exposure result in adverse outcomes.”

As for judicious use, she said, one would be to reduce a high fever, which can cause miscarriage, neural tube defects, and potential heart disease in adulthood. Acetaminophen is the drug of choice in this case since nonsteroidal anti-inflammatory drugs such as ibuprofen are not recommended owing to their known risks to the fetal heart.

Dr. Aagaard emphasized that while acetaminophen use is temporally associated with learning and behavioral problems, and urogenital disorders at birth in male infants such as like hypospadias, so is exposure to multiple environmental chemicals and pollutants, as well as climate change. “It would be a real mistake with real life implications if we associated any congenital disease or disorder with a commonly used medication with known benefits if the true causal link lies elsewhere.”

She said the precautionary statements fall into the time-honored therapeutic principle of first do no harm. “However, the call for research action must be undertaken earnestly and sincerely.”

According to Dr. Bauer, the statement’s essential take-home message is that “physicians should educate themselves and educate women about what we’re learning about the risks of acetaminophen in pregnancy.” Risk can be minimized by using the lowest effective dose for the shortest time and only when medically indicated. “Pregnant women should speak to their physicians about acetaminophen. It’s about empowerment and making smart decisions,” she said.

This study received no specific funding. Coauthor Dr. R.T. Mitchell is supported by a UK Research Institute fellowship.

Pregnant women should use paracetamol/acetaminophen only with a medical indication and at the lowest effective dose for the shortest possible time, according to an international consensus statement published online Sept. 23 in Nature Reviews Endocrinology.

With global rates of use high and risks considered negligible, the expert panel of 13 U.S. and European authors call for focused research into how this analgesic and febrifuge may impair fetal development and lead to adverse outcomes in children. They outline several precautionary measures to be taken in the meantime.

According to first author and epidemiologist Ann Z. Bauer, ScD, a postdoctoral research fellow at the University of Massachusetts in Lowell, and colleagues, this drug is used by an estimated 65% of pregnant women in the United States, and more than 50% worldwide. It is currently the active ingredient in more than 600 prescription and nonprescription medications, including Tylenol, which historically has been deemed safe in all trimesters of pregnancy.

But a growing body of experimental and epidemiological evidence suggests prenatal exposure to paracetamol (N-acetyl-p-aminophenol, or APAP) might alter fetal development and elevate the risks of neurodevelopmental, reproductive and urogenital disorders in both sexes. Exposure in utero has been linked, for example, to potential behavioral problems in children.

The new recommendations are based on a review of experimental animal and cell-based research as well as human epidemiological data published from January 1995 to October 2020. The authors include clinicians, epidemiologists, and scientists specializing in toxicology, endocrinology, reproductive medicine and neurodevelopment.
 

Recommendations

Although the new guidance does not differ markedly from current advice, the authors believe stronger communication and greater awareness of risks are needed. In addition to restricting use of this medication to low doses for short periods when medically necessary, expectant mothers should receive counseling before conception or early in pregnancy. If uncertain about its use, they should consult their physicians or pharmacists.

In other recommendations, the panel said:

• The 2015 FDA Drug Safety Communication recommendations should be updated based on evaluation of all available scientific evidence.
• The European Medicines Agency Pharmacovigilance Risk Assessment Committee should review the most recent epidemiologic and experimental research and issue an updated Drug Safety Communication.
• Obstetric and gynecological associations should update their guidance after reviewing all available research.
• The Acetaminophen Awareness Coalition (“Know Your Dose” Campaign) should add standardized warnings and specifically advise pregnant women to forgo APAP unless it’s medically indicated.
• All sales of APAP-containing medications should be accompanied by recommendations specifically for use in pregnancy. This information should include warning labels on packaging, and if possible, APAP should be sold only in pharmacies (as in France).

Mechanism of action

APAP is an endocrine disruptor (Neuroscientist. 2020 Sep 11. doi: 10.1177/1073858420952046). “Chemicals that disrupt the endocrine system are concerning because they can interfere with the activity of endogenous hormones that are essential for healthy neurological, urogenital, and reproductive development,” researchers wrote.

“The precise mechanism is not clear but its toxicity is thought to be due mainly to hormone disruption,” Dr. Bauer said in an interview.

Moreover, APAP readily crosses the placenta and blood–brain barrier, and changes in APAP metabolism during pregnancy might make women and their fetuses more vulnerable to its toxic effects. For instance, the molar dose fraction of APAP converted to the oxidative metabolite N-acetyl-p-benzoquinone imine increases during pregnancy. In addition to its hepatotoxicity, this poisonous byproduct is thought to be a genotoxin that increases DNA cleavage by acting on the enzyme topoisomerase II.

Asked for her perspective on the statement, Kjersti Aagaard, MD, PhD, a professor of obstetrics and gynecology at Baylor College of Medicine and Texas Children’s Hospital in Houston, called the expert panel’s statement thoughtful and comprehensive, but she urged caution in interpreting the role of acetaminophen.

The challenge in linking any commonly used medication to adverse effects and congenital defects, she said, is “teasing out an association from causation. Given the commonality of the use of acetaminophen with the relative rarity of the outcomes, it is clear that not all cases of exposure result in adverse outcomes.”

As for judicious use, she said, one would be to reduce a high fever, which can cause miscarriage, neural tube defects, and potential heart disease in adulthood. Acetaminophen is the drug of choice in this case since nonsteroidal anti-inflammatory drugs such as ibuprofen are not recommended owing to their known risks to the fetal heart.

Dr. Aagaard emphasized that while acetaminophen use is temporally associated with learning and behavioral problems, and urogenital disorders at birth in male infants such as like hypospadias, so is exposure to multiple environmental chemicals and pollutants, as well as climate change. “It would be a real mistake with real life implications if we associated any congenital disease or disorder with a commonly used medication with known benefits if the true causal link lies elsewhere.”

She said the precautionary statements fall into the time-honored therapeutic principle of first do no harm. “However, the call for research action must be undertaken earnestly and sincerely.”

According to Dr. Bauer, the statement’s essential take-home message is that “physicians should educate themselves and educate women about what we’re learning about the risks of acetaminophen in pregnancy.” Risk can be minimized by using the lowest effective dose for the shortest time and only when medically indicated. “Pregnant women should speak to their physicians about acetaminophen. It’s about empowerment and making smart decisions,” she said.

This study received no specific funding. Coauthor Dr. R.T. Mitchell is supported by a UK Research Institute fellowship.

Pregnant women should use paracetamol/acetaminophen only with a medical indication and at the lowest effective dose for the shortest possible time, according to an international consensus statement published online Sept. 23 in Nature Reviews Endocrinology.

With global rates of use high and risks considered negligible, the expert panel of 13 U.S. and European authors call for focused research into how this analgesic and febrifuge may impair fetal development and lead to adverse outcomes in children. They outline several precautionary measures to be taken in the meantime.

According to first author and epidemiologist Ann Z. Bauer, ScD, a postdoctoral research fellow at the University of Massachusetts in Lowell, and colleagues, this drug is used by an estimated 65% of pregnant women in the United States, and more than 50% worldwide. It is currently the active ingredient in more than 600 prescription and nonprescription medications, including Tylenol, which historically has been deemed safe in all trimesters of pregnancy.

But a growing body of experimental and epidemiological evidence suggests prenatal exposure to paracetamol (N-acetyl-p-aminophenol, or APAP) might alter fetal development and elevate the risks of neurodevelopmental, reproductive and urogenital disorders in both sexes. Exposure in utero has been linked, for example, to potential behavioral problems in children.

The new recommendations are based on a review of experimental animal and cell-based research as well as human epidemiological data published from January 1995 to October 2020. The authors include clinicians, epidemiologists, and scientists specializing in toxicology, endocrinology, reproductive medicine and neurodevelopment.
 

Recommendations

Although the new guidance does not differ markedly from current advice, the authors believe stronger communication and greater awareness of risks are needed. In addition to restricting use of this medication to low doses for short periods when medically necessary, expectant mothers should receive counseling before conception or early in pregnancy. If uncertain about its use, they should consult their physicians or pharmacists.

In other recommendations, the panel said:

• The 2015 FDA Drug Safety Communication recommendations should be updated based on evaluation of all available scientific evidence.
• The European Medicines Agency Pharmacovigilance Risk Assessment Committee should review the most recent epidemiologic and experimental research and issue an updated Drug Safety Communication.
• Obstetric and gynecological associations should update their guidance after reviewing all available research.
• The Acetaminophen Awareness Coalition (“Know Your Dose” Campaign) should add standardized warnings and specifically advise pregnant women to forgo APAP unless it’s medically indicated.
• All sales of APAP-containing medications should be accompanied by recommendations specifically for use in pregnancy. This information should include warning labels on packaging, and if possible, APAP should be sold only in pharmacies (as in France).

Mechanism of action

APAP is an endocrine disruptor (Neuroscientist. 2020 Sep 11. doi: 10.1177/1073858420952046). “Chemicals that disrupt the endocrine system are concerning because they can interfere with the activity of endogenous hormones that are essential for healthy neurological, urogenital, and reproductive development,” researchers wrote.

“The precise mechanism is not clear but its toxicity is thought to be due mainly to hormone disruption,” Dr. Bauer said in an interview.

Moreover, APAP readily crosses the placenta and blood–brain barrier, and changes in APAP metabolism during pregnancy might make women and their fetuses more vulnerable to its toxic effects. For instance, the molar dose fraction of APAP converted to the oxidative metabolite N-acetyl-p-benzoquinone imine increases during pregnancy. In addition to its hepatotoxicity, this poisonous byproduct is thought to be a genotoxin that increases DNA cleavage by acting on the enzyme topoisomerase II.

Asked for her perspective on the statement, Kjersti Aagaard, MD, PhD, a professor of obstetrics and gynecology at Baylor College of Medicine and Texas Children’s Hospital in Houston, called the expert panel’s statement thoughtful and comprehensive, but she urged caution in interpreting the role of acetaminophen.

The challenge in linking any commonly used medication to adverse effects and congenital defects, she said, is “teasing out an association from causation. Given the commonality of the use of acetaminophen with the relative rarity of the outcomes, it is clear that not all cases of exposure result in adverse outcomes.”

As for judicious use, she said, one would be to reduce a high fever, which can cause miscarriage, neural tube defects, and potential heart disease in adulthood. Acetaminophen is the drug of choice in this case since nonsteroidal anti-inflammatory drugs such as ibuprofen are not recommended owing to their known risks to the fetal heart.

Dr. Aagaard emphasized that while acetaminophen use is temporally associated with learning and behavioral problems, and urogenital disorders at birth in male infants such as like hypospadias, so is exposure to multiple environmental chemicals and pollutants, as well as climate change. “It would be a real mistake with real life implications if we associated any congenital disease or disorder with a commonly used medication with known benefits if the true causal link lies elsewhere.”

She said the precautionary statements fall into the time-honored therapeutic principle of first do no harm. “However, the call for research action must be undertaken earnestly and sincerely.”

According to Dr. Bauer, the statement’s essential take-home message is that “physicians should educate themselves and educate women about what we’re learning about the risks of acetaminophen in pregnancy.” Risk can be minimized by using the lowest effective dose for the shortest time and only when medically indicated. “Pregnant women should speak to their physicians about acetaminophen. It’s about empowerment and making smart decisions,” she said.

This study received no specific funding. Coauthor Dr. R.T. Mitchell is supported by a UK Research Institute fellowship.

Bacteria get the rack ... the towel rack

Obviously, bathrooms have germs. Some people are cleaner about their bathrooms than others, but in general most people just try not to think about the microscopic critters crawling about.

Now you would probably think that the toilet is the dirtiest part of the bathroom because that’s where ... you know, most of the business takes place. Or maybe you’d guess the floor. Truth be told, though, the dirtiest part of the bathroom is where the towels are hung.

pxfuel

Anti-vaxxers would like to be called ‘purebloods’

COVID-19 anti-vaxxers are an interesting bunch, to be kind. And TikTok is a wacky place. So you can just imagine that anti-vaxxer TikTok is a very strange place. The citizens of anti-vax TikTok have decided that the real reason so many people dislike them is branding. They consider anti-vaccination to be a negative word (duh), so they now want to be referred to as “purebloods.”

peterschreiber_media/iStock/Getty Images

Harry Potter doesn’t quite occupy the zeitgeist as it once did, so let’s give you a reminder: In the books, purebloods came from old wizarding families and claimed not to have any Muggle, or nonmagic, blood. While having pure wizard blood was no guarantee of being a villain, most of them were. In addition, it is made quite clear throughout the novels that having supposedly pure blood had no relevance on one’s wizarding ability. Pureblood was a meaningless title, and only the characters with small, cruel minds concerned themselves over it.

Perhaps the anti-vaxxers have decided that they want to be called the same thing. Maybe they just like the name. It does sound impressive and vaguely regal: Pureblood. Like something the nobles of medieval Europe might have used.

Critical-thinking skills may be in short supply here, or maybe the anti-vaxxers know exactly what they’re doing.
 

Hated broccoli? Blame your DNA

Were you that kid who would rather sit at the table for hours than eat your broccoli? Well, as much as your parents might have pushed you, new research suggests that it might be their fault you didn’t like it to begin with.

Hans Braxmeier/Pixabay

Investigators at Australia’s national science agency, CSIRO, recently reported that distaste for Brassica vegetables – broccoli, Brussels sprouts, cabbage, and cauliflower – can be traced to the oral microbiome.

These vegetables have a compound called S-methyl-L-cysteine sulfoxide that gives off sulfurous odors ... mmm, sulfurous ... when mixed with an enzyme in the plant, and that enzyme is also produced by bacteria in some people’s oral microbiomes. So why do adults tolerate these Brassica veggies more than children? It’s all about levels.

The researchers tested the idea by asking 98 child/parent pairs to rate the odors and by using gas chromatography-olfactometry-mass spectrometry to identify the odor-active compounds in both raw and steamed cauliflower and broccoli. The children whose saliva produced high levels of sulfur volatiles disliked Brassica vegetables the most, they reported, and the children with high levels of sulfur volatiles usually had parents who produced high levels.

Despite that connection, however, the distaste for raw Brassica seen in children wasn’t seen in adults.

Maybe it’s not that taste buds change as we age, maybe we just learn to tolerate the sulfurousness.

Bacteria get the rack ... the towel rack

Obviously, bathrooms have germs. Some people are cleaner about their bathrooms than others, but in general most people just try not to think about the microscopic critters crawling about.

Now you would probably think that the toilet is the dirtiest part of the bathroom because that’s where ... you know, most of the business takes place. Or maybe you’d guess the floor. Truth be told, though, the dirtiest part of the bathroom is where the towels are hung.

pxfuel

Anti-vaxxers would like to be called ‘purebloods’

COVID-19 anti-vaxxers are an interesting bunch, to be kind. And TikTok is a wacky place. So you can just imagine that anti-vaxxer TikTok is a very strange place. The citizens of anti-vax TikTok have decided that the real reason so many people dislike them is branding. They consider anti-vaccination to be a negative word (duh), so they now want to be referred to as “purebloods.”

peterschreiber_media/iStock/Getty Images

Harry Potter doesn’t quite occupy the zeitgeist as it once did, so let’s give you a reminder: In the books, purebloods came from old wizarding families and claimed not to have any Muggle, or nonmagic, blood. While having pure wizard blood was no guarantee of being a villain, most of them were. In addition, it is made quite clear throughout the novels that having supposedly pure blood had no relevance on one’s wizarding ability. Pureblood was a meaningless title, and only the characters with small, cruel minds concerned themselves over it.

Perhaps the anti-vaxxers have decided that they want to be called the same thing. Maybe they just like the name. It does sound impressive and vaguely regal: Pureblood. Like something the nobles of medieval Europe might have used.

Critical-thinking skills may be in short supply here, or maybe the anti-vaxxers know exactly what they’re doing.
 

Hated broccoli? Blame your DNA

Were you that kid who would rather sit at the table for hours than eat your broccoli? Well, as much as your parents might have pushed you, new research suggests that it might be their fault you didn’t like it to begin with.

Hans Braxmeier/Pixabay

Investigators at Australia’s national science agency, CSIRO, recently reported that distaste for Brassica vegetables – broccoli, Brussels sprouts, cabbage, and cauliflower – can be traced to the oral microbiome.

These vegetables have a compound called S-methyl-L-cysteine sulfoxide that gives off sulfurous odors ... mmm, sulfurous ... when mixed with an enzyme in the plant, and that enzyme is also produced by bacteria in some people’s oral microbiomes. So why do adults tolerate these Brassica veggies more than children? It’s all about levels.

The researchers tested the idea by asking 98 child/parent pairs to rate the odors and by using gas chromatography-olfactometry-mass spectrometry to identify the odor-active compounds in both raw and steamed cauliflower and broccoli. The children whose saliva produced high levels of sulfur volatiles disliked Brassica vegetables the most, they reported, and the children with high levels of sulfur volatiles usually had parents who produced high levels.

Despite that connection, however, the distaste for raw Brassica seen in children wasn’t seen in adults.

Maybe it’s not that taste buds change as we age, maybe we just learn to tolerate the sulfurousness.

Bacteria get the rack ... the towel rack

Obviously, bathrooms have germs. Some people are cleaner about their bathrooms than others, but in general most people just try not to think about the microscopic critters crawling about.

Now you would probably think that the toilet is the dirtiest part of the bathroom because that’s where ... you know, most of the business takes place. Or maybe you’d guess the floor. Truth be told, though, the dirtiest part of the bathroom is where the towels are hung.

pxfuel

Anti-vaxxers would like to be called ‘purebloods’

COVID-19 anti-vaxxers are an interesting bunch, to be kind. And TikTok is a wacky place. So you can just imagine that anti-vaxxer TikTok is a very strange place. The citizens of anti-vax TikTok have decided that the real reason so many people dislike them is branding. They consider anti-vaccination to be a negative word (duh), so they now want to be referred to as “purebloods.”

peterschreiber_media/iStock/Getty Images

Harry Potter doesn’t quite occupy the zeitgeist as it once did, so let’s give you a reminder: In the books, purebloods came from old wizarding families and claimed not to have any Muggle, or nonmagic, blood. While having pure wizard blood was no guarantee of being a villain, most of them were. In addition, it is made quite clear throughout the novels that having supposedly pure blood had no relevance on one’s wizarding ability. Pureblood was a meaningless title, and only the characters with small, cruel minds concerned themselves over it.

Perhaps the anti-vaxxers have decided that they want to be called the same thing. Maybe they just like the name. It does sound impressive and vaguely regal: Pureblood. Like something the nobles of medieval Europe might have used.

Critical-thinking skills may be in short supply here, or maybe the anti-vaxxers know exactly what they’re doing.
 

Hated broccoli? Blame your DNA

Were you that kid who would rather sit at the table for hours than eat your broccoli? Well, as much as your parents might have pushed you, new research suggests that it might be their fault you didn’t like it to begin with.

Hans Braxmeier/Pixabay

Investigators at Australia’s national science agency, CSIRO, recently reported that distaste for Brassica vegetables – broccoli, Brussels sprouts, cabbage, and cauliflower – can be traced to the oral microbiome.

These vegetables have a compound called S-methyl-L-cysteine sulfoxide that gives off sulfurous odors ... mmm, sulfurous ... when mixed with an enzyme in the plant, and that enzyme is also produced by bacteria in some people’s oral microbiomes. So why do adults tolerate these Brassica veggies more than children? It’s all about levels.

The researchers tested the idea by asking 98 child/parent pairs to rate the odors and by using gas chromatography-olfactometry-mass spectrometry to identify the odor-active compounds in both raw and steamed cauliflower and broccoli. The children whose saliva produced high levels of sulfur volatiles disliked Brassica vegetables the most, they reported, and the children with high levels of sulfur volatiles usually had parents who produced high levels.

Despite that connection, however, the distaste for raw Brassica seen in children wasn’t seen in adults.

Maybe it’s not that taste buds change as we age, maybe we just learn to tolerate the sulfurousness.

The U.S. Food and Drug Administration (FDA) late Sept. 22 granted emergency use authorization (EUA) for a third dose of the Pfizer COVID-19 vaccine for those over the age of 65 and a wide swath of Americans at higher risk for infection.

The agency’s move comes as a Centers for Disease Control and Prevention (CDC) panel ended the first day of a 2-day meeting. That panel, the Advisory Committee on Immunization Practices (ACIP), is expected to vote Sept. 23 to instruct doctors on how to administer the boosters.

The FDA officially authorized the vaccine not only for individuals 65 and older, but also for people 18 through 64 years of age who are at high risk for severe illness from the coronavirus, including essential workers whose jobs increase their risk for infection.

“After considering the totality of the available scientific evidence and the deliberations of our advisory committee of independent, external experts, the FDA amended the EUA for the Pfizer-BioNTech COVID-19 vaccine to allow for a booster dose in certain populations such as health care workers, teachers and daycare staff, grocery workers and those in homeless shelters or prisons, among others,” Acting FDA Commissioner Janet Woodcock, MD, said in a news release.

The recommendations align with those from an FDA advisory panel Sept. 17.

The agency determined that the benefits of a booster dose outweigh the risks for people now authorized to receive it, according to the news release.
 

Other questions remain

So, how will this work? That was the main question weighing on the minds of the CDC’s ACIP during their first day of a 2-day meeting where they are expected to make recommendations on booster doses for Americans.

The panel discussed situations the FDA will still need to consider, such as what should be done for Americans who were originally vaccinated with a Moderna or Johnson and Johnson vaccine, but are not covered under the revised EUA, which is only for those people who received Pfizer’s two-dose vaccine regimen.

“That’s going to leave half of the people immunized in this age group having received the vaccine and being told that they’re at risk now for waning immunity and hospitalization unable to get a booster dose,” said committee member Sarah S. Long, MD, a professor of pediatrics at Drexel University College of Medicine in Philadelphia. “So that’s a big public health panic that we would like to avoid.”

Johnson and Johnson recently reported that second doses of its vaccine boosted its efficacy to almost 94% against COVID-19. A new study, published ahead of peer review, suggests that the efficacy of the single-dose Johnson and Johnson shot has fallen to about 78% against symptomatic infection during the Delta surge.

Moderna has applied for permission to market third doses of its vaccine in the United States, but the FDA has given no timeline on when it might make a decision. 

Doran Fink, MD, PhD, deputy director of the FDA’s Division of Vaccines and Related Products Applications, a representative advising the committee Sept. 22, said the agency was working as rapidly as possible on Moderna’s submission.

Regarding the question of whether it was OK to mix vaccines, rather than match them, Dr. Fink said there are currently not enough data available to inform that decision.

Those answers are coming, though. John Beigel, MD, associate director of clinical research at the National Institute of Allergy and Infectious Diseases, revealed that the federal government has a study underway to see what happens when the vaccines are mixed with each other. 

He said that data from the study would be available later this fall, and would certainly help physicians and other healthcare providers know whether it’s effective or safe to use them interchangeably.
 

Correlates of immunity

The ACIP left much of its schedule open Sept. 23 to discuss extra Pfizer doses and vote on how they should be used.

Pfizer had originally applied to the FDA for an amendment to its FDA approval, which would have given doctors a freer hand to prescribe third doses as they saw fit, in patients as young as 16.

But the FDA’s Vaccines and Related Biological Products Advisory Committee voted Sept. 17 against granting the amendment. The committee was particularly concerned about the lack of data in teens ages 16 and 17, who have the highest risk for a rare side effect that causes heart inflammation that requires hospital care.

Instead, they recommended — and the FDA agreed per their decision Sept. 22 — that third doses should be given to people at higher risk for severe breakthrough infections because of advanced age or because they work in an occupation that puts them at high risk for exposure. 

The CDC panel heard important presentations on new science that is helping to identify the correlates of immunity. 

The correlates of immunity are biomarkers that can be measured in blood that help doctors understand how protected a person may be against COVID-19. These markers of immunity are not yet known for the COVID-19 vaccines.

Emerging evidence shows that booster doses of the Pfizer vaccine cause front-line immune defenders — called binding antibodies — to roughly triple soon after a person gets the third shot. 

Neutralizing antibodies also jump soon after two vaccine doses, but they fall over time, which is natural. The body doesn’t need these foot soldiers to be on guard all the time, so they go away. 

The body retains its memory of how to make them, however, so they can quickly be marshaled again, if needed.

Early studies suggest that antibodies account for about two thirds of a person’s protection against COVID, while the longer-lasting T-cells and B-cells account for about one third.

After the antibody levels fall, it may take a few days to recreate this army. In the meantime, the virus can try to break in. This can cause symptoms, which can make a person feel terrible, but for the most part, vaccinated individuals don’t need hospital care and are nearly always protected from dying — even against the Delta variant.

Those most likely to be at risk for a breakthrough infection are older, because immune function wanes with age.
 

Essential workers

Essential workers, such as those who work in healthcare, may also benefit from high antibody levels, which can minimize symptoms and help them get back to work more quickly.

Helen Talbot, MD, MPH, an associate professor of medicine at Vanderbilt University Medical Center in Nashville, said that in her area staffing levels are critical right now.

“I’m actually sitting in one of the deepest red [states] with high rates of COVID. We don’t have enough health care workers currently to take care of the unvaccinated,” she said. 

“When we have beds, we are often missing staff, and so the idea of vaccinating health care workers is to be a little bit different than our idea of using vaccines in the general population,” Dr. Talbot said.

Oliver Brooks, MD, chief medical officer of the Watts Healthcare Corporation in Los Angeles, said he was in favor of making a public statement about the temporary nature of the potential recommendations Sept. 23, because they probably won’t cover all who might need a third shot.

“We may want to go on record stating what it is that would allow us to broaden our recommendation or restrict our recommendation,” Dr. Brooks said.

The considerations of who should get an extra dose are not always straightforward.

New modeling by the Harvard TH Chan School of Public Health and the CDC to assist the government’s decisions on boosters had a surprise finding: in nursing homes, it’s more effective to vaccinate healthcare workers than it is to give booster doses to these residents. Nursing homes are at the mercy of community transmission. 

In regions with high transmission, it’s easy for a caregiver to bring the virus into a facility — so the models found that the transmission from these workers is a more effective strategy than giving third doses to the already highly vaccinated group of seniors who live in them.

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

The U.S. Food and Drug Administration (FDA) late Sept. 22 granted emergency use authorization (EUA) for a third dose of the Pfizer COVID-19 vaccine for those over the age of 65 and a wide swath of Americans at higher risk for infection.

The agency’s move comes as a Centers for Disease Control and Prevention (CDC) panel ended the first day of a 2-day meeting. That panel, the Advisory Committee on Immunization Practices (ACIP), is expected to vote Sept. 23 to instruct doctors on how to administer the boosters.

The FDA officially authorized the vaccine not only for individuals 65 and older, but also for people 18 through 64 years of age who are at high risk for severe illness from the coronavirus, including essential workers whose jobs increase their risk for infection.

“After considering the totality of the available scientific evidence and the deliberations of our advisory committee of independent, external experts, the FDA amended the EUA for the Pfizer-BioNTech COVID-19 vaccine to allow for a booster dose in certain populations such as health care workers, teachers and daycare staff, grocery workers and those in homeless shelters or prisons, among others,” Acting FDA Commissioner Janet Woodcock, MD, said in a news release.

The recommendations align with those from an FDA advisory panel Sept. 17.

The agency determined that the benefits of a booster dose outweigh the risks for people now authorized to receive it, according to the news release.
 

Other questions remain

So, how will this work? That was the main question weighing on the minds of the CDC’s ACIP during their first day of a 2-day meeting where they are expected to make recommendations on booster doses for Americans.

The panel discussed situations the FDA will still need to consider, such as what should be done for Americans who were originally vaccinated with a Moderna or Johnson and Johnson vaccine, but are not covered under the revised EUA, which is only for those people who received Pfizer’s two-dose vaccine regimen.

“That’s going to leave half of the people immunized in this age group having received the vaccine and being told that they’re at risk now for waning immunity and hospitalization unable to get a booster dose,” said committee member Sarah S. Long, MD, a professor of pediatrics at Drexel University College of Medicine in Philadelphia. “So that’s a big public health panic that we would like to avoid.”

Johnson and Johnson recently reported that second doses of its vaccine boosted its efficacy to almost 94% against COVID-19. A new study, published ahead of peer review, suggests that the efficacy of the single-dose Johnson and Johnson shot has fallen to about 78% against symptomatic infection during the Delta surge.

Moderna has applied for permission to market third doses of its vaccine in the United States, but the FDA has given no timeline on when it might make a decision. 

Doran Fink, MD, PhD, deputy director of the FDA’s Division of Vaccines and Related Products Applications, a representative advising the committee Sept. 22, said the agency was working as rapidly as possible on Moderna’s submission.

Regarding the question of whether it was OK to mix vaccines, rather than match them, Dr. Fink said there are currently not enough data available to inform that decision.

Those answers are coming, though. John Beigel, MD, associate director of clinical research at the National Institute of Allergy and Infectious Diseases, revealed that the federal government has a study underway to see what happens when the vaccines are mixed with each other. 

He said that data from the study would be available later this fall, and would certainly help physicians and other healthcare providers know whether it’s effective or safe to use them interchangeably.
 

Correlates of immunity

The ACIP left much of its schedule open Sept. 23 to discuss extra Pfizer doses and vote on how they should be used.

Pfizer had originally applied to the FDA for an amendment to its FDA approval, which would have given doctors a freer hand to prescribe third doses as they saw fit, in patients as young as 16.

But the FDA’s Vaccines and Related Biological Products Advisory Committee voted Sept. 17 against granting the amendment. The committee was particularly concerned about the lack of data in teens ages 16 and 17, who have the highest risk for a rare side effect that causes heart inflammation that requires hospital care.

Instead, they recommended — and the FDA agreed per their decision Sept. 22 — that third doses should be given to people at higher risk for severe breakthrough infections because of advanced age or because they work in an occupation that puts them at high risk for exposure. 

The CDC panel heard important presentations on new science that is helping to identify the correlates of immunity. 

The correlates of immunity are biomarkers that can be measured in blood that help doctors understand how protected a person may be against COVID-19. These markers of immunity are not yet known for the COVID-19 vaccines.

Emerging evidence shows that booster doses of the Pfizer vaccine cause front-line immune defenders — called binding antibodies — to roughly triple soon after a person gets the third shot. 

Neutralizing antibodies also jump soon after two vaccine doses, but they fall over time, which is natural. The body doesn’t need these foot soldiers to be on guard all the time, so they go away. 

The body retains its memory of how to make them, however, so they can quickly be marshaled again, if needed.

Early studies suggest that antibodies account for about two thirds of a person’s protection against COVID, while the longer-lasting T-cells and B-cells account for about one third.

After the antibody levels fall, it may take a few days to recreate this army. In the meantime, the virus can try to break in. This can cause symptoms, which can make a person feel terrible, but for the most part, vaccinated individuals don’t need hospital care and are nearly always protected from dying — even against the Delta variant.

Those most likely to be at risk for a breakthrough infection are older, because immune function wanes with age.
 

Essential workers

Essential workers, such as those who work in healthcare, may also benefit from high antibody levels, which can minimize symptoms and help them get back to work more quickly.

Helen Talbot, MD, MPH, an associate professor of medicine at Vanderbilt University Medical Center in Nashville, said that in her area staffing levels are critical right now.

“I’m actually sitting in one of the deepest red [states] with high rates of COVID. We don’t have enough health care workers currently to take care of the unvaccinated,” she said. 

“When we have beds, we are often missing staff, and so the idea of vaccinating health care workers is to be a little bit different than our idea of using vaccines in the general population,” Dr. Talbot said.

Oliver Brooks, MD, chief medical officer of the Watts Healthcare Corporation in Los Angeles, said he was in favor of making a public statement about the temporary nature of the potential recommendations Sept. 23, because they probably won’t cover all who might need a third shot.

“We may want to go on record stating what it is that would allow us to broaden our recommendation or restrict our recommendation,” Dr. Brooks said.

The considerations of who should get an extra dose are not always straightforward.

New modeling by the Harvard TH Chan School of Public Health and the CDC to assist the government’s decisions on boosters had a surprise finding: in nursing homes, it’s more effective to vaccinate healthcare workers than it is to give booster doses to these residents. Nursing homes are at the mercy of community transmission. 

In regions with high transmission, it’s easy for a caregiver to bring the virus into a facility — so the models found that the transmission from these workers is a more effective strategy than giving third doses to the already highly vaccinated group of seniors who live in them.

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

The U.S. Food and Drug Administration (FDA) late Sept. 22 granted emergency use authorization (EUA) for a third dose of the Pfizer COVID-19 vaccine for those over the age of 65 and a wide swath of Americans at higher risk for infection.

The agency’s move comes as a Centers for Disease Control and Prevention (CDC) panel ended the first day of a 2-day meeting. That panel, the Advisory Committee on Immunization Practices (ACIP), is expected to vote Sept. 23 to instruct doctors on how to administer the boosters.

The FDA officially authorized the vaccine not only for individuals 65 and older, but also for people 18 through 64 years of age who are at high risk for severe illness from the coronavirus, including essential workers whose jobs increase their risk for infection.

“After considering the totality of the available scientific evidence and the deliberations of our advisory committee of independent, external experts, the FDA amended the EUA for the Pfizer-BioNTech COVID-19 vaccine to allow for a booster dose in certain populations such as health care workers, teachers and daycare staff, grocery workers and those in homeless shelters or prisons, among others,” Acting FDA Commissioner Janet Woodcock, MD, said in a news release.

The recommendations align with those from an FDA advisory panel Sept. 17.

The agency determined that the benefits of a booster dose outweigh the risks for people now authorized to receive it, according to the news release.
 

Other questions remain

So, how will this work? That was the main question weighing on the minds of the CDC’s ACIP during their first day of a 2-day meeting where they are expected to make recommendations on booster doses for Americans.

The panel discussed situations the FDA will still need to consider, such as what should be done for Americans who were originally vaccinated with a Moderna or Johnson and Johnson vaccine, but are not covered under the revised EUA, which is only for those people who received Pfizer’s two-dose vaccine regimen.

“That’s going to leave half of the people immunized in this age group having received the vaccine and being told that they’re at risk now for waning immunity and hospitalization unable to get a booster dose,” said committee member Sarah S. Long, MD, a professor of pediatrics at Drexel University College of Medicine in Philadelphia. “So that’s a big public health panic that we would like to avoid.”

Johnson and Johnson recently reported that second doses of its vaccine boosted its efficacy to almost 94% against COVID-19. A new study, published ahead of peer review, suggests that the efficacy of the single-dose Johnson and Johnson shot has fallen to about 78% against symptomatic infection during the Delta surge.

Moderna has applied for permission to market third doses of its vaccine in the United States, but the FDA has given no timeline on when it might make a decision. 

Doran Fink, MD, PhD, deputy director of the FDA’s Division of Vaccines and Related Products Applications, a representative advising the committee Sept. 22, said the agency was working as rapidly as possible on Moderna’s submission.

Regarding the question of whether it was OK to mix vaccines, rather than match them, Dr. Fink said there are currently not enough data available to inform that decision.

Those answers are coming, though. John Beigel, MD, associate director of clinical research at the National Institute of Allergy and Infectious Diseases, revealed that the federal government has a study underway to see what happens when the vaccines are mixed with each other. 

He said that data from the study would be available later this fall, and would certainly help physicians and other healthcare providers know whether it’s effective or safe to use them interchangeably.
 

Correlates of immunity

The ACIP left much of its schedule open Sept. 23 to discuss extra Pfizer doses and vote on how they should be used.

Pfizer had originally applied to the FDA for an amendment to its FDA approval, which would have given doctors a freer hand to prescribe third doses as they saw fit, in patients as young as 16.

But the FDA’s Vaccines and Related Biological Products Advisory Committee voted Sept. 17 against granting the amendment. The committee was particularly concerned about the lack of data in teens ages 16 and 17, who have the highest risk for a rare side effect that causes heart inflammation that requires hospital care.

Instead, they recommended — and the FDA agreed per their decision Sept. 22 — that third doses should be given to people at higher risk for severe breakthrough infections because of advanced age or because they work in an occupation that puts them at high risk for exposure. 

The CDC panel heard important presentations on new science that is helping to identify the correlates of immunity. 

The correlates of immunity are biomarkers that can be measured in blood that help doctors understand how protected a person may be against COVID-19. These markers of immunity are not yet known for the COVID-19 vaccines.

Emerging evidence shows that booster doses of the Pfizer vaccine cause front-line immune defenders — called binding antibodies — to roughly triple soon after a person gets the third shot. 

Neutralizing antibodies also jump soon after two vaccine doses, but they fall over time, which is natural. The body doesn’t need these foot soldiers to be on guard all the time, so they go away. 

The body retains its memory of how to make them, however, so they can quickly be marshaled again, if needed.

Early studies suggest that antibodies account for about two thirds of a person’s protection against COVID, while the longer-lasting T-cells and B-cells account for about one third.

After the antibody levels fall, it may take a few days to recreate this army. In the meantime, the virus can try to break in. This can cause symptoms, which can make a person feel terrible, but for the most part, vaccinated individuals don’t need hospital care and are nearly always protected from dying — even against the Delta variant.

Those most likely to be at risk for a breakthrough infection are older, because immune function wanes with age.
 

Essential workers

Essential workers, such as those who work in healthcare, may also benefit from high antibody levels, which can minimize symptoms and help them get back to work more quickly.

Helen Talbot, MD, MPH, an associate professor of medicine at Vanderbilt University Medical Center in Nashville, said that in her area staffing levels are critical right now.

“I’m actually sitting in one of the deepest red [states] with high rates of COVID. We don’t have enough health care workers currently to take care of the unvaccinated,” she said. 

“When we have beds, we are often missing staff, and so the idea of vaccinating health care workers is to be a little bit different than our idea of using vaccines in the general population,” Dr. Talbot said.

Oliver Brooks, MD, chief medical officer of the Watts Healthcare Corporation in Los Angeles, said he was in favor of making a public statement about the temporary nature of the potential recommendations Sept. 23, because they probably won’t cover all who might need a third shot.

“We may want to go on record stating what it is that would allow us to broaden our recommendation or restrict our recommendation,” Dr. Brooks said.

The considerations of who should get an extra dose are not always straightforward.

New modeling by the Harvard TH Chan School of Public Health and the CDC to assist the government’s decisions on boosters had a surprise finding: in nursing homes, it’s more effective to vaccinate healthcare workers than it is to give booster doses to these residents. Nursing homes are at the mercy of community transmission. 

In regions with high transmission, it’s easy for a caregiver to bring the virus into a facility — so the models found that the transmission from these workers is a more effective strategy than giving third doses to the already highly vaccinated group of seniors who live in them.

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

Cobra the dog has been hard at work at the Miami International Airport, sniffing masks proffered by American Airlines employees making their way through a security checkpoint. If she identifies a specific scent, she’ll let her handler know simply by sitting down. When this good girl sits, that means Cobra has detected an olfactory signal of the coronavirus, the virus that causes COVID-19.

Cobra, a Belgian Malinois, is one of two canines – her partner is One Betta, a Dutch shepherd – working this checkpoint at Miami International. They are part of a pilot program with the Global Forensic and Justice Center at Florida International University, using the detection dogs as a quick screen for people who have COVID-19.

Their detection rate is high, at more than 98%, and the program has been such a success that it’s being extended for another month at the airport.

If these two dogs continue to accurately detect COVID-19, they and other canines with similar training could be deployed to other places with lots of people coming and going at once, including other airports or even schools. In fact, COVID-sniffing dogs are in use in some university classrooms already.

But building up a big brigade of live animals as disease detectors involves some thorny issues, including where the animals retire once their careers are complete.

“When COVID first arose, we said let’s see if we can train these two dogs on either the virus or the odor of COVID-19,” says Kenneth Furton, PhD, a professor of chemistry and biochemistry, provost, and executive vice president at Florida International University.

His team had completed a study with what he calls “medical detector dogs,” animals that might be able to detect the odor of someone having a seizure. That led them to see how well the animals could detect other kinds of disorders.

Training a dog to sniff out specific odors starts with getting them to understand the task in general. Dr. Furton says that the animals first are trained to grasp that their job is to detect one odor among many. Once the dogs grasp that, they can be trained on just about any specific odor.

In fact, in addition to detecting seizures, dogs reportedly have been able to identify diabetes and even some cancers, such as ovarian cancer.

Dr. Furton says he’s not aware of any previous use of dogs to screen for infectious disease. That may simply be because nothing recently has struck with the global ferocity of COVID, driving humans to turn to their best friends for help.

Cobra and One Betta got their start learning to identify the presence of laurel wilt, a fungus that attacks avocado trees and kills them, costing Florida growers millions. With that expertise under their collars, the two dogs need only a few weeks to get good at detecting other smells assigned to them.
 

Training the dogs, safely

To train Cobra and One Betta on COVID-19 odors, Dr. Furton’s team first acquired mask samples from people hospitalized with COVID and people who did not have the disease. In battling the viruses, people produce certain chemicals that they exhale every time they breathe. When Dr. Furton and his colleagues compared the exhaled components trapped in the masks, they found differences between masks from people with COVID and those without.

Having confirmed that exhalations can be COVID-specific, the research team trained four dogs – Cobra, One Betta, Hubble, and Max – to detect masks from people with COVID among an assortment of mask choices. Before this step, though, the researchers made sure that any trace of active virus was destroyed by ultraviolet light so that the dogs would not be infected.

Each time the dogs accurately selected a mask from a COVID patient, their reward was access to a favorite toy: A red ball to chew on. Although all four dogs performed very well, yes, they did, Cobra and One Betta showed the most accuracy, outperforming their training colleagues. From their training scores, Cobra ranked first, with 99.45% accuracy. Despite her name, says Dr. Furton, One Betta was “not one better,” coming in second at 98.1%, which is still quite high.

Both dogs are good at their airport screening duties. If one of them sits after sniffing a mask at the checkpoint, the next step is for the mask owner to be tested.

From Aug. 23 to Sept. 8, the two canines screened 1,093 people during 8 working days, alerting on only one case, according to Greg Chin, communications director for the Miami-Dade Aviation Department. That person had tested positive for COVID 2 weeks earlier and was returning to work after quarantine, and their rapid test after the dog alerted was negative.

Dr. Furton says that there are some reports of dogs also alerting before tests can show a positive result, suggesting the dogs’ odor detection can be more precise. They hope to expand their study to see how tight the window of dog-based detection is.

For now, the detector dogs are doing so well that the program has been extended for 30 more days, Mr. Chin says.

As promising as this seems, using dogs for screening carries some logistical and ethical tangles. Training a canine army to deploy for high-volume detection points means that once the work is done, a whole lot of dogs will need a safe place to retire. In addition, the initial training takes several months, says Dr. Furton, whereas if a device were developed for screening, manufacturing could likely be ramped up quickly to meet demand.

The dogs might not need to retire right away, though.

“We envision that they could be redeployed to another type of detection for another infectious disease” if the need arises, Dr. Furton says. But in the end, when working with dogs, he says, there is “a moral connection that you don’t have to deal with using instruments.”

Although the pilot screening at Miami International is the first airport test, the dogs have also done this work in other venues, including at a state emergency operations center in Florida and in some university classrooms, says Dr. Furton.

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

Cobra the dog has been hard at work at the Miami International Airport, sniffing masks proffered by American Airlines employees making their way through a security checkpoint. If she identifies a specific scent, she’ll let her handler know simply by sitting down. When this good girl sits, that means Cobra has detected an olfactory signal of the coronavirus, the virus that causes COVID-19.

Cobra, a Belgian Malinois, is one of two canines – her partner is One Betta, a Dutch shepherd – working this checkpoint at Miami International. They are part of a pilot program with the Global Forensic and Justice Center at Florida International University, using the detection dogs as a quick screen for people who have COVID-19.

Their detection rate is high, at more than 98%, and the program has been such a success that it’s being extended for another month at the airport.

If these two dogs continue to accurately detect COVID-19, they and other canines with similar training could be deployed to other places with lots of people coming and going at once, including other airports or even schools. In fact, COVID-sniffing dogs are in use in some university classrooms already.

But building up a big brigade of live animals as disease detectors involves some thorny issues, including where the animals retire once their careers are complete.

“When COVID first arose, we said let’s see if we can train these two dogs on either the virus or the odor of COVID-19,” says Kenneth Furton, PhD, a professor of chemistry and biochemistry, provost, and executive vice president at Florida International University.

His team had completed a study with what he calls “medical detector dogs,” animals that might be able to detect the odor of someone having a seizure. That led them to see how well the animals could detect other kinds of disorders.

Training a dog to sniff out specific odors starts with getting them to understand the task in general. Dr. Furton says that the animals first are trained to grasp that their job is to detect one odor among many. Once the dogs grasp that, they can be trained on just about any specific odor.

In fact, in addition to detecting seizures, dogs reportedly have been able to identify diabetes and even some cancers, such as ovarian cancer.

Dr. Furton says he’s not aware of any previous use of dogs to screen for infectious disease. That may simply be because nothing recently has struck with the global ferocity of COVID, driving humans to turn to their best friends for help.

Cobra and One Betta got their start learning to identify the presence of laurel wilt, a fungus that attacks avocado trees and kills them, costing Florida growers millions. With that expertise under their collars, the two dogs need only a few weeks to get good at detecting other smells assigned to them.
 

Training the dogs, safely

To train Cobra and One Betta on COVID-19 odors, Dr. Furton’s team first acquired mask samples from people hospitalized with COVID and people who did not have the disease. In battling the viruses, people produce certain chemicals that they exhale every time they breathe. When Dr. Furton and his colleagues compared the exhaled components trapped in the masks, they found differences between masks from people with COVID and those without.

Having confirmed that exhalations can be COVID-specific, the research team trained four dogs – Cobra, One Betta, Hubble, and Max – to detect masks from people with COVID among an assortment of mask choices. Before this step, though, the researchers made sure that any trace of active virus was destroyed by ultraviolet light so that the dogs would not be infected.

Each time the dogs accurately selected a mask from a COVID patient, their reward was access to a favorite toy: A red ball to chew on. Although all four dogs performed very well, yes, they did, Cobra and One Betta showed the most accuracy, outperforming their training colleagues. From their training scores, Cobra ranked first, with 99.45% accuracy. Despite her name, says Dr. Furton, One Betta was “not one better,” coming in second at 98.1%, which is still quite high.

Both dogs are good at their airport screening duties. If one of them sits after sniffing a mask at the checkpoint, the next step is for the mask owner to be tested.

From Aug. 23 to Sept. 8, the two canines screened 1,093 people during 8 working days, alerting on only one case, according to Greg Chin, communications director for the Miami-Dade Aviation Department. That person had tested positive for COVID 2 weeks earlier and was returning to work after quarantine, and their rapid test after the dog alerted was negative.

Dr. Furton says that there are some reports of dogs also alerting before tests can show a positive result, suggesting the dogs’ odor detection can be more precise. They hope to expand their study to see how tight the window of dog-based detection is.

For now, the detector dogs are doing so well that the program has been extended for 30 more days, Mr. Chin says.

As promising as this seems, using dogs for screening carries some logistical and ethical tangles. Training a canine army to deploy for high-volume detection points means that once the work is done, a whole lot of dogs will need a safe place to retire. In addition, the initial training takes several months, says Dr. Furton, whereas if a device were developed for screening, manufacturing could likely be ramped up quickly to meet demand.

The dogs might not need to retire right away, though.

“We envision that they could be redeployed to another type of detection for another infectious disease” if the need arises, Dr. Furton says. But in the end, when working with dogs, he says, there is “a moral connection that you don’t have to deal with using instruments.”

Although the pilot screening at Miami International is the first airport test, the dogs have also done this work in other venues, including at a state emergency operations center in Florida and in some university classrooms, says Dr. Furton.

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

Cobra the dog has been hard at work at the Miami International Airport, sniffing masks proffered by American Airlines employees making their way through a security checkpoint. If she identifies a specific scent, she’ll let her handler know simply by sitting down. When this good girl sits, that means Cobra has detected an olfactory signal of the coronavirus, the virus that causes COVID-19.

Cobra, a Belgian Malinois, is one of two canines – her partner is One Betta, a Dutch shepherd – working this checkpoint at Miami International. They are part of a pilot program with the Global Forensic and Justice Center at Florida International University, using the detection dogs as a quick screen for people who have COVID-19.

Their detection rate is high, at more than 98%, and the program has been such a success that it’s being extended for another month at the airport.

If these two dogs continue to accurately detect COVID-19, they and other canines with similar training could be deployed to other places with lots of people coming and going at once, including other airports or even schools. In fact, COVID-sniffing dogs are in use in some university classrooms already.

But building up a big brigade of live animals as disease detectors involves some thorny issues, including where the animals retire once their careers are complete.

“When COVID first arose, we said let’s see if we can train these two dogs on either the virus or the odor of COVID-19,” says Kenneth Furton, PhD, a professor of chemistry and biochemistry, provost, and executive vice president at Florida International University.

His team had completed a study with what he calls “medical detector dogs,” animals that might be able to detect the odor of someone having a seizure. That led them to see how well the animals could detect other kinds of disorders.

Training a dog to sniff out specific odors starts with getting them to understand the task in general. Dr. Furton says that the animals first are trained to grasp that their job is to detect one odor among many. Once the dogs grasp that, they can be trained on just about any specific odor.

In fact, in addition to detecting seizures, dogs reportedly have been able to identify diabetes and even some cancers, such as ovarian cancer.

Dr. Furton says he’s not aware of any previous use of dogs to screen for infectious disease. That may simply be because nothing recently has struck with the global ferocity of COVID, driving humans to turn to their best friends for help.

Cobra and One Betta got their start learning to identify the presence of laurel wilt, a fungus that attacks avocado trees and kills them, costing Florida growers millions. With that expertise under their collars, the two dogs need only a few weeks to get good at detecting other smells assigned to them.
 

Training the dogs, safely

To train Cobra and One Betta on COVID-19 odors, Dr. Furton’s team first acquired mask samples from people hospitalized with COVID and people who did not have the disease. In battling the viruses, people produce certain chemicals that they exhale every time they breathe. When Dr. Furton and his colleagues compared the exhaled components trapped in the masks, they found differences between masks from people with COVID and those without.

Having confirmed that exhalations can be COVID-specific, the research team trained four dogs – Cobra, One Betta, Hubble, and Max – to detect masks from people with COVID among an assortment of mask choices. Before this step, though, the researchers made sure that any trace of active virus was destroyed by ultraviolet light so that the dogs would not be infected.

Each time the dogs accurately selected a mask from a COVID patient, their reward was access to a favorite toy: A red ball to chew on. Although all four dogs performed very well, yes, they did, Cobra and One Betta showed the most accuracy, outperforming their training colleagues. From their training scores, Cobra ranked first, with 99.45% accuracy. Despite her name, says Dr. Furton, One Betta was “not one better,” coming in second at 98.1%, which is still quite high.

Both dogs are good at their airport screening duties. If one of them sits after sniffing a mask at the checkpoint, the next step is for the mask owner to be tested.

From Aug. 23 to Sept. 8, the two canines screened 1,093 people during 8 working days, alerting on only one case, according to Greg Chin, communications director for the Miami-Dade Aviation Department. That person had tested positive for COVID 2 weeks earlier and was returning to work after quarantine, and their rapid test after the dog alerted was negative.

Dr. Furton says that there are some reports of dogs also alerting before tests can show a positive result, suggesting the dogs’ odor detection can be more precise. They hope to expand their study to see how tight the window of dog-based detection is.

For now, the detector dogs are doing so well that the program has been extended for 30 more days, Mr. Chin says.

As promising as this seems, using dogs for screening carries some logistical and ethical tangles. Training a canine army to deploy for high-volume detection points means that once the work is done, a whole lot of dogs will need a safe place to retire. In addition, the initial training takes several months, says Dr. Furton, whereas if a device were developed for screening, manufacturing could likely be ramped up quickly to meet demand.

The dogs might not need to retire right away, though.

“We envision that they could be redeployed to another type of detection for another infectious disease” if the need arises, Dr. Furton says. But in the end, when working with dogs, he says, there is “a moral connection that you don’t have to deal with using instruments.”

Although the pilot screening at Miami International is the first airport test, the dogs have also done this work in other venues, including at a state emergency operations center in Florida and in some university classrooms, says Dr. Furton.

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

On Sept. 5, Rashid Buttar, DO, posted on Twitter that COVID-19 “was a planned operation” and shared an article alleging that most people who got the COVID vaccine would be dead by 2025.

His statement is a recent example in what has been a steady stream of spurious claims surrounding the COVID vaccines and treatments that swirl around the public consciousness. Others include testimony in June by Sherri Jane Tenpenny, DO, before Ohio state legislators that the vaccine could cause people to become magnetized. Clips from the hearing went viral on the Internet. On April 9, 2020, Joseph Mercola, DO, posted a video titled “Could hydrogen peroxide treat coronavirus?” which was shared more than 4,600 times. In the video, Dr. Mercola said inhaling hydrogen peroxide through a nebulizer could prevent or cure COVID.

These physicians are identified as members of the “Disinformation Dozen,” a group of top superspreaders of COVID vaccine misinformation on social media, according to a 2021 report by the nonprofit Center for Countering Digital Hate. The report, based on an analysis of antivaccine content on social media platforms, found that 12 people were responsible for 65% of it. The group is composed of physicians, antivaccine activists, and people known for promoting alternative medicine.

The physician voices are of particular concern because their medical credentials lend credence to their unproven, often dangerous pronouncements. All three continue to hold medical licenses and have not faced consequences for their COVID-related statements.

But leaders of professional medical organizations increasingly are calling for that to change and urging medical oversight boards to take more aggressive action.

In July, the Federation of State Medical Boards, the national umbrella organization for the state-based boards, issued a statement making clear that doctors who generate and spread COVID misinformation could be subject to disciplinary action, including the suspension or revocation of their licenses. The American Board of Family Medicine, American Board of Internal Medicine, and American Board of Pediatrics issued a joint statement Sept. 9 in support of the state boards’ position, warning that “such unethical or unprofessional conduct may prompt their respective board to take action that could put their certification at risk.”

And the superspreaders identified by the center’s report are not alone. KHN identified 20 other doctors who have made false or misleading claims about COVID by combing through published fact checks and other news coverage.

For example, at an Indiana school board meeting in August, Dan Stock, MD, claimed the surge in covid cases this summer was due to “antibody mediated viral enhancement” from people receiving covid vaccines. PolitiFact rated his claim “Pants on Fire” false.

Stella Immanuel, MD, a member of a group America’s Frontline Doctors, which has consistently made false statements about COVID, said in a video that went viral in July 2020 that masks weren’t needed because covid could be cured by hydroxychloroquine. Dr. Immanuel’s website currently promotes a set of vitamins, as well as hydroxychloroquine and ivermectin, as COVID treatments.

Two of the doctors mentioned by name in this article responded to requests for comment. Dr. Mercola offered documents to rebut criticisms of his hydrogen peroxide COVID treatment and took issue with the center’s “Disinformation Dozen” report methodology. Dr. Buttar defended his positions, saying via email that “the science is clear and anyone who contests it, has a suspect agenda at best and/or lacks a moral compass.” He also pointed to data from the Centers for Disease Control and Prevention’s Vaccine Adverse Event Recording System, considered inconclusive by many experts.

Since the onset of the COVID pandemic, misinformation has been widespread on social media platforms. And many experts blame it for undermining efforts to curb the coronavirus’s spread. A recent poll showed that more than 50% of Americans who won’t get vaccinated cited conspiracy theories as their reasons – for example, saying the vaccines cause infertility or alter DNA.

Some physicians have gained notoriety by embracing COVID-related fringe ideas, quack treatments and falsehoods via social media, conservative talk shows, and even in person with patients. Whether promoting the use of ivermectin, an antiparasitic drug for animals, or a mix of vitamins to treat COVID, doctors’ words can be especially powerful. Public opinion polls consistently show that Americans have high trust in doctors.

“There is a sense of credibility that comes with being a doctor,” said Rachel Moran, PhD, a researcher who studies COVID misinformation at the University of Washington. “There is also a sense they have access to insider info that we don’t. This is a very confusing time, and it can seem that if anyone knows what I should be doing in this situation, it’s a doctor.”

While COVID is a novel and complicated infectious disease, physicians spreading misinformation generally have no particular expertise in infectious diseases. Scott Atlas, MD, who endorsed former President Donald Trump’s unproven statements about the course of the pandemic, is a radiation oncologist.

Traditionally, the responsibility of policing physicians has fallen to state medical boards. Beyond overseeing the licensing process, these panels investigate complaints about doctors and discipline those who engage in unethical, unprofessional or, in extreme cases, criminal activity. Any member of the public can submit a complaint about a physician.

“The boards are relatively slow and weak and it’s a long, slow process to pull somebody’s license,” said Arthur Caplan, PhD, founding head of the department of medical ethics at New York University. “In many states, they have their hands full with doctors who have committed felonies, doctors who are molesting their patients. Keeping an eye on misinformation is somewhat down on the priority list.”

To date, only two doctors have reportedly faced such sanctions. In Oregon, Steven LaTulippe, MD, had his license suspended in December 2020 for refusing to wear a face mask at his clinic and telling patients that masks were ineffective in curbing the spread of COVID, and even dangerous. Thomas Cowan, MD, a San Francisco physician who posted a YouTube video that went viral in March 2020 stating that 5G networks cause COVID, voluntarily surrendered his medical license to California’s medical board in February 2021.

Humayun Chaudhry, DO, president of the Federation of State Medical Boards, however, said it’s possible some doctors could already be the subject of inquiries and investigations, since these actions are not made public until sanctions are handed down.

KHN reached out to the medical and osteopathic boards of all 50 states and the District of Columbia to see if they had received COVID misinformation complaints. Of the 43 that responded, only a handful shared specifics.

During a 1-week period in August, Kansas’ medical board received six such complaints. In all, the state has received 35 complaints against 20 licensees about spreading covid misinformation on social media and in person. Indiana has received about 30 in the past year. South Carolina said it had about 10 since January. Rhode Island didn’t share the number of complaints but said it has taken disciplinary action against one doctor for spreading misinformation, though it hasn’t moved to suspend his license. (The disciplinary measures include a fine, a reprimand on the doctor’s record and a mandate to complete an ethics course.) Five states said they had received only a couple, and 11 states reported receiving no complaints regarding COVID misinformation.

Confidentiality laws in 13 states prevented those boards from sharing information about complaints.

Social media companies have also been slow to take action. Some doctors’ accounts – specifically those among the Disinformation Dozen – have been suspended, but others are still active and posting misinformation.

Imran Ahmed, CEO of the Center for Countering Digital Hate, said social media platforms often don’t consistently apply their rules against spreading misinformation.

“Even when it’s the same companies, Facebook will sometimes take posts down, but Instagram will not,” Mr. Ahmed said, referring to Facebook’s ownership of Instagram. “It goes to show their piecemeal, ineffective approach to enforcing their own rules.”

A Facebook spokesperson said the company has removed over 3,000 accounts, pages and groups for repeatedly violating COVID and vaccine misinformation policies since the beginning of the pandemic. Dr. Buttar’s Facebook and Instagram pages and Tenpenny’s Facebook page have been removed, while Dr. Mercola’s Facebook posts have been demoted, which means fewer people will see them. Dr. Tenpenny and Dr. Mercola still have Instagram accounts.

Part of the challenge may be that these doctors sometimes present scientific opinions that aren’t mainstream but are viewed as potentially valid by some of their colleagues.

“It can be difficult to prove that what is being said is outside the range of scientific and medical consensus,” said Dr. Caplan. “The doctors who were advising Trump – like Scott Atlas – recommended herd immunity. That was far from the consensus of epidemiologists, but you couldn’t get a board to take his license away because it was a fringe opinion.”

Even if these physicians don’t face consequences, it is likely, experts said, that the public health will.

“Medical misinformation doesn’t just result in people making bad personal and community health choices, but it also divides communities and families, leaving an emotional toll,” said Dr. Moran. “Misinformation narratives have real sticking power and impact people’s ability to make safe health choices.”

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.

On Sept. 5, Rashid Buttar, DO, posted on Twitter that COVID-19 “was a planned operation” and shared an article alleging that most people who got the COVID vaccine would be dead by 2025.

His statement is a recent example in what has been a steady stream of spurious claims surrounding the COVID vaccines and treatments that swirl around the public consciousness. Others include testimony in June by Sherri Jane Tenpenny, DO, before Ohio state legislators that the vaccine could cause people to become magnetized. Clips from the hearing went viral on the Internet. On April 9, 2020, Joseph Mercola, DO, posted a video titled “Could hydrogen peroxide treat coronavirus?” which was shared more than 4,600 times. In the video, Dr. Mercola said inhaling hydrogen peroxide through a nebulizer could prevent or cure COVID.

These physicians are identified as members of the “Disinformation Dozen,” a group of top superspreaders of COVID vaccine misinformation on social media, according to a 2021 report by the nonprofit Center for Countering Digital Hate. The report, based on an analysis of antivaccine content on social media platforms, found that 12 people were responsible for 65% of it. The group is composed of physicians, antivaccine activists, and people known for promoting alternative medicine.

The physician voices are of particular concern because their medical credentials lend credence to their unproven, often dangerous pronouncements. All three continue to hold medical licenses and have not faced consequences for their COVID-related statements.

But leaders of professional medical organizations increasingly are calling for that to change and urging medical oversight boards to take more aggressive action.

In July, the Federation of State Medical Boards, the national umbrella organization for the state-based boards, issued a statement making clear that doctors who generate and spread COVID misinformation could be subject to disciplinary action, including the suspension or revocation of their licenses. The American Board of Family Medicine, American Board of Internal Medicine, and American Board of Pediatrics issued a joint statement Sept. 9 in support of the state boards’ position, warning that “such unethical or unprofessional conduct may prompt their respective board to take action that could put their certification at risk.”

And the superspreaders identified by the center’s report are not alone. KHN identified 20 other doctors who have made false or misleading claims about COVID by combing through published fact checks and other news coverage.

For example, at an Indiana school board meeting in August, Dan Stock, MD, claimed the surge in covid cases this summer was due to “antibody mediated viral enhancement” from people receiving covid vaccines. PolitiFact rated his claim “Pants on Fire” false.

Stella Immanuel, MD, a member of a group America’s Frontline Doctors, which has consistently made false statements about COVID, said in a video that went viral in July 2020 that masks weren’t needed because covid could be cured by hydroxychloroquine. Dr. Immanuel’s website currently promotes a set of vitamins, as well as hydroxychloroquine and ivermectin, as COVID treatments.

Two of the doctors mentioned by name in this article responded to requests for comment. Dr. Mercola offered documents to rebut criticisms of his hydrogen peroxide COVID treatment and took issue with the center’s “Disinformation Dozen” report methodology. Dr. Buttar defended his positions, saying via email that “the science is clear and anyone who contests it, has a suspect agenda at best and/or lacks a moral compass.” He also pointed to data from the Centers for Disease Control and Prevention’s Vaccine Adverse Event Recording System, considered inconclusive by many experts.

Since the onset of the COVID pandemic, misinformation has been widespread on social media platforms. And many experts blame it for undermining efforts to curb the coronavirus’s spread. A recent poll showed that more than 50% of Americans who won’t get vaccinated cited conspiracy theories as their reasons – for example, saying the vaccines cause infertility or alter DNA.

Some physicians have gained notoriety by embracing COVID-related fringe ideas, quack treatments and falsehoods via social media, conservative talk shows, and even in person with patients. Whether promoting the use of ivermectin, an antiparasitic drug for animals, or a mix of vitamins to treat COVID, doctors’ words can be especially powerful. Public opinion polls consistently show that Americans have high trust in doctors.

“There is a sense of credibility that comes with being a doctor,” said Rachel Moran, PhD, a researcher who studies COVID misinformation at the University of Washington. “There is also a sense they have access to insider info that we don’t. This is a very confusing time, and it can seem that if anyone knows what I should be doing in this situation, it’s a doctor.”

While COVID is a novel and complicated infectious disease, physicians spreading misinformation generally have no particular expertise in infectious diseases. Scott Atlas, MD, who endorsed former President Donald Trump’s unproven statements about the course of the pandemic, is a radiation oncologist.

Traditionally, the responsibility of policing physicians has fallen to state medical boards. Beyond overseeing the licensing process, these panels investigate complaints about doctors and discipline those who engage in unethical, unprofessional or, in extreme cases, criminal activity. Any member of the public can submit a complaint about a physician.

“The boards are relatively slow and weak and it’s a long, slow process to pull somebody’s license,” said Arthur Caplan, PhD, founding head of the department of medical ethics at New York University. “In many states, they have their hands full with doctors who have committed felonies, doctors who are molesting their patients. Keeping an eye on misinformation is somewhat down on the priority list.”

To date, only two doctors have reportedly faced such sanctions. In Oregon, Steven LaTulippe, MD, had his license suspended in December 2020 for refusing to wear a face mask at his clinic and telling patients that masks were ineffective in curbing the spread of COVID, and even dangerous. Thomas Cowan, MD, a San Francisco physician who posted a YouTube video that went viral in March 2020 stating that 5G networks cause COVID, voluntarily surrendered his medical license to California’s medical board in February 2021.

Humayun Chaudhry, DO, president of the Federation of State Medical Boards, however, said it’s possible some doctors could already be the subject of inquiries and investigations, since these actions are not made public until sanctions are handed down.

KHN reached out to the medical and osteopathic boards of all 50 states and the District of Columbia to see if they had received COVID misinformation complaints. Of the 43 that responded, only a handful shared specifics.

During a 1-week period in August, Kansas’ medical board received six such complaints. In all, the state has received 35 complaints against 20 licensees about spreading covid misinformation on social media and in person. Indiana has received about 30 in the past year. South Carolina said it had about 10 since January. Rhode Island didn’t share the number of complaints but said it has taken disciplinary action against one doctor for spreading misinformation, though it hasn’t moved to suspend his license. (The disciplinary measures include a fine, a reprimand on the doctor’s record and a mandate to complete an ethics course.) Five states said they had received only a couple, and 11 states reported receiving no complaints regarding COVID misinformation.

Confidentiality laws in 13 states prevented those boards from sharing information about complaints.

Social media companies have also been slow to take action. Some doctors’ accounts – specifically those among the Disinformation Dozen – have been suspended, but others are still active and posting misinformation.

Imran Ahmed, CEO of the Center for Countering Digital Hate, said social media platforms often don’t consistently apply their rules against spreading misinformation.

“Even when it’s the same companies, Facebook will sometimes take posts down, but Instagram will not,” Mr. Ahmed said, referring to Facebook’s ownership of Instagram. “It goes to show their piecemeal, ineffective approach to enforcing their own rules.”

A Facebook spokesperson said the company has removed over 3,000 accounts, pages and groups for repeatedly violating COVID and vaccine misinformation policies since the beginning of the pandemic. Dr. Buttar’s Facebook and Instagram pages and Tenpenny’s Facebook page have been removed, while Dr. Mercola’s Facebook posts have been demoted, which means fewer people will see them. Dr. Tenpenny and Dr. Mercola still have Instagram accounts.

Part of the challenge may be that these doctors sometimes present scientific opinions that aren’t mainstream but are viewed as potentially valid by some of their colleagues.

“It can be difficult to prove that what is being said is outside the range of scientific and medical consensus,” said Dr. Caplan. “The doctors who were advising Trump – like Scott Atlas – recommended herd immunity. That was far from the consensus of epidemiologists, but you couldn’t get a board to take his license away because it was a fringe opinion.”

Even if these physicians don’t face consequences, it is likely, experts said, that the public health will.

“Medical misinformation doesn’t just result in people making bad personal and community health choices, but it also divides communities and families, leaving an emotional toll,” said Dr. Moran. “Misinformation narratives have real sticking power and impact people’s ability to make safe health choices.”

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.

On Sept. 5, Rashid Buttar, DO, posted on Twitter that COVID-19 “was a planned operation” and shared an article alleging that most people who got the COVID vaccine would be dead by 2025.

His statement is a recent example in what has been a steady stream of spurious claims surrounding the COVID vaccines and treatments that swirl around the public consciousness. Others include testimony in June by Sherri Jane Tenpenny, DO, before Ohio state legislators that the vaccine could cause people to become magnetized. Clips from the hearing went viral on the Internet. On April 9, 2020, Joseph Mercola, DO, posted a video titled “Could hydrogen peroxide treat coronavirus?” which was shared more than 4,600 times. In the video, Dr. Mercola said inhaling hydrogen peroxide through a nebulizer could prevent or cure COVID.

These physicians are identified as members of the “Disinformation Dozen,” a group of top superspreaders of COVID vaccine misinformation on social media, according to a 2021 report by the nonprofit Center for Countering Digital Hate. The report, based on an analysis of antivaccine content on social media platforms, found that 12 people were responsible for 65% of it. The group is composed of physicians, antivaccine activists, and people known for promoting alternative medicine.

The physician voices are of particular concern because their medical credentials lend credence to their unproven, often dangerous pronouncements. All three continue to hold medical licenses and have not faced consequences for their COVID-related statements.

But leaders of professional medical organizations increasingly are calling for that to change and urging medical oversight boards to take more aggressive action.

In July, the Federation of State Medical Boards, the national umbrella organization for the state-based boards, issued a statement making clear that doctors who generate and spread COVID misinformation could be subject to disciplinary action, including the suspension or revocation of their licenses. The American Board of Family Medicine, American Board of Internal Medicine, and American Board of Pediatrics issued a joint statement Sept. 9 in support of the state boards’ position, warning that “such unethical or unprofessional conduct may prompt their respective board to take action that could put their certification at risk.”

And the superspreaders identified by the center’s report are not alone. KHN identified 20 other doctors who have made false or misleading claims about COVID by combing through published fact checks and other news coverage.

For example, at an Indiana school board meeting in August, Dan Stock, MD, claimed the surge in covid cases this summer was due to “antibody mediated viral enhancement” from people receiving covid vaccines. PolitiFact rated his claim “Pants on Fire” false.

Stella Immanuel, MD, a member of a group America’s Frontline Doctors, which has consistently made false statements about COVID, said in a video that went viral in July 2020 that masks weren’t needed because covid could be cured by hydroxychloroquine. Dr. Immanuel’s website currently promotes a set of vitamins, as well as hydroxychloroquine and ivermectin, as COVID treatments.

Two of the doctors mentioned by name in this article responded to requests for comment. Dr. Mercola offered documents to rebut criticisms of his hydrogen peroxide COVID treatment and took issue with the center’s “Disinformation Dozen” report methodology. Dr. Buttar defended his positions, saying via email that “the science is clear and anyone who contests it, has a suspect agenda at best and/or lacks a moral compass.” He also pointed to data from the Centers for Disease Control and Prevention’s Vaccine Adverse Event Recording System, considered inconclusive by many experts.

Since the onset of the COVID pandemic, misinformation has been widespread on social media platforms. And many experts blame it for undermining efforts to curb the coronavirus’s spread. A recent poll showed that more than 50% of Americans who won’t get vaccinated cited conspiracy theories as their reasons – for example, saying the vaccines cause infertility or alter DNA.

Some physicians have gained notoriety by embracing COVID-related fringe ideas, quack treatments and falsehoods via social media, conservative talk shows, and even in person with patients. Whether promoting the use of ivermectin, an antiparasitic drug for animals, or a mix of vitamins to treat COVID, doctors’ words can be especially powerful. Public opinion polls consistently show that Americans have high trust in doctors.

“There is a sense of credibility that comes with being a doctor,” said Rachel Moran, PhD, a researcher who studies COVID misinformation at the University of Washington. “There is also a sense they have access to insider info that we don’t. This is a very confusing time, and it can seem that if anyone knows what I should be doing in this situation, it’s a doctor.”

While COVID is a novel and complicated infectious disease, physicians spreading misinformation generally have no particular expertise in infectious diseases. Scott Atlas, MD, who endorsed former President Donald Trump’s unproven statements about the course of the pandemic, is a radiation oncologist.

Traditionally, the responsibility of policing physicians has fallen to state medical boards. Beyond overseeing the licensing process, these panels investigate complaints about doctors and discipline those who engage in unethical, unprofessional or, in extreme cases, criminal activity. Any member of the public can submit a complaint about a physician.

“The boards are relatively slow and weak and it’s a long, slow process to pull somebody’s license,” said Arthur Caplan, PhD, founding head of the department of medical ethics at New York University. “In many states, they have their hands full with doctors who have committed felonies, doctors who are molesting their patients. Keeping an eye on misinformation is somewhat down on the priority list.”

To date, only two doctors have reportedly faced such sanctions. In Oregon, Steven LaTulippe, MD, had his license suspended in December 2020 for refusing to wear a face mask at his clinic and telling patients that masks were ineffective in curbing the spread of COVID, and even dangerous. Thomas Cowan, MD, a San Francisco physician who posted a YouTube video that went viral in March 2020 stating that 5G networks cause COVID, voluntarily surrendered his medical license to California’s medical board in February 2021.

Humayun Chaudhry, DO, president of the Federation of State Medical Boards, however, said it’s possible some doctors could already be the subject of inquiries and investigations, since these actions are not made public until sanctions are handed down.

KHN reached out to the medical and osteopathic boards of all 50 states and the District of Columbia to see if they had received COVID misinformation complaints. Of the 43 that responded, only a handful shared specifics.

During a 1-week period in August, Kansas’ medical board received six such complaints. In all, the state has received 35 complaints against 20 licensees about spreading covid misinformation on social media and in person. Indiana has received about 30 in the past year. South Carolina said it had about 10 since January. Rhode Island didn’t share the number of complaints but said it has taken disciplinary action against one doctor for spreading misinformation, though it hasn’t moved to suspend his license. (The disciplinary measures include a fine, a reprimand on the doctor’s record and a mandate to complete an ethics course.) Five states said they had received only a couple, and 11 states reported receiving no complaints regarding COVID misinformation.

Confidentiality laws in 13 states prevented those boards from sharing information about complaints.

Social media companies have also been slow to take action. Some doctors’ accounts – specifically those among the Disinformation Dozen – have been suspended, but others are still active and posting misinformation.

Imran Ahmed, CEO of the Center for Countering Digital Hate, said social media platforms often don’t consistently apply their rules against spreading misinformation.

“Even when it’s the same companies, Facebook will sometimes take posts down, but Instagram will not,” Mr. Ahmed said, referring to Facebook’s ownership of Instagram. “It goes to show their piecemeal, ineffective approach to enforcing their own rules.”

A Facebook spokesperson said the company has removed over 3,000 accounts, pages and groups for repeatedly violating COVID and vaccine misinformation policies since the beginning of the pandemic. Dr. Buttar’s Facebook and Instagram pages and Tenpenny’s Facebook page have been removed, while Dr. Mercola’s Facebook posts have been demoted, which means fewer people will see them. Dr. Tenpenny and Dr. Mercola still have Instagram accounts.

Part of the challenge may be that these doctors sometimes present scientific opinions that aren’t mainstream but are viewed as potentially valid by some of their colleagues.

“It can be difficult to prove that what is being said is outside the range of scientific and medical consensus,” said Dr. Caplan. “The doctors who were advising Trump – like Scott Atlas – recommended herd immunity. That was far from the consensus of epidemiologists, but you couldn’t get a board to take his license away because it was a fringe opinion.”

Even if these physicians don’t face consequences, it is likely, experts said, that the public health will.

“Medical misinformation doesn’t just result in people making bad personal and community health choices, but it also divides communities and families, leaving an emotional toll,” said Dr. Moran. “Misinformation narratives have real sticking power and impact people’s ability to make safe health choices.”

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 Oregon Medical Board has revoked the license of a doctor who didn’t follow COVID-19 guidelines in his office and even told some patients that wearing face masks could lead to carbon-dioxide poisoning.

Steven Arthur LaTulippe’s advice to patients about face masking amounted to “gross negligence” in the practice of medicine and was grounds for discipline, the medical board said in a report.

Mr. LaTulippe, who had a family practice in Dallas, was fined $10,000, Insider reported. The board also said he’d overprescribed opioids for some patients.

The medical board report said Mr. LaTulippe and his wife, who ran the clinic with him, didn’t wear face masks while treating patients from March to December 2020.

Mr. LaTulippe told elderly and pediatric patients that mask wearing could hurt their health by exacerbating COPD and asthma and could contribute to heart attacks and other medical problems, the report said.

“Licensee asserts masks are likely to harm patients by increasing the body’s carbon dioxide content through rebreathing of gas trapped behind a mask,” the report said.

The report noted that “the amount of carbon dioxide rebreathed within a mask is trivial and would easily be expelled by an increase in minute ventilation so small it would not be noticed.”

The report said Mr. LaTulippe told patients they didn’t have to wear a mask in the clinic unless they were “acutely ill,” “coughing,” or “congested,” even though the Centers for Disease Control and Prevention and the Oregon governor had recommended masks be worn to prevent the spread of the virus.

Before coming into the office, patients weren’t asked if they’d had recent contact with anybody who was infected or showed COVID symptoms, the report said.

The medical board first suspended his license in September. He said he would not change his conduct concerning face masks.

“Licensee has confirmed that he will refuse to abide by the state’s COVID-19 protocols in the future as well, affirming that in a choice between losing his medical license versus wearing a mask in his clinic and requiring his patients and staff to wear a mask in his clinic, he will, ‘choose to sacrifice my medical license with no hesitation’ ” the medical board’s report said.

Mr. LaTulippe told the medical board that he was “a strong asset to the public in educating them on the real facts about this pandemic” and that “at least 98% of my patients were so extremely thankful that I did not wear a mask or demand wearing a mask in my clinic.”

The medical board found Mr. LaTulippe engaged in 8 instances of unprofessional or dishonorable conduct, 22 instances of negligence in the practice of medicine, and 5 instances of gross negligence in the practice of medicine.

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

The Oregon Medical Board has revoked the license of a doctor who didn’t follow COVID-19 guidelines in his office and even told some patients that wearing face masks could lead to carbon-dioxide poisoning.

Steven Arthur LaTulippe’s advice to patients about face masking amounted to “gross negligence” in the practice of medicine and was grounds for discipline, the medical board said in a report.

Mr. LaTulippe, who had a family practice in Dallas, was fined $10,000, Insider reported. The board also said he’d overprescribed opioids for some patients.

The medical board report said Mr. LaTulippe and his wife, who ran the clinic with him, didn’t wear face masks while treating patients from March to December 2020.

Mr. LaTulippe told elderly and pediatric patients that mask wearing could hurt their health by exacerbating COPD and asthma and could contribute to heart attacks and other medical problems, the report said.

“Licensee asserts masks are likely to harm patients by increasing the body’s carbon dioxide content through rebreathing of gas trapped behind a mask,” the report said.

The report noted that “the amount of carbon dioxide rebreathed within a mask is trivial and would easily be expelled by an increase in minute ventilation so small it would not be noticed.”

The report said Mr. LaTulippe told patients they didn’t have to wear a mask in the clinic unless they were “acutely ill,” “coughing,” or “congested,” even though the Centers for Disease Control and Prevention and the Oregon governor had recommended masks be worn to prevent the spread of the virus.

Before coming into the office, patients weren’t asked if they’d had recent contact with anybody who was infected or showed COVID symptoms, the report said.

The medical board first suspended his license in September. He said he would not change his conduct concerning face masks.

“Licensee has confirmed that he will refuse to abide by the state’s COVID-19 protocols in the future as well, affirming that in a choice between losing his medical license versus wearing a mask in his clinic and requiring his patients and staff to wear a mask in his clinic, he will, ‘choose to sacrifice my medical license with no hesitation’ ” the medical board’s report said.

Mr. LaTulippe told the medical board that he was “a strong asset to the public in educating them on the real facts about this pandemic” and that “at least 98% of my patients were so extremely thankful that I did not wear a mask or demand wearing a mask in my clinic.”

The medical board found Mr. LaTulippe engaged in 8 instances of unprofessional or dishonorable conduct, 22 instances of negligence in the practice of medicine, and 5 instances of gross negligence in the practice of medicine.

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

The Oregon Medical Board has revoked the license of a doctor who didn’t follow COVID-19 guidelines in his office and even told some patients that wearing face masks could lead to carbon-dioxide poisoning.

Steven Arthur LaTulippe’s advice to patients about face masking amounted to “gross negligence” in the practice of medicine and was grounds for discipline, the medical board said in a report.

Mr. LaTulippe, who had a family practice in Dallas, was fined $10,000, Insider reported. The board also said he’d overprescribed opioids for some patients.

The medical board report said Mr. LaTulippe and his wife, who ran the clinic with him, didn’t wear face masks while treating patients from March to December 2020.

Mr. LaTulippe told elderly and pediatric patients that mask wearing could hurt their health by exacerbating COPD and asthma and could contribute to heart attacks and other medical problems, the report said.

“Licensee asserts masks are likely to harm patients by increasing the body’s carbon dioxide content through rebreathing of gas trapped behind a mask,” the report said.

The report noted that “the amount of carbon dioxide rebreathed within a mask is trivial and would easily be expelled by an increase in minute ventilation so small it would not be noticed.”

The report said Mr. LaTulippe told patients they didn’t have to wear a mask in the clinic unless they were “acutely ill,” “coughing,” or “congested,” even though the Centers for Disease Control and Prevention and the Oregon governor had recommended masks be worn to prevent the spread of the virus.

Before coming into the office, patients weren’t asked if they’d had recent contact with anybody who was infected or showed COVID symptoms, the report said.

The medical board first suspended his license in September. He said he would not change his conduct concerning face masks.

“Licensee has confirmed that he will refuse to abide by the state’s COVID-19 protocols in the future as well, affirming that in a choice between losing his medical license versus wearing a mask in his clinic and requiring his patients and staff to wear a mask in his clinic, he will, ‘choose to sacrifice my medical license with no hesitation’ ” the medical board’s report said.

Mr. LaTulippe told the medical board that he was “a strong asset to the public in educating them on the real facts about this pandemic” and that “at least 98% of my patients were so extremely thankful that I did not wear a mask or demand wearing a mask in my clinic.”

The medical board found Mr. LaTulippe engaged in 8 instances of unprofessional or dishonorable conduct, 22 instances of negligence in the practice of medicine, and 5 instances of gross negligence in the practice of medicine.

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

The pandemic was more disruptive to the home life of female primary care doctors who had children than that of those who did not have children, suggests a new survey’s results.

The survey, conducted by the Robert Graham Center and the American Board of Family Medicine from May to June 2020, examined the professional and personal experiences of being a mother and a primary care physician during the pandemic.

“The pandemic was hard for everyone, but for women who had children in the home, and it didn’t really matter what age, it seemed like the emotional impact was much harder,” study author Yalda Jabbarpour, MD, said in an interview.

The results of the survey of 89 female physicians who worked in the primary care specialty were published in the Journal of Mother Studies.

Dr. Jabbapour and her colleagues found that 67% of female physicians with children said the pandemic had a great “impact” on their home life compared with 25% of those without children. Furthermore, 41% of physician moms said COVID-19 greatly affected their work life, as opposed to 17% of their counterparts without children.

“Women are going into medicine at much higher rates. In primary care, it’s becoming close to the majority,” said Dr. Jabbarpour, a family physician and medical director of the Robert Graham Center for Policy Studies. “That has important workforce implications. If we’re not supporting our female physicians and they are greater than 50% of the physician workforce and they’re burning out, who’s going to have a doctor anymore?”
 

Child care challenges

Researchers found that the emotional toll female physicians experienced early on in the pandemic was indicative of the challenges they were facing. Some of those challenges included managing anxiety, increased stress from both work and home, and social isolation from friends and family.

Another challenge physician mothers had to deal with was fulfilling child care and homeschooling needs, as many women didn’t know what to do with their children and didn’t have external support from their employers.

Child care options vanished for many people during the pandemic, Emily Kaye, MD, MPH, who was not involved in the study, said in an interview.

“I think it was incredibly challenging for everyone and uniquely challenging for women who were young mothers, specifically with respect to child care” said Dr. Kaye, assistant professor in the department of oncology at St. Jude Children’s Research Hospital. “Many women were expected to just continue plugging on in the absence of any reasonable or safe form of child care.”

Some of the changes physician-mothers said they were required to make at home or in their personal lives included physical changes related to their family safety, such as decontaminating themselves in their garages before heading home after a shift. Some also reported that they had to find new ways to maintain emotional and mental health because of social isolation from family and friends.

The survey results, which were taken early on in the pandemic, highlight the need for health policies that support physician mothers and families, as women shoulder the burden of parenting and domestic responsibilities in heterosexual relationships, the researchers said.

“I’m hoping that people pay attention and start to implement more family friendly policies within their workplaces,” Dr. Jabbarpour said. “But during a pandemic, it was essential for [female health care workers] to go in, and they had nowhere to put their kids. [Therefore], the choice became leaving young children alone at home, putting them into daycare facilities that did remain open without knowing if they were [safe], or quitting their jobs. None of those choices are good.”
 

Community support as a potential solution

Dr. Kaye said she believes that there should be a “long overdue investment” in community support, affordable and accessible child care, flexible spending, paid family leave, and other forms of caregiving support.

“In order to keep women physicians in the workforce, we need to have a significant increase in investment in the social safety net in this country,” Dr. Kaye said.

Researchers said more studies should evaluate the role the COVID-19 pandemic had on the primary care workforce in the U.S., “with a specific emphasis on how the pandemic impacted mothers, and should more intentionally consider the further intersections of race and ethnicity in the experiences of physician-mothers.”

“I think people are burning out and then there’s all this anti-science, anti-health sentiment out there, which makes it harder,” Dr. Jabbarpour said. “If we did repeat this study now, I think things would be even more dire in the voices of the women that we heard.”

Dr. Jabbarpour and Dr. Kaye reported no disclosures.

The pandemic was more disruptive to the home life of female primary care doctors who had children than that of those who did not have children, suggests a new survey’s results.

The survey, conducted by the Robert Graham Center and the American Board of Family Medicine from May to June 2020, examined the professional and personal experiences of being a mother and a primary care physician during the pandemic.

“The pandemic was hard for everyone, but for women who had children in the home, and it didn’t really matter what age, it seemed like the emotional impact was much harder,” study author Yalda Jabbarpour, MD, said in an interview.

The results of the survey of 89 female physicians who worked in the primary care specialty were published in the Journal of Mother Studies.

Dr. Jabbapour and her colleagues found that 67% of female physicians with children said the pandemic had a great “impact” on their home life compared with 25% of those without children. Furthermore, 41% of physician moms said COVID-19 greatly affected their work life, as opposed to 17% of their counterparts without children.

“Women are going into medicine at much higher rates. In primary care, it’s becoming close to the majority,” said Dr. Jabbarpour, a family physician and medical director of the Robert Graham Center for Policy Studies. “That has important workforce implications. If we’re not supporting our female physicians and they are greater than 50% of the physician workforce and they’re burning out, who’s going to have a doctor anymore?”
 

Child care challenges

Researchers found that the emotional toll female physicians experienced early on in the pandemic was indicative of the challenges they were facing. Some of those challenges included managing anxiety, increased stress from both work and home, and social isolation from friends and family.

Another challenge physician mothers had to deal with was fulfilling child care and homeschooling needs, as many women didn’t know what to do with their children and didn’t have external support from their employers.

Child care options vanished for many people during the pandemic, Emily Kaye, MD, MPH, who was not involved in the study, said in an interview.

“I think it was incredibly challenging for everyone and uniquely challenging for women who were young mothers, specifically with respect to child care” said Dr. Kaye, assistant professor in the department of oncology at St. Jude Children’s Research Hospital. “Many women were expected to just continue plugging on in the absence of any reasonable or safe form of child care.”

Some of the changes physician-mothers said they were required to make at home or in their personal lives included physical changes related to their family safety, such as decontaminating themselves in their garages before heading home after a shift. Some also reported that they had to find new ways to maintain emotional and mental health because of social isolation from family and friends.

The survey results, which were taken early on in the pandemic, highlight the need for health policies that support physician mothers and families, as women shoulder the burden of parenting and domestic responsibilities in heterosexual relationships, the researchers said.

“I’m hoping that people pay attention and start to implement more family friendly policies within their workplaces,” Dr. Jabbarpour said. “But during a pandemic, it was essential for [female health care workers] to go in, and they had nowhere to put their kids. [Therefore], the choice became leaving young children alone at home, putting them into daycare facilities that did remain open without knowing if they were [safe], or quitting their jobs. None of those choices are good.”
 

Community support as a potential solution

Dr. Kaye said she believes that there should be a “long overdue investment” in community support, affordable and accessible child care, flexible spending, paid family leave, and other forms of caregiving support.

“In order to keep women physicians in the workforce, we need to have a significant increase in investment in the social safety net in this country,” Dr. Kaye said.

Researchers said more studies should evaluate the role the COVID-19 pandemic had on the primary care workforce in the U.S., “with a specific emphasis on how the pandemic impacted mothers, and should more intentionally consider the further intersections of race and ethnicity in the experiences of physician-mothers.”

“I think people are burning out and then there’s all this anti-science, anti-health sentiment out there, which makes it harder,” Dr. Jabbarpour said. “If we did repeat this study now, I think things would be even more dire in the voices of the women that we heard.”

Dr. Jabbarpour and Dr. Kaye reported no disclosures.

The pandemic was more disruptive to the home life of female primary care doctors who had children than that of those who did not have children, suggests a new survey’s results.

The survey, conducted by the Robert Graham Center and the American Board of Family Medicine from May to June 2020, examined the professional and personal experiences of being a mother and a primary care physician during the pandemic.

“The pandemic was hard for everyone, but for women who had children in the home, and it didn’t really matter what age, it seemed like the emotional impact was much harder,” study author Yalda Jabbarpour, MD, said in an interview.

The results of the survey of 89 female physicians who worked in the primary care specialty were published in the Journal of Mother Studies.

Dr. Jabbapour and her colleagues found that 67% of female physicians with children said the pandemic had a great “impact” on their home life compared with 25% of those without children. Furthermore, 41% of physician moms said COVID-19 greatly affected their work life, as opposed to 17% of their counterparts without children.

“Women are going into medicine at much higher rates. In primary care, it’s becoming close to the majority,” said Dr. Jabbarpour, a family physician and medical director of the Robert Graham Center for Policy Studies. “That has important workforce implications. If we’re not supporting our female physicians and they are greater than 50% of the physician workforce and they’re burning out, who’s going to have a doctor anymore?”
 

Child care challenges

Researchers found that the emotional toll female physicians experienced early on in the pandemic was indicative of the challenges they were facing. Some of those challenges included managing anxiety, increased stress from both work and home, and social isolation from friends and family.

Another challenge physician mothers had to deal with was fulfilling child care and homeschooling needs, as many women didn’t know what to do with their children and didn’t have external support from their employers.

Child care options vanished for many people during the pandemic, Emily Kaye, MD, MPH, who was not involved in the study, said in an interview.

“I think it was incredibly challenging for everyone and uniquely challenging for women who were young mothers, specifically with respect to child care” said Dr. Kaye, assistant professor in the department of oncology at St. Jude Children’s Research Hospital. “Many women were expected to just continue plugging on in the absence of any reasonable or safe form of child care.”

Some of the changes physician-mothers said they were required to make at home or in their personal lives included physical changes related to their family safety, such as decontaminating themselves in their garages before heading home after a shift. Some also reported that they had to find new ways to maintain emotional and mental health because of social isolation from family and friends.

The survey results, which were taken early on in the pandemic, highlight the need for health policies that support physician mothers and families, as women shoulder the burden of parenting and domestic responsibilities in heterosexual relationships, the researchers said.

“I’m hoping that people pay attention and start to implement more family friendly policies within their workplaces,” Dr. Jabbarpour said. “But during a pandemic, it was essential for [female health care workers] to go in, and they had nowhere to put their kids. [Therefore], the choice became leaving young children alone at home, putting them into daycare facilities that did remain open without knowing if they were [safe], or quitting their jobs. None of those choices are good.”
 

Community support as a potential solution

Dr. Kaye said she believes that there should be a “long overdue investment” in community support, affordable and accessible child care, flexible spending, paid family leave, and other forms of caregiving support.

“In order to keep women physicians in the workforce, we need to have a significant increase in investment in the social safety net in this country,” Dr. Kaye said.

Researchers said more studies should evaluate the role the COVID-19 pandemic had on the primary care workforce in the U.S., “with a specific emphasis on how the pandemic impacted mothers, and should more intentionally consider the further intersections of race and ethnicity in the experiences of physician-mothers.”

“I think people are burning out and then there’s all this anti-science, anti-health sentiment out there, which makes it harder,” Dr. Jabbarpour said. “If we did repeat this study now, I think things would be even more dire in the voices of the women that we heard.”

Dr. Jabbarpour and Dr. Kaye reported no disclosures.

Although most children and adolescents with cancer have mild illness from COVID-19 infection, some do experience severe disease and a small percentage even die, according to a recent analysis.

The findings, published online in Lancet Oncology, represent the first global registry data spanning different income groups to report COVID-19 outcomes in pediatric oncology patients.

“We wanted to create a global pool of evidence to answer the question: Do we see severe [COVID-19] infection [in children with cancer]?” corresponding author Sheena Mukkada, MD, St. Jude Children’s Research Hospital, Memphis, said in an interview.

In a cohort of 1,319 pediatric patients followed for 30 days, Dr. Mukkada and colleagues reported that 80% of these patients had asymptomatic to moderate disease from COVID-19, while 1 in 5 experienced severe or critical illness and almost 4% died – four times the mortality rate observed in published cohorts of general pediatric patients.

The results highlight that “children and adolescents with cancer generally recover without incident from COVID-19, but can have a severe course of infection,” the authors concluded.

And knowing that some children can get very sick, investigators wanted “to identify who these patients are so that we can prioritize and protect that group,” she added.

Echoing that sentiment, Kathy Pritchard-Jones, MD, president of the International Society of Paediatric Oncology and coauthor on the study, noted in a press release that, “by working together to create this global registry, we have enabled hospitals around the world to rapidly share and learn how COVID-19 is affecting children with cancer.”

Dr. Pritchard-Jones commented that overall these results provide reassurance that “many children can continue their cancer treatment safely, but they also highlight important clinical features that may predict a more severe clinical course and the need for greater vigilance for some patients.”
 

Inside the Global Registry data

The Global Registry of COVID-19 in Childhood Cancer, created jointly by St. Jude Children’s Research Hospital and SIOP, included data from 131 institutions in 45 countries. Children recruited into the registry between April 2020 and February 2021 ranged in age from infancy to 18 years old.  

Most patients remained asymptomatic (35%) or experienced mild to moderate illness (45%), though 20% did develop severe or critical illness.

The investigators highlighted several factors associated with a greater risk of developing more severe illness from COVID-19, which included cancer type, intensity of therapy, age, absolute lymphocyte count, and presence of comorbidities or COVID-19 symptoms.

Notably, more than 80% of either severe or critical infections occurred in patients with hematologic malignancies – with 56% of cases in patients with acute lymphoblastic lymphoma or acute lymphoblastic leukemia – followed by extracranial solid tumors (15.8%), and central nervous system tumors (2.7%).

In patients with acute lymphoblastic leukemia or acute lymphoblastic lymphoma, severe or critical disease was most common in those receiving induction therapy (30%), relapse or refractory therapy (30%), and those in the maintenance or continuation phase of therapy (19%).

Older age was associated with a higher likelihood of having severe disease – with the lowest risk in infants (9.7%) and the highest in the 15- to 18-year-old cohort (27.3%).

Patients with lymphopenia who had an absolute lymphocyte count of 300 cells per mm³ or less and an absolute neutrophil count of 500 cells per mm³ or more also had an elevated risk of severe illness from COVID-19.

Regarding whether the presence of lymphopenia or neutropenia should change the treatment approach, Dr. Mukkada noted that, when possible, these patients should receive antiviral treatment, such as remdesivir, if the center has antivirals, or be prioritized for hospital admission.

Modifying cancer treatment might be recommended if patients are highly lymphopenic or have very low neutrophil counts, but a more effective strategy is simply to ensure that age-eligible children and adolescents with cancer or who have had a hematopoietic stem-cell transplantation have been fully vaccinated against COVID-19. For children who are not yet age-eligible, everyone around them should be vaccinated.

Pediatric patients in low- and middle-income countries were also more likely to have severe or critical outcomes from COVID-19 (41.7%), compared with patients in other income groups (23.9%).

The impact of COVID-19 “has been felt in every corner of the world, but particularly in low- and middle-income countries, compared to high-income countries,” senior author Carlos Rodriguez-Galindo, MD, global director at St. Jude, said in a statement.

In terms of the intersection of cancer treatment and COVID diagnosis, almost 83% of pediatric patients were receiving treatment for their cancer. Chemotherapy was withheld in about 45% of these patients and some modification to the treatment regimen occurred in almost 56% of participants on active therapy.

“Treatment modifications were least common in patients from upper-middle–income countries, compared with other income groups,” the authors wrote.

Although an interesting observation, Dr. Mukkada noted that the registry data could not explain why treatment modifications occurred less frequently in upper-middle income countries as opposed to high-income and lower-income countries.
 

U.K. Monitoring Project

Not all studies, however, have found that COVID-19 infection is significantly more severe in children with cancer. In a 2020 report from the U.K. Paediatric Coronavirus Cancer Monitoring Project, researchers evaluated all children in the United Kingdom under the age of 16 diagnosed with COVID and cancer.

“[Given that] we had complete coverage of every center in the U.K. that cares for children with cancer, we are confident that we picked up at least all the severe or critical cases,” lead author Gerard Millen, MD, honorary clinical research fellow, University of Birmingham (England), said in an interview.

Between March 2020 and July 2020, Dr. Millen and colleagues identified 54 positive cases of COVID-19, 15 (28%) of which were asymptomatic, 34 (63%) mild, and 4 (7.4%) severe or critical – more in line with the incidence of severe illness reported in the general pediatric population.

“Thankfully, we had no children with cancer in the U.K. who died from COVID-19,” Dr. Millen noted. “Overall, in the U.K., we have taken the approach that the majority of children with cancer in this country are at very low risk from COVID-19 and that we do not have good evidence to modify their treatment.”

Dr. Millen pointed out that the data in the U.K. study were “remarkably similar” to those from the high-income countries in the global St. Jude/SIOP cohort, where 7.4% of patients in that cohort had severe or critical disease, compared with 7.4% of patients from their own U.K. cohort.

“I think many of the key differences between the two cohorts reflect the fact that access to treatment in many low- to middle-income countries is more challenging with many factors contributing to overall poorer outcomes for both cancer and noncancer metrics,” Dr. Millen said.

Both the U.K. and registry studies were performed prior to vaccinations becoming available to older children, and before the emergence of certain variants, including the Delta variant, which is responsible for the most recent surge of COVID-19 infections around the world.

Data on COVID-19 vaccination in children with cancer are limited but promising so far.

As for whether the Delta variant might affect outcomes for children with cancer and COVID-19, Dr. Mukkada could only speculate, but she noted that “what we are hearing anecdotally about the [Delta] disease being more severe, even in patients who don’t have cancer, is leading us to say that we can’t close the registry yet. We are still actively enrolling children.”

The study was funded by the American Lebanese Syrian Associated Charities and the National Cancer Institute. The study authors and Dr. Millen disclosed no relevant financial relationships.

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

Although most children and adolescents with cancer have mild illness from COVID-19 infection, some do experience severe disease and a small percentage even die, according to a recent analysis.

The findings, published online in Lancet Oncology, represent the first global registry data spanning different income groups to report COVID-19 outcomes in pediatric oncology patients.

“We wanted to create a global pool of evidence to answer the question: Do we see severe [COVID-19] infection [in children with cancer]?” corresponding author Sheena Mukkada, MD, St. Jude Children’s Research Hospital, Memphis, said in an interview.

In a cohort of 1,319 pediatric patients followed for 30 days, Dr. Mukkada and colleagues reported that 80% of these patients had asymptomatic to moderate disease from COVID-19, while 1 in 5 experienced severe or critical illness and almost 4% died – four times the mortality rate observed in published cohorts of general pediatric patients.

The results highlight that “children and adolescents with cancer generally recover without incident from COVID-19, but can have a severe course of infection,” the authors concluded.

And knowing that some children can get very sick, investigators wanted “to identify who these patients are so that we can prioritize and protect that group,” she added.

Echoing that sentiment, Kathy Pritchard-Jones, MD, president of the International Society of Paediatric Oncology and coauthor on the study, noted in a press release that, “by working together to create this global registry, we have enabled hospitals around the world to rapidly share and learn how COVID-19 is affecting children with cancer.”

Dr. Pritchard-Jones commented that overall these results provide reassurance that “many children can continue their cancer treatment safely, but they also highlight important clinical features that may predict a more severe clinical course and the need for greater vigilance for some patients.”
 

Inside the Global Registry data

The Global Registry of COVID-19 in Childhood Cancer, created jointly by St. Jude Children’s Research Hospital and SIOP, included data from 131 institutions in 45 countries. Children recruited into the registry between April 2020 and February 2021 ranged in age from infancy to 18 years old.  

Most patients remained asymptomatic (35%) or experienced mild to moderate illness (45%), though 20% did develop severe or critical illness.

The investigators highlighted several factors associated with a greater risk of developing more severe illness from COVID-19, which included cancer type, intensity of therapy, age, absolute lymphocyte count, and presence of comorbidities or COVID-19 symptoms.

Notably, more than 80% of either severe or critical infections occurred in patients with hematologic malignancies – with 56% of cases in patients with acute lymphoblastic lymphoma or acute lymphoblastic leukemia – followed by extracranial solid tumors (15.8%), and central nervous system tumors (2.7%).

In patients with acute lymphoblastic leukemia or acute lymphoblastic lymphoma, severe or critical disease was most common in those receiving induction therapy (30%), relapse or refractory therapy (30%), and those in the maintenance or continuation phase of therapy (19%).

Older age was associated with a higher likelihood of having severe disease – with the lowest risk in infants (9.7%) and the highest in the 15- to 18-year-old cohort (27.3%).

Patients with lymphopenia who had an absolute lymphocyte count of 300 cells per mm³ or less and an absolute neutrophil count of 500 cells per mm³ or more also had an elevated risk of severe illness from COVID-19.

Regarding whether the presence of lymphopenia or neutropenia should change the treatment approach, Dr. Mukkada noted that, when possible, these patients should receive antiviral treatment, such as remdesivir, if the center has antivirals, or be prioritized for hospital admission.

Modifying cancer treatment might be recommended if patients are highly lymphopenic or have very low neutrophil counts, but a more effective strategy is simply to ensure that age-eligible children and adolescents with cancer or who have had a hematopoietic stem-cell transplantation have been fully vaccinated against COVID-19. For children who are not yet age-eligible, everyone around them should be vaccinated.

Pediatric patients in low- and middle-income countries were also more likely to have severe or critical outcomes from COVID-19 (41.7%), compared with patients in other income groups (23.9%).

The impact of COVID-19 “has been felt in every corner of the world, but particularly in low- and middle-income countries, compared to high-income countries,” senior author Carlos Rodriguez-Galindo, MD, global director at St. Jude, said in a statement.

In terms of the intersection of cancer treatment and COVID diagnosis, almost 83% of pediatric patients were receiving treatment for their cancer. Chemotherapy was withheld in about 45% of these patients and some modification to the treatment regimen occurred in almost 56% of participants on active therapy.

“Treatment modifications were least common in patients from upper-middle–income countries, compared with other income groups,” the authors wrote.

Although an interesting observation, Dr. Mukkada noted that the registry data could not explain why treatment modifications occurred less frequently in upper-middle income countries as opposed to high-income and lower-income countries.
 

U.K. Monitoring Project

Not all studies, however, have found that COVID-19 infection is significantly more severe in children with cancer. In a 2020 report from the U.K. Paediatric Coronavirus Cancer Monitoring Project, researchers evaluated all children in the United Kingdom under the age of 16 diagnosed with COVID and cancer.

“[Given that] we had complete coverage of every center in the U.K. that cares for children with cancer, we are confident that we picked up at least all the severe or critical cases,” lead author Gerard Millen, MD, honorary clinical research fellow, University of Birmingham (England), said in an interview.

Between March 2020 and July 2020, Dr. Millen and colleagues identified 54 positive cases of COVID-19, 15 (28%) of which were asymptomatic, 34 (63%) mild, and 4 (7.4%) severe or critical – more in line with the incidence of severe illness reported in the general pediatric population.

“Thankfully, we had no children with cancer in the U.K. who died from COVID-19,” Dr. Millen noted. “Overall, in the U.K., we have taken the approach that the majority of children with cancer in this country are at very low risk from COVID-19 and that we do not have good evidence to modify their treatment.”

Dr. Millen pointed out that the data in the U.K. study were “remarkably similar” to those from the high-income countries in the global St. Jude/SIOP cohort, where 7.4% of patients in that cohort had severe or critical disease, compared with 7.4% of patients from their own U.K. cohort.

“I think many of the key differences between the two cohorts reflect the fact that access to treatment in many low- to middle-income countries is more challenging with many factors contributing to overall poorer outcomes for both cancer and noncancer metrics,” Dr. Millen said.

Both the U.K. and registry studies were performed prior to vaccinations becoming available to older children, and before the emergence of certain variants, including the Delta variant, which is responsible for the most recent surge of COVID-19 infections around the world.

Data on COVID-19 vaccination in children with cancer are limited but promising so far.

As for whether the Delta variant might affect outcomes for children with cancer and COVID-19, Dr. Mukkada could only speculate, but she noted that “what we are hearing anecdotally about the [Delta] disease being more severe, even in patients who don’t have cancer, is leading us to say that we can’t close the registry yet. We are still actively enrolling children.”

The study was funded by the American Lebanese Syrian Associated Charities and the National Cancer Institute. The study authors and Dr. Millen disclosed no relevant financial relationships.

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

Although most children and adolescents with cancer have mild illness from COVID-19 infection, some do experience severe disease and a small percentage even die, according to a recent analysis.

The findings, published online in Lancet Oncology, represent the first global registry data spanning different income groups to report COVID-19 outcomes in pediatric oncology patients.

“We wanted to create a global pool of evidence to answer the question: Do we see severe [COVID-19] infection [in children with cancer]?” corresponding author Sheena Mukkada, MD, St. Jude Children’s Research Hospital, Memphis, said in an interview.

In a cohort of 1,319 pediatric patients followed for 30 days, Dr. Mukkada and colleagues reported that 80% of these patients had asymptomatic to moderate disease from COVID-19, while 1 in 5 experienced severe or critical illness and almost 4% died – four times the mortality rate observed in published cohorts of general pediatric patients.

The results highlight that “children and adolescents with cancer generally recover without incident from COVID-19, but can have a severe course of infection,” the authors concluded.

And knowing that some children can get very sick, investigators wanted “to identify who these patients are so that we can prioritize and protect that group,” she added.

Echoing that sentiment, Kathy Pritchard-Jones, MD, president of the International Society of Paediatric Oncology and coauthor on the study, noted in a press release that, “by working together to create this global registry, we have enabled hospitals around the world to rapidly share and learn how COVID-19 is affecting children with cancer.”

Dr. Pritchard-Jones commented that overall these results provide reassurance that “many children can continue their cancer treatment safely, but they also highlight important clinical features that may predict a more severe clinical course and the need for greater vigilance for some patients.”
 

Inside the Global Registry data

The Global Registry of COVID-19 in Childhood Cancer, created jointly by St. Jude Children’s Research Hospital and SIOP, included data from 131 institutions in 45 countries. Children recruited into the registry between April 2020 and February 2021 ranged in age from infancy to 18 years old.  

Most patients remained asymptomatic (35%) or experienced mild to moderate illness (45%), though 20% did develop severe or critical illness.

The investigators highlighted several factors associated with a greater risk of developing more severe illness from COVID-19, which included cancer type, intensity of therapy, age, absolute lymphocyte count, and presence of comorbidities or COVID-19 symptoms.

Notably, more than 80% of either severe or critical infections occurred in patients with hematologic malignancies – with 56% of cases in patients with acute lymphoblastic lymphoma or acute lymphoblastic leukemia – followed by extracranial solid tumors (15.8%), and central nervous system tumors (2.7%).

In patients with acute lymphoblastic leukemia or acute lymphoblastic lymphoma, severe or critical disease was most common in those receiving induction therapy (30%), relapse or refractory therapy (30%), and those in the maintenance or continuation phase of therapy (19%).

Older age was associated with a higher likelihood of having severe disease – with the lowest risk in infants (9.7%) and the highest in the 15- to 18-year-old cohort (27.3%).

Patients with lymphopenia who had an absolute lymphocyte count of 300 cells per mm³ or less and an absolute neutrophil count of 500 cells per mm³ or more also had an elevated risk of severe illness from COVID-19.

Regarding whether the presence of lymphopenia or neutropenia should change the treatment approach, Dr. Mukkada noted that, when possible, these patients should receive antiviral treatment, such as remdesivir, if the center has antivirals, or be prioritized for hospital admission.

Modifying cancer treatment might be recommended if patients are highly lymphopenic or have very low neutrophil counts, but a more effective strategy is simply to ensure that age-eligible children and adolescents with cancer or who have had a hematopoietic stem-cell transplantation have been fully vaccinated against COVID-19. For children who are not yet age-eligible, everyone around them should be vaccinated.

Pediatric patients in low- and middle-income countries were also more likely to have severe or critical outcomes from COVID-19 (41.7%), compared with patients in other income groups (23.9%).

The impact of COVID-19 “has been felt in every corner of the world, but particularly in low- and middle-income countries, compared to high-income countries,” senior author Carlos Rodriguez-Galindo, MD, global director at St. Jude, said in a statement.

In terms of the intersection of cancer treatment and COVID diagnosis, almost 83% of pediatric patients were receiving treatment for their cancer. Chemotherapy was withheld in about 45% of these patients and some modification to the treatment regimen occurred in almost 56% of participants on active therapy.

“Treatment modifications were least common in patients from upper-middle–income countries, compared with other income groups,” the authors wrote.

Although an interesting observation, Dr. Mukkada noted that the registry data could not explain why treatment modifications occurred less frequently in upper-middle income countries as opposed to high-income and lower-income countries.
 

U.K. Monitoring Project

Not all studies, however, have found that COVID-19 infection is significantly more severe in children with cancer. In a 2020 report from the U.K. Paediatric Coronavirus Cancer Monitoring Project, researchers evaluated all children in the United Kingdom under the age of 16 diagnosed with COVID and cancer.

“[Given that] we had complete coverage of every center in the U.K. that cares for children with cancer, we are confident that we picked up at least all the severe or critical cases,” lead author Gerard Millen, MD, honorary clinical research fellow, University of Birmingham (England), said in an interview.

Between March 2020 and July 2020, Dr. Millen and colleagues identified 54 positive cases of COVID-19, 15 (28%) of which were asymptomatic, 34 (63%) mild, and 4 (7.4%) severe or critical – more in line with the incidence of severe illness reported in the general pediatric population.

“Thankfully, we had no children with cancer in the U.K. who died from COVID-19,” Dr. Millen noted. “Overall, in the U.K., we have taken the approach that the majority of children with cancer in this country are at very low risk from COVID-19 and that we do not have good evidence to modify their treatment.”

Dr. Millen pointed out that the data in the U.K. study were “remarkably similar” to those from the high-income countries in the global St. Jude/SIOP cohort, where 7.4% of patients in that cohort had severe or critical disease, compared with 7.4% of patients from their own U.K. cohort.

“I think many of the key differences between the two cohorts reflect the fact that access to treatment in many low- to middle-income countries is more challenging with many factors contributing to overall poorer outcomes for both cancer and noncancer metrics,” Dr. Millen said.

Both the U.K. and registry studies were performed prior to vaccinations becoming available to older children, and before the emergence of certain variants, including the Delta variant, which is responsible for the most recent surge of COVID-19 infections around the world.

Data on COVID-19 vaccination in children with cancer are limited but promising so far.

As for whether the Delta variant might affect outcomes for children with cancer and COVID-19, Dr. Mukkada could only speculate, but she noted that “what we are hearing anecdotally about the [Delta] disease being more severe, even in patients who don’t have cancer, is leading us to say that we can’t close the registry yet. We are still actively enrolling children.”

The study was funded by the American Lebanese Syrian Associated Charities and the National Cancer Institute. The study authors and Dr. Millen disclosed no relevant financial relationships.

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

The Food and Drug Administration today gave the nod to topical ruxolitinib cream for the treatment of non-immunocompromised patients with mild to moderate atopic dermatitis ages 12 years and older, making it the first topical JAK inhibitor approved for AD – and the first JAK inhibitor approved for this indication – in the United States.

The approval is limited to patients whose AD is not adequately controlled with topical prescription therapies, or when those therapies are not advisable.

“Approval of topical ruxolitinib fills a major gap in the treatment of atopic dermatitis: a safe, effective, and tolerable non-steroidal topical therapy,” Eric L. Simpson, MD, professor of dermatology and director of the Oregon Health & Science University Dermatology Clinical Research Center, Portland, told this news organization. “This approval will allow for long-term treatment without the concern of steroid side effects. From earlier studies, ruxolitinib cream appears to be as effective as a medium-potency topical steroid. These efficacy levels and low incidence of burning will be a welcome addition to our current nonsteroidal therapies.”

The drug’s approval was based on results from two phase 3, randomized studies of identical design involving 1,249 patients aged 12 years and older with AD: TRuE-AD1 and TRuE-AD2. In these studies, ruxolitinib cream demonstrated anti-inflammatory activity, with rapid and sustained antipruritic action, compared with vehicle. In the trials, patients with an Investigator’s Global Assessment (IGA) score of 2 or 3 and 3%-20% of affected body surface area (BSA) were randomized (2:2:1) to twice-daily 0.75% ruxolitinib cream, 1.5% ruxolitinib cream, or vehicle cream for 8 continuous weeks. The 1.5% concentration was approved by the FDA.

A study first published in May of 2021 found that significantly more patients in TRuE-AD1 and TRuE-AD2 achieved IGA treatment success with 0.75% (50% vs. 39%, respectively) and 1.5% ruxolitinib cream (53.8% vs. 51.3%), compared with vehicle (15.1% vs. 7.6%; P < .0001) at week 8. In addition, significant reductions in itch, compared with vehicle, were reported within 12 hours of first applying 1.5% ruxolitinib cream (P < .05).

More key findings from TRuE-AD1 and TRuE-AD2 are scheduled to be presented during the upcoming European Academy of Dermatology and Venereology meeting Sept. 29-Oct. 2, but during the Revolutionizing Atopic Dermatitis Symposium on June 13, Kim Papp, MD, PhD, presented long-term safety data of ruxolitinib cream in patients who were followed for an additional 44 weeks. Dr. Papp, a dermatologist and founder of Probity Medical Research, Waterloo, Ont., reported that 543 patients from TRuE-AD1 and 530 from TRuE-AD2 entered the long-term analysis and that about 78% of these patients completed the study. From weeks 12 to 52, the proportion of patients with an IGA score of 0 or 1 with 0.75% and 1.5% ruxolitinib cream ranged from 62%-77% and 67%-77%, respectively, in TRuE-AD1, to 60%-77% and 72%-80% in TRuE-AD2.

The measured mean total affected BSA was less than 3% throughout the follow-up period in the 1.5% ruxolitinib cream arm in TRuE-AD1 and TRuE-AD2 and was less than 3% in the 0.75% ruxolitinib cream arm during most of the study period.

In a pooled safety analysis, treatment-emergent adverse events (TEAEs) were reported in 60% and 54% of patients who applied 0.75% and 1.5% ruxolitinib cream, respectively, over 44 weeks. The frequency of application-site reactions remained low. Specifically, treatment-related adverse events were reported in 5% of patients who applied 0.75% ruxolitinib cream and in 3% of patients who applied 1.5% ruxolitinib cream; none were serious. TEAEs led to discontinuation in 2% of patients in the 0.75% ruxolitinib cream group, and no patients in the 1.5% ruxolitinib cream group.

Dr. Papp and his colleagues observed that the most common treatment adverse events were upper respiratory tract infections and nasopharyngitis. According to Incyte’s press release, the most common treatment-emergent adverse reactions in patients treated with ruxolitinib during clinical trials were nasopharyngitis, diarrhea, bronchitis, ear infection, eosinophil count increases, urticaria, folliculitis, tonsillitis, and rhinorrhea. The labeling includes boxed warnings for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis, seen with oral JAK inhibitors for inflammatory conditions.

Incyte will market ruxolitinib under the trade name Opzelura.

Dr. Simpson disclosed that he is a consultant to and/or an investigator for several pharmaceutical companies, including Incyte, Regeneron/Sanofi, Eli Lilly and Company, AbbVie, and Pfizer.

Dr. Papp disclosed that he has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or steering committee member for several pharmaceutical companies, including Incyte.

Commentary by Robert Sidbury, MD, MPH

Another nonsteroidal topical medication approved for atopic dermatitis (AD)? Thank goodness. Topical ruxolitinib 1.5% cream twice daily for mild to moderate AD demonstrated excellent efficacy vs. placebo in duplicative trials (53.8/51.3% vs. 15.1%/7.6%; P < .001), with a reassuring safety profile. Application site reactions were uncommon, though past experience with other new nonsteroidal agents suggests judgment be reserved on that score. More compelling was the fact that no patients discontinued therapy in the 1.5% arm, and adverse events were mild and self-limited such as nasopharyngitis and diarrhea. This stands in contradistinction to the boxed warning attached to JAK inhibitors (topical and systemic) against a daunting list of destructive possibilities: malignancy, infection, cardiovascular disease, and blood clots. None of these things was seen in these topical ruxolitinib trials.

Dr. Sidbury is chief of dermatology at Seattle Children's Hospital and professor, department of pediatrics, University of Washington, Seattle. He is a site principal investigator for dupilumab trials, for which the hospital has a contract with Regeneron.

This article was updated 6/16/22.

The Food and Drug Administration today gave the nod to topical ruxolitinib cream for the treatment of non-immunocompromised patients with mild to moderate atopic dermatitis ages 12 years and older, making it the first topical JAK inhibitor approved for AD – and the first JAK inhibitor approved for this indication – in the United States.

The approval is limited to patients whose AD is not adequately controlled with topical prescription therapies, or when those therapies are not advisable.

“Approval of topical ruxolitinib fills a major gap in the treatment of atopic dermatitis: a safe, effective, and tolerable non-steroidal topical therapy,” Eric L. Simpson, MD, professor of dermatology and director of the Oregon Health & Science University Dermatology Clinical Research Center, Portland, told this news organization. “This approval will allow for long-term treatment without the concern of steroid side effects. From earlier studies, ruxolitinib cream appears to be as effective as a medium-potency topical steroid. These efficacy levels and low incidence of burning will be a welcome addition to our current nonsteroidal therapies.”

The drug’s approval was based on results from two phase 3, randomized studies of identical design involving 1,249 patients aged 12 years and older with AD: TRuE-AD1 and TRuE-AD2. In these studies, ruxolitinib cream demonstrated anti-inflammatory activity, with rapid and sustained antipruritic action, compared with vehicle. In the trials, patients with an Investigator’s Global Assessment (IGA) score of 2 or 3 and 3%-20% of affected body surface area (BSA) were randomized (2:2:1) to twice-daily 0.75% ruxolitinib cream, 1.5% ruxolitinib cream, or vehicle cream for 8 continuous weeks. The 1.5% concentration was approved by the FDA.

A study first published in May of 2021 found that significantly more patients in TRuE-AD1 and TRuE-AD2 achieved IGA treatment success with 0.75% (50% vs. 39%, respectively) and 1.5% ruxolitinib cream (53.8% vs. 51.3%), compared with vehicle (15.1% vs. 7.6%; P < .0001) at week 8. In addition, significant reductions in itch, compared with vehicle, were reported within 12 hours of first applying 1.5% ruxolitinib cream (P < .05).

More key findings from TRuE-AD1 and TRuE-AD2 are scheduled to be presented during the upcoming European Academy of Dermatology and Venereology meeting Sept. 29-Oct. 2, but during the Revolutionizing Atopic Dermatitis Symposium on June 13, Kim Papp, MD, PhD, presented long-term safety data of ruxolitinib cream in patients who were followed for an additional 44 weeks. Dr. Papp, a dermatologist and founder of Probity Medical Research, Waterloo, Ont., reported that 543 patients from TRuE-AD1 and 530 from TRuE-AD2 entered the long-term analysis and that about 78% of these patients completed the study. From weeks 12 to 52, the proportion of patients with an IGA score of 0 or 1 with 0.75% and 1.5% ruxolitinib cream ranged from 62%-77% and 67%-77%, respectively, in TRuE-AD1, to 60%-77% and 72%-80% in TRuE-AD2.

The measured mean total affected BSA was less than 3% throughout the follow-up period in the 1.5% ruxolitinib cream arm in TRuE-AD1 and TRuE-AD2 and was less than 3% in the 0.75% ruxolitinib cream arm during most of the study period.

In a pooled safety analysis, treatment-emergent adverse events (TEAEs) were reported in 60% and 54% of patients who applied 0.75% and 1.5% ruxolitinib cream, respectively, over 44 weeks. The frequency of application-site reactions remained low. Specifically, treatment-related adverse events were reported in 5% of patients who applied 0.75% ruxolitinib cream and in 3% of patients who applied 1.5% ruxolitinib cream; none were serious. TEAEs led to discontinuation in 2% of patients in the 0.75% ruxolitinib cream group, and no patients in the 1.5% ruxolitinib cream group.

Dr. Papp and his colleagues observed that the most common treatment adverse events were upper respiratory tract infections and nasopharyngitis. According to Incyte’s press release, the most common treatment-emergent adverse reactions in patients treated with ruxolitinib during clinical trials were nasopharyngitis, diarrhea, bronchitis, ear infection, eosinophil count increases, urticaria, folliculitis, tonsillitis, and rhinorrhea. The labeling includes boxed warnings for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis, seen with oral JAK inhibitors for inflammatory conditions.

Incyte will market ruxolitinib under the trade name Opzelura.

Dr. Simpson disclosed that he is a consultant to and/or an investigator for several pharmaceutical companies, including Incyte, Regeneron/Sanofi, Eli Lilly and Company, AbbVie, and Pfizer.

Dr. Papp disclosed that he has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or steering committee member for several pharmaceutical companies, including Incyte.

Commentary by Robert Sidbury, MD, MPH

Another nonsteroidal topical medication approved for atopic dermatitis (AD)? Thank goodness. Topical ruxolitinib 1.5% cream twice daily for mild to moderate AD demonstrated excellent efficacy vs. placebo in duplicative trials (53.8/51.3% vs. 15.1%/7.6%; P < .001), with a reassuring safety profile. Application site reactions were uncommon, though past experience with other new nonsteroidal agents suggests judgment be reserved on that score. More compelling was the fact that no patients discontinued therapy in the 1.5% arm, and adverse events were mild and self-limited such as nasopharyngitis and diarrhea. This stands in contradistinction to the boxed warning attached to JAK inhibitors (topical and systemic) against a daunting list of destructive possibilities: malignancy, infection, cardiovascular disease, and blood clots. None of these things was seen in these topical ruxolitinib trials.

Dr. Sidbury is chief of dermatology at Seattle Children's Hospital and professor, department of pediatrics, University of Washington, Seattle. He is a site principal investigator for dupilumab trials, for which the hospital has a contract with Regeneron.

This article was updated 6/16/22.

The Food and Drug Administration today gave the nod to topical ruxolitinib cream for the treatment of non-immunocompromised patients with mild to moderate atopic dermatitis ages 12 years and older, making it the first topical JAK inhibitor approved for AD – and the first JAK inhibitor approved for this indication – in the United States.

The approval is limited to patients whose AD is not adequately controlled with topical prescription therapies, or when those therapies are not advisable.

“Approval of topical ruxolitinib fills a major gap in the treatment of atopic dermatitis: a safe, effective, and tolerable non-steroidal topical therapy,” Eric L. Simpson, MD, professor of dermatology and director of the Oregon Health & Science University Dermatology Clinical Research Center, Portland, told this news organization. “This approval will allow for long-term treatment without the concern of steroid side effects. From earlier studies, ruxolitinib cream appears to be as effective as a medium-potency topical steroid. These efficacy levels and low incidence of burning will be a welcome addition to our current nonsteroidal therapies.”

The drug’s approval was based on results from two phase 3, randomized studies of identical design involving 1,249 patients aged 12 years and older with AD: TRuE-AD1 and TRuE-AD2. In these studies, ruxolitinib cream demonstrated anti-inflammatory activity, with rapid and sustained antipruritic action, compared with vehicle. In the trials, patients with an Investigator’s Global Assessment (IGA) score of 2 or 3 and 3%-20% of affected body surface area (BSA) were randomized (2:2:1) to twice-daily 0.75% ruxolitinib cream, 1.5% ruxolitinib cream, or vehicle cream for 8 continuous weeks. The 1.5% concentration was approved by the FDA.

A study first published in May of 2021 found that significantly more patients in TRuE-AD1 and TRuE-AD2 achieved IGA treatment success with 0.75% (50% vs. 39%, respectively) and 1.5% ruxolitinib cream (53.8% vs. 51.3%), compared with vehicle (15.1% vs. 7.6%; P < .0001) at week 8. In addition, significant reductions in itch, compared with vehicle, were reported within 12 hours of first applying 1.5% ruxolitinib cream (P < .05).

More key findings from TRuE-AD1 and TRuE-AD2 are scheduled to be presented during the upcoming European Academy of Dermatology and Venereology meeting Sept. 29-Oct. 2, but during the Revolutionizing Atopic Dermatitis Symposium on June 13, Kim Papp, MD, PhD, presented long-term safety data of ruxolitinib cream in patients who were followed for an additional 44 weeks. Dr. Papp, a dermatologist and founder of Probity Medical Research, Waterloo, Ont., reported that 543 patients from TRuE-AD1 and 530 from TRuE-AD2 entered the long-term analysis and that about 78% of these patients completed the study. From weeks 12 to 52, the proportion of patients with an IGA score of 0 or 1 with 0.75% and 1.5% ruxolitinib cream ranged from 62%-77% and 67%-77%, respectively, in TRuE-AD1, to 60%-77% and 72%-80% in TRuE-AD2.

The measured mean total affected BSA was less than 3% throughout the follow-up period in the 1.5% ruxolitinib cream arm in TRuE-AD1 and TRuE-AD2 and was less than 3% in the 0.75% ruxolitinib cream arm during most of the study period.

In a pooled safety analysis, treatment-emergent adverse events (TEAEs) were reported in 60% and 54% of patients who applied 0.75% and 1.5% ruxolitinib cream, respectively, over 44 weeks. The frequency of application-site reactions remained low. Specifically, treatment-related adverse events were reported in 5% of patients who applied 0.75% ruxolitinib cream and in 3% of patients who applied 1.5% ruxolitinib cream; none were serious. TEAEs led to discontinuation in 2% of patients in the 0.75% ruxolitinib cream group, and no patients in the 1.5% ruxolitinib cream group.

Dr. Papp and his colleagues observed that the most common treatment adverse events were upper respiratory tract infections and nasopharyngitis. According to Incyte’s press release, the most common treatment-emergent adverse reactions in patients treated with ruxolitinib during clinical trials were nasopharyngitis, diarrhea, bronchitis, ear infection, eosinophil count increases, urticaria, folliculitis, tonsillitis, and rhinorrhea. The labeling includes boxed warnings for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis, seen with oral JAK inhibitors for inflammatory conditions.

Incyte will market ruxolitinib under the trade name Opzelura.

Dr. Simpson disclosed that he is a consultant to and/or an investigator for several pharmaceutical companies, including Incyte, Regeneron/Sanofi, Eli Lilly and Company, AbbVie, and Pfizer.

Dr. Papp disclosed that he has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or steering committee member for several pharmaceutical companies, including Incyte.

Commentary by Robert Sidbury, MD, MPH

Another nonsteroidal topical medication approved for atopic dermatitis (AD)? Thank goodness. Topical ruxolitinib 1.5% cream twice daily for mild to moderate AD demonstrated excellent efficacy vs. placebo in duplicative trials (53.8/51.3% vs. 15.1%/7.6%; P < .001), with a reassuring safety profile. Application site reactions were uncommon, though past experience with other new nonsteroidal agents suggests judgment be reserved on that score. More compelling was the fact that no patients discontinued therapy in the 1.5% arm, and adverse events were mild and self-limited such as nasopharyngitis and diarrhea. This stands in contradistinction to the boxed warning attached to JAK inhibitors (topical and systemic) against a daunting list of destructive possibilities: malignancy, infection, cardiovascular disease, and blood clots. None of these things was seen in these topical ruxolitinib trials.

Dr. Sidbury is chief of dermatology at Seattle Children's Hospital and professor, department of pediatrics, University of Washington, Seattle. He is a site principal investigator for dupilumab trials, for which the hospital has a contract with Regeneron.

This article was updated 6/16/22.