Pediatrics

The Centers for Disease Control and Prevention updated its recommendations for doctors and public health officials regarding the unusual outbreak of acute hepatitis among children.

As of May 5, the CDC and state health departments are investigating 109 children with hepatitis of unknown origin across 25 states and territories.

More than half have tested positive for adenovirus, the CDC said. More than 90% have been hospitalized, and 14% have had liver transplants. Five deaths are under investigation.

This week’s CDC alert provides updated recommendations for testing, given the potential association between adenovirus infection and pediatric hepatitis, or liver inflammation.

“Clinicians are recommended to consider adenovirus testing for patients with hepatitis of unknown etiology and to report such cases to their state or jurisdictional public health authorities,” the CDC said.

Doctors should also consider collecting a blood sample, respiratory sample, and stool sample. They may also collect liver tissue if a biopsy occurred or an autopsy is available.

In November 2021, clinicians at a large children’s hospital in Alabama notified the CDC about five pediatric patients with significant liver injury, including three with acute liver failure, who also tested positive for adenovirus. All children were previously healthy, and none had COVID-19, according to a CDC alert in April.

Four additional pediatric patients with hepatitis and adenovirus infection were identified. After lab testing found adenovirus infection in all nine patients in the initial cluster, public health officials began investigating a possible association between pediatric hepatitis and adenovirus. Among the five specimens that could be sequenced, they were all adenovirus type 41.

Unexplained hepatitis cases have been reported in children worldwide, reaching 450 cases and 11 deaths, according to the latest update from the European Centre for Disease Prevention and Control.

The cases have been reported in more than two dozen countries around the world, with 14 countries reporting more than five cases. The United Kingdom and the United States have reported the largest case counts so far.

In the United Kingdom, officials have identified 163 cases in children under age 16 years, including 11 that required liver transplants.

In the European Union, 14 countries have reported 106 cases collectively, with Italy reporting 35 cases and Spain reporting 22 cases. Outside of the European Union, Brazil has reported 16, Indonesia has reported 15, and Israel has reported 12.

Among the 11 deaths reported globally, the Uniyed States has reported five, Indonesia has reported five, and Palestine has reported one.

The cause of severe hepatitis remains a mystery, according to Ars Technica. Some cases have been identified retrospectively, dating back to the beginning of October 2021.

About 70% of the cases that have been tested for an adenovirus have tested positive, and subtype testing continues to show adenovirus type 41. The cases don’t appear to be linked to common causes, such as hepatitis viruses A, B, C, D, or E, which can cause liver inflammation and injury.

Adenoviruses aren’t known to cause hepatitis in healthy children, though the viruses have been linked to liver damage in children with compromised immune systems, according to Ars Technica. Adenoviruses typically cause respiratory infections in children, although type 41 tends to cause gastrointestinal illness.

“At present, the leading hypotheses remain those which involve adenovirus,” Philippa Easterbrook, a senior scientist at the WHO, said May 10 during a press briefing.

“I think [there’s] also still an important consideration about the role of COVID as well, either as a co-infection or as a past infection,” she said.

WHO officials expect data within a week from U.K. cases, Ms. Easterbrook said, which may indicate whether the adenovirus is an incidental infection or a more direct cause.

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

The Centers for Disease Control and Prevention updated its recommendations for doctors and public health officials regarding the unusual outbreak of acute hepatitis among children.

As of May 5, the CDC and state health departments are investigating 109 children with hepatitis of unknown origin across 25 states and territories.

More than half have tested positive for adenovirus, the CDC said. More than 90% have been hospitalized, and 14% have had liver transplants. Five deaths are under investigation.

This week’s CDC alert provides updated recommendations for testing, given the potential association between adenovirus infection and pediatric hepatitis, or liver inflammation.

“Clinicians are recommended to consider adenovirus testing for patients with hepatitis of unknown etiology and to report such cases to their state or jurisdictional public health authorities,” the CDC said.

Doctors should also consider collecting a blood sample, respiratory sample, and stool sample. They may also collect liver tissue if a biopsy occurred or an autopsy is available.

In November 2021, clinicians at a large children’s hospital in Alabama notified the CDC about five pediatric patients with significant liver injury, including three with acute liver failure, who also tested positive for adenovirus. All children were previously healthy, and none had COVID-19, according to a CDC alert in April.

Four additional pediatric patients with hepatitis and adenovirus infection were identified. After lab testing found adenovirus infection in all nine patients in the initial cluster, public health officials began investigating a possible association between pediatric hepatitis and adenovirus. Among the five specimens that could be sequenced, they were all adenovirus type 41.

Unexplained hepatitis cases have been reported in children worldwide, reaching 450 cases and 11 deaths, according to the latest update from the European Centre for Disease Prevention and Control.

The cases have been reported in more than two dozen countries around the world, with 14 countries reporting more than five cases. The United Kingdom and the United States have reported the largest case counts so far.

In the United Kingdom, officials have identified 163 cases in children under age 16 years, including 11 that required liver transplants.

In the European Union, 14 countries have reported 106 cases collectively, with Italy reporting 35 cases and Spain reporting 22 cases. Outside of the European Union, Brazil has reported 16, Indonesia has reported 15, and Israel has reported 12.

Among the 11 deaths reported globally, the Uniyed States has reported five, Indonesia has reported five, and Palestine has reported one.

The cause of severe hepatitis remains a mystery, according to Ars Technica. Some cases have been identified retrospectively, dating back to the beginning of October 2021.

About 70% of the cases that have been tested for an adenovirus have tested positive, and subtype testing continues to show adenovirus type 41. The cases don’t appear to be linked to common causes, such as hepatitis viruses A, B, C, D, or E, which can cause liver inflammation and injury.

Adenoviruses aren’t known to cause hepatitis in healthy children, though the viruses have been linked to liver damage in children with compromised immune systems, according to Ars Technica. Adenoviruses typically cause respiratory infections in children, although type 41 tends to cause gastrointestinal illness.

“At present, the leading hypotheses remain those which involve adenovirus,” Philippa Easterbrook, a senior scientist at the WHO, said May 10 during a press briefing.

“I think [there’s] also still an important consideration about the role of COVID as well, either as a co-infection or as a past infection,” she said.

WHO officials expect data within a week from U.K. cases, Ms. Easterbrook said, which may indicate whether the adenovirus is an incidental infection or a more direct cause.

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

The Centers for Disease Control and Prevention updated its recommendations for doctors and public health officials regarding the unusual outbreak of acute hepatitis among children.

As of May 5, the CDC and state health departments are investigating 109 children with hepatitis of unknown origin across 25 states and territories.

More than half have tested positive for adenovirus, the CDC said. More than 90% have been hospitalized, and 14% have had liver transplants. Five deaths are under investigation.

This week’s CDC alert provides updated recommendations for testing, given the potential association between adenovirus infection and pediatric hepatitis, or liver inflammation.

“Clinicians are recommended to consider adenovirus testing for patients with hepatitis of unknown etiology and to report such cases to their state or jurisdictional public health authorities,” the CDC said.

Doctors should also consider collecting a blood sample, respiratory sample, and stool sample. They may also collect liver tissue if a biopsy occurred or an autopsy is available.

In November 2021, clinicians at a large children’s hospital in Alabama notified the CDC about five pediatric patients with significant liver injury, including three with acute liver failure, who also tested positive for adenovirus. All children were previously healthy, and none had COVID-19, according to a CDC alert in April.

Four additional pediatric patients with hepatitis and adenovirus infection were identified. After lab testing found adenovirus infection in all nine patients in the initial cluster, public health officials began investigating a possible association between pediatric hepatitis and adenovirus. Among the five specimens that could be sequenced, they were all adenovirus type 41.

Unexplained hepatitis cases have been reported in children worldwide, reaching 450 cases and 11 deaths, according to the latest update from the European Centre for Disease Prevention and Control.

The cases have been reported in more than two dozen countries around the world, with 14 countries reporting more than five cases. The United Kingdom and the United States have reported the largest case counts so far.

In the United Kingdom, officials have identified 163 cases in children under age 16 years, including 11 that required liver transplants.

In the European Union, 14 countries have reported 106 cases collectively, with Italy reporting 35 cases and Spain reporting 22 cases. Outside of the European Union, Brazil has reported 16, Indonesia has reported 15, and Israel has reported 12.

Among the 11 deaths reported globally, the Uniyed States has reported five, Indonesia has reported five, and Palestine has reported one.

The cause of severe hepatitis remains a mystery, according to Ars Technica. Some cases have been identified retrospectively, dating back to the beginning of October 2021.

About 70% of the cases that have been tested for an adenovirus have tested positive, and subtype testing continues to show adenovirus type 41. The cases don’t appear to be linked to common causes, such as hepatitis viruses A, B, C, D, or E, which can cause liver inflammation and injury.

Adenoviruses aren’t known to cause hepatitis in healthy children, though the viruses have been linked to liver damage in children with compromised immune systems, according to Ars Technica. Adenoviruses typically cause respiratory infections in children, although type 41 tends to cause gastrointestinal illness.

“At present, the leading hypotheses remain those which involve adenovirus,” Philippa Easterbrook, a senior scientist at the WHO, said May 10 during a press briefing.

“I think [there’s] also still an important consideration about the role of COVID as well, either as a co-infection or as a past infection,” she said.

WHO officials expect data within a week from U.K. cases, Ms. Easterbrook said, which may indicate whether the adenovirus is an incidental infection or a more direct cause.

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

A study that tracked psychopathology in 13,000 children and adolescents found that mental health difficulties fluctuate over time, especially in younger children, and those trajectories differ among boys and girls.

Investigators also found a strong correlation between new incidence of high psychopathology and externalizing problems such as hyperactivity. “It is of paramount importance to identify factors that distinguish those with persisting problems and escalating trajectories so that resources can be appropriately directed,” wrote the authors of the study published online in JAMA Network Open.

Recent studies have shown that concurrent and sequential comorbidity of psychiatric disorders are very common in adult populations, lead author Colm Healy, PhD, a postdoctoral researcher for psychiatry with the University of Medicine and Health Sciences, Ireland, said in an interview.

The speculation is that this occurs in early life when psychiatry symptoms experience high fluidity. “This presents a complex scenario to model, where young people’s mental health appears to shift and change across development. Few investigations to date have had the data available to examine these trajectories over the full range of child development,” said Dr. Healy.

He and his colleagues attempted to map the profiles and trajectories of psychopathology in children and adolescents, using latent profile transition analysis (LPTA), a person-centered method, to assess comorbidity and movement in the various phases of childhood development.

“The idea behind person-centered methods such as LTPA is that it identifies unobserved subgroups of participants who respond similarly to specific variables – in this case responses to a broad measure of psychopathology,” explained Dr. Healy.

The study included 7,507 children from the child sample (ages 3, 5, and 9 years) and 6,039 children from the adolescent sample (ages 9, 13, and 17 or 18 years). Data analysis took place from October 2020 to September 2021.

Dr. Healy and colleagues in a supplementary investigation compared cohorts at age 9 years to look for sex and generational differences.
 

Four developmental profiles

Researchers identified 4 distinct developmental profies for person-centered psychopathological trajectories: no psychopathology (incidence range, 60%-70%), high psychopathology (incidence range, 3%-5%), externalizing problems (incidence range, 15%-25%), and internalizing problems (incidence range, 7%-12%).

Internalizing problems reflect issues with peers and emotional problems whereas externalizing problems more closely associate with hyperactivity and conduct.

Less than 5% of the youth studied experienced persistent symptoms. However, 48.6% in the child cohort and 44.1% in the adolescent cohort moved into one of the 3 psychopathology profiles (high psychopathology, externalizing, internalizing problems) at some point in development.

The spread of trajectories was more diverse in the child cohort, said Dr. Healy. “Children ebbed and flowed between the different profiles over time with a large proportion falling into one of the psychopathology categories and then switching between these profiles.” Switching was also evident in the adolescent cohort but to a lesser extent, he said.
 

Externalizing problems link to high psychopathology

Rates of remittance were higher among individuals in both cohorts for internalizing problems, compared with externalizing problems.

It’s possible that for some of these young people, internalizing problems are a reaction to environmental stressors such as bullying,” said Dr. Healy. “When that stress is relieved, the internalizing problems may dissipate.”

In a clinically relevant finding, children with externalizing problems (age 5, 129 [61.3%] and age 9, 95 [74.3%]) were more likely to present with new incidents of high psychopathology. This was also true in the adolescent group (age 13, 129 [91.1%] and age 17, 146 [89.9%]).

This suggests that a proportion of youth with externalizing problems have an escalating trajectory of psychopathology. “Thus, it may be possible to distinguish those with an escalating trajectory from a stable or remitting trajectory. The specific distinguishing factors require further investigation, but it has been observed before that some of those reporting externalizing problems in early life continue to have difficulties into later life,” noted Dr. Healy.

A combination of environmental or biological factors may explain this escalation, which could respond to early intervention, he said.

Overall, few children in the study transitioned directly from no psychopathology to high psychopathology.
 

Differences between boys, girls

In both cohorts, investigators noticed significant differences between the sexes.

Boys in childhood made up a larger proportion of the three psychopathology profiles. But by late adolescence, girls made up a larger proportion of the internalizing profile whereas boys made up a larger proportion of the externalizing profile. “These differences were in line with our expectations,” said Dr. Healy.

Trajectories also differed among boys and girls. In childhood, girls had a higher percentage of de-escalating trajectories relative to boys. “More girls than boys in the psychopathology profiles switched to a non or less severe profile. In adolescence, differences in trajectories were less obvious, with the exception that girls were more likely than boys to transition to internalizing problems from all of the other profiles at age 17,” said Dr. Healy.

Most young people who experience psychopathology will eventually see an improvement in symptoms, noted Dr. Healy. Next steps are to identify markers that distinguish individuals with persistent trajectories from remitting trajectories at the different phases of development, he said.
 

Study draws mixed reviews

Clinical psychiatrists not involved in the study had varying reactions to the results.

“This study is notable for its data-driven and powerful illustration of how childhood and adolescence are dynamic periods during which psychiatric symptoms can emerge and evolve,” said Sunny X. Tang, MD, a psychiatrist and an assistant professor at the Institute of Behavioral Science and the Feinstein Institutes for Medical Research, Manhasset, New York.

The clinical call for action is for person-centered mental health screening to be a routine part of pediatric and adolescent primary care or school-based services, noted Dr. Tang.

Paul S. Nestadt, MD, an assistant professor and public mental health researcher at Johns Hopkins University, Baltimore, did not think the study would have a significant impact on clinical practice.

He noted that Dr. Healy and coauthors found that some children stayed true to type, but many fluctuated between the four profile groups. The finding that fluctuation occurred more frequently in younger children is not surprising “and is consistent with what we know about the ‘moving targets’ that make diagnosing children so difficult,” said Dr. Nestadt.

“It would have been helpful to have identified clinical indicators of likely persistence in psychopathology, but the measure employed here did not allow that. It is also frustrating to not have any information on treatment, such that we cannot know whether the children who shifted to ‘no psychopathology’ did so because of treatment or spontaneously,” he added.

Victor M. Fornari, MD, MS, director of the Division of Child & Adolescent Psychiatry at The Zucker Hillside Hospital and Cohen’s Children’s Medical Center, New York, said the study is an important contribution to understanding the development of psychopathology during childhood.

“Generally, it is felt that nearly one in five youth will meet criteria for at least one psychiatric disorder by the age of 18. It is well known that externalizing disorders like ADHD manifest earlier in childhood and that depression often manifests later in adolescence,” he said.

No disclosures were reported.

A study that tracked psychopathology in 13,000 children and adolescents found that mental health difficulties fluctuate over time, especially in younger children, and those trajectories differ among boys and girls.

Investigators also found a strong correlation between new incidence of high psychopathology and externalizing problems such as hyperactivity. “It is of paramount importance to identify factors that distinguish those with persisting problems and escalating trajectories so that resources can be appropriately directed,” wrote the authors of the study published online in JAMA Network Open.

Recent studies have shown that concurrent and sequential comorbidity of psychiatric disorders are very common in adult populations, lead author Colm Healy, PhD, a postdoctoral researcher for psychiatry with the University of Medicine and Health Sciences, Ireland, said in an interview.

The speculation is that this occurs in early life when psychiatry symptoms experience high fluidity. “This presents a complex scenario to model, where young people’s mental health appears to shift and change across development. Few investigations to date have had the data available to examine these trajectories over the full range of child development,” said Dr. Healy.

He and his colleagues attempted to map the profiles and trajectories of psychopathology in children and adolescents, using latent profile transition analysis (LPTA), a person-centered method, to assess comorbidity and movement in the various phases of childhood development.

“The idea behind person-centered methods such as LTPA is that it identifies unobserved subgroups of participants who respond similarly to specific variables – in this case responses to a broad measure of psychopathology,” explained Dr. Healy.

The study included 7,507 children from the child sample (ages 3, 5, and 9 years) and 6,039 children from the adolescent sample (ages 9, 13, and 17 or 18 years). Data analysis took place from October 2020 to September 2021.

Dr. Healy and colleagues in a supplementary investigation compared cohorts at age 9 years to look for sex and generational differences.
 

Four developmental profiles

Researchers identified 4 distinct developmental profies for person-centered psychopathological trajectories: no psychopathology (incidence range, 60%-70%), high psychopathology (incidence range, 3%-5%), externalizing problems (incidence range, 15%-25%), and internalizing problems (incidence range, 7%-12%).

Internalizing problems reflect issues with peers and emotional problems whereas externalizing problems more closely associate with hyperactivity and conduct.

Less than 5% of the youth studied experienced persistent symptoms. However, 48.6% in the child cohort and 44.1% in the adolescent cohort moved into one of the 3 psychopathology profiles (high psychopathology, externalizing, internalizing problems) at some point in development.

The spread of trajectories was more diverse in the child cohort, said Dr. Healy. “Children ebbed and flowed between the different profiles over time with a large proportion falling into one of the psychopathology categories and then switching between these profiles.” Switching was also evident in the adolescent cohort but to a lesser extent, he said.
 

Externalizing problems link to high psychopathology

Rates of remittance were higher among individuals in both cohorts for internalizing problems, compared with externalizing problems.

It’s possible that for some of these young people, internalizing problems are a reaction to environmental stressors such as bullying,” said Dr. Healy. “When that stress is relieved, the internalizing problems may dissipate.”

In a clinically relevant finding, children with externalizing problems (age 5, 129 [61.3%] and age 9, 95 [74.3%]) were more likely to present with new incidents of high psychopathology. This was also true in the adolescent group (age 13, 129 [91.1%] and age 17, 146 [89.9%]).

This suggests that a proportion of youth with externalizing problems have an escalating trajectory of psychopathology. “Thus, it may be possible to distinguish those with an escalating trajectory from a stable or remitting trajectory. The specific distinguishing factors require further investigation, but it has been observed before that some of those reporting externalizing problems in early life continue to have difficulties into later life,” noted Dr. Healy.

A combination of environmental or biological factors may explain this escalation, which could respond to early intervention, he said.

Overall, few children in the study transitioned directly from no psychopathology to high psychopathology.
 

Differences between boys, girls

In both cohorts, investigators noticed significant differences between the sexes.

Boys in childhood made up a larger proportion of the three psychopathology profiles. But by late adolescence, girls made up a larger proportion of the internalizing profile whereas boys made up a larger proportion of the externalizing profile. “These differences were in line with our expectations,” said Dr. Healy.

Trajectories also differed among boys and girls. In childhood, girls had a higher percentage of de-escalating trajectories relative to boys. “More girls than boys in the psychopathology profiles switched to a non or less severe profile. In adolescence, differences in trajectories were less obvious, with the exception that girls were more likely than boys to transition to internalizing problems from all of the other profiles at age 17,” said Dr. Healy.

Most young people who experience psychopathology will eventually see an improvement in symptoms, noted Dr. Healy. Next steps are to identify markers that distinguish individuals with persistent trajectories from remitting trajectories at the different phases of development, he said.
 

Study draws mixed reviews

Clinical psychiatrists not involved in the study had varying reactions to the results.

“This study is notable for its data-driven and powerful illustration of how childhood and adolescence are dynamic periods during which psychiatric symptoms can emerge and evolve,” said Sunny X. Tang, MD, a psychiatrist and an assistant professor at the Institute of Behavioral Science and the Feinstein Institutes for Medical Research, Manhasset, New York.

The clinical call for action is for person-centered mental health screening to be a routine part of pediatric and adolescent primary care or school-based services, noted Dr. Tang.

Paul S. Nestadt, MD, an assistant professor and public mental health researcher at Johns Hopkins University, Baltimore, did not think the study would have a significant impact on clinical practice.

He noted that Dr. Healy and coauthors found that some children stayed true to type, but many fluctuated between the four profile groups. The finding that fluctuation occurred more frequently in younger children is not surprising “and is consistent with what we know about the ‘moving targets’ that make diagnosing children so difficult,” said Dr. Nestadt.

“It would have been helpful to have identified clinical indicators of likely persistence in psychopathology, but the measure employed here did not allow that. It is also frustrating to not have any information on treatment, such that we cannot know whether the children who shifted to ‘no psychopathology’ did so because of treatment or spontaneously,” he added.

Victor M. Fornari, MD, MS, director of the Division of Child & Adolescent Psychiatry at The Zucker Hillside Hospital and Cohen’s Children’s Medical Center, New York, said the study is an important contribution to understanding the development of psychopathology during childhood.

“Generally, it is felt that nearly one in five youth will meet criteria for at least one psychiatric disorder by the age of 18. It is well known that externalizing disorders like ADHD manifest earlier in childhood and that depression often manifests later in adolescence,” he said.

No disclosures were reported.

A study that tracked psychopathology in 13,000 children and adolescents found that mental health difficulties fluctuate over time, especially in younger children, and those trajectories differ among boys and girls.

Investigators also found a strong correlation between new incidence of high psychopathology and externalizing problems such as hyperactivity. “It is of paramount importance to identify factors that distinguish those with persisting problems and escalating trajectories so that resources can be appropriately directed,” wrote the authors of the study published online in JAMA Network Open.

Recent studies have shown that concurrent and sequential comorbidity of psychiatric disorders are very common in adult populations, lead author Colm Healy, PhD, a postdoctoral researcher for psychiatry with the University of Medicine and Health Sciences, Ireland, said in an interview.

The speculation is that this occurs in early life when psychiatry symptoms experience high fluidity. “This presents a complex scenario to model, where young people’s mental health appears to shift and change across development. Few investigations to date have had the data available to examine these trajectories over the full range of child development,” said Dr. Healy.

He and his colleagues attempted to map the profiles and trajectories of psychopathology in children and adolescents, using latent profile transition analysis (LPTA), a person-centered method, to assess comorbidity and movement in the various phases of childhood development.

“The idea behind person-centered methods such as LTPA is that it identifies unobserved subgroups of participants who respond similarly to specific variables – in this case responses to a broad measure of psychopathology,” explained Dr. Healy.

The study included 7,507 children from the child sample (ages 3, 5, and 9 years) and 6,039 children from the adolescent sample (ages 9, 13, and 17 or 18 years). Data analysis took place from October 2020 to September 2021.

Dr. Healy and colleagues in a supplementary investigation compared cohorts at age 9 years to look for sex and generational differences.
 

Four developmental profiles

Researchers identified 4 distinct developmental profies for person-centered psychopathological trajectories: no psychopathology (incidence range, 60%-70%), high psychopathology (incidence range, 3%-5%), externalizing problems (incidence range, 15%-25%), and internalizing problems (incidence range, 7%-12%).

Internalizing problems reflect issues with peers and emotional problems whereas externalizing problems more closely associate with hyperactivity and conduct.

Less than 5% of the youth studied experienced persistent symptoms. However, 48.6% in the child cohort and 44.1% in the adolescent cohort moved into one of the 3 psychopathology profiles (high psychopathology, externalizing, internalizing problems) at some point in development.

The spread of trajectories was more diverse in the child cohort, said Dr. Healy. “Children ebbed and flowed between the different profiles over time with a large proportion falling into one of the psychopathology categories and then switching between these profiles.” Switching was also evident in the adolescent cohort but to a lesser extent, he said.
 

Externalizing problems link to high psychopathology

Rates of remittance were higher among individuals in both cohorts for internalizing problems, compared with externalizing problems.

It’s possible that for some of these young people, internalizing problems are a reaction to environmental stressors such as bullying,” said Dr. Healy. “When that stress is relieved, the internalizing problems may dissipate.”

In a clinically relevant finding, children with externalizing problems (age 5, 129 [61.3%] and age 9, 95 [74.3%]) were more likely to present with new incidents of high psychopathology. This was also true in the adolescent group (age 13, 129 [91.1%] and age 17, 146 [89.9%]).

This suggests that a proportion of youth with externalizing problems have an escalating trajectory of psychopathology. “Thus, it may be possible to distinguish those with an escalating trajectory from a stable or remitting trajectory. The specific distinguishing factors require further investigation, but it has been observed before that some of those reporting externalizing problems in early life continue to have difficulties into later life,” noted Dr. Healy.

A combination of environmental or biological factors may explain this escalation, which could respond to early intervention, he said.

Overall, few children in the study transitioned directly from no psychopathology to high psychopathology.
 

Differences between boys, girls

In both cohorts, investigators noticed significant differences between the sexes.

Boys in childhood made up a larger proportion of the three psychopathology profiles. But by late adolescence, girls made up a larger proportion of the internalizing profile whereas boys made up a larger proportion of the externalizing profile. “These differences were in line with our expectations,” said Dr. Healy.

Trajectories also differed among boys and girls. In childhood, girls had a higher percentage of de-escalating trajectories relative to boys. “More girls than boys in the psychopathology profiles switched to a non or less severe profile. In adolescence, differences in trajectories were less obvious, with the exception that girls were more likely than boys to transition to internalizing problems from all of the other profiles at age 17,” said Dr. Healy.

Most young people who experience psychopathology will eventually see an improvement in symptoms, noted Dr. Healy. Next steps are to identify markers that distinguish individuals with persistent trajectories from remitting trajectories at the different phases of development, he said.
 

Study draws mixed reviews

Clinical psychiatrists not involved in the study had varying reactions to the results.

“This study is notable for its data-driven and powerful illustration of how childhood and adolescence are dynamic periods during which psychiatric symptoms can emerge and evolve,” said Sunny X. Tang, MD, a psychiatrist and an assistant professor at the Institute of Behavioral Science and the Feinstein Institutes for Medical Research, Manhasset, New York.

The clinical call for action is for person-centered mental health screening to be a routine part of pediatric and adolescent primary care or school-based services, noted Dr. Tang.

Paul S. Nestadt, MD, an assistant professor and public mental health researcher at Johns Hopkins University, Baltimore, did not think the study would have a significant impact on clinical practice.

He noted that Dr. Healy and coauthors found that some children stayed true to type, but many fluctuated between the four profile groups. The finding that fluctuation occurred more frequently in younger children is not surprising “and is consistent with what we know about the ‘moving targets’ that make diagnosing children so difficult,” said Dr. Nestadt.

“It would have been helpful to have identified clinical indicators of likely persistence in psychopathology, but the measure employed here did not allow that. It is also frustrating to not have any information on treatment, such that we cannot know whether the children who shifted to ‘no psychopathology’ did so because of treatment or spontaneously,” he added.

Victor M. Fornari, MD, MS, director of the Division of Child & Adolescent Psychiatry at The Zucker Hillside Hospital and Cohen’s Children’s Medical Center, New York, said the study is an important contribution to understanding the development of psychopathology during childhood.

“Generally, it is felt that nearly one in five youth will meet criteria for at least one psychiatric disorder by the age of 18. It is well known that externalizing disorders like ADHD manifest earlier in childhood and that depression often manifests later in adolescence,” he said.

No disclosures were reported.

The U.S. immunization program is one of the best public health success stories. Physicians who provide care for children are familiar with the routine childhood immunization schedule and administer a measles-containing vaccine at age-appropriate times. Thanks to its rigorous implementation and acceptance, endemic measles (absence of continuous virus transmission for > 1 year) was eliminated in the U.S. in 2000. Loss of this status was in jeopardy in 2019 when 22 measles outbreaks occurred in 17 states (7 were multistate outbreaks). That year, 1,163 cases were reported.¹ Most cases occurred in unvaccinated persons (89%) and 81 cases were imported of which 54 were in U.S. citizens returning from international travel. All outbreaks were linked to travel. Fortunately, the outbreaks were controlled prior to the elimination deadline, or the United States would have lost its measles elimination status. Restrictions on travel because of COVID-19 have relaxed significantly since the introduction of COVID-19 vaccines, resulting in increased regional and international travel. Multiple countries, including the United States noted a decline in routine immunizations rates during the last 2 years. Recent U.S. data for the 2020-2021 school year indicates that MMR immunizations rates (two doses) for kindergarteners declined to 93.9% (range 78.9% to > 98.9%), while the overall percentage of those students with an exemption remained low at 2.2%. Vaccine coverage greater than 95% was reported in only 16 states. Coverage of less than 90% was reported in seven states and the District of Columbia (Georgia, Idaho, Kentucky, Maryland, Minnesota, Ohio, and Wisconsin).² Vaccine coverage should be 95% or higher to maintain herd immunity and control outbreaks.

Why is measles prevention so important? Many physicians practicing in the United States today have never seen a case or know its potential complications. I saw my first case as a resident in an immigrant child. It took our training director to point out the subtle signs and symptoms. It was the first time I saw Kolpik spots. Measles is transmitted person to person via large respiratory droplets and less often by airborne spread. It is highly contagious for susceptible individuals with an attack rate of 90%. In this case, a medical student on the team developed symptoms about 10 days later. Six years would pass before I diagnosed my next case of measles. An HIV patient acquired it after close contact with someone who was in the prodromal stage. He presented with the 3 C’s: Cough, coryza, and conjunctivitis, in addition to fever and an erythematous rash. He did not recover from complications of the disease.

Prior to the routine administration of a measles vaccine, 3-4 million cases with almost 500 deaths occurred annually in the United States. Worldwide, 35 million cases and more than 6 million deaths occurred each year. Here, most patients recover completely; however, complications including otitis media, pneumonia, croup, and encephalitis can develop. Complications commonly occur in immunocompromised individuals and young children. Groups with the highest fatality rates include children aged less than 5 years, immunocompromised persons, and pregnant women. Worldwide, fatality rates are dependent on the patients underlying nutritional and health status in addition to the quality of health care available.³

Measles vaccine was licensed in 1963 and cases began to decline (Figure 1). There was a resurgence in 1989 but it was not limited to the United States. The cause of the U.S. resurgence was multifactorial: Widespread viral transmission among unvaccinated preschool-age children residing in inner cities, outbreaks in vaccinated school-age children, outbreaks in students and personnel on college campuses, and primary vaccine failure (2%-5% of recipients failed to have an adequate response). In 1989, to help prevent future outbreaks, the United States recommended a two-dose schedule for measles and in 1993, the Vaccines for Children Program, a federally funded program, was established to improve access to vaccines for all children.
 

What is going on internationally?

Figure 2 lists the top 10 countries with current measles outbreaks.

Most countries on the list may not be typical travel destinations for tourists; however, they are common destinations for individuals visiting friends and relatives after immigrating to the United States. In contrast to the United States, most countries with limited resources and infrastructure have mass-vaccination campaigns to ensure vaccine administration to large segments of the population. They too have been affected by the COVID-19 pandemic. By report, at least 41 countries delayed implementation of their measles campaign in 2020 and 2021, thus, leading to the potential for even larger outbreaks.⁴

Progress toward the global elimination of measles is evidenced by the following: All 194 countries now include one dose of measles in their routine schedules; between 2000 and 2019 coverage of one dose of measles increased from 72% to 85% and countries with more than 90% coverage increased from 45% to 63%. Finally, the number of countries offering two doses of measles increased from 50% to 91% and vaccine coverage increased from 18% to 71% over the same time period.³

What can you do for your patients and their parents before they travel abroad?

• Inform all staff that the MMR vaccine can be administered to children as young as 6 months and at times other than those listed on the routine immunization schedule. This will help avoid parents seeking vaccine being denied an appointment.
• Children 6-11 months need 1 dose of MMR. Two additional doses will still need to be administered at the routine time.
• Children 12 months or older need 2 doses of MMR at least 4 weeks apart.
• If yellow fever vaccine is needed, coordinate administration with a travel medicine clinic since both are live vaccines and must be given on the same day.
• Any person born after 1956 should have 2 doses of MMR at least 4 weeks apart if they have no evidence of immunity.
• Encourage parents to always inform you and your staff of any international travel plans.

Moving forward, remember this increased global activity and the presence of inadequately vaccinated individuals/communities keeps the United States at continued risk for measles outbreaks. The source of the next outbreak may only be one plane ride away.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures.

This article was updated 6/29/22.

References

1. Patel M et al. MMWR. 2019 Oct 11; 68(40):893-6.

2. Seither R et al. MMWR. 2022 Apr 22;71(16):561-8.

3. Gastañaduy PA et al. J Infect Dis. 2021 Sep 30;224(12 Suppl 2):S420-8. doi: 10.1093/infdis/jiaa793.

4. Centers for Disease Control and Prevention. Measles (Rubeola). http://www.CDC.gov/Measles.

The U.S. immunization program is one of the best public health success stories. Physicians who provide care for children are familiar with the routine childhood immunization schedule and administer a measles-containing vaccine at age-appropriate times. Thanks to its rigorous implementation and acceptance, endemic measles (absence of continuous virus transmission for > 1 year) was eliminated in the U.S. in 2000. Loss of this status was in jeopardy in 2019 when 22 measles outbreaks occurred in 17 states (7 were multistate outbreaks). That year, 1,163 cases were reported.¹ Most cases occurred in unvaccinated persons (89%) and 81 cases were imported of which 54 were in U.S. citizens returning from international travel. All outbreaks were linked to travel. Fortunately, the outbreaks were controlled prior to the elimination deadline, or the United States would have lost its measles elimination status. Restrictions on travel because of COVID-19 have relaxed significantly since the introduction of COVID-19 vaccines, resulting in increased regional and international travel. Multiple countries, including the United States noted a decline in routine immunizations rates during the last 2 years. Recent U.S. data for the 2020-2021 school year indicates that MMR immunizations rates (two doses) for kindergarteners declined to 93.9% (range 78.9% to > 98.9%), while the overall percentage of those students with an exemption remained low at 2.2%. Vaccine coverage greater than 95% was reported in only 16 states. Coverage of less than 90% was reported in seven states and the District of Columbia (Georgia, Idaho, Kentucky, Maryland, Minnesota, Ohio, and Wisconsin).² Vaccine coverage should be 95% or higher to maintain herd immunity and control outbreaks.

Why is measles prevention so important? Many physicians practicing in the United States today have never seen a case or know its potential complications. I saw my first case as a resident in an immigrant child. It took our training director to point out the subtle signs and symptoms. It was the first time I saw Kolpik spots. Measles is transmitted person to person via large respiratory droplets and less often by airborne spread. It is highly contagious for susceptible individuals with an attack rate of 90%. In this case, a medical student on the team developed symptoms about 10 days later. Six years would pass before I diagnosed my next case of measles. An HIV patient acquired it after close contact with someone who was in the prodromal stage. He presented with the 3 C’s: Cough, coryza, and conjunctivitis, in addition to fever and an erythematous rash. He did not recover from complications of the disease.

Prior to the routine administration of a measles vaccine, 3-4 million cases with almost 500 deaths occurred annually in the United States. Worldwide, 35 million cases and more than 6 million deaths occurred each year. Here, most patients recover completely; however, complications including otitis media, pneumonia, croup, and encephalitis can develop. Complications commonly occur in immunocompromised individuals and young children. Groups with the highest fatality rates include children aged less than 5 years, immunocompromised persons, and pregnant women. Worldwide, fatality rates are dependent on the patients underlying nutritional and health status in addition to the quality of health care available.³

Measles vaccine was licensed in 1963 and cases began to decline (Figure 1). There was a resurgence in 1989 but it was not limited to the United States. The cause of the U.S. resurgence was multifactorial: Widespread viral transmission among unvaccinated preschool-age children residing in inner cities, outbreaks in vaccinated school-age children, outbreaks in students and personnel on college campuses, and primary vaccine failure (2%-5% of recipients failed to have an adequate response). In 1989, to help prevent future outbreaks, the United States recommended a two-dose schedule for measles and in 1993, the Vaccines for Children Program, a federally funded program, was established to improve access to vaccines for all children.
 

What is going on internationally?

Figure 2 lists the top 10 countries with current measles outbreaks.

Most countries on the list may not be typical travel destinations for tourists; however, they are common destinations for individuals visiting friends and relatives after immigrating to the United States. In contrast to the United States, most countries with limited resources and infrastructure have mass-vaccination campaigns to ensure vaccine administration to large segments of the population. They too have been affected by the COVID-19 pandemic. By report, at least 41 countries delayed implementation of their measles campaign in 2020 and 2021, thus, leading to the potential for even larger outbreaks.⁴

Progress toward the global elimination of measles is evidenced by the following: All 194 countries now include one dose of measles in their routine schedules; between 2000 and 2019 coverage of one dose of measles increased from 72% to 85% and countries with more than 90% coverage increased from 45% to 63%. Finally, the number of countries offering two doses of measles increased from 50% to 91% and vaccine coverage increased from 18% to 71% over the same time period.³

What can you do for your patients and their parents before they travel abroad?

• Inform all staff that the MMR vaccine can be administered to children as young as 6 months and at times other than those listed on the routine immunization schedule. This will help avoid parents seeking vaccine being denied an appointment.
• Children 6-11 months need 1 dose of MMR. Two additional doses will still need to be administered at the routine time.
• Children 12 months or older need 2 doses of MMR at least 4 weeks apart.
• If yellow fever vaccine is needed, coordinate administration with a travel medicine clinic since both are live vaccines and must be given on the same day.
• Any person born after 1956 should have 2 doses of MMR at least 4 weeks apart if they have no evidence of immunity.
• Encourage parents to always inform you and your staff of any international travel plans.

Moving forward, remember this increased global activity and the presence of inadequately vaccinated individuals/communities keeps the United States at continued risk for measles outbreaks. The source of the next outbreak may only be one plane ride away.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures.

This article was updated 6/29/22.

References

1. Patel M et al. MMWR. 2019 Oct 11; 68(40):893-6.

2. Seither R et al. MMWR. 2022 Apr 22;71(16):561-8.

3. Gastañaduy PA et al. J Infect Dis. 2021 Sep 30;224(12 Suppl 2):S420-8. doi: 10.1093/infdis/jiaa793.

4. Centers for Disease Control and Prevention. Measles (Rubeola). http://www.CDC.gov/Measles.

The U.S. immunization program is one of the best public health success stories. Physicians who provide care for children are familiar with the routine childhood immunization schedule and administer a measles-containing vaccine at age-appropriate times. Thanks to its rigorous implementation and acceptance, endemic measles (absence of continuous virus transmission for > 1 year) was eliminated in the U.S. in 2000. Loss of this status was in jeopardy in 2019 when 22 measles outbreaks occurred in 17 states (7 were multistate outbreaks). That year, 1,163 cases were reported.¹ Most cases occurred in unvaccinated persons (89%) and 81 cases were imported of which 54 were in U.S. citizens returning from international travel. All outbreaks were linked to travel. Fortunately, the outbreaks were controlled prior to the elimination deadline, or the United States would have lost its measles elimination status. Restrictions on travel because of COVID-19 have relaxed significantly since the introduction of COVID-19 vaccines, resulting in increased regional and international travel. Multiple countries, including the United States noted a decline in routine immunizations rates during the last 2 years. Recent U.S. data for the 2020-2021 school year indicates that MMR immunizations rates (two doses) for kindergarteners declined to 93.9% (range 78.9% to > 98.9%), while the overall percentage of those students with an exemption remained low at 2.2%. Vaccine coverage greater than 95% was reported in only 16 states. Coverage of less than 90% was reported in seven states and the District of Columbia (Georgia, Idaho, Kentucky, Maryland, Minnesota, Ohio, and Wisconsin).² Vaccine coverage should be 95% or higher to maintain herd immunity and control outbreaks.

Why is measles prevention so important? Many physicians practicing in the United States today have never seen a case or know its potential complications. I saw my first case as a resident in an immigrant child. It took our training director to point out the subtle signs and symptoms. It was the first time I saw Kolpik spots. Measles is transmitted person to person via large respiratory droplets and less often by airborne spread. It is highly contagious for susceptible individuals with an attack rate of 90%. In this case, a medical student on the team developed symptoms about 10 days later. Six years would pass before I diagnosed my next case of measles. An HIV patient acquired it after close contact with someone who was in the prodromal stage. He presented with the 3 C’s: Cough, coryza, and conjunctivitis, in addition to fever and an erythematous rash. He did not recover from complications of the disease.

Prior to the routine administration of a measles vaccine, 3-4 million cases with almost 500 deaths occurred annually in the United States. Worldwide, 35 million cases and more than 6 million deaths occurred each year. Here, most patients recover completely; however, complications including otitis media, pneumonia, croup, and encephalitis can develop. Complications commonly occur in immunocompromised individuals and young children. Groups with the highest fatality rates include children aged less than 5 years, immunocompromised persons, and pregnant women. Worldwide, fatality rates are dependent on the patients underlying nutritional and health status in addition to the quality of health care available.³

Measles vaccine was licensed in 1963 and cases began to decline (Figure 1). There was a resurgence in 1989 but it was not limited to the United States. The cause of the U.S. resurgence was multifactorial: Widespread viral transmission among unvaccinated preschool-age children residing in inner cities, outbreaks in vaccinated school-age children, outbreaks in students and personnel on college campuses, and primary vaccine failure (2%-5% of recipients failed to have an adequate response). In 1989, to help prevent future outbreaks, the United States recommended a two-dose schedule for measles and in 1993, the Vaccines for Children Program, a federally funded program, was established to improve access to vaccines for all children.
 

What is going on internationally?

Figure 2 lists the top 10 countries with current measles outbreaks.

Most countries on the list may not be typical travel destinations for tourists; however, they are common destinations for individuals visiting friends and relatives after immigrating to the United States. In contrast to the United States, most countries with limited resources and infrastructure have mass-vaccination campaigns to ensure vaccine administration to large segments of the population. They too have been affected by the COVID-19 pandemic. By report, at least 41 countries delayed implementation of their measles campaign in 2020 and 2021, thus, leading to the potential for even larger outbreaks.⁴

Progress toward the global elimination of measles is evidenced by the following: All 194 countries now include one dose of measles in their routine schedules; between 2000 and 2019 coverage of one dose of measles increased from 72% to 85% and countries with more than 90% coverage increased from 45% to 63%. Finally, the number of countries offering two doses of measles increased from 50% to 91% and vaccine coverage increased from 18% to 71% over the same time period.³

What can you do for your patients and their parents before they travel abroad?

• Inform all staff that the MMR vaccine can be administered to children as young as 6 months and at times other than those listed on the routine immunization schedule. This will help avoid parents seeking vaccine being denied an appointment.
• Children 6-11 months need 1 dose of MMR. Two additional doses will still need to be administered at the routine time.
• Children 12 months or older need 2 doses of MMR at least 4 weeks apart.
• If yellow fever vaccine is needed, coordinate administration with a travel medicine clinic since both are live vaccines and must be given on the same day.
• Any person born after 1956 should have 2 doses of MMR at least 4 weeks apart if they have no evidence of immunity.
• Encourage parents to always inform you and your staff of any international travel plans.

Moving forward, remember this increased global activity and the presence of inadequately vaccinated individuals/communities keeps the United States at continued risk for measles outbreaks. The source of the next outbreak may only be one plane ride away.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures.

This article was updated 6/29/22.

References

1. Patel M et al. MMWR. 2019 Oct 11; 68(40):893-6.

2. Seither R et al. MMWR. 2022 Apr 22;71(16):561-8.

3. Gastañaduy PA et al. J Infect Dis. 2021 Sep 30;224(12 Suppl 2):S420-8. doi: 10.1093/infdis/jiaa793.

4. Centers for Disease Control and Prevention. Measles (Rubeola). http://www.CDC.gov/Measles.

Reduced levels of the cholinergic-system enzyme butyrylcholinesterase (BChE) may provide another piece of the puzzle for sudden infant death syndrome (SIDS), preliminary data from Australian researchers suggested.

A small case-control study led by Carmel T. Harrington, PhD,* a sleep medicine expert and honorary research fellow at the Children’s Hospital at Westmead (Australia), found that measurements in 722 dried blood spots taken during neonatal screening 2 or 3 days after birth were lower in babies who subsequently died of SIDS, compared with those of matched surviving controls and other babies who died of non-SIDS causes.

* This story was corrected on 5/20/2022.

Reduced levels of the cholinergic-system enzyme butyrylcholinesterase (BChE) may provide another piece of the puzzle for sudden infant death syndrome (SIDS), preliminary data from Australian researchers suggested.

A small case-control study led by Carmel T. Harrington, PhD,* a sleep medicine expert and honorary research fellow at the Children’s Hospital at Westmead (Australia), found that measurements in 722 dried blood spots taken during neonatal screening 2 or 3 days after birth were lower in babies who subsequently died of SIDS, compared with those of matched surviving controls and other babies who died of non-SIDS causes.

* This story was corrected on 5/20/2022.

Reduced levels of the cholinergic-system enzyme butyrylcholinesterase (BChE) may provide another piece of the puzzle for sudden infant death syndrome (SIDS), preliminary data from Australian researchers suggested.

A small case-control study led by Carmel T. Harrington, PhD,* a sleep medicine expert and honorary research fellow at the Children’s Hospital at Westmead (Australia), found that measurements in 722 dried blood spots taken during neonatal screening 2 or 3 days after birth were lower in babies who subsequently died of SIDS, compared with those of matched surviving controls and other babies who died of non-SIDS causes.

* This story was corrected on 5/20/2022.

All patients with idiopathic inflammatory myopathies (IIM) should be screened for swallowing difficulties, according to the first evidence-based guideline to be produced.

The guideline, which has been developed by a working group of the British Society for Rheumatology (BSR), also advises that all diagnosed patients should have their myositis antibody levels checked and have their overall well-being assessed. Other recommendations for all patients include the use of glucocorticoids to reduce muscle inflammation and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for long-term treatment.

“Finally, now, we’re able to standardize the way we treat adults and children with IIM,” senior guideline author Hector Chinoy, PhD, said at the society’s annual meeting.

It has been a long labor of love, however, taking 4 years to get the guideline published, said Dr. Chinoy, professor of rheumatology and neuromuscular disease at the University of Manchester (England), and a consultant at Salford (England) Royal Hospital.

“We’re not covering diagnosis, classification, or the investigation of suspected IIM,” said Dr. Chinoy. Inclusion body myositis also is not included.

Altogether, there are 13 recommendations that have been developed using a PICO (patient or population, intervention, comparison, outcome) format, graded based on the quality of the available evidence, and then voted on by the working group members to give a score of the strength of agreement. Dr. Chinoy noted that there was a checklist included in the Supplementary Data section of the guideline to help follow the recommendations.

“The target audience for the guideline reflects the variety of clinicians caring for patients with IIM,” Dr. Chinoy said. So that is not just pediatric and adult rheumatologists, but also neurologists, dermatologists, respiratory physicians, oncologists, gastroenterologists, cardiologists, and of course other health care professionals. This includes rheumatology and neurology nurses, psychologists, speech and language therapists, and podiatrists, as well as rheumatology specialist pharmacists, physiotherapists, and occupational therapists.

With reference to the latter, Liza McCann, MBBS, who co-led the development of the guideline, said in a statement released by the BSR that the guideline “highlights the importance of exercise, led and monitored by specialist physiotherapists and occupational therapists.”

Dr. McCann, a consultant pediatric rheumatologist at Alder Hey Hospital, Liverpool, England, and Honorary Clinical Lecturer at the University of Liverpool, added that the guidelines also cover “the need to address psychological wellbeing as an integral part of treatment, in parallel with pharmacological therapies.”

Recommendation highlights

Some of the highlights of the recommendations include the use of high-dose glucocorticoids to manage skeletal muscle inflammation at the time of treatment induction, with specific guidance on the different doses to use in adults and in children. There also is guidance on the use of csDMARDs in both populations and what to use if there is refractory disease – with the strongest evidence supporting the use of intravenous immunoglobulin (IVIG) or cyclophosphamide, and possibly rituximab and abatacept.

“There is insufficient evidence to recommend JAK inhibition,” Dr. Chinoy said. The data search used to develop the guideline had a cutoff of October 2020, but even now there is only anecdotal evidence from case studies, he added.

Importantly, the guidelines recognize that childhood IIM differs from adult disease and call for children to be managed by pediatric specialists.

“Routine assessment of dysphagia should be considered in all patients,” Dr. Chinoy said, “so ask the question.” The recommendation is that a swallowing assessment should involve a speech and language therapist or gastroenterologist, and that IVIG be considered for active disease and dysphagia that is resistant to other treatments.

There also are recommendations to screen adult patients for interstitial lung disease, consider fracture risk, and screen adult patients for cancer if they have specific risk factors that include older age at onset, male gender, dysphagia, and rapid disease onset, among others.
 

Separate cancer screening guidelines on cards

“Around one in four patients with myositis will develop cancer within the 3 years either before or after myositis onset,” Alexander Oldroyd, MBChB, PhD, said in a separate presentation at the BSR annual meeting.

“It’s a hugely increased risk compared to the general population, and a great worry for patients,” he added. Exactly why there is an increased risk is not known, but “there’s a big link between the biological onset of cancer and myositis.”

Dr. Oldroyd, who is an NIHR Academic Clinical Lecturer at the University of Manchester in England and a coauthor of the BSR myositis guideline, is part of a special interest group set up by the International Myositis Assessment and Clinical Studies Group (IMACS) that is in the process of developing separate guidelines for cancer screening in people newly diagnosed with IIM.

The aim was to produce evidence-based recommendations that were both “pragmatic and practical,” that could help clinicians answer patient’s questions on their risk and how best and how often to screen them, Dr. Oldroyd explained. Importantly, IMACS has endeavored to create recommendations that should be applicable across different countries and health care systems.

“We had to acknowledge that there’s not a lot of evidence base there,” Dr. Oldroyd said, noting that he and colleagues conducted a systematic literature review and meta-analysis and used a Delphi process to draft 20 recommendations. These cover identifying risk factors for cancer in people with myositis and categorizing people into low, medium, and high-risk categories. The recommendations also cover what should constitute basic and enhanced screening, and how often someone should be screened.

Moreover, the authors make recommendations on the use of imaging modalities such as PET and CT scans, as well as upper and lower gastrointestinal endoscopy and naso-endoscopy.

“As rheumatologists, we don’t talk about cancer a lot,” Dr. Oldroyd said. “We pick up a lot of incidental cancers, but we don’t usually talk about cancer screening with patients.” That’s something that needs to change, he said.

“It’s important – just get it out in the open, talk to people about it,” Dr. Oldroyd said.

“Tell them what you’re wanting to do, how you’re wanting to investigate for it, clearly communicate their risk,” he said. “But also acknowledge the limited evidence as well, and clearly communicate the results.”

Dr. Chinoy acknowledged he had received fees for presentations (UCB, Biogen), consultancy (Alexion, Novartis, Eli Lilly, Orphazyme, AstraZeneca), or grant support (Eli Lilly, UCB) that had been paid via his institution for the purpose of furthering myositis research. Dr. Oldroyd had no conflicts of interest to disclose.

All patients with idiopathic inflammatory myopathies (IIM) should be screened for swallowing difficulties, according to the first evidence-based guideline to be produced.

The guideline, which has been developed by a working group of the British Society for Rheumatology (BSR), also advises that all diagnosed patients should have their myositis antibody levels checked and have their overall well-being assessed. Other recommendations for all patients include the use of glucocorticoids to reduce muscle inflammation and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for long-term treatment.

“Finally, now, we’re able to standardize the way we treat adults and children with IIM,” senior guideline author Hector Chinoy, PhD, said at the society’s annual meeting.

It has been a long labor of love, however, taking 4 years to get the guideline published, said Dr. Chinoy, professor of rheumatology and neuromuscular disease at the University of Manchester (England), and a consultant at Salford (England) Royal Hospital.

“We’re not covering diagnosis, classification, or the investigation of suspected IIM,” said Dr. Chinoy. Inclusion body myositis also is not included.

Altogether, there are 13 recommendations that have been developed using a PICO (patient or population, intervention, comparison, outcome) format, graded based on the quality of the available evidence, and then voted on by the working group members to give a score of the strength of agreement. Dr. Chinoy noted that there was a checklist included in the Supplementary Data section of the guideline to help follow the recommendations.

“The target audience for the guideline reflects the variety of clinicians caring for patients with IIM,” Dr. Chinoy said. So that is not just pediatric and adult rheumatologists, but also neurologists, dermatologists, respiratory physicians, oncologists, gastroenterologists, cardiologists, and of course other health care professionals. This includes rheumatology and neurology nurses, psychologists, speech and language therapists, and podiatrists, as well as rheumatology specialist pharmacists, physiotherapists, and occupational therapists.

With reference to the latter, Liza McCann, MBBS, who co-led the development of the guideline, said in a statement released by the BSR that the guideline “highlights the importance of exercise, led and monitored by specialist physiotherapists and occupational therapists.”

Dr. McCann, a consultant pediatric rheumatologist at Alder Hey Hospital, Liverpool, England, and Honorary Clinical Lecturer at the University of Liverpool, added that the guidelines also cover “the need to address psychological wellbeing as an integral part of treatment, in parallel with pharmacological therapies.”

Recommendation highlights

Some of the highlights of the recommendations include the use of high-dose glucocorticoids to manage skeletal muscle inflammation at the time of treatment induction, with specific guidance on the different doses to use in adults and in children. There also is guidance on the use of csDMARDs in both populations and what to use if there is refractory disease – with the strongest evidence supporting the use of intravenous immunoglobulin (IVIG) or cyclophosphamide, and possibly rituximab and abatacept.

“There is insufficient evidence to recommend JAK inhibition,” Dr. Chinoy said. The data search used to develop the guideline had a cutoff of October 2020, but even now there is only anecdotal evidence from case studies, he added.

Importantly, the guidelines recognize that childhood IIM differs from adult disease and call for children to be managed by pediatric specialists.

“Routine assessment of dysphagia should be considered in all patients,” Dr. Chinoy said, “so ask the question.” The recommendation is that a swallowing assessment should involve a speech and language therapist or gastroenterologist, and that IVIG be considered for active disease and dysphagia that is resistant to other treatments.

There also are recommendations to screen adult patients for interstitial lung disease, consider fracture risk, and screen adult patients for cancer if they have specific risk factors that include older age at onset, male gender, dysphagia, and rapid disease onset, among others.
 

Separate cancer screening guidelines on cards

“Around one in four patients with myositis will develop cancer within the 3 years either before or after myositis onset,” Alexander Oldroyd, MBChB, PhD, said in a separate presentation at the BSR annual meeting.

“It’s a hugely increased risk compared to the general population, and a great worry for patients,” he added. Exactly why there is an increased risk is not known, but “there’s a big link between the biological onset of cancer and myositis.”

Dr. Oldroyd, who is an NIHR Academic Clinical Lecturer at the University of Manchester in England and a coauthor of the BSR myositis guideline, is part of a special interest group set up by the International Myositis Assessment and Clinical Studies Group (IMACS) that is in the process of developing separate guidelines for cancer screening in people newly diagnosed with IIM.

The aim was to produce evidence-based recommendations that were both “pragmatic and practical,” that could help clinicians answer patient’s questions on their risk and how best and how often to screen them, Dr. Oldroyd explained. Importantly, IMACS has endeavored to create recommendations that should be applicable across different countries and health care systems.

“We had to acknowledge that there’s not a lot of evidence base there,” Dr. Oldroyd said, noting that he and colleagues conducted a systematic literature review and meta-analysis and used a Delphi process to draft 20 recommendations. These cover identifying risk factors for cancer in people with myositis and categorizing people into low, medium, and high-risk categories. The recommendations also cover what should constitute basic and enhanced screening, and how often someone should be screened.

Moreover, the authors make recommendations on the use of imaging modalities such as PET and CT scans, as well as upper and lower gastrointestinal endoscopy and naso-endoscopy.

“As rheumatologists, we don’t talk about cancer a lot,” Dr. Oldroyd said. “We pick up a lot of incidental cancers, but we don’t usually talk about cancer screening with patients.” That’s something that needs to change, he said.

“It’s important – just get it out in the open, talk to people about it,” Dr. Oldroyd said.

“Tell them what you’re wanting to do, how you’re wanting to investigate for it, clearly communicate their risk,” he said. “But also acknowledge the limited evidence as well, and clearly communicate the results.”

Dr. Chinoy acknowledged he had received fees for presentations (UCB, Biogen), consultancy (Alexion, Novartis, Eli Lilly, Orphazyme, AstraZeneca), or grant support (Eli Lilly, UCB) that had been paid via his institution for the purpose of furthering myositis research. Dr. Oldroyd had no conflicts of interest to disclose.

All patients with idiopathic inflammatory myopathies (IIM) should be screened for swallowing difficulties, according to the first evidence-based guideline to be produced.

The guideline, which has been developed by a working group of the British Society for Rheumatology (BSR), also advises that all diagnosed patients should have their myositis antibody levels checked and have their overall well-being assessed. Other recommendations for all patients include the use of glucocorticoids to reduce muscle inflammation and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for long-term treatment.

“Finally, now, we’re able to standardize the way we treat adults and children with IIM,” senior guideline author Hector Chinoy, PhD, said at the society’s annual meeting.

It has been a long labor of love, however, taking 4 years to get the guideline published, said Dr. Chinoy, professor of rheumatology and neuromuscular disease at the University of Manchester (England), and a consultant at Salford (England) Royal Hospital.

“We’re not covering diagnosis, classification, or the investigation of suspected IIM,” said Dr. Chinoy. Inclusion body myositis also is not included.

Altogether, there are 13 recommendations that have been developed using a PICO (patient or population, intervention, comparison, outcome) format, graded based on the quality of the available evidence, and then voted on by the working group members to give a score of the strength of agreement. Dr. Chinoy noted that there was a checklist included in the Supplementary Data section of the guideline to help follow the recommendations.

“The target audience for the guideline reflects the variety of clinicians caring for patients with IIM,” Dr. Chinoy said. So that is not just pediatric and adult rheumatologists, but also neurologists, dermatologists, respiratory physicians, oncologists, gastroenterologists, cardiologists, and of course other health care professionals. This includes rheumatology and neurology nurses, psychologists, speech and language therapists, and podiatrists, as well as rheumatology specialist pharmacists, physiotherapists, and occupational therapists.

With reference to the latter, Liza McCann, MBBS, who co-led the development of the guideline, said in a statement released by the BSR that the guideline “highlights the importance of exercise, led and monitored by specialist physiotherapists and occupational therapists.”

Dr. McCann, a consultant pediatric rheumatologist at Alder Hey Hospital, Liverpool, England, and Honorary Clinical Lecturer at the University of Liverpool, added that the guidelines also cover “the need to address psychological wellbeing as an integral part of treatment, in parallel with pharmacological therapies.”

Recommendation highlights

Some of the highlights of the recommendations include the use of high-dose glucocorticoids to manage skeletal muscle inflammation at the time of treatment induction, with specific guidance on the different doses to use in adults and in children. There also is guidance on the use of csDMARDs in both populations and what to use if there is refractory disease – with the strongest evidence supporting the use of intravenous immunoglobulin (IVIG) or cyclophosphamide, and possibly rituximab and abatacept.

“There is insufficient evidence to recommend JAK inhibition,” Dr. Chinoy said. The data search used to develop the guideline had a cutoff of October 2020, but even now there is only anecdotal evidence from case studies, he added.

Importantly, the guidelines recognize that childhood IIM differs from adult disease and call for children to be managed by pediatric specialists.

“Routine assessment of dysphagia should be considered in all patients,” Dr. Chinoy said, “so ask the question.” The recommendation is that a swallowing assessment should involve a speech and language therapist or gastroenterologist, and that IVIG be considered for active disease and dysphagia that is resistant to other treatments.

There also are recommendations to screen adult patients for interstitial lung disease, consider fracture risk, and screen adult patients for cancer if they have specific risk factors that include older age at onset, male gender, dysphagia, and rapid disease onset, among others.
 

Separate cancer screening guidelines on cards

“Around one in four patients with myositis will develop cancer within the 3 years either before or after myositis onset,” Alexander Oldroyd, MBChB, PhD, said in a separate presentation at the BSR annual meeting.

“It’s a hugely increased risk compared to the general population, and a great worry for patients,” he added. Exactly why there is an increased risk is not known, but “there’s a big link between the biological onset of cancer and myositis.”

Dr. Oldroyd, who is an NIHR Academic Clinical Lecturer at the University of Manchester in England and a coauthor of the BSR myositis guideline, is part of a special interest group set up by the International Myositis Assessment and Clinical Studies Group (IMACS) that is in the process of developing separate guidelines for cancer screening in people newly diagnosed with IIM.

The aim was to produce evidence-based recommendations that were both “pragmatic and practical,” that could help clinicians answer patient’s questions on their risk and how best and how often to screen them, Dr. Oldroyd explained. Importantly, IMACS has endeavored to create recommendations that should be applicable across different countries and health care systems.

“We had to acknowledge that there’s not a lot of evidence base there,” Dr. Oldroyd said, noting that he and colleagues conducted a systematic literature review and meta-analysis and used a Delphi process to draft 20 recommendations. These cover identifying risk factors for cancer in people with myositis and categorizing people into low, medium, and high-risk categories. The recommendations also cover what should constitute basic and enhanced screening, and how often someone should be screened.

Moreover, the authors make recommendations on the use of imaging modalities such as PET and CT scans, as well as upper and lower gastrointestinal endoscopy and naso-endoscopy.

“As rheumatologists, we don’t talk about cancer a lot,” Dr. Oldroyd said. “We pick up a lot of incidental cancers, but we don’t usually talk about cancer screening with patients.” That’s something that needs to change, he said.

“It’s important – just get it out in the open, talk to people about it,” Dr. Oldroyd said.

“Tell them what you’re wanting to do, how you’re wanting to investigate for it, clearly communicate their risk,” he said. “But also acknowledge the limited evidence as well, and clearly communicate the results.”

Dr. Chinoy acknowledged he had received fees for presentations (UCB, Biogen), consultancy (Alexion, Novartis, Eli Lilly, Orphazyme, AstraZeneca), or grant support (Eli Lilly, UCB) that had been paid via his institution for the purpose of furthering myositis research. Dr. Oldroyd had no conflicts of interest to disclose.

The Food and Drug Administration announced on May 10 that it is taking several steps to improve the supply of baby formula in the United States.

The nationwide formula shortage has grown worse in recent weeks due to supply chain issues and a recall of certain Abbott Nutrition products, including major labels such as Similac, Alimentum, and EleCare.

“We recognize that many consumers have been unable to access infant formula and critical medical foods they are accustomed to using and are frustrated by their inability to do so,” FDA Commissioner Robert Califf, MD, said in a statement.

“We are doing everything in our power to ensure there is adequate product available where and when they need it,” he said.

About three-quarters of babies are fed formula for the first 6 months of their lives as a substitute for human milk, Axios reported.

In mid-February, the FDA warned consumers not to use certain powdered infant formula products from Abbott’s facility in Sturgis, Mich. Since then, the FDA has been working with Abbott and other manufacturers to increase the supply in the U.S. market.

“In fact, other infant formula manufacturers are meeting or exceeding capacity levels to meet current demand,” the FDA said in the statement. “Notably, more infant formula was purchased in the month of April than in the month prior to the recall.”

The FDA released a list of steps the agency is taking to increase supply, such as meeting with major infant formula makers to increase output and prioritize product lines in high demand, particularly specialty formulas for infants with allergies or specific diet needs.

But other manufacturers have struggled to quickly increase production because their operations tend to focus on a steady level of supply, according to The New York Times.

“Some industries are very good at ramping up and ramping down,” Rudi Leuschner, PhD, an associate professor of supply chain management at Rutgers Business School, Newark, N.J., told the newspaper.

“You flip a switch and they can produce 10 times as much,” he said. “Baby formula is not that type of a product.”

The FDA is also keeping an eye on the infant formula shortage by using the agency’s 21 Forward food supply chain continuity system. The system was developed during the pandemic to provide a full understanding of how COVID-19 is impacting food supply chains, the FDA said.

The FDA is compiling data on trends for in-stock rates at national and regional levels to understand where infant formula is available and where it should go.

Products are also being brought in from other countries, the FDA said. The agency is trying to speed up the process to get more formula into the U.S. and move it more quickly around the country.

For babies on a special diet, the FDA has decided to release some Abbott products that have been on hold at the Sturgis facility to those who need an urgent supply of metabolic formulas, on a case-by-case basis.

“In these circumstances, the benefit of allowing caregivers, in consultation with their health care providers, to access these products may outweigh the potential risk of bacterial infection,” the FDA said in the statement.

The FDA continues to advise against making homemade infant formulas and recommends talking to the child’s health care provider for recommendations on changing feeding practices or switching to other formulas, if necessary.

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

The Food and Drug Administration announced on May 10 that it is taking several steps to improve the supply of baby formula in the United States.

The nationwide formula shortage has grown worse in recent weeks due to supply chain issues and a recall of certain Abbott Nutrition products, including major labels such as Similac, Alimentum, and EleCare.

“We recognize that many consumers have been unable to access infant formula and critical medical foods they are accustomed to using and are frustrated by their inability to do so,” FDA Commissioner Robert Califf, MD, said in a statement.

“We are doing everything in our power to ensure there is adequate product available where and when they need it,” he said.

About three-quarters of babies are fed formula for the first 6 months of their lives as a substitute for human milk, Axios reported.

In mid-February, the FDA warned consumers not to use certain powdered infant formula products from Abbott’s facility in Sturgis, Mich. Since then, the FDA has been working with Abbott and other manufacturers to increase the supply in the U.S. market.

“In fact, other infant formula manufacturers are meeting or exceeding capacity levels to meet current demand,” the FDA said in the statement. “Notably, more infant formula was purchased in the month of April than in the month prior to the recall.”

The FDA released a list of steps the agency is taking to increase supply, such as meeting with major infant formula makers to increase output and prioritize product lines in high demand, particularly specialty formulas for infants with allergies or specific diet needs.

But other manufacturers have struggled to quickly increase production because their operations tend to focus on a steady level of supply, according to The New York Times.

“Some industries are very good at ramping up and ramping down,” Rudi Leuschner, PhD, an associate professor of supply chain management at Rutgers Business School, Newark, N.J., told the newspaper.

“You flip a switch and they can produce 10 times as much,” he said. “Baby formula is not that type of a product.”

The FDA is also keeping an eye on the infant formula shortage by using the agency’s 21 Forward food supply chain continuity system. The system was developed during the pandemic to provide a full understanding of how COVID-19 is impacting food supply chains, the FDA said.

The FDA is compiling data on trends for in-stock rates at national and regional levels to understand where infant formula is available and where it should go.

Products are also being brought in from other countries, the FDA said. The agency is trying to speed up the process to get more formula into the U.S. and move it more quickly around the country.

For babies on a special diet, the FDA has decided to release some Abbott products that have been on hold at the Sturgis facility to those who need an urgent supply of metabolic formulas, on a case-by-case basis.

“In these circumstances, the benefit of allowing caregivers, in consultation with their health care providers, to access these products may outweigh the potential risk of bacterial infection,” the FDA said in the statement.

The FDA continues to advise against making homemade infant formulas and recommends talking to the child’s health care provider for recommendations on changing feeding practices or switching to other formulas, if necessary.

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

The Food and Drug Administration announced on May 10 that it is taking several steps to improve the supply of baby formula in the United States.

The nationwide formula shortage has grown worse in recent weeks due to supply chain issues and a recall of certain Abbott Nutrition products, including major labels such as Similac, Alimentum, and EleCare.

“We recognize that many consumers have been unable to access infant formula and critical medical foods they are accustomed to using and are frustrated by their inability to do so,” FDA Commissioner Robert Califf, MD, said in a statement.

“We are doing everything in our power to ensure there is adequate product available where and when they need it,” he said.

About three-quarters of babies are fed formula for the first 6 months of their lives as a substitute for human milk, Axios reported.

In mid-February, the FDA warned consumers not to use certain powdered infant formula products from Abbott’s facility in Sturgis, Mich. Since then, the FDA has been working with Abbott and other manufacturers to increase the supply in the U.S. market.

“In fact, other infant formula manufacturers are meeting or exceeding capacity levels to meet current demand,” the FDA said in the statement. “Notably, more infant formula was purchased in the month of April than in the month prior to the recall.”

The FDA released a list of steps the agency is taking to increase supply, such as meeting with major infant formula makers to increase output and prioritize product lines in high demand, particularly specialty formulas for infants with allergies or specific diet needs.

But other manufacturers have struggled to quickly increase production because their operations tend to focus on a steady level of supply, according to The New York Times.

“Some industries are very good at ramping up and ramping down,” Rudi Leuschner, PhD, an associate professor of supply chain management at Rutgers Business School, Newark, N.J., told the newspaper.

“You flip a switch and they can produce 10 times as much,” he said. “Baby formula is not that type of a product.”

The FDA is also keeping an eye on the infant formula shortage by using the agency’s 21 Forward food supply chain continuity system. The system was developed during the pandemic to provide a full understanding of how COVID-19 is impacting food supply chains, the FDA said.

The FDA is compiling data on trends for in-stock rates at national and regional levels to understand where infant formula is available and where it should go.

Products are also being brought in from other countries, the FDA said. The agency is trying to speed up the process to get more formula into the U.S. and move it more quickly around the country.

For babies on a special diet, the FDA has decided to release some Abbott products that have been on hold at the Sturgis facility to those who need an urgent supply of metabolic formulas, on a case-by-case basis.

“In these circumstances, the benefit of allowing caregivers, in consultation with their health care providers, to access these products may outweigh the potential risk of bacterial infection,” the FDA said in the statement.

The FDA continues to advise against making homemade infant formulas and recommends talking to the child’s health care provider for recommendations on changing feeding practices or switching to other formulas, if necessary.

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

Children with juvenile idiopathic arthritis (JIA) who need a tumor necrosis factor (TNF) inhibitor after failing conventional disease-modifying antirheumatic drug (DMARD) treatment often experience insurance delays before beginning the new drug because of prior authorization denials, according to research presented at the 2022 annual meeting of the Childhood Arthritis and Rheumatology Research Alliance (CARRA). The findings were also published  as a research letter in JAMA Network Open.

“Prompt escalation to TNF inhibitors is recommended for children with JIA refractory to DMARDs,” author Jordan Roberts, MD, a clinical fellow of the Harvard Medical School Rheumatology Program, Boston, told CARRA attendees. TNF inhibitors are increasingly used as first-line treatment in JIA since growing evidence suggests better outcomes from early treatment with biologics. “Prior authorization requirements that delay TNF inhibitor initiation among children with JIA are common in clinical practice,” Dr. Roberts said, but little evidence exists to understand the extent of this problem and its causes.

The researchers therefore conducted a retrospective cohort study using a search of electronic health records from January 2018 to December 2019 to find all children at a single center with a new diagnosis of nonsystemic JIA. Then the authors pulled the timing of prior authorization requests, approvals, denials, and first TNF inhibitor dose from the medical notes. They also sought out any children who had been recommended a TNF inhibitor but never started one.

The total population included 54 children with an average age of 10 years, about two-thirds of whom had private insurance (63%). The group was predominantly White (63%), although 13% declined to provide race, and 7% were Hispanic. Most subtypes of disease were represented: oligoarticular persistent (28%), oligoarticular extended (2%), polyarticular rheumatoid factor-negative (15%), polyarticular rheumatoid factor-positive (15%), psoriatic arthritis (26%), enthesitis-related arthritis (12%), and undifferentiated arthritis (2%).

The 44 participants with private insurance had an average of two joints with active disease, while the 10 patients with public insurance had an average of four involved joints. Nearly all the patients (91%) had previously taken or were currently taking DMARDs when the prior authorization was submitted, and 61% had received NSAIDs.

All but one of the patients’ insurance plans required a prior authorization. The first prior authorization was denied for about one-third of the public insurance patients (30%) and a quarter of the private insurance patients. About 1 in 5 patients overall (22%) required a written appeal to override the denial, and 4% required peer-to-peer review. Meanwhile, 7% of patients began another medication because of the denial.

It took a median of 3 days for prior authorizations to be approved and a median of 24 days from the time the TNF inhibitor was recommended to the patient receiving the first dose. However, 22% of patients waited at least 2 weeks before the prior authorization was approved, and more than a quarter of the requests took over 30 days before the patient could begin the medication. In the public insurance group in particular, a quarter of children waited at least 19 days for approval and at least 44 days before starting the medication.

In fact, when the researchers looked at the difference in approval time between those who did and did not receive an initial denial, the difference was stark. Median approval time was 16 days when the prior authorization was denied, compared with a median of 5 days when the first prior authorization was approved. Similarly, time to initiation of the drug after recommendation was a median of 35 days for those whose prior authorization was first denied and 17 days for those with an initial approval.

The most common reason for an initial denial was the insurance company requiring a different TNF inhibitor than the one the rheumatologist wanted to prescribe. “These were all children whose rheumatologist has recommended either infliximab or etanercept that were required to use adalimumab instead,” Dr. Roberts said.

The other reasons for initial denial were similarly familiar ones:

• Required submission to another insurer
• Additional documentation required
• Lack of medical necessity
• Prescription was for an indication not approved by the Food and Drug Administration
• Age of patient
• Nonbiologic DMARD required
• NSAID required for step therapy

Only three children who were advised to begin a TNF inhibitor did not do so, including one who was lost to follow-up, one who had injection-related anxiety, and one who had safety concerns about the medication.

“Several children were required to use alternative TNF inhibitors than the one that was recommended due to restricted formularies, which may reduce shared decisionmaking between physicians and families and may not be the optimal clinical choice for an individual child,” Dr. Roberts said in her conclusion. Most children, however, were able to get approval for the TNF inhibitor originally requested, “suggesting that utilization management strategies present barriers to timely care despite appropriate specialty medication requests,” she said. “Therefore, it’s important for us to advocate for access to medications for children with JIA.”

Findings are not surprising

“I have these same experiences at my institution – often insurance will dictate clinical practice, and step therapy is the only option, causing a delay to initiation of TNFi even if we think, as the pediatric rheumatologist, that a child needs this medicine to be initiated on presentation to our clinic,” Nayimisha Balmuri, MD, assistant professor of pediatrics in the division of allergy, immunology, and rheumatology at the Johns Hopkins School of Medicine, Baltimore, told this news organization.

Dr. Balmuri, who was not involved in the study, noted that in her clinic at Johns Hopkins, it is hit or miss if an appeal to insurance companies or to the state (if it is Medicaid coverage) will be successful. “Unfortunately, [we are] mostly unsuccessful, and we have to try another DMARD for 8 to 12 weeks first before trying to get TNFi,” she said.

Dr. Balmuri called for bringing these issues to the attention of state and federal legislators. “It’s so important for us to continue to advocate for our patients at the state and national level! We are the advocates for our patients, and we are uniquely trained to know the best medications to initiate to help patients maximize their chance to reach remission of arthritis. Insurance companies need to hear our voices!”

Dr. Roberts reported grants from CARRA, the Lupus Foundation of America, and the National Institute of Allergy and Infectious Diseases during the conduct of the study.

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

Children with juvenile idiopathic arthritis (JIA) who need a tumor necrosis factor (TNF) inhibitor after failing conventional disease-modifying antirheumatic drug (DMARD) treatment often experience insurance delays before beginning the new drug because of prior authorization denials, according to research presented at the 2022 annual meeting of the Childhood Arthritis and Rheumatology Research Alliance (CARRA). The findings were also published  as a research letter in JAMA Network Open.

“Prompt escalation to TNF inhibitors is recommended for children with JIA refractory to DMARDs,” author Jordan Roberts, MD, a clinical fellow of the Harvard Medical School Rheumatology Program, Boston, told CARRA attendees. TNF inhibitors are increasingly used as first-line treatment in JIA since growing evidence suggests better outcomes from early treatment with biologics. “Prior authorization requirements that delay TNF inhibitor initiation among children with JIA are common in clinical practice,” Dr. Roberts said, but little evidence exists to understand the extent of this problem and its causes.

The researchers therefore conducted a retrospective cohort study using a search of electronic health records from January 2018 to December 2019 to find all children at a single center with a new diagnosis of nonsystemic JIA. Then the authors pulled the timing of prior authorization requests, approvals, denials, and first TNF inhibitor dose from the medical notes. They also sought out any children who had been recommended a TNF inhibitor but never started one.

The total population included 54 children with an average age of 10 years, about two-thirds of whom had private insurance (63%). The group was predominantly White (63%), although 13% declined to provide race, and 7% were Hispanic. Most subtypes of disease were represented: oligoarticular persistent (28%), oligoarticular extended (2%), polyarticular rheumatoid factor-negative (15%), polyarticular rheumatoid factor-positive (15%), psoriatic arthritis (26%), enthesitis-related arthritis (12%), and undifferentiated arthritis (2%).

The 44 participants with private insurance had an average of two joints with active disease, while the 10 patients with public insurance had an average of four involved joints. Nearly all the patients (91%) had previously taken or were currently taking DMARDs when the prior authorization was submitted, and 61% had received NSAIDs.

All but one of the patients’ insurance plans required a prior authorization. The first prior authorization was denied for about one-third of the public insurance patients (30%) and a quarter of the private insurance patients. About 1 in 5 patients overall (22%) required a written appeal to override the denial, and 4% required peer-to-peer review. Meanwhile, 7% of patients began another medication because of the denial.

It took a median of 3 days for prior authorizations to be approved and a median of 24 days from the time the TNF inhibitor was recommended to the patient receiving the first dose. However, 22% of patients waited at least 2 weeks before the prior authorization was approved, and more than a quarter of the requests took over 30 days before the patient could begin the medication. In the public insurance group in particular, a quarter of children waited at least 19 days for approval and at least 44 days before starting the medication.

In fact, when the researchers looked at the difference in approval time between those who did and did not receive an initial denial, the difference was stark. Median approval time was 16 days when the prior authorization was denied, compared with a median of 5 days when the first prior authorization was approved. Similarly, time to initiation of the drug after recommendation was a median of 35 days for those whose prior authorization was first denied and 17 days for those with an initial approval.

The most common reason for an initial denial was the insurance company requiring a different TNF inhibitor than the one the rheumatologist wanted to prescribe. “These were all children whose rheumatologist has recommended either infliximab or etanercept that were required to use adalimumab instead,” Dr. Roberts said.

The other reasons for initial denial were similarly familiar ones:

• Required submission to another insurer
• Additional documentation required
• Lack of medical necessity
• Prescription was for an indication not approved by the Food and Drug Administration
• Age of patient
• Nonbiologic DMARD required
• NSAID required for step therapy

Only three children who were advised to begin a TNF inhibitor did not do so, including one who was lost to follow-up, one who had injection-related anxiety, and one who had safety concerns about the medication.

“Several children were required to use alternative TNF inhibitors than the one that was recommended due to restricted formularies, which may reduce shared decisionmaking between physicians and families and may not be the optimal clinical choice for an individual child,” Dr. Roberts said in her conclusion. Most children, however, were able to get approval for the TNF inhibitor originally requested, “suggesting that utilization management strategies present barriers to timely care despite appropriate specialty medication requests,” she said. “Therefore, it’s important for us to advocate for access to medications for children with JIA.”

Findings are not surprising

“I have these same experiences at my institution – often insurance will dictate clinical practice, and step therapy is the only option, causing a delay to initiation of TNFi even if we think, as the pediatric rheumatologist, that a child needs this medicine to be initiated on presentation to our clinic,” Nayimisha Balmuri, MD, assistant professor of pediatrics in the division of allergy, immunology, and rheumatology at the Johns Hopkins School of Medicine, Baltimore, told this news organization.

Dr. Balmuri, who was not involved in the study, noted that in her clinic at Johns Hopkins, it is hit or miss if an appeal to insurance companies or to the state (if it is Medicaid coverage) will be successful. “Unfortunately, [we are] mostly unsuccessful, and we have to try another DMARD for 8 to 12 weeks first before trying to get TNFi,” she said.

Dr. Balmuri called for bringing these issues to the attention of state and federal legislators. “It’s so important for us to continue to advocate for our patients at the state and national level! We are the advocates for our patients, and we are uniquely trained to know the best medications to initiate to help patients maximize their chance to reach remission of arthritis. Insurance companies need to hear our voices!”

Dr. Roberts reported grants from CARRA, the Lupus Foundation of America, and the National Institute of Allergy and Infectious Diseases during the conduct of the study.

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

Children with juvenile idiopathic arthritis (JIA) who need a tumor necrosis factor (TNF) inhibitor after failing conventional disease-modifying antirheumatic drug (DMARD) treatment often experience insurance delays before beginning the new drug because of prior authorization denials, according to research presented at the 2022 annual meeting of the Childhood Arthritis and Rheumatology Research Alliance (CARRA). The findings were also published  as a research letter in JAMA Network Open.

“Prompt escalation to TNF inhibitors is recommended for children with JIA refractory to DMARDs,” author Jordan Roberts, MD, a clinical fellow of the Harvard Medical School Rheumatology Program, Boston, told CARRA attendees. TNF inhibitors are increasingly used as first-line treatment in JIA since growing evidence suggests better outcomes from early treatment with biologics. “Prior authorization requirements that delay TNF inhibitor initiation among children with JIA are common in clinical practice,” Dr. Roberts said, but little evidence exists to understand the extent of this problem and its causes.

The researchers therefore conducted a retrospective cohort study using a search of electronic health records from January 2018 to December 2019 to find all children at a single center with a new diagnosis of nonsystemic JIA. Then the authors pulled the timing of prior authorization requests, approvals, denials, and first TNF inhibitor dose from the medical notes. They also sought out any children who had been recommended a TNF inhibitor but never started one.

The total population included 54 children with an average age of 10 years, about two-thirds of whom had private insurance (63%). The group was predominantly White (63%), although 13% declined to provide race, and 7% were Hispanic. Most subtypes of disease were represented: oligoarticular persistent (28%), oligoarticular extended (2%), polyarticular rheumatoid factor-negative (15%), polyarticular rheumatoid factor-positive (15%), psoriatic arthritis (26%), enthesitis-related arthritis (12%), and undifferentiated arthritis (2%).

The 44 participants with private insurance had an average of two joints with active disease, while the 10 patients with public insurance had an average of four involved joints. Nearly all the patients (91%) had previously taken or were currently taking DMARDs when the prior authorization was submitted, and 61% had received NSAIDs.

All but one of the patients’ insurance plans required a prior authorization. The first prior authorization was denied for about one-third of the public insurance patients (30%) and a quarter of the private insurance patients. About 1 in 5 patients overall (22%) required a written appeal to override the denial, and 4% required peer-to-peer review. Meanwhile, 7% of patients began another medication because of the denial.

It took a median of 3 days for prior authorizations to be approved and a median of 24 days from the time the TNF inhibitor was recommended to the patient receiving the first dose. However, 22% of patients waited at least 2 weeks before the prior authorization was approved, and more than a quarter of the requests took over 30 days before the patient could begin the medication. In the public insurance group in particular, a quarter of children waited at least 19 days for approval and at least 44 days before starting the medication.

In fact, when the researchers looked at the difference in approval time between those who did and did not receive an initial denial, the difference was stark. Median approval time was 16 days when the prior authorization was denied, compared with a median of 5 days when the first prior authorization was approved. Similarly, time to initiation of the drug after recommendation was a median of 35 days for those whose prior authorization was first denied and 17 days for those with an initial approval.

The most common reason for an initial denial was the insurance company requiring a different TNF inhibitor than the one the rheumatologist wanted to prescribe. “These were all children whose rheumatologist has recommended either infliximab or etanercept that were required to use adalimumab instead,” Dr. Roberts said.

The other reasons for initial denial were similarly familiar ones:

• Required submission to another insurer
• Additional documentation required
• Lack of medical necessity
• Prescription was for an indication not approved by the Food and Drug Administration
• Age of patient
• Nonbiologic DMARD required
• NSAID required for step therapy

Only three children who were advised to begin a TNF inhibitor did not do so, including one who was lost to follow-up, one who had injection-related anxiety, and one who had safety concerns about the medication.

“Several children were required to use alternative TNF inhibitors than the one that was recommended due to restricted formularies, which may reduce shared decisionmaking between physicians and families and may not be the optimal clinical choice for an individual child,” Dr. Roberts said in her conclusion. Most children, however, were able to get approval for the TNF inhibitor originally requested, “suggesting that utilization management strategies present barriers to timely care despite appropriate specialty medication requests,” she said. “Therefore, it’s important for us to advocate for access to medications for children with JIA.”

Findings are not surprising

“I have these same experiences at my institution – often insurance will dictate clinical practice, and step therapy is the only option, causing a delay to initiation of TNFi even if we think, as the pediatric rheumatologist, that a child needs this medicine to be initiated on presentation to our clinic,” Nayimisha Balmuri, MD, assistant professor of pediatrics in the division of allergy, immunology, and rheumatology at the Johns Hopkins School of Medicine, Baltimore, told this news organization.

Dr. Balmuri, who was not involved in the study, noted that in her clinic at Johns Hopkins, it is hit or miss if an appeal to insurance companies or to the state (if it is Medicaid coverage) will be successful. “Unfortunately, [we are] mostly unsuccessful, and we have to try another DMARD for 8 to 12 weeks first before trying to get TNFi,” she said.

Dr. Balmuri called for bringing these issues to the attention of state and federal legislators. “It’s so important for us to continue to advocate for our patients at the state and national level! We are the advocates for our patients, and we are uniquely trained to know the best medications to initiate to help patients maximize their chance to reach remission of arthritis. Insurance companies need to hear our voices!”

Dr. Roberts reported grants from CARRA, the Lupus Foundation of America, and the National Institute of Allergy and Infectious Diseases during the conduct of the study.

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

We have a half-forgotten Indian immigrant to thank – a hospital night porter turned biochemist –for revolutionizing treatment of leukemia, the once deadly childhood scourge that is still the most common pediatric cancer.

Dr. Yellapragada SubbaRow has been called the “father of chemotherapy” for developing methotrexate, a powerful, inexpensive therapy for leukemia and other diseases, and he is celebrated for additional scientific achievements. Yet Dr. SubbaRow’s life was marked more by struggle than glory.

1995 Indian stamp; photo in public domain

Born poor in southeastern India, he nearly succumbed to a tropical disease that killed two older brothers, and he didn’t focus on schoolwork until his father died. Later, prejudice dogged his years as an immigrant to the United States, and a blood clot took his life at the age of 53.

Scientifically, however, Dr. SubbaRow (pronounced sue-buh-rao) triumphed, despite mammoth challenges and a lack of recognition that persists to this day. National Cancer Research Month is a fitting time to look back on his extraordinary life and work and pay tribute to his accomplishments.
 

‘Yella,’ folic acid, and a paradigm shift

No one appreciates Dr. SubbaRow more than a cadre of Indian-born physicians who have kept his legacy alive in journal articles, presentations, and a Pulitzer Prize-winning book. Among them is author and oncologist Siddhartha Mukherjee, MD, who chronicled Dr. SubbaRow’s achievements in his New York Times No. 1 bestseller, “The Emperor of All Maladies: A Biography of Cancer.”

As Dr. Mukherjee wrote, Dr. SubbaRow was a “pioneer in many ways, a physician turned cellular physiologist, a chemist who had accidentally wandered into biology.” (Per Indian tradition, SubbaRow is the doctor’s first name, and Yellapragada is his surname, but medical literature uses SubbaRow as his cognomen, with some variations in spelling. Dr. Mukherjee wrote that his friends called him “Yella.”)

Dr. SubbaRow came to the United States in 1923, after enduring a difficult childhood and young adulthood. He’d survived bouts of religious fervor, childhood rebellion (including a bid to run away from home and become a banana trader), and a failed arranged marriage. His wife bore him a child who died in infancy. He left it all behind.

In Boston, medical officials rejected his degree. Broke, he worked for a time as a night porter at Brigham and Women’s Hospital in Boston, changing sheets and cleaning urinals. To a poor but proud high-caste Indian Brahmin, the culture shock of carrying out these tasks must have been especially jarring.

Dr. SubbaRow went on to earn a diploma from Harvard Medical School, also in Boston, and became a junior faculty member. As a foreigner, Dr. Mukherjee wrote, Dr. SubbaRow was a “reclusive, nocturnal, heavily accented vegetarian,” so different from his colleagues that advancement seemed impossible. Despite his pioneering biochemistry work, Harvard later declined to offer Dr. SubbaRow a tenured faculty position.

By the early 1940s, he took a job at an upstate New York pharmaceutical company called Lederle Labs (later purchased by Pfizer). At Lederle, Dr. SubbaRow strove to synthesize the vitamin known as folic acid. He ended up creating a kind of antivitamin, a lookalike that acted like folic acid but only succeeded in gumming up the works in receptors. But what good would it do to stop the body from absorbing folic acid? Plenty, it turned out.
 

Discoveries pile up, but credit and fame prove elusive

Dr. SubbaRow was no stranger to producing landmark biological work. He’d previously codiscovered phosphocreatine and ATP, which are crucial to muscular contractions. However, “in 1935, he had to disown the extent of his role in the discovery of the color test related to phosphorus, instead giving the credit to his co-author, who was being considered for promotion to a full professorship at Harvard,” wrote author Gerald Posner in his 2020 book, “Pharma: Greed, Lies and the Poisoning of America.”

Houston-area oncologist Kirtan Nautiyal, MD, who paid tribute to Dr. SubbaRow in a 2018 article, contended that “with his Indian instinct for self-effacement, he had irreparably sabotaged his own career.”

Dr. SubbaRow and his team also developed “the first effective treatment of filariasis, which causes elephantiasis of the lower limbs and genitals in millions of people, mainly in tropical countries,” Dr. Nautiyal wrote. “Later in the decade, his antibiotic program generated polymyxin, the first effective treatment against the class of bacteria called Gram negatives, and aureomycin, the first “broad-spectrum’ antibiotic.” (Aureomycin is also the first tetracycline antibiotic.)

Dr. SubbaRow’s discovery of a folic acid antagonist would again go largely unheralded. But first came the realization that folic acid made childhood leukemia worse, not better, and the prospect that this process could potentially be reversed.
 

Rise of methotrexate and fall of leukemia

In Boston, Sidney Farber, MD, a Boston pathologist, was desperate to help Robert Sandler, a 2-year-old leukemia patient. Dr. Farber contacted his ex-colleague Dr. SubbaRow to request a supply of aminopterin, an early version of methotrexate that Dr. SubbaRow and his team had developed. Dr. Farber injected Robert with the substance and within 3 days, the toddler’s white blood count started falling – fast. He stopped bleeding, resumed eating, and once again seemed almost identical to his twin brother, as Dr. Mukherjee wrote in his book.

Leukemia had never gone into remission before. Unfortunately, the treatment only worked temporarily. Robert, like other children treated with the drug, relapsed and died within months. But Dr. Farber “saw a door open” – a chemical, a kind of chemotherapy, that could turn back cancer. In the case of folic acid antagonists, they do so by stopping cancer cells from replicating.

Methotrexate, a related agent synthesized by Dr. SubbaRow, would become a mainstay of leukemia treatment and begin to produce long-term remission from acute lymphoblastic leukemia in 1970, when combination chemotherapy was developed.

Other cancers fell to methotrexate treatment. “Previous assumptions that cancer was nearly always fatal were revised, and the field of medical oncology (treatment of cancer with chemotherapy), which had not previously existed, was formally established in 1971,” according to the National Cancer Institute’s history of methotrexate. This account does not mention Dr. SubbaRow.
 

Death takes the doctor, but his legacy remains

In biographies, as well as his own words, Dr. SubbaRow comes across as a prickly, hard-driving workaholic who had little interest in intimate human connections. “It is not good to ask in every letter when I will be back,” he wrote to his wife back in India, before cutting off ties completely in the early 1930s. “I will come as early as possible. ... I do not want to write anything more.”

It seems, as his biographer S.P.K. Gupta noted, that “he was quite determined that the time allotted to him on Earth should be completely devoted to finding cures for ailments that plagued mankind.”

Still, Dr. SubbaRow’s research team was devoted to him, and he had plenty of reasons to be bitter, such as the prejudice and isolation he encountered in the United States and earlier, in British-run India. According to Mr. Posner’s book, even as a young medical student, Dr. SubbaRow heeded the call of Indian independence activist Mohandas Gandhi. He “refused the British surgical gown given him at school and instead donned a traditional and simple cotton Khadi. That act of defiance cost SubbaRow the college degree that was necessary for him to get into the State Medical College.”

During the last year of his life, Dr. SubbaRow faced yet another humiliation: In his landmark 1948 study about aminopterin as a treatment for leukemia, his colleague Dr. Farber failed to credit him, an “astonishing omission” as Yaddanapudi Ravindranath, MBBS, a pediatric hematologist/oncologist at Wayne State University, Detroit, put it. “From everything I know, Dr. Farber spent the rest of his career apologizing and trying to make amends for it,” Dr. Ravindranath said in an interview.
 

A career cut short, and a lasting legacy

In 1948, at the age of 53, Dr. SubbaRow suddenly died. “Many think Dr. SubbaRow would have won [the] Nobel Prize had he lived a few years longer,” said Dr. Ravindranath.

Like Dr. SubbaRow, Dr. Ravindranath was born in Andhra Pradesh state, near the city of Chennai formerly known as Madras. “Being a compatriot, in a way I continue his legacy, and I am obviously proud of him,” said Dr. Ravindranath, who has conducted his own landmark research regarding methotrexate and leukemia.

Nearly 75 years after Dr. SubbaRow’s death, Indian-born physicians like Dr. Ravindranath continue to honor him in print, trying to ensure that he’s not forgotten. Methotrexate remains a crucial treatment for leukemia, along with a long list of other ailments, including psoriasis.

Recognition for “Yella” may have come late and infrequently, but a Lederle Laboratories research library named after him offered Dr. SubbaRow a kind of immortality. A plaque there memorialized him in stone as a scientist, teacher, philosopher, and humanitarian, featuring the quote: “Science simply prolongs life. Religion deepens it.”

By all accounts, Dr. SubbaRow was a man of science and faith who had faith in science.

We have a half-forgotten Indian immigrant to thank – a hospital night porter turned biochemist –for revolutionizing treatment of leukemia, the once deadly childhood scourge that is still the most common pediatric cancer.

Dr. Yellapragada SubbaRow has been called the “father of chemotherapy” for developing methotrexate, a powerful, inexpensive therapy for leukemia and other diseases, and he is celebrated for additional scientific achievements. Yet Dr. SubbaRow’s life was marked more by struggle than glory.

1995 Indian stamp; photo in public domain

Born poor in southeastern India, he nearly succumbed to a tropical disease that killed two older brothers, and he didn’t focus on schoolwork until his father died. Later, prejudice dogged his years as an immigrant to the United States, and a blood clot took his life at the age of 53.

Scientifically, however, Dr. SubbaRow (pronounced sue-buh-rao) triumphed, despite mammoth challenges and a lack of recognition that persists to this day. National Cancer Research Month is a fitting time to look back on his extraordinary life and work and pay tribute to his accomplishments.
 

‘Yella,’ folic acid, and a paradigm shift

No one appreciates Dr. SubbaRow more than a cadre of Indian-born physicians who have kept his legacy alive in journal articles, presentations, and a Pulitzer Prize-winning book. Among them is author and oncologist Siddhartha Mukherjee, MD, who chronicled Dr. SubbaRow’s achievements in his New York Times No. 1 bestseller, “The Emperor of All Maladies: A Biography of Cancer.”

As Dr. Mukherjee wrote, Dr. SubbaRow was a “pioneer in many ways, a physician turned cellular physiologist, a chemist who had accidentally wandered into biology.” (Per Indian tradition, SubbaRow is the doctor’s first name, and Yellapragada is his surname, but medical literature uses SubbaRow as his cognomen, with some variations in spelling. Dr. Mukherjee wrote that his friends called him “Yella.”)

Dr. SubbaRow came to the United States in 1923, after enduring a difficult childhood and young adulthood. He’d survived bouts of religious fervor, childhood rebellion (including a bid to run away from home and become a banana trader), and a failed arranged marriage. His wife bore him a child who died in infancy. He left it all behind.

In Boston, medical officials rejected his degree. Broke, he worked for a time as a night porter at Brigham and Women’s Hospital in Boston, changing sheets and cleaning urinals. To a poor but proud high-caste Indian Brahmin, the culture shock of carrying out these tasks must have been especially jarring.

Dr. SubbaRow went on to earn a diploma from Harvard Medical School, also in Boston, and became a junior faculty member. As a foreigner, Dr. Mukherjee wrote, Dr. SubbaRow was a “reclusive, nocturnal, heavily accented vegetarian,” so different from his colleagues that advancement seemed impossible. Despite his pioneering biochemistry work, Harvard later declined to offer Dr. SubbaRow a tenured faculty position.

By the early 1940s, he took a job at an upstate New York pharmaceutical company called Lederle Labs (later purchased by Pfizer). At Lederle, Dr. SubbaRow strove to synthesize the vitamin known as folic acid. He ended up creating a kind of antivitamin, a lookalike that acted like folic acid but only succeeded in gumming up the works in receptors. But what good would it do to stop the body from absorbing folic acid? Plenty, it turned out.
 

Discoveries pile up, but credit and fame prove elusive

Dr. SubbaRow was no stranger to producing landmark biological work. He’d previously codiscovered phosphocreatine and ATP, which are crucial to muscular contractions. However, “in 1935, he had to disown the extent of his role in the discovery of the color test related to phosphorus, instead giving the credit to his co-author, who was being considered for promotion to a full professorship at Harvard,” wrote author Gerald Posner in his 2020 book, “Pharma: Greed, Lies and the Poisoning of America.”

Houston-area oncologist Kirtan Nautiyal, MD, who paid tribute to Dr. SubbaRow in a 2018 article, contended that “with his Indian instinct for self-effacement, he had irreparably sabotaged his own career.”

Dr. SubbaRow and his team also developed “the first effective treatment of filariasis, which causes elephantiasis of the lower limbs and genitals in millions of people, mainly in tropical countries,” Dr. Nautiyal wrote. “Later in the decade, his antibiotic program generated polymyxin, the first effective treatment against the class of bacteria called Gram negatives, and aureomycin, the first “broad-spectrum’ antibiotic.” (Aureomycin is also the first tetracycline antibiotic.)

Dr. SubbaRow’s discovery of a folic acid antagonist would again go largely unheralded. But first came the realization that folic acid made childhood leukemia worse, not better, and the prospect that this process could potentially be reversed.
 

Rise of methotrexate and fall of leukemia

In Boston, Sidney Farber, MD, a Boston pathologist, was desperate to help Robert Sandler, a 2-year-old leukemia patient. Dr. Farber contacted his ex-colleague Dr. SubbaRow to request a supply of aminopterin, an early version of methotrexate that Dr. SubbaRow and his team had developed. Dr. Farber injected Robert with the substance and within 3 days, the toddler’s white blood count started falling – fast. He stopped bleeding, resumed eating, and once again seemed almost identical to his twin brother, as Dr. Mukherjee wrote in his book.

Leukemia had never gone into remission before. Unfortunately, the treatment only worked temporarily. Robert, like other children treated with the drug, relapsed and died within months. But Dr. Farber “saw a door open” – a chemical, a kind of chemotherapy, that could turn back cancer. In the case of folic acid antagonists, they do so by stopping cancer cells from replicating.

Methotrexate, a related agent synthesized by Dr. SubbaRow, would become a mainstay of leukemia treatment and begin to produce long-term remission from acute lymphoblastic leukemia in 1970, when combination chemotherapy was developed.

Other cancers fell to methotrexate treatment. “Previous assumptions that cancer was nearly always fatal were revised, and the field of medical oncology (treatment of cancer with chemotherapy), which had not previously existed, was formally established in 1971,” according to the National Cancer Institute’s history of methotrexate. This account does not mention Dr. SubbaRow.
 

Death takes the doctor, but his legacy remains

In biographies, as well as his own words, Dr. SubbaRow comes across as a prickly, hard-driving workaholic who had little interest in intimate human connections. “It is not good to ask in every letter when I will be back,” he wrote to his wife back in India, before cutting off ties completely in the early 1930s. “I will come as early as possible. ... I do not want to write anything more.”

It seems, as his biographer S.P.K. Gupta noted, that “he was quite determined that the time allotted to him on Earth should be completely devoted to finding cures for ailments that plagued mankind.”

Still, Dr. SubbaRow’s research team was devoted to him, and he had plenty of reasons to be bitter, such as the prejudice and isolation he encountered in the United States and earlier, in British-run India. According to Mr. Posner’s book, even as a young medical student, Dr. SubbaRow heeded the call of Indian independence activist Mohandas Gandhi. He “refused the British surgical gown given him at school and instead donned a traditional and simple cotton Khadi. That act of defiance cost SubbaRow the college degree that was necessary for him to get into the State Medical College.”

During the last year of his life, Dr. SubbaRow faced yet another humiliation: In his landmark 1948 study about aminopterin as a treatment for leukemia, his colleague Dr. Farber failed to credit him, an “astonishing omission” as Yaddanapudi Ravindranath, MBBS, a pediatric hematologist/oncologist at Wayne State University, Detroit, put it. “From everything I know, Dr. Farber spent the rest of his career apologizing and trying to make amends for it,” Dr. Ravindranath said in an interview.
 

A career cut short, and a lasting legacy

In 1948, at the age of 53, Dr. SubbaRow suddenly died. “Many think Dr. SubbaRow would have won [the] Nobel Prize had he lived a few years longer,” said Dr. Ravindranath.

Like Dr. SubbaRow, Dr. Ravindranath was born in Andhra Pradesh state, near the city of Chennai formerly known as Madras. “Being a compatriot, in a way I continue his legacy, and I am obviously proud of him,” said Dr. Ravindranath, who has conducted his own landmark research regarding methotrexate and leukemia.

Nearly 75 years after Dr. SubbaRow’s death, Indian-born physicians like Dr. Ravindranath continue to honor him in print, trying to ensure that he’s not forgotten. Methotrexate remains a crucial treatment for leukemia, along with a long list of other ailments, including psoriasis.

Recognition for “Yella” may have come late and infrequently, but a Lederle Laboratories research library named after him offered Dr. SubbaRow a kind of immortality. A plaque there memorialized him in stone as a scientist, teacher, philosopher, and humanitarian, featuring the quote: “Science simply prolongs life. Religion deepens it.”

By all accounts, Dr. SubbaRow was a man of science and faith who had faith in science.

We have a half-forgotten Indian immigrant to thank – a hospital night porter turned biochemist –for revolutionizing treatment of leukemia, the once deadly childhood scourge that is still the most common pediatric cancer.

Dr. Yellapragada SubbaRow has been called the “father of chemotherapy” for developing methotrexate, a powerful, inexpensive therapy for leukemia and other diseases, and he is celebrated for additional scientific achievements. Yet Dr. SubbaRow’s life was marked more by struggle than glory.

1995 Indian stamp; photo in public domain

Born poor in southeastern India, he nearly succumbed to a tropical disease that killed two older brothers, and he didn’t focus on schoolwork until his father died. Later, prejudice dogged his years as an immigrant to the United States, and a blood clot took his life at the age of 53.

Scientifically, however, Dr. SubbaRow (pronounced sue-buh-rao) triumphed, despite mammoth challenges and a lack of recognition that persists to this day. National Cancer Research Month is a fitting time to look back on his extraordinary life and work and pay tribute to his accomplishments.
 

‘Yella,’ folic acid, and a paradigm shift

No one appreciates Dr. SubbaRow more than a cadre of Indian-born physicians who have kept his legacy alive in journal articles, presentations, and a Pulitzer Prize-winning book. Among them is author and oncologist Siddhartha Mukherjee, MD, who chronicled Dr. SubbaRow’s achievements in his New York Times No. 1 bestseller, “The Emperor of All Maladies: A Biography of Cancer.”

As Dr. Mukherjee wrote, Dr. SubbaRow was a “pioneer in many ways, a physician turned cellular physiologist, a chemist who had accidentally wandered into biology.” (Per Indian tradition, SubbaRow is the doctor’s first name, and Yellapragada is his surname, but medical literature uses SubbaRow as his cognomen, with some variations in spelling. Dr. Mukherjee wrote that his friends called him “Yella.”)

Dr. SubbaRow came to the United States in 1923, after enduring a difficult childhood and young adulthood. He’d survived bouts of religious fervor, childhood rebellion (including a bid to run away from home and become a banana trader), and a failed arranged marriage. His wife bore him a child who died in infancy. He left it all behind.

In Boston, medical officials rejected his degree. Broke, he worked for a time as a night porter at Brigham and Women’s Hospital in Boston, changing sheets and cleaning urinals. To a poor but proud high-caste Indian Brahmin, the culture shock of carrying out these tasks must have been especially jarring.

Dr. SubbaRow went on to earn a diploma from Harvard Medical School, also in Boston, and became a junior faculty member. As a foreigner, Dr. Mukherjee wrote, Dr. SubbaRow was a “reclusive, nocturnal, heavily accented vegetarian,” so different from his colleagues that advancement seemed impossible. Despite his pioneering biochemistry work, Harvard later declined to offer Dr. SubbaRow a tenured faculty position.

By the early 1940s, he took a job at an upstate New York pharmaceutical company called Lederle Labs (later purchased by Pfizer). At Lederle, Dr. SubbaRow strove to synthesize the vitamin known as folic acid. He ended up creating a kind of antivitamin, a lookalike that acted like folic acid but only succeeded in gumming up the works in receptors. But what good would it do to stop the body from absorbing folic acid? Plenty, it turned out.
 

Discoveries pile up, but credit and fame prove elusive

Dr. SubbaRow was no stranger to producing landmark biological work. He’d previously codiscovered phosphocreatine and ATP, which are crucial to muscular contractions. However, “in 1935, he had to disown the extent of his role in the discovery of the color test related to phosphorus, instead giving the credit to his co-author, who was being considered for promotion to a full professorship at Harvard,” wrote author Gerald Posner in his 2020 book, “Pharma: Greed, Lies and the Poisoning of America.”

Houston-area oncologist Kirtan Nautiyal, MD, who paid tribute to Dr. SubbaRow in a 2018 article, contended that “with his Indian instinct for self-effacement, he had irreparably sabotaged his own career.”

Dr. SubbaRow and his team also developed “the first effective treatment of filariasis, which causes elephantiasis of the lower limbs and genitals in millions of people, mainly in tropical countries,” Dr. Nautiyal wrote. “Later in the decade, his antibiotic program generated polymyxin, the first effective treatment against the class of bacteria called Gram negatives, and aureomycin, the first “broad-spectrum’ antibiotic.” (Aureomycin is also the first tetracycline antibiotic.)

Dr. SubbaRow’s discovery of a folic acid antagonist would again go largely unheralded. But first came the realization that folic acid made childhood leukemia worse, not better, and the prospect that this process could potentially be reversed.
 

Rise of methotrexate and fall of leukemia

In Boston, Sidney Farber, MD, a Boston pathologist, was desperate to help Robert Sandler, a 2-year-old leukemia patient. Dr. Farber contacted his ex-colleague Dr. SubbaRow to request a supply of aminopterin, an early version of methotrexate that Dr. SubbaRow and his team had developed. Dr. Farber injected Robert with the substance and within 3 days, the toddler’s white blood count started falling – fast. He stopped bleeding, resumed eating, and once again seemed almost identical to his twin brother, as Dr. Mukherjee wrote in his book.

Leukemia had never gone into remission before. Unfortunately, the treatment only worked temporarily. Robert, like other children treated with the drug, relapsed and died within months. But Dr. Farber “saw a door open” – a chemical, a kind of chemotherapy, that could turn back cancer. In the case of folic acid antagonists, they do so by stopping cancer cells from replicating.

Methotrexate, a related agent synthesized by Dr. SubbaRow, would become a mainstay of leukemia treatment and begin to produce long-term remission from acute lymphoblastic leukemia in 1970, when combination chemotherapy was developed.

Other cancers fell to methotrexate treatment. “Previous assumptions that cancer was nearly always fatal were revised, and the field of medical oncology (treatment of cancer with chemotherapy), which had not previously existed, was formally established in 1971,” according to the National Cancer Institute’s history of methotrexate. This account does not mention Dr. SubbaRow.
 

Death takes the doctor, but his legacy remains

In biographies, as well as his own words, Dr. SubbaRow comes across as a prickly, hard-driving workaholic who had little interest in intimate human connections. “It is not good to ask in every letter when I will be back,” he wrote to his wife back in India, before cutting off ties completely in the early 1930s. “I will come as early as possible. ... I do not want to write anything more.”

It seems, as his biographer S.P.K. Gupta noted, that “he was quite determined that the time allotted to him on Earth should be completely devoted to finding cures for ailments that plagued mankind.”

Still, Dr. SubbaRow’s research team was devoted to him, and he had plenty of reasons to be bitter, such as the prejudice and isolation he encountered in the United States and earlier, in British-run India. According to Mr. Posner’s book, even as a young medical student, Dr. SubbaRow heeded the call of Indian independence activist Mohandas Gandhi. He “refused the British surgical gown given him at school and instead donned a traditional and simple cotton Khadi. That act of defiance cost SubbaRow the college degree that was necessary for him to get into the State Medical College.”

During the last year of his life, Dr. SubbaRow faced yet another humiliation: In his landmark 1948 study about aminopterin as a treatment for leukemia, his colleague Dr. Farber failed to credit him, an “astonishing omission” as Yaddanapudi Ravindranath, MBBS, a pediatric hematologist/oncologist at Wayne State University, Detroit, put it. “From everything I know, Dr. Farber spent the rest of his career apologizing and trying to make amends for it,” Dr. Ravindranath said in an interview.
 

A career cut short, and a lasting legacy

In 1948, at the age of 53, Dr. SubbaRow suddenly died. “Many think Dr. SubbaRow would have won [the] Nobel Prize had he lived a few years longer,” said Dr. Ravindranath.

Like Dr. SubbaRow, Dr. Ravindranath was born in Andhra Pradesh state, near the city of Chennai formerly known as Madras. “Being a compatriot, in a way I continue his legacy, and I am obviously proud of him,” said Dr. Ravindranath, who has conducted his own landmark research regarding methotrexate and leukemia.

Nearly 75 years after Dr. SubbaRow’s death, Indian-born physicians like Dr. Ravindranath continue to honor him in print, trying to ensure that he’s not forgotten. Methotrexate remains a crucial treatment for leukemia, along with a long list of other ailments, including psoriasis.

Recognition for “Yella” may have come late and infrequently, but a Lederle Laboratories research library named after him offered Dr. SubbaRow a kind of immortality. A plaque there memorialized him in stone as a scientist, teacher, philosopher, and humanitarian, featuring the quote: “Science simply prolongs life. Religion deepens it.”

By all accounts, Dr. SubbaRow was a man of science and faith who had faith in science.

Madhu Manivannan, a third-year medical student at Emory University, Atlanta, is on the vanguard of a new approach to clinical education. Ms. Manivannan, copresident of Emory Medical Students for Climate Action, was in the first class of Emory’s medical students to experience the birth of a refined curriculum – lobbied for and partially created by students themselves. The new course of study addresses the myriad ways climate affects health: from air pollution and its effects on the lungs and cardiovascular system to heat-related kidney disease.

“We have known that climate has affected health for decades,” Ms. Manivannan said in a recent interview. “The narrative used to be that icebergs were melting and in 2050 polar bears would be extinct. The piece that’s different now is people are linking climate to increases in asthma and various diseases. We have a way to directly communicate that it’s not a far-off thing. It’s happening to your friends and family right now.”

Hospitals, medical schools, and public health programs are stepping up to educate the next generation of doctors as well as veteran medical workers on one of the most widespread, insidious health threats of our time – climate change – and specific ways it could affect their patients.

Although climate change may seem to many Americans like a distant threat, Marilyn Howarth, MD, a pediatrician in Philadelphia, is trying to make sure physicians are better prepared to treat a growing number of health problems associated with global warming.

“There isn’t a lot of education for pediatricians and internists on environmental health issues. It has not been a standard part of education in medical school or residency training,” Dr. Howarth, deputy director of the new Philadelphia Regional Center for Children’s Environmental Health, said. “With increasing attention on our climate, we really recognize there’s a real gap in physician knowledge, both in pediatric and adult care.”

Scientists have found that climate change can alter just about every system within the human body. Studies show that more extreme weather events, such as heat waves, thunderstorms, and floods, can worsen asthma and produce more pollen and mold, triggering debilitating respiratory problems.

According to the American Lung Association, ultrafine particles of air pollution can be inhaled and then travel throughout the bloodstream, wreaking havoc on organs and increasing risk of heart attack and stroke. Various types of air pollution also cause changes to the climate by trapping heat in the atmosphere, which leads to problems such as rising sea levels and extreme weather. Plus, in a new study published in Nature, scientists warn that warming climates are forcing animals to migrate to different areas, raising the risk that new infectious diseases will hop from animals – such as bats – to humans, a process called “zoonotic spillover” that many researchers believe is responsible for the COVID-19 pandemic.
 

The Philadelphia Regional Center for Children’s Environmental Health

One of the latest initiatives aimed at disseminating information about children’s health to health care providers is the Philadelphia Regional Center for Children’s Environmental Health, part of Children’s Hospital of Philadelphia and Penn Medicine. CHOP and Penn Medicine are jointly funding this center’s work, which will include educating health care providers on how to better screen for climate-caused health risks and treat related conditions, such as lead poisoning and asthma.

Outreach will focus on providers who treat patients with illnesses that researchers have linked to climate change, Dr. Howarth said. The center will offer clinicians access to seminars and webinars, along with online resources to help doctors treat environmental illnesses. For example, doctors at CHOP’s Poison Control Center are developing a toolkit for physicians to treat patients with elevated levels of lead in the blood. Scientists have linked extreme weather events related to climate change to flooding that pushes metals away from river banks where they were previously contained, allowing them to more easily contaminate homes, soils, and yards.

The initiative builds on CHOP’s Community Asthma Prevention Program (CAPP), which was launched in 1997 by Tyra Bryant-Stephens, MD, its current medical director. CAPP deploys community health workers into homes armed with supplies and tips for managing asthma. The new center will use similar tactics to provide education and resources to patients. The goal is to reach as many at-risk local children as possible.
 

Future generation of doctors fuel growth in climate change education

Lisa Doggett, MD, cofounder and president of the board of directors of Texas Physicians for Social Responsibility, announced in March that the University of Texas at Austin, Baylor College of Medicine, Houston, and the University of Texas Southwestern in Dallas have all decided to begin offering a course on environmental threats. Emory’s new curriculum has become more comprehensive every year since its start – thanks in part to the input of students like Ms. Manivannan. Faculty members tasked her with approving the new additions to the curriculum on how climate affects health, which in 2019 had consisted of a few slides about issues such as extreme heat exposure and air pollution and their effects on childbirth outcomes.

Material on climate change has now been woven into 13 courses. It is discussed at length in relation to pulmonology, cardiology, and gastropulmonology, for example, said Rebecca Philipsborn, MD, MPA, FAAP, faculty lead for the environmental and health curriculum at Emory.

The curriculum has only been incorporated into Emory’s program for the past 2 years. Dr. Philipsborn said the school plans to expand it to the clinical years to help trainees learn to treat conditions such as pediatric asthma.

“In the past few years, there has been so much momentum, and part of that is a testament to already seeing effects of climate change and how they affect delivery of health care,” she said.

At least one medical journal has recently ramped up its efforts to educate physicians on the links between health issues and climate change. Editors of Family Practice, from Oxford University Press, have announced that they plan to publish a special Climate Crisis and Primary Health Care issue in September.

Of course, not all climate initiatives in medicine are new. A select few have existed for decades.

But only now are physicians widely seeing the links between health and environment, according to Aaron Bernstein, MD, MPH, interim director of the Center for Climate, Health, and the Global Environment (C-CHANGE) at Harvard School of Public Health, Boston.

C-CHANGE, founded in 1996, was the first center in the world to focus on the health effects of environmental change.

“It’s taken 20 years, but what we’re seeing, I think, is the fruits of education,” Dr. Bernstein said. “There’s clearly a wave building here, and I think it really started with education and people younger than the people in charge calling them into account.”

Like the Philadelphia center, Harvard’s program conducts research on climate and health and educates people from high schoolers to health care veterans. Dr. Bernstein helps lead Climate MD, a program that aims to prepare health care workers for climate crises. The Climate MD team has published several articles in peer-reviewed journals on how to better treat patients struggling with environmental health problems. For example, an article on mapping patients in hurricane zones helped shed light on how systems can identify climate-vulnerable patients using public data.

They also developed a tool to help pediatricians provide “climate-informed primary care” – guidance on how to assess whether children are at risk of any harmful environmental exposures, a feature that is not part of standard pediatric visits.

Like the other programs, Climate MD uses community outreach to treat as many local patients as possible. Staff work with providers at more than 100 health clinics, particularly in areas where climate change disproportionately affects residents.

The next major step is to bring some of this into clinical practice, Dr. Bernstein said. In February 2020, C-CHANGE held its first symposium to address that issue.

“The key is to understand climate issues from a provider’s perspective,” he said. “Then those issues can really be brought to the bedside.”

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

Madhu Manivannan, a third-year medical student at Emory University, Atlanta, is on the vanguard of a new approach to clinical education. Ms. Manivannan, copresident of Emory Medical Students for Climate Action, was in the first class of Emory’s medical students to experience the birth of a refined curriculum – lobbied for and partially created by students themselves. The new course of study addresses the myriad ways climate affects health: from air pollution and its effects on the lungs and cardiovascular system to heat-related kidney disease.

“We have known that climate has affected health for decades,” Ms. Manivannan said in a recent interview. “The narrative used to be that icebergs were melting and in 2050 polar bears would be extinct. The piece that’s different now is people are linking climate to increases in asthma and various diseases. We have a way to directly communicate that it’s not a far-off thing. It’s happening to your friends and family right now.”

Hospitals, medical schools, and public health programs are stepping up to educate the next generation of doctors as well as veteran medical workers on one of the most widespread, insidious health threats of our time – climate change – and specific ways it could affect their patients.

Although climate change may seem to many Americans like a distant threat, Marilyn Howarth, MD, a pediatrician in Philadelphia, is trying to make sure physicians are better prepared to treat a growing number of health problems associated with global warming.

“There isn’t a lot of education for pediatricians and internists on environmental health issues. It has not been a standard part of education in medical school or residency training,” Dr. Howarth, deputy director of the new Philadelphia Regional Center for Children’s Environmental Health, said. “With increasing attention on our climate, we really recognize there’s a real gap in physician knowledge, both in pediatric and adult care.”

Scientists have found that climate change can alter just about every system within the human body. Studies show that more extreme weather events, such as heat waves, thunderstorms, and floods, can worsen asthma and produce more pollen and mold, triggering debilitating respiratory problems.

According to the American Lung Association, ultrafine particles of air pollution can be inhaled and then travel throughout the bloodstream, wreaking havoc on organs and increasing risk of heart attack and stroke. Various types of air pollution also cause changes to the climate by trapping heat in the atmosphere, which leads to problems such as rising sea levels and extreme weather. Plus, in a new study published in Nature, scientists warn that warming climates are forcing animals to migrate to different areas, raising the risk that new infectious diseases will hop from animals – such as bats – to humans, a process called “zoonotic spillover” that many researchers believe is responsible for the COVID-19 pandemic.
 

The Philadelphia Regional Center for Children’s Environmental Health

One of the latest initiatives aimed at disseminating information about children’s health to health care providers is the Philadelphia Regional Center for Children’s Environmental Health, part of Children’s Hospital of Philadelphia and Penn Medicine. CHOP and Penn Medicine are jointly funding this center’s work, which will include educating health care providers on how to better screen for climate-caused health risks and treat related conditions, such as lead poisoning and asthma.

Outreach will focus on providers who treat patients with illnesses that researchers have linked to climate change, Dr. Howarth said. The center will offer clinicians access to seminars and webinars, along with online resources to help doctors treat environmental illnesses. For example, doctors at CHOP’s Poison Control Center are developing a toolkit for physicians to treat patients with elevated levels of lead in the blood. Scientists have linked extreme weather events related to climate change to flooding that pushes metals away from river banks where they were previously contained, allowing them to more easily contaminate homes, soils, and yards.

The initiative builds on CHOP’s Community Asthma Prevention Program (CAPP), which was launched in 1997 by Tyra Bryant-Stephens, MD, its current medical director. CAPP deploys community health workers into homes armed with supplies and tips for managing asthma. The new center will use similar tactics to provide education and resources to patients. The goal is to reach as many at-risk local children as possible.
 

Future generation of doctors fuel growth in climate change education

Lisa Doggett, MD, cofounder and president of the board of directors of Texas Physicians for Social Responsibility, announced in March that the University of Texas at Austin, Baylor College of Medicine, Houston, and the University of Texas Southwestern in Dallas have all decided to begin offering a course on environmental threats. Emory’s new curriculum has become more comprehensive every year since its start – thanks in part to the input of students like Ms. Manivannan. Faculty members tasked her with approving the new additions to the curriculum on how climate affects health, which in 2019 had consisted of a few slides about issues such as extreme heat exposure and air pollution and their effects on childbirth outcomes.

Material on climate change has now been woven into 13 courses. It is discussed at length in relation to pulmonology, cardiology, and gastropulmonology, for example, said Rebecca Philipsborn, MD, MPA, FAAP, faculty lead for the environmental and health curriculum at Emory.

The curriculum has only been incorporated into Emory’s program for the past 2 years. Dr. Philipsborn said the school plans to expand it to the clinical years to help trainees learn to treat conditions such as pediatric asthma.

“In the past few years, there has been so much momentum, and part of that is a testament to already seeing effects of climate change and how they affect delivery of health care,” she said.

At least one medical journal has recently ramped up its efforts to educate physicians on the links between health issues and climate change. Editors of Family Practice, from Oxford University Press, have announced that they plan to publish a special Climate Crisis and Primary Health Care issue in September.

Of course, not all climate initiatives in medicine are new. A select few have existed for decades.

But only now are physicians widely seeing the links between health and environment, according to Aaron Bernstein, MD, MPH, interim director of the Center for Climate, Health, and the Global Environment (C-CHANGE) at Harvard School of Public Health, Boston.

C-CHANGE, founded in 1996, was the first center in the world to focus on the health effects of environmental change.

“It’s taken 20 years, but what we’re seeing, I think, is the fruits of education,” Dr. Bernstein said. “There’s clearly a wave building here, and I think it really started with education and people younger than the people in charge calling them into account.”

Like the Philadelphia center, Harvard’s program conducts research on climate and health and educates people from high schoolers to health care veterans. Dr. Bernstein helps lead Climate MD, a program that aims to prepare health care workers for climate crises. The Climate MD team has published several articles in peer-reviewed journals on how to better treat patients struggling with environmental health problems. For example, an article on mapping patients in hurricane zones helped shed light on how systems can identify climate-vulnerable patients using public data.

They also developed a tool to help pediatricians provide “climate-informed primary care” – guidance on how to assess whether children are at risk of any harmful environmental exposures, a feature that is not part of standard pediatric visits.

Like the other programs, Climate MD uses community outreach to treat as many local patients as possible. Staff work with providers at more than 100 health clinics, particularly in areas where climate change disproportionately affects residents.

The next major step is to bring some of this into clinical practice, Dr. Bernstein said. In February 2020, C-CHANGE held its first symposium to address that issue.

“The key is to understand climate issues from a provider’s perspective,” he said. “Then those issues can really be brought to the bedside.”

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

Madhu Manivannan, a third-year medical student at Emory University, Atlanta, is on the vanguard of a new approach to clinical education. Ms. Manivannan, copresident of Emory Medical Students for Climate Action, was in the first class of Emory’s medical students to experience the birth of a refined curriculum – lobbied for and partially created by students themselves. The new course of study addresses the myriad ways climate affects health: from air pollution and its effects on the lungs and cardiovascular system to heat-related kidney disease.

“We have known that climate has affected health for decades,” Ms. Manivannan said in a recent interview. “The narrative used to be that icebergs were melting and in 2050 polar bears would be extinct. The piece that’s different now is people are linking climate to increases in asthma and various diseases. We have a way to directly communicate that it’s not a far-off thing. It’s happening to your friends and family right now.”

Hospitals, medical schools, and public health programs are stepping up to educate the next generation of doctors as well as veteran medical workers on one of the most widespread, insidious health threats of our time – climate change – and specific ways it could affect their patients.

Although climate change may seem to many Americans like a distant threat, Marilyn Howarth, MD, a pediatrician in Philadelphia, is trying to make sure physicians are better prepared to treat a growing number of health problems associated with global warming.

“There isn’t a lot of education for pediatricians and internists on environmental health issues. It has not been a standard part of education in medical school or residency training,” Dr. Howarth, deputy director of the new Philadelphia Regional Center for Children’s Environmental Health, said. “With increasing attention on our climate, we really recognize there’s a real gap in physician knowledge, both in pediatric and adult care.”

Scientists have found that climate change can alter just about every system within the human body. Studies show that more extreme weather events, such as heat waves, thunderstorms, and floods, can worsen asthma and produce more pollen and mold, triggering debilitating respiratory problems.

According to the American Lung Association, ultrafine particles of air pollution can be inhaled and then travel throughout the bloodstream, wreaking havoc on organs and increasing risk of heart attack and stroke. Various types of air pollution also cause changes to the climate by trapping heat in the atmosphere, which leads to problems such as rising sea levels and extreme weather. Plus, in a new study published in Nature, scientists warn that warming climates are forcing animals to migrate to different areas, raising the risk that new infectious diseases will hop from animals – such as bats – to humans, a process called “zoonotic spillover” that many researchers believe is responsible for the COVID-19 pandemic.
 

The Philadelphia Regional Center for Children’s Environmental Health

One of the latest initiatives aimed at disseminating information about children’s health to health care providers is the Philadelphia Regional Center for Children’s Environmental Health, part of Children’s Hospital of Philadelphia and Penn Medicine. CHOP and Penn Medicine are jointly funding this center’s work, which will include educating health care providers on how to better screen for climate-caused health risks and treat related conditions, such as lead poisoning and asthma.

Outreach will focus on providers who treat patients with illnesses that researchers have linked to climate change, Dr. Howarth said. The center will offer clinicians access to seminars and webinars, along with online resources to help doctors treat environmental illnesses. For example, doctors at CHOP’s Poison Control Center are developing a toolkit for physicians to treat patients with elevated levels of lead in the blood. Scientists have linked extreme weather events related to climate change to flooding that pushes metals away from river banks where they were previously contained, allowing them to more easily contaminate homes, soils, and yards.

The initiative builds on CHOP’s Community Asthma Prevention Program (CAPP), which was launched in 1997 by Tyra Bryant-Stephens, MD, its current medical director. CAPP deploys community health workers into homes armed with supplies and tips for managing asthma. The new center will use similar tactics to provide education and resources to patients. The goal is to reach as many at-risk local children as possible.
 

Future generation of doctors fuel growth in climate change education

Lisa Doggett, MD, cofounder and president of the board of directors of Texas Physicians for Social Responsibility, announced in March that the University of Texas at Austin, Baylor College of Medicine, Houston, and the University of Texas Southwestern in Dallas have all decided to begin offering a course on environmental threats. Emory’s new curriculum has become more comprehensive every year since its start – thanks in part to the input of students like Ms. Manivannan. Faculty members tasked her with approving the new additions to the curriculum on how climate affects health, which in 2019 had consisted of a few slides about issues such as extreme heat exposure and air pollution and their effects on childbirth outcomes.

Material on climate change has now been woven into 13 courses. It is discussed at length in relation to pulmonology, cardiology, and gastropulmonology, for example, said Rebecca Philipsborn, MD, MPA, FAAP, faculty lead for the environmental and health curriculum at Emory.

The curriculum has only been incorporated into Emory’s program for the past 2 years. Dr. Philipsborn said the school plans to expand it to the clinical years to help trainees learn to treat conditions such as pediatric asthma.

“In the past few years, there has been so much momentum, and part of that is a testament to already seeing effects of climate change and how they affect delivery of health care,” she said.

At least one medical journal has recently ramped up its efforts to educate physicians on the links between health issues and climate change. Editors of Family Practice, from Oxford University Press, have announced that they plan to publish a special Climate Crisis and Primary Health Care issue in September.

Of course, not all climate initiatives in medicine are new. A select few have existed for decades.

But only now are physicians widely seeing the links between health and environment, according to Aaron Bernstein, MD, MPH, interim director of the Center for Climate, Health, and the Global Environment (C-CHANGE) at Harvard School of Public Health, Boston.

C-CHANGE, founded in 1996, was the first center in the world to focus on the health effects of environmental change.

“It’s taken 20 years, but what we’re seeing, I think, is the fruits of education,” Dr. Bernstein said. “There’s clearly a wave building here, and I think it really started with education and people younger than the people in charge calling them into account.”

Like the Philadelphia center, Harvard’s program conducts research on climate and health and educates people from high schoolers to health care veterans. Dr. Bernstein helps lead Climate MD, a program that aims to prepare health care workers for climate crises. The Climate MD team has published several articles in peer-reviewed journals on how to better treat patients struggling with environmental health problems. For example, an article on mapping patients in hurricane zones helped shed light on how systems can identify climate-vulnerable patients using public data.

They also developed a tool to help pediatricians provide “climate-informed primary care” – guidance on how to assess whether children are at risk of any harmful environmental exposures, a feature that is not part of standard pediatric visits.

Like the other programs, Climate MD uses community outreach to treat as many local patients as possible. Staff work with providers at more than 100 health clinics, particularly in areas where climate change disproportionately affects residents.

The next major step is to bring some of this into clinical practice, Dr. Bernstein said. In February 2020, C-CHANGE held its first symposium to address that issue.

“The key is to understand climate issues from a provider’s perspective,” he said. “Then those issues can really be brought to the bedside.”

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

The current sustained increase in COVID-19 has brought the total number of cases in children to over 13 million since the start of the pandemic, according to the American Academy of Pediatrics and the Children’s Hospital Association.

The latest weekly count – 62,467 reported for the week ending May 5 – was 17.4% higher than the previous week and marks four consecutive increases since early April, when cases dropped to their lowest point since last summer. The cumulative number of cases in children is 13,052,988, which accounts for 19.0% of all cases reported in the United States, the AAP and CHA said in their weekly COVID-19 report.

Other measures of incidence show the same steady rise. The rate of new admissions of children aged 0-17 with confirmed COVID-19, which had dipped as low as 0.13 per 100,000 population on April 11, was up to 0.19 per 100,000 on May 6, and the 7-day average for total admissions was 136 per day for May 1-7, compared with 118 for the last week of April, according to the Centers for Disease Control and Prevention.

At the state level, new admission rates for May 6 show wide variation, even regionally. Rhode Island came in with a 0.00 per 100,000 on that day, while Vermont recorded 0.88 admissions per 100,000, the highest of any state and lower only than the District of Columbia’s 1.23 per 100,000. Connecticut (0.45) and Massachusetts (0.33) also were in the highest group (see map), while Maine was in the lowest, CDC data show.

Nationally, emergency department visits also have been rising over the last month or so. Children aged 0-11 years, who were down to a 7-day average of 0.5% of ED visits with diagnosed COVID-19 in early April, saw that number rise to 1.4% on May 5. Children aged 12-15 years went from a rate of 0.3% in late March to the current 1.2%, as did 16- to 17-year-olds, the CDC said on its COVID Data Tracker.

The vaccination effort, meanwhile, continues to lose steam, at least among children who are currently eligible. Initial vaccinations in those aged 5-11 slipped to their lowest-ever 1-week total, 47,000 for April 28 to May 4, while children aged 16-17 continued a long-term slide that has the weekly count down to just 29,000, the AAP said in its weekly vaccination report.

Here’s how those latest recipients changed the populations of vaccinated children in the last week: 35.4% of all 5- to 11-year-olds had received at least one dose as of May 4, compared with 35.3% on April 27, with increases from 67.4% to 67.5% for 12- to 15-year-olds and 72.7% to 72.8% among those aged 16-17, the CDC reported.
 

The current sustained increase in COVID-19 has brought the total number of cases in children to over 13 million since the start of the pandemic, according to the American Academy of Pediatrics and the Children’s Hospital Association.

The latest weekly count – 62,467 reported for the week ending May 5 – was 17.4% higher than the previous week and marks four consecutive increases since early April, when cases dropped to their lowest point since last summer. The cumulative number of cases in children is 13,052,988, which accounts for 19.0% of all cases reported in the United States, the AAP and CHA said in their weekly COVID-19 report.

Other measures of incidence show the same steady rise. The rate of new admissions of children aged 0-17 with confirmed COVID-19, which had dipped as low as 0.13 per 100,000 population on April 11, was up to 0.19 per 100,000 on May 6, and the 7-day average for total admissions was 136 per day for May 1-7, compared with 118 for the last week of April, according to the Centers for Disease Control and Prevention.

At the state level, new admission rates for May 6 show wide variation, even regionally. Rhode Island came in with a 0.00 per 100,000 on that day, while Vermont recorded 0.88 admissions per 100,000, the highest of any state and lower only than the District of Columbia’s 1.23 per 100,000. Connecticut (0.45) and Massachusetts (0.33) also were in the highest group (see map), while Maine was in the lowest, CDC data show.

Nationally, emergency department visits also have been rising over the last month or so. Children aged 0-11 years, who were down to a 7-day average of 0.5% of ED visits with diagnosed COVID-19 in early April, saw that number rise to 1.4% on May 5. Children aged 12-15 years went from a rate of 0.3% in late March to the current 1.2%, as did 16- to 17-year-olds, the CDC said on its COVID Data Tracker.

The vaccination effort, meanwhile, continues to lose steam, at least among children who are currently eligible. Initial vaccinations in those aged 5-11 slipped to their lowest-ever 1-week total, 47,000 for April 28 to May 4, while children aged 16-17 continued a long-term slide that has the weekly count down to just 29,000, the AAP said in its weekly vaccination report.

Here’s how those latest recipients changed the populations of vaccinated children in the last week: 35.4% of all 5- to 11-year-olds had received at least one dose as of May 4, compared with 35.3% on April 27, with increases from 67.4% to 67.5% for 12- to 15-year-olds and 72.7% to 72.8% among those aged 16-17, the CDC reported.
 

The current sustained increase in COVID-19 has brought the total number of cases in children to over 13 million since the start of the pandemic, according to the American Academy of Pediatrics and the Children’s Hospital Association.

The latest weekly count – 62,467 reported for the week ending May 5 – was 17.4% higher than the previous week and marks four consecutive increases since early April, when cases dropped to their lowest point since last summer. The cumulative number of cases in children is 13,052,988, which accounts for 19.0% of all cases reported in the United States, the AAP and CHA said in their weekly COVID-19 report.

Other measures of incidence show the same steady rise. The rate of new admissions of children aged 0-17 with confirmed COVID-19, which had dipped as low as 0.13 per 100,000 population on April 11, was up to 0.19 per 100,000 on May 6, and the 7-day average for total admissions was 136 per day for May 1-7, compared with 118 for the last week of April, according to the Centers for Disease Control and Prevention.

At the state level, new admission rates for May 6 show wide variation, even regionally. Rhode Island came in with a 0.00 per 100,000 on that day, while Vermont recorded 0.88 admissions per 100,000, the highest of any state and lower only than the District of Columbia’s 1.23 per 100,000. Connecticut (0.45) and Massachusetts (0.33) also were in the highest group (see map), while Maine was in the lowest, CDC data show.

Nationally, emergency department visits also have been rising over the last month or so. Children aged 0-11 years, who were down to a 7-day average of 0.5% of ED visits with diagnosed COVID-19 in early April, saw that number rise to 1.4% on May 5. Children aged 12-15 years went from a rate of 0.3% in late March to the current 1.2%, as did 16- to 17-year-olds, the CDC said on its COVID Data Tracker.

The vaccination effort, meanwhile, continues to lose steam, at least among children who are currently eligible. Initial vaccinations in those aged 5-11 slipped to their lowest-ever 1-week total, 47,000 for April 28 to May 4, while children aged 16-17 continued a long-term slide that has the weekly count down to just 29,000, the AAP said in its weekly vaccination report.

Here’s how those latest recipients changed the populations of vaccinated children in the last week: 35.4% of all 5- to 11-year-olds had received at least one dose as of May 4, compared with 35.3% on April 27, with increases from 67.4% to 67.5% for 12- to 15-year-olds and 72.7% to 72.8% among those aged 16-17, the CDC reported.