Adolescent Medicine

While 34 million adults in the United States have received a COVID-19 vaccine, children and teenagers are waiting at the back of the line, mostly ineligible for the authorized vaccines. That secondary status is rapidly changing though, as experts expect vaccinations of adolescents to begin by this summer.

The vaccinations can’t come soon enough for parents like Stacy Hillenburg, a developmental therapist in Aurora, Ill., whose 9-year-old son takes immunosuppressants because he had a heart transplant when he was 7 weeks old. Although school-age children aren’t yet included in clinical trials, if her 12- and 13-year-old daughters could get vaccinated, along with both parents, then the family could relax some of the protocols they currently follow to prevent infection.

Whenever they are around other people, even masked and socially distanced, they come home and immediately shower and change their clothes. So far, no one in the family has been infected with COVID, but the anxiety is ever-present. “I can’t wait for it to come out,” Ms. Hillenburg said of a pediatric COVID vaccine. “It will ease my mind so much.”

She isn’t alone in that anticipation. In the fall, the American Academy of Pediatrics and other pediatric vaccine experts urged faster action on pediatric vaccine trials and worried that children would be left behind as adults gained protection from COVID. But recent developments have eased those concerns.

“Over the next couple of months, we will be doing trials in an age-deescalation manner,” with studies moving gradually to younger children, Anthony S. Fauci, MD, chief medical adviser on COVID-19 to the president, said in a coronavirus response team briefing on Jan. 29. “So that hopefully, as we get to the late spring and summer, we will have children being able to be vaccinated.”

Pfizer completed enrollment of 2,259 teens aged 12-15 years in late January and expects to move forward with a separate pediatric trial of children aged 5-11 years by this spring, Keanna Ghazvini, senior associate for global media relations at Pfizer, said in an interview.

Enrollment in Moderna’s TeenCove study of adolescents ages 12-17 years began slowly in late December, but the pace has since picked up, said company spokesperson Colleen Hussey. “We continue to bring clinical trial sites online, and we are on track to provide updated data around mid-year 2021.” A trial extension in children 11 years and younger is expected to begin later in 2021.

Johnson & Johnson and AstraZeneca said they expect to begin adolescent trials in early 2021, according to data shared by the Advisory Committee on Immunization Practices. An interim analysis of J&J’s Janssen COVID-19 vaccine trial data, released on Jan. 29, showed it was 72% effective in US participants aged 18 years or older. AstraZeneca’s U.S. trial in adults is ongoing.
 

Easing the burden

Vaccination could lessen children’s risk of severe disease as well as the social and emotional burdens of the pandemic, says James Campbell, MD, a pediatric infectious disease specialist at the University of Maryland’s Center for Vaccine Development in Baltimore, which was involved in the Moderna and early-phase Pfizer trials. He coauthored a September 2020 article in Clinical Infectious Diseases titled: “Warp Speed for COVID-19 vaccines: Why are children stuck in neutral?”

The adolescent trials are a vital step to ensure timely vaccine access for teens and younger children. “It is reasonable, when you have limited vaccine, that your rollout goes to the highest priority and then moves to lower and lower priorities. In adults, we’re just saying: ‘Wait your turn,’ ” he said of the current vaccination effort. “If we didn’t have the [vaccine trial] data in children, we’d be saying: ‘You don’t have a turn.’ ”

As the pandemic has worn on, the burden on children has grown. As of Tuesday, 269 children had died of COVID-19. That is well above the highest annual death toll recorded during a regular flu season – 188 flu deaths among children and adolescents under 18 in the 2019-2020 and 2017-2018 flu seasons.

Children are less likely to transmit COVID-19 in their household than adults, according to a meta-analysis of 54 studies published in JAMA Network Open. But that does not necessarily mean children are less infectious, the authors said, noting that unmeasured factors could have affected the spread of infection among adults.

Moreover, children and adolescents need protection from COVID infection – and from the potential for severe disease or lingering effects – and, given that there are 74 million children and teens in the United States, their vaccination is an important part of stopping the pandemic, said Grace Lee, MD, professor of pediatrics at Stanford (Calif.) University, and cochair of ACIP’s COVID-19 Vaccine Safety Technical Subgroup.

“In order to interrupt transmission, I don’t see how we’re going to do that without vaccinating children and adolescents,” she said.

Dr. Lee said her 16-year-old daughter misses the normal teenage social life and is excited about getting the vaccine when she is eligible. (Adolescents without high-risk conditions are in the lowest vaccination tier, according to ACIP recommendations.) “There is truly individual protection to be gained,” Dr. Lee said.

She noted that researchers continue to assess the immune responses to the adult vaccines – even looking at immune characteristics of the small percentage of people who aren’t protected from infection – and that information helps in the evaluation of the pediatric immune responses. As the trials expand to younger children and infants, dosing will be a major focus. “How many doses do they need they need to receive the same immunity? Safety considerations will be critically important,” she said.
 

Teen trials underway

Pfizer/BioNTech extended its adult trial to 16- and 17-year-olds in October, which enabled older teens to be included in its emergency-use authorization. They and younger teens, ages 12-15, receive the same dose as adults.

The ongoing trials with Pfizer and Moderna vaccines are immunobridging trials, designed to study safety and immunogenicity. Investigators will compare the teens’ immune response with the findings from the larger adult trials. When the trials expand to school-age children (6-12 years), protocols call for testing the safety and immunogenicity of a half-dose vaccine as well as the full dose.

Children ages 2-5 years and infants and toddlers will be enrolled in future trials, studying safety and immunogenicity of full, half, or even quarter dosages. The Pediatric Research Equity Act of 2003 requires licensed vaccines to be tested for safety and efficacy in children, unless they are not appropriate for a pediatric population.

Demand for the teen trials has been strong. At Cincinnati Children’s Hospital Medical Center, 259 teenagers joined the Pfizer/BioNTech trial, but some teenagers were turned away when the trial’s national enrollment closed in late January.

“Many of the children are having no side effects, and if they are, they’re having the same [effects] as the young adults – local redness or pain, fatigue, and headaches,” said Robert Frenck, MD, director of the Cincinnati Children’s Gamble Program for Clinical Studies.

Parents may share some of the vaccine hesitancy that has affected adult vaccination. But that is balanced by the hope that vaccines will end the pandemic and usher in a new normal. “If it looks like [vaccines] will increase the likelihood of children returning to school safely, that may be a motivating factor,” Dr. Frenck said.

Cody Meissner, MD, chief of the pediatric infectious disease service at Tufts Medical Center, Boston, was initially cautious about the extension of vaccination to adolescents. A member of the Vaccine and Related Biological Products Advisory Committee, which evaluates data and makes recommendations to the Food and Drug Administration, Dr. Meissner initially abstained in the vote on the Pfizer/BioNTech emergency-use authorization for people 16 and older.

He noted that, at the time the committee reviewed the Pfizer vaccine, the company had data available for just 134 teenagers, half of whom received a placebo. But the vaccination of 34 million adults has provided robust data about the vaccine’s safety, and the trial expansion into adolescents is important.

“I’m comfortable with the way these trials are going now,” he said. “This is the way I was hoping they would go.”

Ms. Hillenburg is on the parent advisory board of Voices for Vaccines, an organization of parents supporting vaccination that is affiliated with the Task Force for Global Health, an Atlanta-based independent public health organization. Dr. Campbell’s institution has received funds to conduct clinical trials from the National Institutes of Health and several companies, including Merck, GlaxoSmithKline, Sanofi, Pfizer, and Moderna. He has served pro bono on many safety and data monitoring committees. Dr. Frenck’s institution is receiving funds to conduct the Pfizer trial. In the past 5 years, he has also participated in clinical trials for GlaxoSmithKline, Merck, and Meissa vaccines. Dr. Lee and Dr. Meissner disclosed no relevant financial relationships.

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

While 34 million adults in the United States have received a COVID-19 vaccine, children and teenagers are waiting at the back of the line, mostly ineligible for the authorized vaccines. That secondary status is rapidly changing though, as experts expect vaccinations of adolescents to begin by this summer.

The vaccinations can’t come soon enough for parents like Stacy Hillenburg, a developmental therapist in Aurora, Ill., whose 9-year-old son takes immunosuppressants because he had a heart transplant when he was 7 weeks old. Although school-age children aren’t yet included in clinical trials, if her 12- and 13-year-old daughters could get vaccinated, along with both parents, then the family could relax some of the protocols they currently follow to prevent infection.

Whenever they are around other people, even masked and socially distanced, they come home and immediately shower and change their clothes. So far, no one in the family has been infected with COVID, but the anxiety is ever-present. “I can’t wait for it to come out,” Ms. Hillenburg said of a pediatric COVID vaccine. “It will ease my mind so much.”

She isn’t alone in that anticipation. In the fall, the American Academy of Pediatrics and other pediatric vaccine experts urged faster action on pediatric vaccine trials and worried that children would be left behind as adults gained protection from COVID. But recent developments have eased those concerns.

“Over the next couple of months, we will be doing trials in an age-deescalation manner,” with studies moving gradually to younger children, Anthony S. Fauci, MD, chief medical adviser on COVID-19 to the president, said in a coronavirus response team briefing on Jan. 29. “So that hopefully, as we get to the late spring and summer, we will have children being able to be vaccinated.”

Pfizer completed enrollment of 2,259 teens aged 12-15 years in late January and expects to move forward with a separate pediatric trial of children aged 5-11 years by this spring, Keanna Ghazvini, senior associate for global media relations at Pfizer, said in an interview.

Enrollment in Moderna’s TeenCove study of adolescents ages 12-17 years began slowly in late December, but the pace has since picked up, said company spokesperson Colleen Hussey. “We continue to bring clinical trial sites online, and we are on track to provide updated data around mid-year 2021.” A trial extension in children 11 years and younger is expected to begin later in 2021.

Johnson & Johnson and AstraZeneca said they expect to begin adolescent trials in early 2021, according to data shared by the Advisory Committee on Immunization Practices. An interim analysis of J&J’s Janssen COVID-19 vaccine trial data, released on Jan. 29, showed it was 72% effective in US participants aged 18 years or older. AstraZeneca’s U.S. trial in adults is ongoing.
 

Easing the burden

Vaccination could lessen children’s risk of severe disease as well as the social and emotional burdens of the pandemic, says James Campbell, MD, a pediatric infectious disease specialist at the University of Maryland’s Center for Vaccine Development in Baltimore, which was involved in the Moderna and early-phase Pfizer trials. He coauthored a September 2020 article in Clinical Infectious Diseases titled: “Warp Speed for COVID-19 vaccines: Why are children stuck in neutral?”

The adolescent trials are a vital step to ensure timely vaccine access for teens and younger children. “It is reasonable, when you have limited vaccine, that your rollout goes to the highest priority and then moves to lower and lower priorities. In adults, we’re just saying: ‘Wait your turn,’ ” he said of the current vaccination effort. “If we didn’t have the [vaccine trial] data in children, we’d be saying: ‘You don’t have a turn.’ ”

As the pandemic has worn on, the burden on children has grown. As of Tuesday, 269 children had died of COVID-19. That is well above the highest annual death toll recorded during a regular flu season – 188 flu deaths among children and adolescents under 18 in the 2019-2020 and 2017-2018 flu seasons.

Children are less likely to transmit COVID-19 in their household than adults, according to a meta-analysis of 54 studies published in JAMA Network Open. But that does not necessarily mean children are less infectious, the authors said, noting that unmeasured factors could have affected the spread of infection among adults.

Moreover, children and adolescents need protection from COVID infection – and from the potential for severe disease or lingering effects – and, given that there are 74 million children and teens in the United States, their vaccination is an important part of stopping the pandemic, said Grace Lee, MD, professor of pediatrics at Stanford (Calif.) University, and cochair of ACIP’s COVID-19 Vaccine Safety Technical Subgroup.

“In order to interrupt transmission, I don’t see how we’re going to do that without vaccinating children and adolescents,” she said.

Dr. Lee said her 16-year-old daughter misses the normal teenage social life and is excited about getting the vaccine when she is eligible. (Adolescents without high-risk conditions are in the lowest vaccination tier, according to ACIP recommendations.) “There is truly individual protection to be gained,” Dr. Lee said.

She noted that researchers continue to assess the immune responses to the adult vaccines – even looking at immune characteristics of the small percentage of people who aren’t protected from infection – and that information helps in the evaluation of the pediatric immune responses. As the trials expand to younger children and infants, dosing will be a major focus. “How many doses do they need they need to receive the same immunity? Safety considerations will be critically important,” she said.
 

Teen trials underway

Pfizer/BioNTech extended its adult trial to 16- and 17-year-olds in October, which enabled older teens to be included in its emergency-use authorization. They and younger teens, ages 12-15, receive the same dose as adults.

The ongoing trials with Pfizer and Moderna vaccines are immunobridging trials, designed to study safety and immunogenicity. Investigators will compare the teens’ immune response with the findings from the larger adult trials. When the trials expand to school-age children (6-12 years), protocols call for testing the safety and immunogenicity of a half-dose vaccine as well as the full dose.

Children ages 2-5 years and infants and toddlers will be enrolled in future trials, studying safety and immunogenicity of full, half, or even quarter dosages. The Pediatric Research Equity Act of 2003 requires licensed vaccines to be tested for safety and efficacy in children, unless they are not appropriate for a pediatric population.

Demand for the teen trials has been strong. At Cincinnati Children’s Hospital Medical Center, 259 teenagers joined the Pfizer/BioNTech trial, but some teenagers were turned away when the trial’s national enrollment closed in late January.

“Many of the children are having no side effects, and if they are, they’re having the same [effects] as the young adults – local redness or pain, fatigue, and headaches,” said Robert Frenck, MD, director of the Cincinnati Children’s Gamble Program for Clinical Studies.

Parents may share some of the vaccine hesitancy that has affected adult vaccination. But that is balanced by the hope that vaccines will end the pandemic and usher in a new normal. “If it looks like [vaccines] will increase the likelihood of children returning to school safely, that may be a motivating factor,” Dr. Frenck said.

Cody Meissner, MD, chief of the pediatric infectious disease service at Tufts Medical Center, Boston, was initially cautious about the extension of vaccination to adolescents. A member of the Vaccine and Related Biological Products Advisory Committee, which evaluates data and makes recommendations to the Food and Drug Administration, Dr. Meissner initially abstained in the vote on the Pfizer/BioNTech emergency-use authorization for people 16 and older.

He noted that, at the time the committee reviewed the Pfizer vaccine, the company had data available for just 134 teenagers, half of whom received a placebo. But the vaccination of 34 million adults has provided robust data about the vaccine’s safety, and the trial expansion into adolescents is important.

“I’m comfortable with the way these trials are going now,” he said. “This is the way I was hoping they would go.”

Ms. Hillenburg is on the parent advisory board of Voices for Vaccines, an organization of parents supporting vaccination that is affiliated with the Task Force for Global Health, an Atlanta-based independent public health organization. Dr. Campbell’s institution has received funds to conduct clinical trials from the National Institutes of Health and several companies, including Merck, GlaxoSmithKline, Sanofi, Pfizer, and Moderna. He has served pro bono on many safety and data monitoring committees. Dr. Frenck’s institution is receiving funds to conduct the Pfizer trial. In the past 5 years, he has also participated in clinical trials for GlaxoSmithKline, Merck, and Meissa vaccines. Dr. Lee and Dr. Meissner disclosed no relevant financial relationships.

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

While 34 million adults in the United States have received a COVID-19 vaccine, children and teenagers are waiting at the back of the line, mostly ineligible for the authorized vaccines. That secondary status is rapidly changing though, as experts expect vaccinations of adolescents to begin by this summer.

The vaccinations can’t come soon enough for parents like Stacy Hillenburg, a developmental therapist in Aurora, Ill., whose 9-year-old son takes immunosuppressants because he had a heart transplant when he was 7 weeks old. Although school-age children aren’t yet included in clinical trials, if her 12- and 13-year-old daughters could get vaccinated, along with both parents, then the family could relax some of the protocols they currently follow to prevent infection.

Whenever they are around other people, even masked and socially distanced, they come home and immediately shower and change their clothes. So far, no one in the family has been infected with COVID, but the anxiety is ever-present. “I can’t wait for it to come out,” Ms. Hillenburg said of a pediatric COVID vaccine. “It will ease my mind so much.”

She isn’t alone in that anticipation. In the fall, the American Academy of Pediatrics and other pediatric vaccine experts urged faster action on pediatric vaccine trials and worried that children would be left behind as adults gained protection from COVID. But recent developments have eased those concerns.

“Over the next couple of months, we will be doing trials in an age-deescalation manner,” with studies moving gradually to younger children, Anthony S. Fauci, MD, chief medical adviser on COVID-19 to the president, said in a coronavirus response team briefing on Jan. 29. “So that hopefully, as we get to the late spring and summer, we will have children being able to be vaccinated.”

Pfizer completed enrollment of 2,259 teens aged 12-15 years in late January and expects to move forward with a separate pediatric trial of children aged 5-11 years by this spring, Keanna Ghazvini, senior associate for global media relations at Pfizer, said in an interview.

Enrollment in Moderna’s TeenCove study of adolescents ages 12-17 years began slowly in late December, but the pace has since picked up, said company spokesperson Colleen Hussey. “We continue to bring clinical trial sites online, and we are on track to provide updated data around mid-year 2021.” A trial extension in children 11 years and younger is expected to begin later in 2021.

Johnson & Johnson and AstraZeneca said they expect to begin adolescent trials in early 2021, according to data shared by the Advisory Committee on Immunization Practices. An interim analysis of J&J’s Janssen COVID-19 vaccine trial data, released on Jan. 29, showed it was 72% effective in US participants aged 18 years or older. AstraZeneca’s U.S. trial in adults is ongoing.
 

Easing the burden

Vaccination could lessen children’s risk of severe disease as well as the social and emotional burdens of the pandemic, says James Campbell, MD, a pediatric infectious disease specialist at the University of Maryland’s Center for Vaccine Development in Baltimore, which was involved in the Moderna and early-phase Pfizer trials. He coauthored a September 2020 article in Clinical Infectious Diseases titled: “Warp Speed for COVID-19 vaccines: Why are children stuck in neutral?”

The adolescent trials are a vital step to ensure timely vaccine access for teens and younger children. “It is reasonable, when you have limited vaccine, that your rollout goes to the highest priority and then moves to lower and lower priorities. In adults, we’re just saying: ‘Wait your turn,’ ” he said of the current vaccination effort. “If we didn’t have the [vaccine trial] data in children, we’d be saying: ‘You don’t have a turn.’ ”

As the pandemic has worn on, the burden on children has grown. As of Tuesday, 269 children had died of COVID-19. That is well above the highest annual death toll recorded during a regular flu season – 188 flu deaths among children and adolescents under 18 in the 2019-2020 and 2017-2018 flu seasons.

Children are less likely to transmit COVID-19 in their household than adults, according to a meta-analysis of 54 studies published in JAMA Network Open. But that does not necessarily mean children are less infectious, the authors said, noting that unmeasured factors could have affected the spread of infection among adults.

Moreover, children and adolescents need protection from COVID infection – and from the potential for severe disease or lingering effects – and, given that there are 74 million children and teens in the United States, their vaccination is an important part of stopping the pandemic, said Grace Lee, MD, professor of pediatrics at Stanford (Calif.) University, and cochair of ACIP’s COVID-19 Vaccine Safety Technical Subgroup.

“In order to interrupt transmission, I don’t see how we’re going to do that without vaccinating children and adolescents,” she said.

Dr. Lee said her 16-year-old daughter misses the normal teenage social life and is excited about getting the vaccine when she is eligible. (Adolescents without high-risk conditions are in the lowest vaccination tier, according to ACIP recommendations.) “There is truly individual protection to be gained,” Dr. Lee said.

She noted that researchers continue to assess the immune responses to the adult vaccines – even looking at immune characteristics of the small percentage of people who aren’t protected from infection – and that information helps in the evaluation of the pediatric immune responses. As the trials expand to younger children and infants, dosing will be a major focus. “How many doses do they need they need to receive the same immunity? Safety considerations will be critically important,” she said.
 

Teen trials underway

Pfizer/BioNTech extended its adult trial to 16- and 17-year-olds in October, which enabled older teens to be included in its emergency-use authorization. They and younger teens, ages 12-15, receive the same dose as adults.

The ongoing trials with Pfizer and Moderna vaccines are immunobridging trials, designed to study safety and immunogenicity. Investigators will compare the teens’ immune response with the findings from the larger adult trials. When the trials expand to school-age children (6-12 years), protocols call for testing the safety and immunogenicity of a half-dose vaccine as well as the full dose.

Children ages 2-5 years and infants and toddlers will be enrolled in future trials, studying safety and immunogenicity of full, half, or even quarter dosages. The Pediatric Research Equity Act of 2003 requires licensed vaccines to be tested for safety and efficacy in children, unless they are not appropriate for a pediatric population.

Demand for the teen trials has been strong. At Cincinnati Children’s Hospital Medical Center, 259 teenagers joined the Pfizer/BioNTech trial, but some teenagers were turned away when the trial’s national enrollment closed in late January.

“Many of the children are having no side effects, and if they are, they’re having the same [effects] as the young adults – local redness or pain, fatigue, and headaches,” said Robert Frenck, MD, director of the Cincinnati Children’s Gamble Program for Clinical Studies.

Parents may share some of the vaccine hesitancy that has affected adult vaccination. But that is balanced by the hope that vaccines will end the pandemic and usher in a new normal. “If it looks like [vaccines] will increase the likelihood of children returning to school safely, that may be a motivating factor,” Dr. Frenck said.

Cody Meissner, MD, chief of the pediatric infectious disease service at Tufts Medical Center, Boston, was initially cautious about the extension of vaccination to adolescents. A member of the Vaccine and Related Biological Products Advisory Committee, which evaluates data and makes recommendations to the Food and Drug Administration, Dr. Meissner initially abstained in the vote on the Pfizer/BioNTech emergency-use authorization for people 16 and older.

He noted that, at the time the committee reviewed the Pfizer vaccine, the company had data available for just 134 teenagers, half of whom received a placebo. But the vaccination of 34 million adults has provided robust data about the vaccine’s safety, and the trial expansion into adolescents is important.

“I’m comfortable with the way these trials are going now,” he said. “This is the way I was hoping they would go.”

Ms. Hillenburg is on the parent advisory board of Voices for Vaccines, an organization of parents supporting vaccination that is affiliated with the Task Force for Global Health, an Atlanta-based independent public health organization. Dr. Campbell’s institution has received funds to conduct clinical trials from the National Institutes of Health and several companies, including Merck, GlaxoSmithKline, Sanofi, Pfizer, and Moderna. He has served pro bono on many safety and data monitoring committees. Dr. Frenck’s institution is receiving funds to conduct the Pfizer trial. In the past 5 years, he has also participated in clinical trials for GlaxoSmithKline, Merck, and Meissa vaccines. Dr. Lee and Dr. Meissner disclosed no relevant financial relationships.

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

Moderna probably will not have clinical trial results anytime soon on how its COVID-19 vaccine affects children and adolescents, according to the company CEO and a federal official.

The Moderna vaccine was authorized for use in December and is now being given to people 18 and over. But children would receive lower doses, so new clinical trials must be done, Moderna CEO Stephane Bancel said at the JPMorgan virtual Health Care Conference on Monday.

Clinical trials on children 11 and younger “will take much longer, because we have to age deescalate and start at a lower dose. So we should not anticipate clinical data in 2021, but more in 2022,” Ms. Bancel said, according to Business Insider.

Moderna’s clinical trials for 12- to 17-year-olds started 4 weeks ago, but the company is having trouble getting enough participants, said Moncef Slaoui, PhD, the scientific head of Operation Warp Speed, the U.S. government’s vaccine effort. That could delay Food and Drug Administration approval, he said.

“It’s really very important for all of us, for all the population in America, to realize that we can’t have that indication unless adolescents aged 12-18 decide to participate,” Dr. Slaoui said, according to USA Today.

He said the adolescent trials are getting only about 800 volunteers a month, but need at least 3,000 volunteers to complete the study, USA Today reported. Parents interested in having their child participate can check eligibility and sign at this website.

The Pfizer/BioNTech vaccine won authorization for use in 16- to 17-year-olds as well as adults.

The coronavirus doesn’t appear to have as serious complications for children as for adults.

“At this time, it appears that severe illness due to COVID-19 is rare among children,” the American Association of Pediatrics says. “However, there is an urgent need to collect more data on longer-term impacts of the pandemic on children, including ways the virus may harm the long-term physical health of infected children, as well as its emotional and mental health effects.”

The association says 179 children had died of COVID-related reasons in 43 states and New York City as of Dec. 31, 2020. That’s about 0.06% of total COVID deaths, it says.

But children do get sick. As of Jan. 7, 2021, nearly 2.3 million children had tested positive for COVID-19 since the start of the pandemic, the association says.

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

Moderna probably will not have clinical trial results anytime soon on how its COVID-19 vaccine affects children and adolescents, according to the company CEO and a federal official.

The Moderna vaccine was authorized for use in December and is now being given to people 18 and over. But children would receive lower doses, so new clinical trials must be done, Moderna CEO Stephane Bancel said at the JPMorgan virtual Health Care Conference on Monday.

Clinical trials on children 11 and younger “will take much longer, because we have to age deescalate and start at a lower dose. So we should not anticipate clinical data in 2021, but more in 2022,” Ms. Bancel said, according to Business Insider.

Moderna’s clinical trials for 12- to 17-year-olds started 4 weeks ago, but the company is having trouble getting enough participants, said Moncef Slaoui, PhD, the scientific head of Operation Warp Speed, the U.S. government’s vaccine effort. That could delay Food and Drug Administration approval, he said.

“It’s really very important for all of us, for all the population in America, to realize that we can’t have that indication unless adolescents aged 12-18 decide to participate,” Dr. Slaoui said, according to USA Today.

He said the adolescent trials are getting only about 800 volunteers a month, but need at least 3,000 volunteers to complete the study, USA Today reported. Parents interested in having their child participate can check eligibility and sign at this website.

The Pfizer/BioNTech vaccine won authorization for use in 16- to 17-year-olds as well as adults.

The coronavirus doesn’t appear to have as serious complications for children as for adults.

“At this time, it appears that severe illness due to COVID-19 is rare among children,” the American Association of Pediatrics says. “However, there is an urgent need to collect more data on longer-term impacts of the pandemic on children, including ways the virus may harm the long-term physical health of infected children, as well as its emotional and mental health effects.”

The association says 179 children had died of COVID-related reasons in 43 states and New York City as of Dec. 31, 2020. That’s about 0.06% of total COVID deaths, it says.

But children do get sick. As of Jan. 7, 2021, nearly 2.3 million children had tested positive for COVID-19 since the start of the pandemic, the association says.

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

Moderna probably will not have clinical trial results anytime soon on how its COVID-19 vaccine affects children and adolescents, according to the company CEO and a federal official.

The Moderna vaccine was authorized for use in December and is now being given to people 18 and over. But children would receive lower doses, so new clinical trials must be done, Moderna CEO Stephane Bancel said at the JPMorgan virtual Health Care Conference on Monday.

Clinical trials on children 11 and younger “will take much longer, because we have to age deescalate and start at a lower dose. So we should not anticipate clinical data in 2021, but more in 2022,” Ms. Bancel said, according to Business Insider.

Moderna’s clinical trials for 12- to 17-year-olds started 4 weeks ago, but the company is having trouble getting enough participants, said Moncef Slaoui, PhD, the scientific head of Operation Warp Speed, the U.S. government’s vaccine effort. That could delay Food and Drug Administration approval, he said.

“It’s really very important for all of us, for all the population in America, to realize that we can’t have that indication unless adolescents aged 12-18 decide to participate,” Dr. Slaoui said, according to USA Today.

He said the adolescent trials are getting only about 800 volunteers a month, but need at least 3,000 volunteers to complete the study, USA Today reported. Parents interested in having their child participate can check eligibility and sign at this website.

The Pfizer/BioNTech vaccine won authorization for use in 16- to 17-year-olds as well as adults.

The coronavirus doesn’t appear to have as serious complications for children as for adults.

“At this time, it appears that severe illness due to COVID-19 is rare among children,” the American Association of Pediatrics says. “However, there is an urgent need to collect more data on longer-term impacts of the pandemic on children, including ways the virus may harm the long-term physical health of infected children, as well as its emotional and mental health effects.”

The association says 179 children had died of COVID-related reasons in 43 states and New York City as of Dec. 31, 2020. That’s about 0.06% of total COVID deaths, it says.

But children do get sick. As of Jan. 7, 2021, nearly 2.3 million children had tested positive for COVID-19 since the start of the pandemic, the association says.

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

Several updates in the strategy for prevention of and treatment of sexually transmitted infections were recently published in the United States.

Among these are the U.S. Department of Health and Human Services’ first “Sexually Transmitted Infections (STIs) National Strategic Plan for the United States,” which has a strong encompassing vision.

• Prevent New STIs.
• Improve the health of people by reducing adverse outcomes of STIs.
• Accelerate progress in STI research, technology, and innovation.
• Reduce STI-related health disparities and health inequities.
• Achieve integrated, coordinated efforts that address the STI epidemic.¹

In my opinion, family physicians have important roles to play in order for each of these goals to be achieved.Unfortunately, there are approximately 20 million new cases of STIs each year, and the U.S. has seen increases in the rates of STIs in the past decade.

“Sexually transmitted infections are frequently asymptomatic, which may delay diagnosis and treatment and lead persons to unknowingly transmit STIs to others,” according to a new recommendation statement from the USPSTF.² STIs may lead to serious health consequences for patients, cause harms to a mother and infant during pregnancy, and lead to cases of cancer among other concerning outcomes. As such, following the HHS new national strategic plan is critical for us to address the needs of our communities.
 

Preventing new STIs

Family physicians can be vital in achieving the first goal of the plan by helping to prevent new STIs. In August 2020, the USPSTF updated its guideline on behavioral counseling interventions to prevent STIs. In my opinion, the USPSTF offers some practical improvements from the earlier version of this guideline.

The task force provides a grade B recommendation that all sexually active adolescents and adults at increased risk for STIs be provided with behavioral counseling to prevent STIs. The guideline indicates that behavioral counseling interventions reduce the likelihood of those at increased risk for acquiring STIs.²

The 2014 guideline had recommended intensive interventions with a minimum of 30 minutes of counseling. Many family physicians may have found this previous recommendation impractical to implement. These updated recommendations now include a variety of interventions, such as those that take less than 30 minutes.

Although interventions with more than 120 minutes of contact time had the most effect, those with less than 30 minutes still demonstrated statistically significant fewer acquisitions of STIs during follow-up. These options include in-person counseling, and providing written materials, websites, videos, and telephone and text support to patients. These interventions can be delivered directly by the family physician, or patients may be referred to other settings or the media interventions.

The task force’s updated recommendation statement refers to a variety of resources that can be used to identify these interventions. Many of the studies reviewed for this guideline were conducted in STI clinics, and the guideline authors recommended further studies in primary care as opportunities for more generalizability.

In addition to behavioral counseling for STI prevention, family physicians can help prevent STIs in their patients through HPV vaccination and HIV pre-exposure prophylaxis (PrEP provision) within their practices. As the first contact for health care for many patients, we have an opportunity to significantly impact this first goal of prevention.
 

Treating STIs

Within the second goal of the national strategic plan is treatment of STIs, which family physicians should include in their practices as well as the diagnosis of STIs.

In December 2020, an update to the CDC’s treatment guideline for gonococcal infection was released. Prior to the publishing of this updated recommendation, the CDC recommended combination therapy of 250 mg intramuscular (IM) dose of ceftriaxone and either doxycycline or azithromycin. This recommendation has been changed to a single 500-mg IM dose of ceftriaxone for uncomplicated urogenital, anorectal, and pharyngeal gonorrhea. If chlamydia cannot be excluded, then the addition of oral doxycycline 100 mg twice daily for 7 days is recommended for nonpregnant persons, and 1 g oral azithromycin for pregnant persons. The previous treatment was recommended based on a concern for gonococcal resistance.

This updated guideline reflects increasing concerns for antimicrobial stewardship and emerging azithromycin resistance. It does not recommend a test-of-cure for urogenital or rectal gonorrhea, though did recommend a test-of-cure 7-14 days after treatment of pharyngeal gonorrhea. The guideline also recommends testing for reinfection 3-12 months after treatment as the rate of reinfection ranges from 7% to 12% among those previously treated.³

For some offices, the provision of the IM injection may be challenging, though having this medication in stock with the possibility of provision can greatly improve access and ease of treatment for patients. Family physicians can incorporate these updated recommendations along with those for other STIs such as chlamydia and syphilis with standing orders for treatment and testing within their offices.
 

Accelerating progress in STI research

Family physicians can also support the national strategic plan by participating in studies looking at the impact of behavioral counseling in the primary care office as opposed to in STI clinics. In addition, by following the STI treatment and screening guidelines, family physicians will contribute to the body of knowledge of prevalence, treatment failure, and reinfection rates of STIs. We can also help advance the research by providing feedback on interventions that have success within our practices.

Reducing STI-related health disparities and inequities

Family physicians are also in important places to support the strategic plan’s fourth goal of reducing health disparities and health inequities.

If we continue to ask the questions to identify those at high risk and ensure that we are offering appropriate STI prevention, care, and treatment services within our clinics, we can expand access to all who need services and improve equity. By offering these services within the primary care office, we may be able to decrease the stigma some may feel going to an STI clinic for services.

By incorporating additional screening and counseling in our practices we may identify some patients who were not aware that they were at risk for an STI and offer them preventive services.
 

Achieving integrated and coordinated efforts

Finally, as many family physicians have integrated practices, we are uniquely poised to support the fifth goal of the strategic plan of achieving integrated and coordinated efforts addressing the STI epidemic. In our practices we can participate in, lead, and refer to programs for substance use disorders, viral hepatitis, STIs, and HIV as part of full scope primary care.

Family physicians and other primary care providers should work to support the entire strategic plan to ensure that we are fully caring for our patients and communities and stopping the past decade’s increase in STIs. We have an opportunity to use this strategy and make a large impact in our communities.
 

Dr. Wheat is a family physician at Erie Family Health Center in Chicago. She is program director of Northwestern’s McGaw Family Medicine residency program at Humboldt Park, Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at [email protected].

References

1. U.S. Department of Health and Human Services. 2020. Sexually Transmitted Infections National Strategic Plan for the United States: 2021-2025. Washington.

2. U.S. Preventive Services Task Force. Behavioral counseling interventions to prevent sexually transmitted infections: U.S. Preventive Services Task Force Recommendation Statement. JAMA. 2020;324(7):674-81. doi: 10.1001/jama.2020.13095.

3. St. Cyr S et al. Update to CDC’s Treatment Guideline for Gonococcal Infection, 2020. MMWR Morb Mortal Wkly Rep 2020;69:1911-6. doi: 10.15585/mmwr.mm6950a6external_icon.

Several updates in the strategy for prevention of and treatment of sexually transmitted infections were recently published in the United States.

Among these are the U.S. Department of Health and Human Services’ first “Sexually Transmitted Infections (STIs) National Strategic Plan for the United States,” which has a strong encompassing vision.

• Prevent New STIs.
• Improve the health of people by reducing adverse outcomes of STIs.
• Accelerate progress in STI research, technology, and innovation.
• Reduce STI-related health disparities and health inequities.
• Achieve integrated, coordinated efforts that address the STI epidemic.¹

In my opinion, family physicians have important roles to play in order for each of these goals to be achieved.Unfortunately, there are approximately 20 million new cases of STIs each year, and the U.S. has seen increases in the rates of STIs in the past decade.

“Sexually transmitted infections are frequently asymptomatic, which may delay diagnosis and treatment and lead persons to unknowingly transmit STIs to others,” according to a new recommendation statement from the USPSTF.² STIs may lead to serious health consequences for patients, cause harms to a mother and infant during pregnancy, and lead to cases of cancer among other concerning outcomes. As such, following the HHS new national strategic plan is critical for us to address the needs of our communities.
 

Preventing new STIs

Family physicians can be vital in achieving the first goal of the plan by helping to prevent new STIs. In August 2020, the USPSTF updated its guideline on behavioral counseling interventions to prevent STIs. In my opinion, the USPSTF offers some practical improvements from the earlier version of this guideline.

The task force provides a grade B recommendation that all sexually active adolescents and adults at increased risk for STIs be provided with behavioral counseling to prevent STIs. The guideline indicates that behavioral counseling interventions reduce the likelihood of those at increased risk for acquiring STIs.²

The 2014 guideline had recommended intensive interventions with a minimum of 30 minutes of counseling. Many family physicians may have found this previous recommendation impractical to implement. These updated recommendations now include a variety of interventions, such as those that take less than 30 minutes.

Although interventions with more than 120 minutes of contact time had the most effect, those with less than 30 minutes still demonstrated statistically significant fewer acquisitions of STIs during follow-up. These options include in-person counseling, and providing written materials, websites, videos, and telephone and text support to patients. These interventions can be delivered directly by the family physician, or patients may be referred to other settings or the media interventions.

The task force’s updated recommendation statement refers to a variety of resources that can be used to identify these interventions. Many of the studies reviewed for this guideline were conducted in STI clinics, and the guideline authors recommended further studies in primary care as opportunities for more generalizability.

In addition to behavioral counseling for STI prevention, family physicians can help prevent STIs in their patients through HPV vaccination and HIV pre-exposure prophylaxis (PrEP provision) within their practices. As the first contact for health care for many patients, we have an opportunity to significantly impact this first goal of prevention.
 

Treating STIs

Within the second goal of the national strategic plan is treatment of STIs, which family physicians should include in their practices as well as the diagnosis of STIs.

In December 2020, an update to the CDC’s treatment guideline for gonococcal infection was released. Prior to the publishing of this updated recommendation, the CDC recommended combination therapy of 250 mg intramuscular (IM) dose of ceftriaxone and either doxycycline or azithromycin. This recommendation has been changed to a single 500-mg IM dose of ceftriaxone for uncomplicated urogenital, anorectal, and pharyngeal gonorrhea. If chlamydia cannot be excluded, then the addition of oral doxycycline 100 mg twice daily for 7 days is recommended for nonpregnant persons, and 1 g oral azithromycin for pregnant persons. The previous treatment was recommended based on a concern for gonococcal resistance.

This updated guideline reflects increasing concerns for antimicrobial stewardship and emerging azithromycin resistance. It does not recommend a test-of-cure for urogenital or rectal gonorrhea, though did recommend a test-of-cure 7-14 days after treatment of pharyngeal gonorrhea. The guideline also recommends testing for reinfection 3-12 months after treatment as the rate of reinfection ranges from 7% to 12% among those previously treated.³

For some offices, the provision of the IM injection may be challenging, though having this medication in stock with the possibility of provision can greatly improve access and ease of treatment for patients. Family physicians can incorporate these updated recommendations along with those for other STIs such as chlamydia and syphilis with standing orders for treatment and testing within their offices.
 

Accelerating progress in STI research

Family physicians can also support the national strategic plan by participating in studies looking at the impact of behavioral counseling in the primary care office as opposed to in STI clinics. In addition, by following the STI treatment and screening guidelines, family physicians will contribute to the body of knowledge of prevalence, treatment failure, and reinfection rates of STIs. We can also help advance the research by providing feedback on interventions that have success within our practices.

Reducing STI-related health disparities and inequities

Family physicians are also in important places to support the strategic plan’s fourth goal of reducing health disparities and health inequities.

If we continue to ask the questions to identify those at high risk and ensure that we are offering appropriate STI prevention, care, and treatment services within our clinics, we can expand access to all who need services and improve equity. By offering these services within the primary care office, we may be able to decrease the stigma some may feel going to an STI clinic for services.

By incorporating additional screening and counseling in our practices we may identify some patients who were not aware that they were at risk for an STI and offer them preventive services.
 

Achieving integrated and coordinated efforts

Finally, as many family physicians have integrated practices, we are uniquely poised to support the fifth goal of the strategic plan of achieving integrated and coordinated efforts addressing the STI epidemic. In our practices we can participate in, lead, and refer to programs for substance use disorders, viral hepatitis, STIs, and HIV as part of full scope primary care.

Family physicians and other primary care providers should work to support the entire strategic plan to ensure that we are fully caring for our patients and communities and stopping the past decade’s increase in STIs. We have an opportunity to use this strategy and make a large impact in our communities.
 

Dr. Wheat is a family physician at Erie Family Health Center in Chicago. She is program director of Northwestern’s McGaw Family Medicine residency program at Humboldt Park, Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at [email protected].

References

1. U.S. Department of Health and Human Services. 2020. Sexually Transmitted Infections National Strategic Plan for the United States: 2021-2025. Washington.

2. U.S. Preventive Services Task Force. Behavioral counseling interventions to prevent sexually transmitted infections: U.S. Preventive Services Task Force Recommendation Statement. JAMA. 2020;324(7):674-81. doi: 10.1001/jama.2020.13095.

3. St. Cyr S et al. Update to CDC’s Treatment Guideline for Gonococcal Infection, 2020. MMWR Morb Mortal Wkly Rep 2020;69:1911-6. doi: 10.15585/mmwr.mm6950a6external_icon.

Several updates in the strategy for prevention of and treatment of sexually transmitted infections were recently published in the United States.

Among these are the U.S. Department of Health and Human Services’ first “Sexually Transmitted Infections (STIs) National Strategic Plan for the United States,” which has a strong encompassing vision.

• Prevent New STIs.
• Improve the health of people by reducing adverse outcomes of STIs.
• Accelerate progress in STI research, technology, and innovation.
• Reduce STI-related health disparities and health inequities.
• Achieve integrated, coordinated efforts that address the STI epidemic.¹

In my opinion, family physicians have important roles to play in order for each of these goals to be achieved.Unfortunately, there are approximately 20 million new cases of STIs each year, and the U.S. has seen increases in the rates of STIs in the past decade.

“Sexually transmitted infections are frequently asymptomatic, which may delay diagnosis and treatment and lead persons to unknowingly transmit STIs to others,” according to a new recommendation statement from the USPSTF.² STIs may lead to serious health consequences for patients, cause harms to a mother and infant during pregnancy, and lead to cases of cancer among other concerning outcomes. As such, following the HHS new national strategic plan is critical for us to address the needs of our communities.
 

Preventing new STIs

Family physicians can be vital in achieving the first goal of the plan by helping to prevent new STIs. In August 2020, the USPSTF updated its guideline on behavioral counseling interventions to prevent STIs. In my opinion, the USPSTF offers some practical improvements from the earlier version of this guideline.

The task force provides a grade B recommendation that all sexually active adolescents and adults at increased risk for STIs be provided with behavioral counseling to prevent STIs. The guideline indicates that behavioral counseling interventions reduce the likelihood of those at increased risk for acquiring STIs.²

The 2014 guideline had recommended intensive interventions with a minimum of 30 minutes of counseling. Many family physicians may have found this previous recommendation impractical to implement. These updated recommendations now include a variety of interventions, such as those that take less than 30 minutes.

Although interventions with more than 120 minutes of contact time had the most effect, those with less than 30 minutes still demonstrated statistically significant fewer acquisitions of STIs during follow-up. These options include in-person counseling, and providing written materials, websites, videos, and telephone and text support to patients. These interventions can be delivered directly by the family physician, or patients may be referred to other settings or the media interventions.

The task force’s updated recommendation statement refers to a variety of resources that can be used to identify these interventions. Many of the studies reviewed for this guideline were conducted in STI clinics, and the guideline authors recommended further studies in primary care as opportunities for more generalizability.

In addition to behavioral counseling for STI prevention, family physicians can help prevent STIs in their patients through HPV vaccination and HIV pre-exposure prophylaxis (PrEP provision) within their practices. As the first contact for health care for many patients, we have an opportunity to significantly impact this first goal of prevention.
 

Treating STIs

Within the second goal of the national strategic plan is treatment of STIs, which family physicians should include in their practices as well as the diagnosis of STIs.

In December 2020, an update to the CDC’s treatment guideline for gonococcal infection was released. Prior to the publishing of this updated recommendation, the CDC recommended combination therapy of 250 mg intramuscular (IM) dose of ceftriaxone and either doxycycline or azithromycin. This recommendation has been changed to a single 500-mg IM dose of ceftriaxone for uncomplicated urogenital, anorectal, and pharyngeal gonorrhea. If chlamydia cannot be excluded, then the addition of oral doxycycline 100 mg twice daily for 7 days is recommended for nonpregnant persons, and 1 g oral azithromycin for pregnant persons. The previous treatment was recommended based on a concern for gonococcal resistance.

This updated guideline reflects increasing concerns for antimicrobial stewardship and emerging azithromycin resistance. It does not recommend a test-of-cure for urogenital or rectal gonorrhea, though did recommend a test-of-cure 7-14 days after treatment of pharyngeal gonorrhea. The guideline also recommends testing for reinfection 3-12 months after treatment as the rate of reinfection ranges from 7% to 12% among those previously treated.³

For some offices, the provision of the IM injection may be challenging, though having this medication in stock with the possibility of provision can greatly improve access and ease of treatment for patients. Family physicians can incorporate these updated recommendations along with those for other STIs such as chlamydia and syphilis with standing orders for treatment and testing within their offices.
 

Accelerating progress in STI research

Family physicians can also support the national strategic plan by participating in studies looking at the impact of behavioral counseling in the primary care office as opposed to in STI clinics. In addition, by following the STI treatment and screening guidelines, family physicians will contribute to the body of knowledge of prevalence, treatment failure, and reinfection rates of STIs. We can also help advance the research by providing feedback on interventions that have success within our practices.

Reducing STI-related health disparities and inequities

Family physicians are also in important places to support the strategic plan’s fourth goal of reducing health disparities and health inequities.

If we continue to ask the questions to identify those at high risk and ensure that we are offering appropriate STI prevention, care, and treatment services within our clinics, we can expand access to all who need services and improve equity. By offering these services within the primary care office, we may be able to decrease the stigma some may feel going to an STI clinic for services.

By incorporating additional screening and counseling in our practices we may identify some patients who were not aware that they were at risk for an STI and offer them preventive services.
 

Achieving integrated and coordinated efforts

Finally, as many family physicians have integrated practices, we are uniquely poised to support the fifth goal of the strategic plan of achieving integrated and coordinated efforts addressing the STI epidemic. In our practices we can participate in, lead, and refer to programs for substance use disorders, viral hepatitis, STIs, and HIV as part of full scope primary care.

Family physicians and other primary care providers should work to support the entire strategic plan to ensure that we are fully caring for our patients and communities and stopping the past decade’s increase in STIs. We have an opportunity to use this strategy and make a large impact in our communities.
 

Dr. Wheat is a family physician at Erie Family Health Center in Chicago. She is program director of Northwestern’s McGaw Family Medicine residency program at Humboldt Park, Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at [email protected].

References

1. U.S. Department of Health and Human Services. 2020. Sexually Transmitted Infections National Strategic Plan for the United States: 2021-2025. Washington.

2. U.S. Preventive Services Task Force. Behavioral counseling interventions to prevent sexually transmitted infections: U.S. Preventive Services Task Force Recommendation Statement. JAMA. 2020;324(7):674-81. doi: 10.1001/jama.2020.13095.

3. St. Cyr S et al. Update to CDC’s Treatment Guideline for Gonococcal Infection, 2020. MMWR Morb Mortal Wkly Rep 2020;69:1911-6. doi: 10.15585/mmwr.mm6950a6external_icon.

Depression and tobacco use in childhood significantly increased the risk for opioid use in young adults, according to data from a prospective study of approximately 1,000 individuals.

Previous research, including the annual Monitoring the Future study, documents opioid use among adolescents in the United States, but childhood risk factors for opioid use in young adults have not been well studied, wrote Lilly Shanahan, PhD, of the University of Zürich, and colleagues.

In a prospective cohort study published in JAMA Pediatrics, the researchers identified 1,252 non-Hispanic White and American Indian opioid-naive individuals aged 9-16 years in rural North Carolina. They interviewed participants and parents up to 7 times between January 1993 and December 2000, and interviewed participants only at ages 19, 21, 25, and 30 years between January 1999 and December 2015.

Overall, 24.2% of study participants had used a nonheroin opioid by age 30 years, and both chronic depression and dysthymia were significantly associated with this use (odds ratios 5.43 and 7.13, respectively).

In addition, 155 participants (8.8%) reported weekly use of a nonheroin opioid, and 95 (6.6%) reported weekly heroin use by age 30 years. Chronic depression and dysthymia also were strongly associated with weekly nonheroin opioid use (OR 8.89 and 11.51, respectively).

In a multivariate analysis, depression, tobacco use, and cannabis use at ages 9-16 years were strongly associated with overall opioid use at ages 19-30 years.

“One possible reason childhood chronic depression increases the risk of later opioid use is self-medication, including the use of psychoactive substances, to alleviate depression,” the researchers noted. In addition, the mood-altering properties of opioids may increase their appeal to depressed youth as a way to relieve impaired reward system function, they said.

Potential mechanisms for the association between early tobacco use and later opioid use include the alterations to neurodevelopment caused by nicotine exposure in adolescence, as well as increased risk for depression, reduced pain thresholds, and use of nicotine as a gateway to harder drugs, the researchers added.

Several childhood risk factors were not associated with young adult opioid use in multivariate analysis in this study, including alcohol use, sociodemographic status, maltreatment, family dysfunction, and anxiety, the researchers wrote. “Previous studies typically measured these risk factors retrospectively or in late adolescence and young adulthood, and most did not consider depressive disorders, which may mediate associations between select childhood risk factors and later opioid use,” they said.

The study findings were limited by several factors, including the inability to distinguish between medical and nonmedical opioid use, the incomplete list of available opioids, and the exclusion of Black participants because of low sample size, the researchers noted. However, the results were strengthened by the longitudinal, community-representative design and the inclusion of up to 11 assessments of opioid use, they said.

“Our findings suggest strong opportunities for early prevention and intervention, including in primary care settings,” using known evidence-based strategies, they concluded.
 

More screening is needed

“Children in the United States are at high risk of serious adult health issues as a result of childhood factors such as ACEs (adverse childhood experiences),” said Suzanne C. Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H. “This study looks prospectively at other factors in childhood over a long period of time leading to opioid usage, with its serious risks and health consequences including overdose death,” she said. “It is unclear what the effects of COVID-19 will be on the population of children growing up now and how opioid usage might change as a result,” she noted.

“Some of the links to adult usage are predictable, such as depression, tobacco use, and cannabis use in early adolescence,” said Dr. Boulter. “Surprising was the lack of correlation between anxiety, early alcohol use, child mistreatment, and sociodemographic factors with future opioid use,” she said.

The take-home message for clinicians is to screen children and adolescents for factors leading to opioid usage in young adults “with preventive strategies including avoidance of pain medication prescriptions and early referral and treatment for depression and use of cannabis and tobacco products using tools like SBIRT (Screening, Brief Intervention, and Referral to Treatment),” Dr. Boulter emphasized.

As for additional research, “It would be interesting to study e-cigarette usage and see if the correlation with future opioid usage is similar to older tobacco products,” she said. “Also helpful would be to delve deeper into connections between medical or dental diagnoses when opioids were first prescribed and later usage of those products,” Dr. Boulter noted.

The study was supported in part by the by the National Institute of Mental Health and the National Institute on Drug Abuse. The researchers had no financial conflicts to disclose. Dr. Boulter had no disclosures but serves on the Pediatric News Editorial Advisory Board.

Depression and tobacco use in childhood significantly increased the risk for opioid use in young adults, according to data from a prospective study of approximately 1,000 individuals.

Previous research, including the annual Monitoring the Future study, documents opioid use among adolescents in the United States, but childhood risk factors for opioid use in young adults have not been well studied, wrote Lilly Shanahan, PhD, of the University of Zürich, and colleagues.

In a prospective cohort study published in JAMA Pediatrics, the researchers identified 1,252 non-Hispanic White and American Indian opioid-naive individuals aged 9-16 years in rural North Carolina. They interviewed participants and parents up to 7 times between January 1993 and December 2000, and interviewed participants only at ages 19, 21, 25, and 30 years between January 1999 and December 2015.

Overall, 24.2% of study participants had used a nonheroin opioid by age 30 years, and both chronic depression and dysthymia were significantly associated with this use (odds ratios 5.43 and 7.13, respectively).

In addition, 155 participants (8.8%) reported weekly use of a nonheroin opioid, and 95 (6.6%) reported weekly heroin use by age 30 years. Chronic depression and dysthymia also were strongly associated with weekly nonheroin opioid use (OR 8.89 and 11.51, respectively).

In a multivariate analysis, depression, tobacco use, and cannabis use at ages 9-16 years were strongly associated with overall opioid use at ages 19-30 years.

“One possible reason childhood chronic depression increases the risk of later opioid use is self-medication, including the use of psychoactive substances, to alleviate depression,” the researchers noted. In addition, the mood-altering properties of opioids may increase their appeal to depressed youth as a way to relieve impaired reward system function, they said.

Potential mechanisms for the association between early tobacco use and later opioid use include the alterations to neurodevelopment caused by nicotine exposure in adolescence, as well as increased risk for depression, reduced pain thresholds, and use of nicotine as a gateway to harder drugs, the researchers added.

Several childhood risk factors were not associated with young adult opioid use in multivariate analysis in this study, including alcohol use, sociodemographic status, maltreatment, family dysfunction, and anxiety, the researchers wrote. “Previous studies typically measured these risk factors retrospectively or in late adolescence and young adulthood, and most did not consider depressive disorders, which may mediate associations between select childhood risk factors and later opioid use,” they said.

The study findings were limited by several factors, including the inability to distinguish between medical and nonmedical opioid use, the incomplete list of available opioids, and the exclusion of Black participants because of low sample size, the researchers noted. However, the results were strengthened by the longitudinal, community-representative design and the inclusion of up to 11 assessments of opioid use, they said.

“Our findings suggest strong opportunities for early prevention and intervention, including in primary care settings,” using known evidence-based strategies, they concluded.
 

More screening is needed

“Children in the United States are at high risk of serious adult health issues as a result of childhood factors such as ACEs (adverse childhood experiences),” said Suzanne C. Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H. “This study looks prospectively at other factors in childhood over a long period of time leading to opioid usage, with its serious risks and health consequences including overdose death,” she said. “It is unclear what the effects of COVID-19 will be on the population of children growing up now and how opioid usage might change as a result,” she noted.

“Some of the links to adult usage are predictable, such as depression, tobacco use, and cannabis use in early adolescence,” said Dr. Boulter. “Surprising was the lack of correlation between anxiety, early alcohol use, child mistreatment, and sociodemographic factors with future opioid use,” she said.

The take-home message for clinicians is to screen children and adolescents for factors leading to opioid usage in young adults “with preventive strategies including avoidance of pain medication prescriptions and early referral and treatment for depression and use of cannabis and tobacco products using tools like SBIRT (Screening, Brief Intervention, and Referral to Treatment),” Dr. Boulter emphasized.

As for additional research, “It would be interesting to study e-cigarette usage and see if the correlation with future opioid usage is similar to older tobacco products,” she said. “Also helpful would be to delve deeper into connections between medical or dental diagnoses when opioids were first prescribed and later usage of those products,” Dr. Boulter noted.

The study was supported in part by the by the National Institute of Mental Health and the National Institute on Drug Abuse. The researchers had no financial conflicts to disclose. Dr. Boulter had no disclosures but serves on the Pediatric News Editorial Advisory Board.

Depression and tobacco use in childhood significantly increased the risk for opioid use in young adults, according to data from a prospective study of approximately 1,000 individuals.

Previous research, including the annual Monitoring the Future study, documents opioid use among adolescents in the United States, but childhood risk factors for opioid use in young adults have not been well studied, wrote Lilly Shanahan, PhD, of the University of Zürich, and colleagues.

In a prospective cohort study published in JAMA Pediatrics, the researchers identified 1,252 non-Hispanic White and American Indian opioid-naive individuals aged 9-16 years in rural North Carolina. They interviewed participants and parents up to 7 times between January 1993 and December 2000, and interviewed participants only at ages 19, 21, 25, and 30 years between January 1999 and December 2015.

Overall, 24.2% of study participants had used a nonheroin opioid by age 30 years, and both chronic depression and dysthymia were significantly associated with this use (odds ratios 5.43 and 7.13, respectively).

In addition, 155 participants (8.8%) reported weekly use of a nonheroin opioid, and 95 (6.6%) reported weekly heroin use by age 30 years. Chronic depression and dysthymia also were strongly associated with weekly nonheroin opioid use (OR 8.89 and 11.51, respectively).

In a multivariate analysis, depression, tobacco use, and cannabis use at ages 9-16 years were strongly associated with overall opioid use at ages 19-30 years.

“One possible reason childhood chronic depression increases the risk of later opioid use is self-medication, including the use of psychoactive substances, to alleviate depression,” the researchers noted. In addition, the mood-altering properties of opioids may increase their appeal to depressed youth as a way to relieve impaired reward system function, they said.

Potential mechanisms for the association between early tobacco use and later opioid use include the alterations to neurodevelopment caused by nicotine exposure in adolescence, as well as increased risk for depression, reduced pain thresholds, and use of nicotine as a gateway to harder drugs, the researchers added.

Several childhood risk factors were not associated with young adult opioid use in multivariate analysis in this study, including alcohol use, sociodemographic status, maltreatment, family dysfunction, and anxiety, the researchers wrote. “Previous studies typically measured these risk factors retrospectively or in late adolescence and young adulthood, and most did not consider depressive disorders, which may mediate associations between select childhood risk factors and later opioid use,” they said.

The study findings were limited by several factors, including the inability to distinguish between medical and nonmedical opioid use, the incomplete list of available opioids, and the exclusion of Black participants because of low sample size, the researchers noted. However, the results were strengthened by the longitudinal, community-representative design and the inclusion of up to 11 assessments of opioid use, they said.

“Our findings suggest strong opportunities for early prevention and intervention, including in primary care settings,” using known evidence-based strategies, they concluded.
 

More screening is needed

“Children in the United States are at high risk of serious adult health issues as a result of childhood factors such as ACEs (adverse childhood experiences),” said Suzanne C. Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H. “This study looks prospectively at other factors in childhood over a long period of time leading to opioid usage, with its serious risks and health consequences including overdose death,” she said. “It is unclear what the effects of COVID-19 will be on the population of children growing up now and how opioid usage might change as a result,” she noted.

“Some of the links to adult usage are predictable, such as depression, tobacco use, and cannabis use in early adolescence,” said Dr. Boulter. “Surprising was the lack of correlation between anxiety, early alcohol use, child mistreatment, and sociodemographic factors with future opioid use,” she said.

The take-home message for clinicians is to screen children and adolescents for factors leading to opioid usage in young adults “with preventive strategies including avoidance of pain medication prescriptions and early referral and treatment for depression and use of cannabis and tobacco products using tools like SBIRT (Screening, Brief Intervention, and Referral to Treatment),” Dr. Boulter emphasized.

As for additional research, “It would be interesting to study e-cigarette usage and see if the correlation with future opioid usage is similar to older tobacco products,” she said. “Also helpful would be to delve deeper into connections between medical or dental diagnoses when opioids were first prescribed and later usage of those products,” Dr. Boulter noted.

The study was supported in part by the by the National Institute of Mental Health and the National Institute on Drug Abuse. The researchers had no financial conflicts to disclose. Dr. Boulter had no disclosures but serves on the Pediatric News Editorial Advisory Board.

Heavy alcohol use in adolescence is linked to disruptions in white-matter integrity, new research suggests.

Highwaystarz-Photography/Thinkstock

In a case-control study of more than 400 participants, the association was more pronounced in younger adolescents and in the anterior and middle corpus callosum, which serve the interhemispheric integration of frontal networking and communication.

The results provide clinicians with yet another reason to ask adolescents about their alcohol use, said investigator Adolf Pfefferbaum, MD, Center for Health Sciences, SRI International, Menlo Park, Calif., and professor emeritus at Stanford (Calif.) University.

However, when questioning adolescents about their alcohol use, “sometimes it’s better to ask: ‘How much alcohol do you drink?’ ” instead of just asking if they drink, Dr. Pfefferbaum said in an interview. That’s because they may be more willing to answer the first question honestly.

It’s also important for clinicians to nonjudgmentally tell teens there is evidence “that heavy drinking is bad for their brain,” he added.

The findings were published online Dec. 30, 2020, in JAMA Psychiatry.
 

Fractional anisotropy

Adolescence is a critical period of physiological and social maturation accompanied by significant structural, functional, and neurochemical brain changes, the investigators noted.

Diffusion tensor imaging (DTI) produces a measure called fractional anisotropy (FA), which characterizes some of these brain changes by measuring molecular water diffusion in the brain.

“FA is a measure of the integrity of brain white matter; so, the part of the brain that connects neurons with each other,” Dr. Pfefferbaum said. He added that FA decreases in diseases such as multiple sclerosis (MS), reflecting “some kind of pathology.”

Affected fiber systems include the corpus callosum, superior longitudinal fasciculus, internal and external capsule, brain stem, and cortical projection fibers. Disruption of these neural systems may degrade neural signal transmission and affect certain cognitive functions, possibly resulting in enhanced impulsivity, poor inhibitory control, and restricted working memory capacity, the researchers wrote.

FA follows an inverted U-shaped pattern. “The natural trajectory is to increase from infancy up to middle adolescence and then, as we get older, from about age 25 to 30 years, starts to go down. Our brains are starting to show signs of aging a bit by then,” said Dr. Pfefferbaum.

The current analysis assessed 451 adolescents (228 boys and 223 girls) from the NCANDA study, for whom researchers had four years of longitudinal DTI data. All were aged 12- 21 years at baseline.

The NCANDA cohort was recruited across five U.S. sites. Participants are assessed yearly on psychobiologic measures, including brain maturation. The cohort, which did not have any significant substance abuse upon entry, is balanced in terms of gender and ethnicity.

The investigators quantified the developmental change of white-matter (WM) integrity within each individual as the slope of FA over visits. They also examined altered developmental trajectories associated with drinking onset during adolescence and the differential alcohol associations by age with specific regional WM fiber tracts.

Researchers assessed drinking on a scale of 1-4, based on the youth-adjusted Cahalan score. The scale considers quantity and frequency to classify drinking levels based on past-year self-reported patterns.
 

Altered trajectory

Results showed that 291 participants (37.2%) remained at no to low drinking levels (youth-adjusted Cahalan score, 0) throughout the time points examined, and 160 (20.5%) were classified as heavy drinkers for at least two consecutive visits (youth-adjusted Cahalan score >1).

Among the no to low drinkers, 48.4% were boys with a mean age of 16.5 years and 51.2% were girls with a mean age of 16.5 years. About two thirds of the group (66%) were White.

Among heavy drinkers, 53.8% were boys with a mean age of 20.1 years and 46.3% were girls with a mean age of 20.5 years. In this group, 88.8% were White.

The investigators did not analyze moderate drinkers or those who initiated heavy drinking for only one visit.

The findings also showed that heavy drinkers exhibited significant reduction of whole-brain FA. The slopes of the 78 heavy drinkers were significantly more negative than the 78 matched no to low drinkers (mean, –0.0013 vs. 0.0001; P = .008).

“The concept of the slopes is really important here because it’s the trajectory that seems to be the most sensitive measure,” Dr. Pfefferbaum said. “Probably what’s happening is the exposure to alcohol is interfering with the normal myelination and normal development of the adolescent’s white matter.”

The no to low drinkers had relatively stable FA measures across all visits.

A reduction in FA was significantly linked to heavy drinking. An analysis of 63 youth who transitioned from being a no to low drinker to a heavy drinker showed that before the transition, they had significantly increased FA over visits (95% CI of slope, 0.0011-0.0024; P < .001). In addition, their corresponding slopes were not different from other no to low drinkers of the same age range.

However, this group’s FA declined significantly after they reported heavy drinking, resulting in slopes significantly below zero (95% CI of slope, –0.0036 to –0.0014; P < .001) and that were lower than the no to low participants of the same age range.

The findings of this unique before-and-after assessment “bring us one step closer to causality,” and further illustrates that heavy drinking in adolescence affects WM integrity, Dr. Pfefferbaum said.
 

Potential markers

None of the slope measures correlated with number of visits or use of tobacco or cannabis. The association of alcohol with the slope measures was more apparent in the younger cohort (<19 years).

“The effects were seen more readily in younger adolescents because they are the ones who are still progressing along this normal developmental trajectory,” Dr. Pfefferbaum noted. “In a sense, the younger you are when you’re exposed to alcohol, probably the more vulnerable you are.”

Previous studies have suggested that damage in WM tracts is associated with heightened neural reactivity to alcohol cues in adults with alcohol use disorder. Given this evidence, the greater WM degradation at younger versus older ages might help explain why adolescents who initiate early drinking are more likely to develop addiction later in life, the investigators wrote.

Of the five major fiber tracts, only the commissural fibers (corpus callosum) showed a significant association with alcohol. The researchers noted that WM volume shrinkage and callosal demyelination are two of the most prominent markers in adult alcoholism and are potential markers in adolescent alcohol abuse.

Upon further extending the analysis to the four subregions of the corpus callosum, the investigators found that only the anterior and middle callosal regions (genu and body) showed significant age-alcohol interactions.

This could be a result of the timing of fiber myelination in these regions of the brain, compared with others, Dr. Pfefferbaum said.

He noted that these fibers connect the left and right part of the anterior regions of the brain, especially the frontal lobes, which are particularly vulnerable to the effects of alcohol. “It may well be that we have this interaction of the developmental time and the sensitivity of the frontal parts of the brain.”
 

Cognitive effects?

Although the researchers did not find any sex effects, Dr. Pfefferbaum stressed that this doesn’t mean they do not exist. “We just may not have the power to see them,” he said.

The study did not look specifically at binge drinkers, defined as consuming five drinks in 2 hours for men and four drinks in 2 hours for women. Dr. Pfefferbaum noted that it is difficult to get “good quantification” of binge drinking. “We don’t have a fine enough grain analysis to separate that out,” he said.

Asked whether the altered FA trajectory in heavy drinkers affects cognition, Dr. Pfefferbaum said “those studies are still in progress,” with results hopefully available within about a year.

Dr. Pfefferbaum said he and his colleagues are continuing to follow these adolescents and hope to see if the altered FA trajectory in heavy drinkers returns to normal, adding: “The real question now is: If they stop heavy drinking, will they get back on track?”

This study is believed to be the first to suggest in vivo differential vulnerability in WM microstructure with respect to age, the authors note.

In addition to asking teens about their alcohol use, the clinician’s role should be to “counsel and refer,” said Dr. Pfefferbaum. He also suggested accessing resources from the National Institute on Alcohol Abuse and Alcoholism.
 

Important data, but several limitations

In an interview, Oscar G. Bukstein, MD, MPH, medical director of outpatient psychiatry service at Boston Children’s Hospital, and professor of psychiatry at Harvard Medical School, also in Boston, said the findings provide further evidence that alcohol affects the maturing brain.

This study, and others that have examined cannabis use, “show that you have a dynamically growing brain with certain sections, particularly in this case the anterior and middle corpus callosum, that mature later [and] that are more likely to be affected by early alcohol use,” said Dr. Bukstein, who was not involved with the research.

He stressed the importance of determining the mechanism involved and noted some study limitations. For example, the DTI technology used may “already be out of date,” he said.

Using older technology may have prevented finding an impact of heavy drinking on parts of the brain other than the anterior and middle corpus callosum, Dr. Bukstein noted.

Newer technology might provide “a finer-grain nonlinear voxel-wise analysis,” although using more updated scanning techniques may not have detected additional differences in study groups, he added.

Dr. Bukstein also noted that there were limitations: The study did not have “gradations,” but only looked at heavy drinking and no to low drinking. “You’d like to find out about kids who are somewhere in the middle.” It also didn’t determine a “cutoff” where deleterious effects of alcohol on the brain begin, Dr. Bukstein added.

Additionally, the study didn’t look at brain development outcomes in children with conditions such as depression and ADHD that are known to lead to substance use – something a larger study may have been able to do, he said.

Dr. Bukstein noted that a newer and much larger study, the Adolescent Brain Cognitive Development study, has begun assessing kids for risk factors such as substance use, starting at age 10 years.

The study was funded by grants from NIAAA and by the National Institute on Drug Abuse, the National Institute of Mental Health, the National Institute of Child Health and Human Development, and the Stanford Institute for Human-Centered Artificial Intelligence–AWS Cloud Credits for Research. Dr. Pfefferbaum reported receiving an NIAAA grant during the conduct of the study. Dr. Bukstein disclosed no relevant financial relationships.

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

Heavy alcohol use in adolescence is linked to disruptions in white-matter integrity, new research suggests.

Highwaystarz-Photography/Thinkstock

In a case-control study of more than 400 participants, the association was more pronounced in younger adolescents and in the anterior and middle corpus callosum, which serve the interhemispheric integration of frontal networking and communication.

The results provide clinicians with yet another reason to ask adolescents about their alcohol use, said investigator Adolf Pfefferbaum, MD, Center for Health Sciences, SRI International, Menlo Park, Calif., and professor emeritus at Stanford (Calif.) University.

However, when questioning adolescents about their alcohol use, “sometimes it’s better to ask: ‘How much alcohol do you drink?’ ” instead of just asking if they drink, Dr. Pfefferbaum said in an interview. That’s because they may be more willing to answer the first question honestly.

It’s also important for clinicians to nonjudgmentally tell teens there is evidence “that heavy drinking is bad for their brain,” he added.

The findings were published online Dec. 30, 2020, in JAMA Psychiatry.
 

Fractional anisotropy

Adolescence is a critical period of physiological and social maturation accompanied by significant structural, functional, and neurochemical brain changes, the investigators noted.

Diffusion tensor imaging (DTI) produces a measure called fractional anisotropy (FA), which characterizes some of these brain changes by measuring molecular water diffusion in the brain.

“FA is a measure of the integrity of brain white matter; so, the part of the brain that connects neurons with each other,” Dr. Pfefferbaum said. He added that FA decreases in diseases such as multiple sclerosis (MS), reflecting “some kind of pathology.”

Affected fiber systems include the corpus callosum, superior longitudinal fasciculus, internal and external capsule, brain stem, and cortical projection fibers. Disruption of these neural systems may degrade neural signal transmission and affect certain cognitive functions, possibly resulting in enhanced impulsivity, poor inhibitory control, and restricted working memory capacity, the researchers wrote.

FA follows an inverted U-shaped pattern. “The natural trajectory is to increase from infancy up to middle adolescence and then, as we get older, from about age 25 to 30 years, starts to go down. Our brains are starting to show signs of aging a bit by then,” said Dr. Pfefferbaum.

The current analysis assessed 451 adolescents (228 boys and 223 girls) from the NCANDA study, for whom researchers had four years of longitudinal DTI data. All were aged 12- 21 years at baseline.

The NCANDA cohort was recruited across five U.S. sites. Participants are assessed yearly on psychobiologic measures, including brain maturation. The cohort, which did not have any significant substance abuse upon entry, is balanced in terms of gender and ethnicity.

The investigators quantified the developmental change of white-matter (WM) integrity within each individual as the slope of FA over visits. They also examined altered developmental trajectories associated with drinking onset during adolescence and the differential alcohol associations by age with specific regional WM fiber tracts.

Researchers assessed drinking on a scale of 1-4, based on the youth-adjusted Cahalan score. The scale considers quantity and frequency to classify drinking levels based on past-year self-reported patterns.
 

Altered trajectory

Results showed that 291 participants (37.2%) remained at no to low drinking levels (youth-adjusted Cahalan score, 0) throughout the time points examined, and 160 (20.5%) were classified as heavy drinkers for at least two consecutive visits (youth-adjusted Cahalan score >1).

Among the no to low drinkers, 48.4% were boys with a mean age of 16.5 years and 51.2% were girls with a mean age of 16.5 years. About two thirds of the group (66%) were White.

Among heavy drinkers, 53.8% were boys with a mean age of 20.1 years and 46.3% were girls with a mean age of 20.5 years. In this group, 88.8% were White.

The investigators did not analyze moderate drinkers or those who initiated heavy drinking for only one visit.

The findings also showed that heavy drinkers exhibited significant reduction of whole-brain FA. The slopes of the 78 heavy drinkers were significantly more negative than the 78 matched no to low drinkers (mean, –0.0013 vs. 0.0001; P = .008).

“The concept of the slopes is really important here because it’s the trajectory that seems to be the most sensitive measure,” Dr. Pfefferbaum said. “Probably what’s happening is the exposure to alcohol is interfering with the normal myelination and normal development of the adolescent’s white matter.”

The no to low drinkers had relatively stable FA measures across all visits.

A reduction in FA was significantly linked to heavy drinking. An analysis of 63 youth who transitioned from being a no to low drinker to a heavy drinker showed that before the transition, they had significantly increased FA over visits (95% CI of slope, 0.0011-0.0024; P < .001). In addition, their corresponding slopes were not different from other no to low drinkers of the same age range.

However, this group’s FA declined significantly after they reported heavy drinking, resulting in slopes significantly below zero (95% CI of slope, –0.0036 to –0.0014; P < .001) and that were lower than the no to low participants of the same age range.

The findings of this unique before-and-after assessment “bring us one step closer to causality,” and further illustrates that heavy drinking in adolescence affects WM integrity, Dr. Pfefferbaum said.
 

Potential markers

None of the slope measures correlated with number of visits or use of tobacco or cannabis. The association of alcohol with the slope measures was more apparent in the younger cohort (<19 years).

“The effects were seen more readily in younger adolescents because they are the ones who are still progressing along this normal developmental trajectory,” Dr. Pfefferbaum noted. “In a sense, the younger you are when you’re exposed to alcohol, probably the more vulnerable you are.”

Previous studies have suggested that damage in WM tracts is associated with heightened neural reactivity to alcohol cues in adults with alcohol use disorder. Given this evidence, the greater WM degradation at younger versus older ages might help explain why adolescents who initiate early drinking are more likely to develop addiction later in life, the investigators wrote.

Of the five major fiber tracts, only the commissural fibers (corpus callosum) showed a significant association with alcohol. The researchers noted that WM volume shrinkage and callosal demyelination are two of the most prominent markers in adult alcoholism and are potential markers in adolescent alcohol abuse.

Upon further extending the analysis to the four subregions of the corpus callosum, the investigators found that only the anterior and middle callosal regions (genu and body) showed significant age-alcohol interactions.

This could be a result of the timing of fiber myelination in these regions of the brain, compared with others, Dr. Pfefferbaum said.

He noted that these fibers connect the left and right part of the anterior regions of the brain, especially the frontal lobes, which are particularly vulnerable to the effects of alcohol. “It may well be that we have this interaction of the developmental time and the sensitivity of the frontal parts of the brain.”
 

Cognitive effects?

Although the researchers did not find any sex effects, Dr. Pfefferbaum stressed that this doesn’t mean they do not exist. “We just may not have the power to see them,” he said.

The study did not look specifically at binge drinkers, defined as consuming five drinks in 2 hours for men and four drinks in 2 hours for women. Dr. Pfefferbaum noted that it is difficult to get “good quantification” of binge drinking. “We don’t have a fine enough grain analysis to separate that out,” he said.

Asked whether the altered FA trajectory in heavy drinkers affects cognition, Dr. Pfefferbaum said “those studies are still in progress,” with results hopefully available within about a year.

Dr. Pfefferbaum said he and his colleagues are continuing to follow these adolescents and hope to see if the altered FA trajectory in heavy drinkers returns to normal, adding: “The real question now is: If they stop heavy drinking, will they get back on track?”

This study is believed to be the first to suggest in vivo differential vulnerability in WM microstructure with respect to age, the authors note.

In addition to asking teens about their alcohol use, the clinician’s role should be to “counsel and refer,” said Dr. Pfefferbaum. He also suggested accessing resources from the National Institute on Alcohol Abuse and Alcoholism.
 

Important data, but several limitations

In an interview, Oscar G. Bukstein, MD, MPH, medical director of outpatient psychiatry service at Boston Children’s Hospital, and professor of psychiatry at Harvard Medical School, also in Boston, said the findings provide further evidence that alcohol affects the maturing brain.

This study, and others that have examined cannabis use, “show that you have a dynamically growing brain with certain sections, particularly in this case the anterior and middle corpus callosum, that mature later [and] that are more likely to be affected by early alcohol use,” said Dr. Bukstein, who was not involved with the research.

He stressed the importance of determining the mechanism involved and noted some study limitations. For example, the DTI technology used may “already be out of date,” he said.

Using older technology may have prevented finding an impact of heavy drinking on parts of the brain other than the anterior and middle corpus callosum, Dr. Bukstein noted.

Newer technology might provide “a finer-grain nonlinear voxel-wise analysis,” although using more updated scanning techniques may not have detected additional differences in study groups, he added.

Dr. Bukstein also noted that there were limitations: The study did not have “gradations,” but only looked at heavy drinking and no to low drinking. “You’d like to find out about kids who are somewhere in the middle.” It also didn’t determine a “cutoff” where deleterious effects of alcohol on the brain begin, Dr. Bukstein added.

Additionally, the study didn’t look at brain development outcomes in children with conditions such as depression and ADHD that are known to lead to substance use – something a larger study may have been able to do, he said.

Dr. Bukstein noted that a newer and much larger study, the Adolescent Brain Cognitive Development study, has begun assessing kids for risk factors such as substance use, starting at age 10 years.

The study was funded by grants from NIAAA and by the National Institute on Drug Abuse, the National Institute of Mental Health, the National Institute of Child Health and Human Development, and the Stanford Institute for Human-Centered Artificial Intelligence–AWS Cloud Credits for Research. Dr. Pfefferbaum reported receiving an NIAAA grant during the conduct of the study. Dr. Bukstein disclosed no relevant financial relationships.

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

Heavy alcohol use in adolescence is linked to disruptions in white-matter integrity, new research suggests.

Highwaystarz-Photography/Thinkstock

In a case-control study of more than 400 participants, the association was more pronounced in younger adolescents and in the anterior and middle corpus callosum, which serve the interhemispheric integration of frontal networking and communication.

The results provide clinicians with yet another reason to ask adolescents about their alcohol use, said investigator Adolf Pfefferbaum, MD, Center for Health Sciences, SRI International, Menlo Park, Calif., and professor emeritus at Stanford (Calif.) University.

However, when questioning adolescents about their alcohol use, “sometimes it’s better to ask: ‘How much alcohol do you drink?’ ” instead of just asking if they drink, Dr. Pfefferbaum said in an interview. That’s because they may be more willing to answer the first question honestly.

It’s also important for clinicians to nonjudgmentally tell teens there is evidence “that heavy drinking is bad for their brain,” he added.

The findings were published online Dec. 30, 2020, in JAMA Psychiatry.
 

Fractional anisotropy

Adolescence is a critical period of physiological and social maturation accompanied by significant structural, functional, and neurochemical brain changes, the investigators noted.

Diffusion tensor imaging (DTI) produces a measure called fractional anisotropy (FA), which characterizes some of these brain changes by measuring molecular water diffusion in the brain.

“FA is a measure of the integrity of brain white matter; so, the part of the brain that connects neurons with each other,” Dr. Pfefferbaum said. He added that FA decreases in diseases such as multiple sclerosis (MS), reflecting “some kind of pathology.”

Affected fiber systems include the corpus callosum, superior longitudinal fasciculus, internal and external capsule, brain stem, and cortical projection fibers. Disruption of these neural systems may degrade neural signal transmission and affect certain cognitive functions, possibly resulting in enhanced impulsivity, poor inhibitory control, and restricted working memory capacity, the researchers wrote.

FA follows an inverted U-shaped pattern. “The natural trajectory is to increase from infancy up to middle adolescence and then, as we get older, from about age 25 to 30 years, starts to go down. Our brains are starting to show signs of aging a bit by then,” said Dr. Pfefferbaum.

The current analysis assessed 451 adolescents (228 boys and 223 girls) from the NCANDA study, for whom researchers had four years of longitudinal DTI data. All were aged 12- 21 years at baseline.

The NCANDA cohort was recruited across five U.S. sites. Participants are assessed yearly on psychobiologic measures, including brain maturation. The cohort, which did not have any significant substance abuse upon entry, is balanced in terms of gender and ethnicity.

The investigators quantified the developmental change of white-matter (WM) integrity within each individual as the slope of FA over visits. They also examined altered developmental trajectories associated with drinking onset during adolescence and the differential alcohol associations by age with specific regional WM fiber tracts.

Researchers assessed drinking on a scale of 1-4, based on the youth-adjusted Cahalan score. The scale considers quantity and frequency to classify drinking levels based on past-year self-reported patterns.
 

Altered trajectory

Results showed that 291 participants (37.2%) remained at no to low drinking levels (youth-adjusted Cahalan score, 0) throughout the time points examined, and 160 (20.5%) were classified as heavy drinkers for at least two consecutive visits (youth-adjusted Cahalan score >1).

Among the no to low drinkers, 48.4% were boys with a mean age of 16.5 years and 51.2% were girls with a mean age of 16.5 years. About two thirds of the group (66%) were White.

Among heavy drinkers, 53.8% were boys with a mean age of 20.1 years and 46.3% were girls with a mean age of 20.5 years. In this group, 88.8% were White.

The investigators did not analyze moderate drinkers or those who initiated heavy drinking for only one visit.

The findings also showed that heavy drinkers exhibited significant reduction of whole-brain FA. The slopes of the 78 heavy drinkers were significantly more negative than the 78 matched no to low drinkers (mean, –0.0013 vs. 0.0001; P = .008).

“The concept of the slopes is really important here because it’s the trajectory that seems to be the most sensitive measure,” Dr. Pfefferbaum said. “Probably what’s happening is the exposure to alcohol is interfering with the normal myelination and normal development of the adolescent’s white matter.”

The no to low drinkers had relatively stable FA measures across all visits.

A reduction in FA was significantly linked to heavy drinking. An analysis of 63 youth who transitioned from being a no to low drinker to a heavy drinker showed that before the transition, they had significantly increased FA over visits (95% CI of slope, 0.0011-0.0024; P < .001). In addition, their corresponding slopes were not different from other no to low drinkers of the same age range.

However, this group’s FA declined significantly after they reported heavy drinking, resulting in slopes significantly below zero (95% CI of slope, –0.0036 to –0.0014; P < .001) and that were lower than the no to low participants of the same age range.

The findings of this unique before-and-after assessment “bring us one step closer to causality,” and further illustrates that heavy drinking in adolescence affects WM integrity, Dr. Pfefferbaum said.
 

Potential markers

None of the slope measures correlated with number of visits or use of tobacco or cannabis. The association of alcohol with the slope measures was more apparent in the younger cohort (<19 years).

“The effects were seen more readily in younger adolescents because they are the ones who are still progressing along this normal developmental trajectory,” Dr. Pfefferbaum noted. “In a sense, the younger you are when you’re exposed to alcohol, probably the more vulnerable you are.”

Previous studies have suggested that damage in WM tracts is associated with heightened neural reactivity to alcohol cues in adults with alcohol use disorder. Given this evidence, the greater WM degradation at younger versus older ages might help explain why adolescents who initiate early drinking are more likely to develop addiction later in life, the investigators wrote.

Of the five major fiber tracts, only the commissural fibers (corpus callosum) showed a significant association with alcohol. The researchers noted that WM volume shrinkage and callosal demyelination are two of the most prominent markers in adult alcoholism and are potential markers in adolescent alcohol abuse.

Upon further extending the analysis to the four subregions of the corpus callosum, the investigators found that only the anterior and middle callosal regions (genu and body) showed significant age-alcohol interactions.

This could be a result of the timing of fiber myelination in these regions of the brain, compared with others, Dr. Pfefferbaum said.

He noted that these fibers connect the left and right part of the anterior regions of the brain, especially the frontal lobes, which are particularly vulnerable to the effects of alcohol. “It may well be that we have this interaction of the developmental time and the sensitivity of the frontal parts of the brain.”
 

Cognitive effects?

Although the researchers did not find any sex effects, Dr. Pfefferbaum stressed that this doesn’t mean they do not exist. “We just may not have the power to see them,” he said.

The study did not look specifically at binge drinkers, defined as consuming five drinks in 2 hours for men and four drinks in 2 hours for women. Dr. Pfefferbaum noted that it is difficult to get “good quantification” of binge drinking. “We don’t have a fine enough grain analysis to separate that out,” he said.

Asked whether the altered FA trajectory in heavy drinkers affects cognition, Dr. Pfefferbaum said “those studies are still in progress,” with results hopefully available within about a year.

Dr. Pfefferbaum said he and his colleagues are continuing to follow these adolescents and hope to see if the altered FA trajectory in heavy drinkers returns to normal, adding: “The real question now is: If they stop heavy drinking, will they get back on track?”

This study is believed to be the first to suggest in vivo differential vulnerability in WM microstructure with respect to age, the authors note.

In addition to asking teens about their alcohol use, the clinician’s role should be to “counsel and refer,” said Dr. Pfefferbaum. He also suggested accessing resources from the National Institute on Alcohol Abuse and Alcoholism.
 

Important data, but several limitations

In an interview, Oscar G. Bukstein, MD, MPH, medical director of outpatient psychiatry service at Boston Children’s Hospital, and professor of psychiatry at Harvard Medical School, also in Boston, said the findings provide further evidence that alcohol affects the maturing brain.

This study, and others that have examined cannabis use, “show that you have a dynamically growing brain with certain sections, particularly in this case the anterior and middle corpus callosum, that mature later [and] that are more likely to be affected by early alcohol use,” said Dr. Bukstein, who was not involved with the research.

He stressed the importance of determining the mechanism involved and noted some study limitations. For example, the DTI technology used may “already be out of date,” he said.

Using older technology may have prevented finding an impact of heavy drinking on parts of the brain other than the anterior and middle corpus callosum, Dr. Bukstein noted.

Newer technology might provide “a finer-grain nonlinear voxel-wise analysis,” although using more updated scanning techniques may not have detected additional differences in study groups, he added.

Dr. Bukstein also noted that there were limitations: The study did not have “gradations,” but only looked at heavy drinking and no to low drinking. “You’d like to find out about kids who are somewhere in the middle.” It also didn’t determine a “cutoff” where deleterious effects of alcohol on the brain begin, Dr. Bukstein added.

Additionally, the study didn’t look at brain development outcomes in children with conditions such as depression and ADHD that are known to lead to substance use – something a larger study may have been able to do, he said.

Dr. Bukstein noted that a newer and much larger study, the Adolescent Brain Cognitive Development study, has begun assessing kids for risk factors such as substance use, starting at age 10 years.

The study was funded by grants from NIAAA and by the National Institute on Drug Abuse, the National Institute of Mental Health, the National Institute of Child Health and Human Development, and the Stanford Institute for Human-Centered Artificial Intelligence–AWS Cloud Credits for Research. Dr. Pfefferbaum reported receiving an NIAAA grant during the conduct of the study. Dr. Bukstein disclosed no relevant financial relationships.

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

Children with enthesitis-related arthritis often have a high burden of disease and could benefit from medications currently approved for adults with spondyloarthritis, according to a review published in Arthritis Care & Research.

“Enthesitis-related arthritis (ERA) was the JIA [juvenile idiopathic arthritis] category applied to children with spondyloarthritis (SpA), recognizing enthesitis as a defining characteristic,” wrote Pamela F. Weiss, MD, of Children’s Hospital of Philadelphia, and colleagues.

The ERA criteria include “arthritis plus enthesitis; or arthritis or enthesitis plus at least two of the following: sacroiliac tenderness or inflammatory back pain, HLA-B27 positivity, first-degree relative with HLA-B27–associated disease, acute anterior uveitis, and arthritis in a male older than 6 years,” the review authors noted.

“None of the [Food and Drug Administration]–approved therapies for peripheral SpA or nonradiographic axial SpA” have been studied or approved for use in children with ERA, but data support biologic similarity to SpA in adults; notably, studies of the HLA-B27 allele have identified it as a risk factor for both SpA and ERA, they said.
 

Common factors in adult and childhood conditions

“The principal commonalities of children with ERA and axial arthritis, and adults with nonradiographic axial SpA, include enthesitis, arthritis, inflammatory back pain, anterior uveitis, HLA-B27 positivity, and family history of HLA-B27–associated disease,” the review authors wrote.

The first-line treatment for both ERA with axial arthritis and nonradiographic axial SpA is NSAIDs, followed by tumor necrosis factor (TNF) inhibitors if needed, they said. However, conventional disease-modifying antirheumatic drugs (cDMARDs) may be used in cases of peripheral disease affecting five or more joints. Studies of treatment response show similarities between ERA in children and SpA in adults, the authors added, with nearly half of adults with axial disease unable to achieve remission and approximately one-third of children with ERA failing to respond to therapy.

Clinical trials could improve options and outcomes for those with ERA who need advanced therapy and such trials should evaluate response of axial and peripheral disease separately, the review authors emphasized. For example, “Eligibility criteria for children with ERA and axial features could include the presence of some of the following disease features: active inflammatory sacroiliitis based on typical MRI changes according to ASAS/OMERACT [Assessment of SpondyloArthritis international Society/Outcome Measures in Rheumatology Clinical Trials] criteria; elevated CRP [C-reactive protein]; and inadequate response or intolerance to NSAIDs,” they noted. “Considering the similarities between adult spondyloarthritis and ERA in terms of etiology, genetics, pathogenesis, and clinical manifestations, it is evident that medications approved for axial or peripheral SpA should be studied in children with ERA involving axial or peripheral joints, respectively, with the intent to achieve labeling for use in children,” they concluded.

New data highlight ERA disease burden

The need for additional therapies for ERA patients gained more support from a recent study in which a majority of children with ERA or juvenile psoriatic arthritis (jPsA) used biologics, but those with sacroiliitis in particular showed a significant disease burden despite high biologic use.

The International Leagues Against Rheumatism criteria include seven categories of juvenile idiopathic arthritis, of which ERA and jPsA are the most common; however, characteristics of these children have not been well described, wrote Dax G. Rumsey, MD, of the University of Alberta, Edmonton, and colleagues.

“Children with ERA are more likely to have a clinical picture with predominantly peripheral arthritis, typically described as an oligoarthritis involving the lower limbs with high risk of axial disease, relative to the other categories of JIA,” and report more intense pain and worse health status, compared with children in other categories, the researchers wrote.

To more completely characterize children with ERA and jPsA, the researchers assessed 522 children with ERA and 380 with jPsA. The children were enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. The findings were published in a brief report in Arthritis Care & Research.

Overall, 69% of the children took at least one biologic, including 72% with ERA and 64% with jPsA. Biologic use was even higher (81%) among the 28% of patients with sacroiliitis (40% of ERA patients and 12% of jPsA patients). Approximately 36% of the patients with sacroiliitis were positive for HLA-B27. In addition, Physician Global Assessment scores and clinical Juvenile Arthritis Disease Activity Score-10 (cJADAS10) scores were significantly higher at the first clinical visit with sacroiliitis, compared with the first visit without, which confirms “the clinical impression that active sacroiliitis significantly impacts children and their families,” the researchers said.

The average age at diagnosis was 10.8 years for ERA and 8.2 years for jPsA, and significantly more ERA patients were male (56% vs. 38%). However, more of the patients with sacroiliitis (54%) were female. More than half of the patients reported polyarticular involvement.

The study findings were limited by several factors, including the classification of ERA or jPsA and the reliance on physician diagnoses, as well as the variation in identifying sacroiliitis, the researchers said. However, the results increase understanding of the pathophysiology of ERA and jPsA to help determine optimal treatment, they concluded.
 

Data highlight research and treatment gaps

“Recent research demonstrates a large, unmet medical need in the treatment of JIA with 52%-65% of all JIA patients, including those with ERA and jPsA, having been treated with at least one biologic DMARD and 15%-19% having been treated with an FDA-unapproved biologic. In those with ERA or jPsA, 72%-79% of the children had been treated with a biologic DMARD, although no biologic DMARD has ever been FDA approved for these JIA categories,” Daniel J. Lovell, MD, and Hermine I. Brunner, MD, both with Cincinnati Children’s Hospital Medical Center, wrote in an editorial that accompanied the new study. Dr. Lovell and Dr. Brunner also were coauthors of the review article.

The new study supports findings from other recent publications, the editorialists noted. The new results showed “a significant proportion of the JIA population with active sacroiliitis with high disease burden despite very frequent (over 80% of the population) [treatment] with unstudied and unapproved biologic DMARDs,” they said. “These children with sacroiliitis had significantly greater disease burden with higher physician assessment of disease activity, higher parent assessment of disease impact, and higher disease activity as measured by the Juvenile Idiopathic Arthritis Disease Activity Score, compared to the children with ERA or jPsA without sacroiliitis,” they noted.

Jeff Craven/MDedge News

Previously, “the FDA granted pharmaceutical companies studying new treatments in adult SpA automatic full waivers from doing studies in children for new medications for ‘axial spondyloarthropathies including ankylosing spondylitis’ up until July 2020,” the editorialists said. However, “It is now time now for the pharmaceutical industry to perform FDA-monitored clinical trials of children and adolescents with SpA,” they emphasized. “This will allow for the scientific assessment of proper dosing, efficacy, and safety of the increasing number of new medications that are being licensed by the FDA for the treatment of SpA, such as the anti-TNF, anti–IL[interleukin]-17, and anti–IL-23 biologics, and perhaps JAK [Janus kinase] agents, to address this unmet medical need in these patients with juvenile SpA,” they concluded.

Dr. Weiss disclosed grant support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and financial relationships with Eli Lilly and Pfizer. Dr. Lovell disclosed relationships with companies including Abbott, AbbVie Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Novartis, Pfizer, Takeda, UCB, and Wyeth, as well as serving on the data and safety monitoring board for Forest Research and NIAMS. Dr. Brunner disclosed relationships with companies including Ablynx, AbbVie, AstraZeneca-MedImmune, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, EMD Serono, F. Hoffmann-La Roche, Genzyme, GlaxoSmithKline, Merck, Novartis, R-Pharm, and Sanofi. The study by Dr. Rumsey and colleagues was supported by Amgen. Dr. Rumsey and colleagues had no relevant financial conflicts to disclose.

SOURCES: Weiss PF et al. Arthritis Care Res. 2020 Dec 5. doi: 10.1002/acr.24529; Rumsey DG et al. Arthritis Care Res. 2020 Dec. 16. doi: 10.1002/acr.24537; Lovell DJ and Brunner HI. Arthritis Care Res. 2020 Dec 16. doi: 10.1002/acr.24536.

Children with enthesitis-related arthritis often have a high burden of disease and could benefit from medications currently approved for adults with spondyloarthritis, according to a review published in Arthritis Care & Research.

“Enthesitis-related arthritis (ERA) was the JIA [juvenile idiopathic arthritis] category applied to children with spondyloarthritis (SpA), recognizing enthesitis as a defining characteristic,” wrote Pamela F. Weiss, MD, of Children’s Hospital of Philadelphia, and colleagues.

The ERA criteria include “arthritis plus enthesitis; or arthritis or enthesitis plus at least two of the following: sacroiliac tenderness or inflammatory back pain, HLA-B27 positivity, first-degree relative with HLA-B27–associated disease, acute anterior uveitis, and arthritis in a male older than 6 years,” the review authors noted.

“None of the [Food and Drug Administration]–approved therapies for peripheral SpA or nonradiographic axial SpA” have been studied or approved for use in children with ERA, but data support biologic similarity to SpA in adults; notably, studies of the HLA-B27 allele have identified it as a risk factor for both SpA and ERA, they said.
 

Common factors in adult and childhood conditions

“The principal commonalities of children with ERA and axial arthritis, and adults with nonradiographic axial SpA, include enthesitis, arthritis, inflammatory back pain, anterior uveitis, HLA-B27 positivity, and family history of HLA-B27–associated disease,” the review authors wrote.

The first-line treatment for both ERA with axial arthritis and nonradiographic axial SpA is NSAIDs, followed by tumor necrosis factor (TNF) inhibitors if needed, they said. However, conventional disease-modifying antirheumatic drugs (cDMARDs) may be used in cases of peripheral disease affecting five or more joints. Studies of treatment response show similarities between ERA in children and SpA in adults, the authors added, with nearly half of adults with axial disease unable to achieve remission and approximately one-third of children with ERA failing to respond to therapy.

Clinical trials could improve options and outcomes for those with ERA who need advanced therapy and such trials should evaluate response of axial and peripheral disease separately, the review authors emphasized. For example, “Eligibility criteria for children with ERA and axial features could include the presence of some of the following disease features: active inflammatory sacroiliitis based on typical MRI changes according to ASAS/OMERACT [Assessment of SpondyloArthritis international Society/Outcome Measures in Rheumatology Clinical Trials] criteria; elevated CRP [C-reactive protein]; and inadequate response or intolerance to NSAIDs,” they noted. “Considering the similarities between adult spondyloarthritis and ERA in terms of etiology, genetics, pathogenesis, and clinical manifestations, it is evident that medications approved for axial or peripheral SpA should be studied in children with ERA involving axial or peripheral joints, respectively, with the intent to achieve labeling for use in children,” they concluded.

New data highlight ERA disease burden

The need for additional therapies for ERA patients gained more support from a recent study in which a majority of children with ERA or juvenile psoriatic arthritis (jPsA) used biologics, but those with sacroiliitis in particular showed a significant disease burden despite high biologic use.

The International Leagues Against Rheumatism criteria include seven categories of juvenile idiopathic arthritis, of which ERA and jPsA are the most common; however, characteristics of these children have not been well described, wrote Dax G. Rumsey, MD, of the University of Alberta, Edmonton, and colleagues.

“Children with ERA are more likely to have a clinical picture with predominantly peripheral arthritis, typically described as an oligoarthritis involving the lower limbs with high risk of axial disease, relative to the other categories of JIA,” and report more intense pain and worse health status, compared with children in other categories, the researchers wrote.

To more completely characterize children with ERA and jPsA, the researchers assessed 522 children with ERA and 380 with jPsA. The children were enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. The findings were published in a brief report in Arthritis Care & Research.

Overall, 69% of the children took at least one biologic, including 72% with ERA and 64% with jPsA. Biologic use was even higher (81%) among the 28% of patients with sacroiliitis (40% of ERA patients and 12% of jPsA patients). Approximately 36% of the patients with sacroiliitis were positive for HLA-B27. In addition, Physician Global Assessment scores and clinical Juvenile Arthritis Disease Activity Score-10 (cJADAS10) scores were significantly higher at the first clinical visit with sacroiliitis, compared with the first visit without, which confirms “the clinical impression that active sacroiliitis significantly impacts children and their families,” the researchers said.

The average age at diagnosis was 10.8 years for ERA and 8.2 years for jPsA, and significantly more ERA patients were male (56% vs. 38%). However, more of the patients with sacroiliitis (54%) were female. More than half of the patients reported polyarticular involvement.

The study findings were limited by several factors, including the classification of ERA or jPsA and the reliance on physician diagnoses, as well as the variation in identifying sacroiliitis, the researchers said. However, the results increase understanding of the pathophysiology of ERA and jPsA to help determine optimal treatment, they concluded.
 

Data highlight research and treatment gaps

“Recent research demonstrates a large, unmet medical need in the treatment of JIA with 52%-65% of all JIA patients, including those with ERA and jPsA, having been treated with at least one biologic DMARD and 15%-19% having been treated with an FDA-unapproved biologic. In those with ERA or jPsA, 72%-79% of the children had been treated with a biologic DMARD, although no biologic DMARD has ever been FDA approved for these JIA categories,” Daniel J. Lovell, MD, and Hermine I. Brunner, MD, both with Cincinnati Children’s Hospital Medical Center, wrote in an editorial that accompanied the new study. Dr. Lovell and Dr. Brunner also were coauthors of the review article.

The new study supports findings from other recent publications, the editorialists noted. The new results showed “a significant proportion of the JIA population with active sacroiliitis with high disease burden despite very frequent (over 80% of the population) [treatment] with unstudied and unapproved biologic DMARDs,” they said. “These children with sacroiliitis had significantly greater disease burden with higher physician assessment of disease activity, higher parent assessment of disease impact, and higher disease activity as measured by the Juvenile Idiopathic Arthritis Disease Activity Score, compared to the children with ERA or jPsA without sacroiliitis,” they noted.

Jeff Craven/MDedge News

Previously, “the FDA granted pharmaceutical companies studying new treatments in adult SpA automatic full waivers from doing studies in children for new medications for ‘axial spondyloarthropathies including ankylosing spondylitis’ up until July 2020,” the editorialists said. However, “It is now time now for the pharmaceutical industry to perform FDA-monitored clinical trials of children and adolescents with SpA,” they emphasized. “This will allow for the scientific assessment of proper dosing, efficacy, and safety of the increasing number of new medications that are being licensed by the FDA for the treatment of SpA, such as the anti-TNF, anti–IL[interleukin]-17, and anti–IL-23 biologics, and perhaps JAK [Janus kinase] agents, to address this unmet medical need in these patients with juvenile SpA,” they concluded.

Dr. Weiss disclosed grant support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and financial relationships with Eli Lilly and Pfizer. Dr. Lovell disclosed relationships with companies including Abbott, AbbVie Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Novartis, Pfizer, Takeda, UCB, and Wyeth, as well as serving on the data and safety monitoring board for Forest Research and NIAMS. Dr. Brunner disclosed relationships with companies including Ablynx, AbbVie, AstraZeneca-MedImmune, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, EMD Serono, F. Hoffmann-La Roche, Genzyme, GlaxoSmithKline, Merck, Novartis, R-Pharm, and Sanofi. The study by Dr. Rumsey and colleagues was supported by Amgen. Dr. Rumsey and colleagues had no relevant financial conflicts to disclose.

SOURCES: Weiss PF et al. Arthritis Care Res. 2020 Dec 5. doi: 10.1002/acr.24529; Rumsey DG et al. Arthritis Care Res. 2020 Dec. 16. doi: 10.1002/acr.24537; Lovell DJ and Brunner HI. Arthritis Care Res. 2020 Dec 16. doi: 10.1002/acr.24536.

Children with enthesitis-related arthritis often have a high burden of disease and could benefit from medications currently approved for adults with spondyloarthritis, according to a review published in Arthritis Care & Research.

“Enthesitis-related arthritis (ERA) was the JIA [juvenile idiopathic arthritis] category applied to children with spondyloarthritis (SpA), recognizing enthesitis as a defining characteristic,” wrote Pamela F. Weiss, MD, of Children’s Hospital of Philadelphia, and colleagues.

The ERA criteria include “arthritis plus enthesitis; or arthritis or enthesitis plus at least two of the following: sacroiliac tenderness or inflammatory back pain, HLA-B27 positivity, first-degree relative with HLA-B27–associated disease, acute anterior uveitis, and arthritis in a male older than 6 years,” the review authors noted.

“None of the [Food and Drug Administration]–approved therapies for peripheral SpA or nonradiographic axial SpA” have been studied or approved for use in children with ERA, but data support biologic similarity to SpA in adults; notably, studies of the HLA-B27 allele have identified it as a risk factor for both SpA and ERA, they said.
 

Common factors in adult and childhood conditions

“The principal commonalities of children with ERA and axial arthritis, and adults with nonradiographic axial SpA, include enthesitis, arthritis, inflammatory back pain, anterior uveitis, HLA-B27 positivity, and family history of HLA-B27–associated disease,” the review authors wrote.

The first-line treatment for both ERA with axial arthritis and nonradiographic axial SpA is NSAIDs, followed by tumor necrosis factor (TNF) inhibitors if needed, they said. However, conventional disease-modifying antirheumatic drugs (cDMARDs) may be used in cases of peripheral disease affecting five or more joints. Studies of treatment response show similarities between ERA in children and SpA in adults, the authors added, with nearly half of adults with axial disease unable to achieve remission and approximately one-third of children with ERA failing to respond to therapy.

Clinical trials could improve options and outcomes for those with ERA who need advanced therapy and such trials should evaluate response of axial and peripheral disease separately, the review authors emphasized. For example, “Eligibility criteria for children with ERA and axial features could include the presence of some of the following disease features: active inflammatory sacroiliitis based on typical MRI changes according to ASAS/OMERACT [Assessment of SpondyloArthritis international Society/Outcome Measures in Rheumatology Clinical Trials] criteria; elevated CRP [C-reactive protein]; and inadequate response or intolerance to NSAIDs,” they noted. “Considering the similarities between adult spondyloarthritis and ERA in terms of etiology, genetics, pathogenesis, and clinical manifestations, it is evident that medications approved for axial or peripheral SpA should be studied in children with ERA involving axial or peripheral joints, respectively, with the intent to achieve labeling for use in children,” they concluded.

New data highlight ERA disease burden

The need for additional therapies for ERA patients gained more support from a recent study in which a majority of children with ERA or juvenile psoriatic arthritis (jPsA) used biologics, but those with sacroiliitis in particular showed a significant disease burden despite high biologic use.

The International Leagues Against Rheumatism criteria include seven categories of juvenile idiopathic arthritis, of which ERA and jPsA are the most common; however, characteristics of these children have not been well described, wrote Dax G. Rumsey, MD, of the University of Alberta, Edmonton, and colleagues.

“Children with ERA are more likely to have a clinical picture with predominantly peripheral arthritis, typically described as an oligoarthritis involving the lower limbs with high risk of axial disease, relative to the other categories of JIA,” and report more intense pain and worse health status, compared with children in other categories, the researchers wrote.

To more completely characterize children with ERA and jPsA, the researchers assessed 522 children with ERA and 380 with jPsA. The children were enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. The findings were published in a brief report in Arthritis Care & Research.

Overall, 69% of the children took at least one biologic, including 72% with ERA and 64% with jPsA. Biologic use was even higher (81%) among the 28% of patients with sacroiliitis (40% of ERA patients and 12% of jPsA patients). Approximately 36% of the patients with sacroiliitis were positive for HLA-B27. In addition, Physician Global Assessment scores and clinical Juvenile Arthritis Disease Activity Score-10 (cJADAS10) scores were significantly higher at the first clinical visit with sacroiliitis, compared with the first visit without, which confirms “the clinical impression that active sacroiliitis significantly impacts children and their families,” the researchers said.

The average age at diagnosis was 10.8 years for ERA and 8.2 years for jPsA, and significantly more ERA patients were male (56% vs. 38%). However, more of the patients with sacroiliitis (54%) were female. More than half of the patients reported polyarticular involvement.

The study findings were limited by several factors, including the classification of ERA or jPsA and the reliance on physician diagnoses, as well as the variation in identifying sacroiliitis, the researchers said. However, the results increase understanding of the pathophysiology of ERA and jPsA to help determine optimal treatment, they concluded.
 

Data highlight research and treatment gaps

“Recent research demonstrates a large, unmet medical need in the treatment of JIA with 52%-65% of all JIA patients, including those with ERA and jPsA, having been treated with at least one biologic DMARD and 15%-19% having been treated with an FDA-unapproved biologic. In those with ERA or jPsA, 72%-79% of the children had been treated with a biologic DMARD, although no biologic DMARD has ever been FDA approved for these JIA categories,” Daniel J. Lovell, MD, and Hermine I. Brunner, MD, both with Cincinnati Children’s Hospital Medical Center, wrote in an editorial that accompanied the new study. Dr. Lovell and Dr. Brunner also were coauthors of the review article.

The new study supports findings from other recent publications, the editorialists noted. The new results showed “a significant proportion of the JIA population with active sacroiliitis with high disease burden despite very frequent (over 80% of the population) [treatment] with unstudied and unapproved biologic DMARDs,” they said. “These children with sacroiliitis had significantly greater disease burden with higher physician assessment of disease activity, higher parent assessment of disease impact, and higher disease activity as measured by the Juvenile Idiopathic Arthritis Disease Activity Score, compared to the children with ERA or jPsA without sacroiliitis,” they noted.

Jeff Craven/MDedge News

Previously, “the FDA granted pharmaceutical companies studying new treatments in adult SpA automatic full waivers from doing studies in children for new medications for ‘axial spondyloarthropathies including ankylosing spondylitis’ up until July 2020,” the editorialists said. However, “It is now time now for the pharmaceutical industry to perform FDA-monitored clinical trials of children and adolescents with SpA,” they emphasized. “This will allow for the scientific assessment of proper dosing, efficacy, and safety of the increasing number of new medications that are being licensed by the FDA for the treatment of SpA, such as the anti-TNF, anti–IL[interleukin]-17, and anti–IL-23 biologics, and perhaps JAK [Janus kinase] agents, to address this unmet medical need in these patients with juvenile SpA,” they concluded.

Dr. Weiss disclosed grant support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and financial relationships with Eli Lilly and Pfizer. Dr. Lovell disclosed relationships with companies including Abbott, AbbVie Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Novartis, Pfizer, Takeda, UCB, and Wyeth, as well as serving on the data and safety monitoring board for Forest Research and NIAMS. Dr. Brunner disclosed relationships with companies including Ablynx, AbbVie, AstraZeneca-MedImmune, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, EMD Serono, F. Hoffmann-La Roche, Genzyme, GlaxoSmithKline, Merck, Novartis, R-Pharm, and Sanofi. The study by Dr. Rumsey and colleagues was supported by Amgen. Dr. Rumsey and colleagues had no relevant financial conflicts to disclose.

SOURCES: Weiss PF et al. Arthritis Care Res. 2020 Dec 5. doi: 10.1002/acr.24529; Rumsey DG et al. Arthritis Care Res. 2020 Dec. 16. doi: 10.1002/acr.24537; Lovell DJ and Brunner HI. Arthritis Care Res. 2020 Dec 16. doi: 10.1002/acr.24536.

For too long, eating disorders have been considered a disease that afflicted mostly affluent white teenage girls, but there really is no type for eating disorders, said Laurie L. Hornberger, MD, MPH, lead author of a new clinical report on eating disorders in children and adolescents prepared by the American Academy of Pediatrics Committee on Adolescence.

FatCamera/E+

In a separate interview with Pediatric News, Dr. Hornberger, associate professor of pediatrics, University of Missouri–Kansas City, explained that eating disorders occur across the spectrum of races, ethnicities, sexes, and socioeconomic statuses, so “getting caught up in that stereotype can cause you to overlook kids with significant problems.” Pediatricians are on the front line in identifying and referring eating disorders for treatment, which is crucial to earlier detection, intervention, and better outcomes, she said.

“Once you become familiar with the signs and symptoms of EDs [eating disorders] and actively start screening for them, you realize how common they are,” she noted, adding that pediatricians should be inquiring routinely about body image, attempts at weight management and what was involved in that weight management. Efforts to restrict calories, limit food choices/groups, exercise excessively, force vomiting, abuse laxatives, etc., are all signs. If the child/adolescent experiences guilt with eating, feels the need to compensate for their eating with exercise or purging, is preoccupied with thoughts of food or calorie counting, feels he/she has lost control of their eating, or experiences uncontrollable binges where they are unable to stop eating despite feeling full and wanting to stop, these are all further evidence of an eating disorder, she added.

There are also physical clues to alert pediatricians. Abrupt or sharp increases or decreases in weight, as measured in growth charts, should be monitored and questioned, Dr. Hornberger cautioned. Physicians should be careful to hold compliments on weight loss until learning how the weight loss was achieved. “Vital signs, such as a resting bradycardia and orthostatic tachycardia, can reflect malnutrition, as can other physical findings. Although lab screening is frequently normal, it should not, by itself, rule out an [eating disorder]. Pediatricians should also be aware of the signs and symptoms of medical instability in an [eating disorder] patient that warrant hospitalization for renourishment,” she explained.
 

Number of eating disorders increased in 2020

Current pandemic conditions have shown an uptick in the number of referrals and long wait lists for eating disorder centers, noted Dr. Hornberger. Having a formal eating disorder treatment program nearby is a luxury not all communities have, so being able to call upon primary care pediatricians to be an active part of a treatment team, which ideally includes a mental health provider and dietitian, both experienced in eating disorders, is pretty important. In coordination with the team, pediatricians are responsible for monitoring physical recovery and remaining alert for signs of struggle to recover and the need for a higher level of care.

In a separate interview with Pediatric News, Margaret Thew, DNP, FNP-BC, medical director of adolescent medicine at the Medical College of Wisconsin, Milwaukee, observed, “COVID-19 has created a surge of children and adolescents struggling with eating disorders. Eating disorder numbers have been associated with social media promoting the avoidance of COVID-19–related weight gain and influencers promoting thin body image. The abrupt end of face-to-face learning, sports participation, and generalized anxiety have further influenced mental health and disordered eating behaviors. Early in the pandemic, the true impact on the psychosocial well-being of children and teens was not known. We are only now seeing the impact months into this pandemic. The timeliness of the American Association of Pediatrics guidelines on the identification and management of children and teens presenting with an eating disorder is pivotal to recognition and treatment,” she said.

“I applaud the AAP for presenting timely guidelines on the evaluation and management of eating disorders for the general pediatrician, yet feel the authors fell short in recognizing the challenges of mitigating management of an eating disorder,” Ms. Thew added.

“Treatment of disordered eating requires all parties to accept the diagnosis and no longer support unhealthy eating patterns. The environment rationalizing the disordered eating may require changes to reduce behaviors and improve nutrition,” she cautioned.
 

New guidelines offer a range of diagnostic and treatment resources

In preparing the current report, the authors included the most recent definitions of eating disorders outlined in the “Diagnostic and Statistical Manual of Mental Disorders,” 5th Edition (DSM-5). Special attention was paid to four classifications of eating disorders in particular – anorexia nervosa (AN), avoidant/restrictive food intake disorder (ARFID); binge-eating disorder (BED); and bulimia nervosa (BN) – because so many disorders are subclassified under these.

Beyond providing a list of comprehensive definitions, the guidance reviews prevalence data for eating disorders, and provides detailed screening, assessment, and laboratory evaluation guidelines. Medical complications, including psychological, neurologic, dermatologic, dental and/or oral, cardiovascular, gastrointestinal, renal and electrolyte, and endocrine effects are discussed in detail as are treatment principles, financial considerations, and prognosis. Besides the important prevention and advocacy roles the authors identify for pediatricians, the guidelines highlight four key areas where pediatricians play a key role in the screening and management of eating disorders, as touched on previously by the guidance authors in this article.

In a separate AAP press release, Margo Lane, MD, coauthor of the report, noted, “As pediatricians, there is much we can also do outside the clinic to advocate for our patients, through legislation and policy that support services, including medical care, nutritional intervention, mental health treatment, and care coordination.” Physicians can also play an important role in reprograming familial and societal attitudes and behaviors by encouraging more positive language that deemphasizes weight and embraces and celebrates kids of all shapes and sizes, added Dr. Lane.

Dr. Hornberger and colleagues as well as Ms. Thew had no conflicts of interest and no relevant financial disclosures.

SOURCE: Pediatrics. 2021;147(1):e2020040279. doi: 10.1542/peds.2020-040279.

For too long, eating disorders have been considered a disease that afflicted mostly affluent white teenage girls, but there really is no type for eating disorders, said Laurie L. Hornberger, MD, MPH, lead author of a new clinical report on eating disorders in children and adolescents prepared by the American Academy of Pediatrics Committee on Adolescence.

FatCamera/E+

In a separate interview with Pediatric News, Dr. Hornberger, associate professor of pediatrics, University of Missouri–Kansas City, explained that eating disorders occur across the spectrum of races, ethnicities, sexes, and socioeconomic statuses, so “getting caught up in that stereotype can cause you to overlook kids with significant problems.” Pediatricians are on the front line in identifying and referring eating disorders for treatment, which is crucial to earlier detection, intervention, and better outcomes, she said.

“Once you become familiar with the signs and symptoms of EDs [eating disorders] and actively start screening for them, you realize how common they are,” she noted, adding that pediatricians should be inquiring routinely about body image, attempts at weight management and what was involved in that weight management. Efforts to restrict calories, limit food choices/groups, exercise excessively, force vomiting, abuse laxatives, etc., are all signs. If the child/adolescent experiences guilt with eating, feels the need to compensate for their eating with exercise or purging, is preoccupied with thoughts of food or calorie counting, feels he/she has lost control of their eating, or experiences uncontrollable binges where they are unable to stop eating despite feeling full and wanting to stop, these are all further evidence of an eating disorder, she added.

There are also physical clues to alert pediatricians. Abrupt or sharp increases or decreases in weight, as measured in growth charts, should be monitored and questioned, Dr. Hornberger cautioned. Physicians should be careful to hold compliments on weight loss until learning how the weight loss was achieved. “Vital signs, such as a resting bradycardia and orthostatic tachycardia, can reflect malnutrition, as can other physical findings. Although lab screening is frequently normal, it should not, by itself, rule out an [eating disorder]. Pediatricians should also be aware of the signs and symptoms of medical instability in an [eating disorder] patient that warrant hospitalization for renourishment,” she explained.
 

Number of eating disorders increased in 2020

Current pandemic conditions have shown an uptick in the number of referrals and long wait lists for eating disorder centers, noted Dr. Hornberger. Having a formal eating disorder treatment program nearby is a luxury not all communities have, so being able to call upon primary care pediatricians to be an active part of a treatment team, which ideally includes a mental health provider and dietitian, both experienced in eating disorders, is pretty important. In coordination with the team, pediatricians are responsible for monitoring physical recovery and remaining alert for signs of struggle to recover and the need for a higher level of care.

In a separate interview with Pediatric News, Margaret Thew, DNP, FNP-BC, medical director of adolescent medicine at the Medical College of Wisconsin, Milwaukee, observed, “COVID-19 has created a surge of children and adolescents struggling with eating disorders. Eating disorder numbers have been associated with social media promoting the avoidance of COVID-19–related weight gain and influencers promoting thin body image. The abrupt end of face-to-face learning, sports participation, and generalized anxiety have further influenced mental health and disordered eating behaviors. Early in the pandemic, the true impact on the psychosocial well-being of children and teens was not known. We are only now seeing the impact months into this pandemic. The timeliness of the American Association of Pediatrics guidelines on the identification and management of children and teens presenting with an eating disorder is pivotal to recognition and treatment,” she said.

“I applaud the AAP for presenting timely guidelines on the evaluation and management of eating disorders for the general pediatrician, yet feel the authors fell short in recognizing the challenges of mitigating management of an eating disorder,” Ms. Thew added.

“Treatment of disordered eating requires all parties to accept the diagnosis and no longer support unhealthy eating patterns. The environment rationalizing the disordered eating may require changes to reduce behaviors and improve nutrition,” she cautioned.
 

New guidelines offer a range of diagnostic and treatment resources

In preparing the current report, the authors included the most recent definitions of eating disorders outlined in the “Diagnostic and Statistical Manual of Mental Disorders,” 5th Edition (DSM-5). Special attention was paid to four classifications of eating disorders in particular – anorexia nervosa (AN), avoidant/restrictive food intake disorder (ARFID); binge-eating disorder (BED); and bulimia nervosa (BN) – because so many disorders are subclassified under these.

Beyond providing a list of comprehensive definitions, the guidance reviews prevalence data for eating disorders, and provides detailed screening, assessment, and laboratory evaluation guidelines. Medical complications, including psychological, neurologic, dermatologic, dental and/or oral, cardiovascular, gastrointestinal, renal and electrolyte, and endocrine effects are discussed in detail as are treatment principles, financial considerations, and prognosis. Besides the important prevention and advocacy roles the authors identify for pediatricians, the guidelines highlight four key areas where pediatricians play a key role in the screening and management of eating disorders, as touched on previously by the guidance authors in this article.

In a separate AAP press release, Margo Lane, MD, coauthor of the report, noted, “As pediatricians, there is much we can also do outside the clinic to advocate for our patients, through legislation and policy that support services, including medical care, nutritional intervention, mental health treatment, and care coordination.” Physicians can also play an important role in reprograming familial and societal attitudes and behaviors by encouraging more positive language that deemphasizes weight and embraces and celebrates kids of all shapes and sizes, added Dr. Lane.

Dr. Hornberger and colleagues as well as Ms. Thew had no conflicts of interest and no relevant financial disclosures.

SOURCE: Pediatrics. 2021;147(1):e2020040279. doi: 10.1542/peds.2020-040279.

For too long, eating disorders have been considered a disease that afflicted mostly affluent white teenage girls, but there really is no type for eating disorders, said Laurie L. Hornberger, MD, MPH, lead author of a new clinical report on eating disorders in children and adolescents prepared by the American Academy of Pediatrics Committee on Adolescence.

FatCamera/E+

In a separate interview with Pediatric News, Dr. Hornberger, associate professor of pediatrics, University of Missouri–Kansas City, explained that eating disorders occur across the spectrum of races, ethnicities, sexes, and socioeconomic statuses, so “getting caught up in that stereotype can cause you to overlook kids with significant problems.” Pediatricians are on the front line in identifying and referring eating disorders for treatment, which is crucial to earlier detection, intervention, and better outcomes, she said.

“Once you become familiar with the signs and symptoms of EDs [eating disorders] and actively start screening for them, you realize how common they are,” she noted, adding that pediatricians should be inquiring routinely about body image, attempts at weight management and what was involved in that weight management. Efforts to restrict calories, limit food choices/groups, exercise excessively, force vomiting, abuse laxatives, etc., are all signs. If the child/adolescent experiences guilt with eating, feels the need to compensate for their eating with exercise or purging, is preoccupied with thoughts of food or calorie counting, feels he/she has lost control of their eating, or experiences uncontrollable binges where they are unable to stop eating despite feeling full and wanting to stop, these are all further evidence of an eating disorder, she added.

There are also physical clues to alert pediatricians. Abrupt or sharp increases or decreases in weight, as measured in growth charts, should be monitored and questioned, Dr. Hornberger cautioned. Physicians should be careful to hold compliments on weight loss until learning how the weight loss was achieved. “Vital signs, such as a resting bradycardia and orthostatic tachycardia, can reflect malnutrition, as can other physical findings. Although lab screening is frequently normal, it should not, by itself, rule out an [eating disorder]. Pediatricians should also be aware of the signs and symptoms of medical instability in an [eating disorder] patient that warrant hospitalization for renourishment,” she explained.
 

Number of eating disorders increased in 2020

Current pandemic conditions have shown an uptick in the number of referrals and long wait lists for eating disorder centers, noted Dr. Hornberger. Having a formal eating disorder treatment program nearby is a luxury not all communities have, so being able to call upon primary care pediatricians to be an active part of a treatment team, which ideally includes a mental health provider and dietitian, both experienced in eating disorders, is pretty important. In coordination with the team, pediatricians are responsible for monitoring physical recovery and remaining alert for signs of struggle to recover and the need for a higher level of care.

In a separate interview with Pediatric News, Margaret Thew, DNP, FNP-BC, medical director of adolescent medicine at the Medical College of Wisconsin, Milwaukee, observed, “COVID-19 has created a surge of children and adolescents struggling with eating disorders. Eating disorder numbers have been associated with social media promoting the avoidance of COVID-19–related weight gain and influencers promoting thin body image. The abrupt end of face-to-face learning, sports participation, and generalized anxiety have further influenced mental health and disordered eating behaviors. Early in the pandemic, the true impact on the psychosocial well-being of children and teens was not known. We are only now seeing the impact months into this pandemic. The timeliness of the American Association of Pediatrics guidelines on the identification and management of children and teens presenting with an eating disorder is pivotal to recognition and treatment,” she said.

“I applaud the AAP for presenting timely guidelines on the evaluation and management of eating disorders for the general pediatrician, yet feel the authors fell short in recognizing the challenges of mitigating management of an eating disorder,” Ms. Thew added.

“Treatment of disordered eating requires all parties to accept the diagnosis and no longer support unhealthy eating patterns. The environment rationalizing the disordered eating may require changes to reduce behaviors and improve nutrition,” she cautioned.
 

New guidelines offer a range of diagnostic and treatment resources

In preparing the current report, the authors included the most recent definitions of eating disorders outlined in the “Diagnostic and Statistical Manual of Mental Disorders,” 5th Edition (DSM-5). Special attention was paid to four classifications of eating disorders in particular – anorexia nervosa (AN), avoidant/restrictive food intake disorder (ARFID); binge-eating disorder (BED); and bulimia nervosa (BN) – because so many disorders are subclassified under these.

Beyond providing a list of comprehensive definitions, the guidance reviews prevalence data for eating disorders, and provides detailed screening, assessment, and laboratory evaluation guidelines. Medical complications, including psychological, neurologic, dermatologic, dental and/or oral, cardiovascular, gastrointestinal, renal and electrolyte, and endocrine effects are discussed in detail as are treatment principles, financial considerations, and prognosis. Besides the important prevention and advocacy roles the authors identify for pediatricians, the guidelines highlight four key areas where pediatricians play a key role in the screening and management of eating disorders, as touched on previously by the guidance authors in this article.

In a separate AAP press release, Margo Lane, MD, coauthor of the report, noted, “As pediatricians, there is much we can also do outside the clinic to advocate for our patients, through legislation and policy that support services, including medical care, nutritional intervention, mental health treatment, and care coordination.” Physicians can also play an important role in reprograming familial and societal attitudes and behaviors by encouraging more positive language that deemphasizes weight and embraces and celebrates kids of all shapes and sizes, added Dr. Lane.

Dr. Hornberger and colleagues as well as Ms. Thew had no conflicts of interest and no relevant financial disclosures.

SOURCE: Pediatrics. 2021;147(1):e2020040279. doi: 10.1542/peds.2020-040279.

An intense and assertive “won’t take no for an answer” approach is effective for engaging in treatment young adults with substance abuse who have been in and out of various recovery programs for years, new research suggests.

The Youth Opioid Recovery Support (YORS) program is a team effort that includes home delivery of the prescribed medication, family engagement, assertive outreach, and contingency management.

In a new study of 42 patients in recovery for substance use disorder (SUD), those who were treated with extended-release naltrexone or extended-release buprenorphine plus YORS received more outpatient doses of their medication, and rates of opioid relapse at 12 and 24 weeks were lower compared with their peers who received only treatment as usual.

“These developmentally vulnerable youths need something extra that is specifically targeted to who they are and their vulnerabilities,” coinvestigator Marc Fishman, MD, director of the Maryland Treatment Centers, Johns Hopkins University, Baltimore, said in an interview.

The findings were presented at the virtual American Academy of Addiction Psychiatry 31st Annual Meeting.
 

Treatment barriers

Young adults with SUD are difficult to reach, which leads to decreased addiction program retention, decreased medication adherence, early drop out, waxing and waning motivation, and worse outcomes, compared with older adults with SUD, Dr. Fishman said.

In July, positive results from a pilot trial conducted by the investigators of YORS were published online in Addiction.

In that study, 41 young adults aged 18-26 years who intended to undergo treatment for SUD with extended-release naltrexone were randomly assigned to also undergo YORS or treatment as usual, which consisted of a standard referral to outpatient care following an inpatient stay.

The primary outcomes were number of medication doses received over 24 weeks and relapse to opioid use, which was defined as 10 or more days of use within 28 days at 24 weeks.

Participants in the YORS group received more doses of extended-release naltrexone (mean, 4.28; standard deviation, 2.3) than participants in the treatment-as-usual group (mean, 0.70; SD, 1.2; P < .01).

In the YORS group, rates of relapse at both 12 and 24 weeks were lower, and there were fewer overall days of opioid use.

For the current study, the investigators wanted to test whether there was a possible effect when patients were given a choice of medication. In the earlier trial, patients did not have a choice – they had to take extended-release naltrexone. In this study, they could opt for it or extended-release buprenorphine.

The researchers recruited 22 young adults (aged 18-26 years) from their inpatient clinic to participate. Half the patients chose to take extended-release naltrexone, and the other half chose extended-release buprenorphine.

The groups were then compared to a historical group of 20 patients who received treatment as usual and served as the control group.
 

Positive outcomes

As in the first study, outcomes in the new study were better with YORS.

All participants who underwent YORS received more outpatient medication doses at 12 weeks and 24 weeks than those who received treatment as usual (1.91 vs. 0.40 and 3.76 vs. 0.70, respectively; P < .001).

For the YORS group, rates of opioid relapse were lower at 12 weeks (27.3% vs. 75.0%) and at 24 weeks (52.9% vs. 95.0%; P < .01.)

All components of YORS work together to improve retention, Dr. Fishman noted. Patients do much better if a relative such as a mother, father, or grandmother is closely involved, he added.

Also important is drug delivery.

“In some ways, this is similar to the assertive community treatment, or ACT, for schizophrenia. Like substance use disorder, schizophrenia requires long-acting injectable antipsychotics. When that is delivered to the patient through an organized delivery service like YORS, it improves outcomes,” said Dr. Fishman.

SUD is a chronic, relapsing illness in which an individual’s judgment is impaired, he added.

“ACT has become a relatively standard feature of treatment in most communities in this country and internationally and is sustainable under public sector funding, so it’s not an impossible leap to say it could be done. But it will not be cheap,” Dr. Fishman said.
 

Removing barriers

In a comment, Serra Akyar, MD, a psychiatry resident at Northwell Health’s Staten Island University Hospital, New York, said that the YORS program may appear to be labor intensive.

“However, the combination of medication-assisted treatment and support are essential to the treatment of opioid use disorder, especially for young adults. Developing effective interventions for young adults is particularly important, given the plasticity of their brains,” said Dr. Akyar, who was not involved with the research.

Inability to access medication and a lack of a supportive environment, both in everyday life and in regards to therapy, are barriers to successful treatment, she noted.

“The YORS intervention aims to remove these barriers to further enhance engagement to care through a combination of medication delivery and family engagement and assertive outreach via text messaging, a modality presumed to be well received by youth,” Dr. Akyar said.

Despite having a limited sample size, the study shows how a comprehensive intervention can have a large impact on the maintenance of medication adherence and reduction of relapse in young adults, she added.

“Its early success is encouraging and warrants further study on a larger scale to determine long-term effectiveness, overall costs and feasibility, generalizability, and whether certain independent factors exist that may predict medication adherence and reduction of relapse,” she said.
 

Wraparound support

The study is also a significant reminder that the opioid crisis has affected the young adult population, who are very vulnerable to OUD, said Jose Vito, MD, child, adolescent, and addiction psychiatrist at New York University.

“The study made me realize the importance of the four components of YORS, which were the outreach, family involvement, home delivery, and monetary incentives,” Dr. Vito said in an interview.

All of these components, in addition to extended-release naltrexone or extended-release buprenorphine, “have contributed to lower rates of opioid relapse, and the relapses are much later in the course of treatment if they do occur,” he said.

Overall, the findings demonstrate the importance of not giving up on these youths, he noted.

“Programs like YORS that provide wraparound support can help alleviate the opioid health care crisis by keeping these young adults in treatment,” Dr. Vito concluded.

The study was funded by the University of Maryland Center for Addiction Research, Education, and Service. Dr. Fishman has a financial relationship with Alkermes.

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

An intense and assertive “won’t take no for an answer” approach is effective for engaging in treatment young adults with substance abuse who have been in and out of various recovery programs for years, new research suggests.

The Youth Opioid Recovery Support (YORS) program is a team effort that includes home delivery of the prescribed medication, family engagement, assertive outreach, and contingency management.

In a new study of 42 patients in recovery for substance use disorder (SUD), those who were treated with extended-release naltrexone or extended-release buprenorphine plus YORS received more outpatient doses of their medication, and rates of opioid relapse at 12 and 24 weeks were lower compared with their peers who received only treatment as usual.

“These developmentally vulnerable youths need something extra that is specifically targeted to who they are and their vulnerabilities,” coinvestigator Marc Fishman, MD, director of the Maryland Treatment Centers, Johns Hopkins University, Baltimore, said in an interview.

The findings were presented at the virtual American Academy of Addiction Psychiatry 31st Annual Meeting.
 

Treatment barriers

Young adults with SUD are difficult to reach, which leads to decreased addiction program retention, decreased medication adherence, early drop out, waxing and waning motivation, and worse outcomes, compared with older adults with SUD, Dr. Fishman said.

In July, positive results from a pilot trial conducted by the investigators of YORS were published online in Addiction.

In that study, 41 young adults aged 18-26 years who intended to undergo treatment for SUD with extended-release naltrexone were randomly assigned to also undergo YORS or treatment as usual, which consisted of a standard referral to outpatient care following an inpatient stay.

The primary outcomes were number of medication doses received over 24 weeks and relapse to opioid use, which was defined as 10 or more days of use within 28 days at 24 weeks.

Participants in the YORS group received more doses of extended-release naltrexone (mean, 4.28; standard deviation, 2.3) than participants in the treatment-as-usual group (mean, 0.70; SD, 1.2; P < .01).

In the YORS group, rates of relapse at both 12 and 24 weeks were lower, and there were fewer overall days of opioid use.

For the current study, the investigators wanted to test whether there was a possible effect when patients were given a choice of medication. In the earlier trial, patients did not have a choice – they had to take extended-release naltrexone. In this study, they could opt for it or extended-release buprenorphine.

The researchers recruited 22 young adults (aged 18-26 years) from their inpatient clinic to participate. Half the patients chose to take extended-release naltrexone, and the other half chose extended-release buprenorphine.

The groups were then compared to a historical group of 20 patients who received treatment as usual and served as the control group.
 

Positive outcomes

As in the first study, outcomes in the new study were better with YORS.

All participants who underwent YORS received more outpatient medication doses at 12 weeks and 24 weeks than those who received treatment as usual (1.91 vs. 0.40 and 3.76 vs. 0.70, respectively; P < .001).

For the YORS group, rates of opioid relapse were lower at 12 weeks (27.3% vs. 75.0%) and at 24 weeks (52.9% vs. 95.0%; P < .01.)

All components of YORS work together to improve retention, Dr. Fishman noted. Patients do much better if a relative such as a mother, father, or grandmother is closely involved, he added.

Also important is drug delivery.

“In some ways, this is similar to the assertive community treatment, or ACT, for schizophrenia. Like substance use disorder, schizophrenia requires long-acting injectable antipsychotics. When that is delivered to the patient through an organized delivery service like YORS, it improves outcomes,” said Dr. Fishman.

SUD is a chronic, relapsing illness in which an individual’s judgment is impaired, he added.

“ACT has become a relatively standard feature of treatment in most communities in this country and internationally and is sustainable under public sector funding, so it’s not an impossible leap to say it could be done. But it will not be cheap,” Dr. Fishman said.
 

Removing barriers

In a comment, Serra Akyar, MD, a psychiatry resident at Northwell Health’s Staten Island University Hospital, New York, said that the YORS program may appear to be labor intensive.

“However, the combination of medication-assisted treatment and support are essential to the treatment of opioid use disorder, especially for young adults. Developing effective interventions for young adults is particularly important, given the plasticity of their brains,” said Dr. Akyar, who was not involved with the research.

Inability to access medication and a lack of a supportive environment, both in everyday life and in regards to therapy, are barriers to successful treatment, she noted.

“The YORS intervention aims to remove these barriers to further enhance engagement to care through a combination of medication delivery and family engagement and assertive outreach via text messaging, a modality presumed to be well received by youth,” Dr. Akyar said.

Despite having a limited sample size, the study shows how a comprehensive intervention can have a large impact on the maintenance of medication adherence and reduction of relapse in young adults, she added.

“Its early success is encouraging and warrants further study on a larger scale to determine long-term effectiveness, overall costs and feasibility, generalizability, and whether certain independent factors exist that may predict medication adherence and reduction of relapse,” she said.
 

Wraparound support

The study is also a significant reminder that the opioid crisis has affected the young adult population, who are very vulnerable to OUD, said Jose Vito, MD, child, adolescent, and addiction psychiatrist at New York University.

“The study made me realize the importance of the four components of YORS, which were the outreach, family involvement, home delivery, and monetary incentives,” Dr. Vito said in an interview.

All of these components, in addition to extended-release naltrexone or extended-release buprenorphine, “have contributed to lower rates of opioid relapse, and the relapses are much later in the course of treatment if they do occur,” he said.

Overall, the findings demonstrate the importance of not giving up on these youths, he noted.

“Programs like YORS that provide wraparound support can help alleviate the opioid health care crisis by keeping these young adults in treatment,” Dr. Vito concluded.

The study was funded by the University of Maryland Center for Addiction Research, Education, and Service. Dr. Fishman has a financial relationship with Alkermes.

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

An intense and assertive “won’t take no for an answer” approach is effective for engaging in treatment young adults with substance abuse who have been in and out of various recovery programs for years, new research suggests.

The Youth Opioid Recovery Support (YORS) program is a team effort that includes home delivery of the prescribed medication, family engagement, assertive outreach, and contingency management.

In a new study of 42 patients in recovery for substance use disorder (SUD), those who were treated with extended-release naltrexone or extended-release buprenorphine plus YORS received more outpatient doses of their medication, and rates of opioid relapse at 12 and 24 weeks were lower compared with their peers who received only treatment as usual.

“These developmentally vulnerable youths need something extra that is specifically targeted to who they are and their vulnerabilities,” coinvestigator Marc Fishman, MD, director of the Maryland Treatment Centers, Johns Hopkins University, Baltimore, said in an interview.

The findings were presented at the virtual American Academy of Addiction Psychiatry 31st Annual Meeting.
 

Treatment barriers

Young adults with SUD are difficult to reach, which leads to decreased addiction program retention, decreased medication adherence, early drop out, waxing and waning motivation, and worse outcomes, compared with older adults with SUD, Dr. Fishman said.

In July, positive results from a pilot trial conducted by the investigators of YORS were published online in Addiction.

In that study, 41 young adults aged 18-26 years who intended to undergo treatment for SUD with extended-release naltrexone were randomly assigned to also undergo YORS or treatment as usual, which consisted of a standard referral to outpatient care following an inpatient stay.

The primary outcomes were number of medication doses received over 24 weeks and relapse to opioid use, which was defined as 10 or more days of use within 28 days at 24 weeks.

Participants in the YORS group received more doses of extended-release naltrexone (mean, 4.28; standard deviation, 2.3) than participants in the treatment-as-usual group (mean, 0.70; SD, 1.2; P < .01).

In the YORS group, rates of relapse at both 12 and 24 weeks were lower, and there were fewer overall days of opioid use.

For the current study, the investigators wanted to test whether there was a possible effect when patients were given a choice of medication. In the earlier trial, patients did not have a choice – they had to take extended-release naltrexone. In this study, they could opt for it or extended-release buprenorphine.

The researchers recruited 22 young adults (aged 18-26 years) from their inpatient clinic to participate. Half the patients chose to take extended-release naltrexone, and the other half chose extended-release buprenorphine.

The groups were then compared to a historical group of 20 patients who received treatment as usual and served as the control group.
 

Positive outcomes

As in the first study, outcomes in the new study were better with YORS.

All participants who underwent YORS received more outpatient medication doses at 12 weeks and 24 weeks than those who received treatment as usual (1.91 vs. 0.40 and 3.76 vs. 0.70, respectively; P < .001).

For the YORS group, rates of opioid relapse were lower at 12 weeks (27.3% vs. 75.0%) and at 24 weeks (52.9% vs. 95.0%; P < .01.)

All components of YORS work together to improve retention, Dr. Fishman noted. Patients do much better if a relative such as a mother, father, or grandmother is closely involved, he added.

Also important is drug delivery.

“In some ways, this is similar to the assertive community treatment, or ACT, for schizophrenia. Like substance use disorder, schizophrenia requires long-acting injectable antipsychotics. When that is delivered to the patient through an organized delivery service like YORS, it improves outcomes,” said Dr. Fishman.

SUD is a chronic, relapsing illness in which an individual’s judgment is impaired, he added.

“ACT has become a relatively standard feature of treatment in most communities in this country and internationally and is sustainable under public sector funding, so it’s not an impossible leap to say it could be done. But it will not be cheap,” Dr. Fishman said.
 

Removing barriers

In a comment, Serra Akyar, MD, a psychiatry resident at Northwell Health’s Staten Island University Hospital, New York, said that the YORS program may appear to be labor intensive.

“However, the combination of medication-assisted treatment and support are essential to the treatment of opioid use disorder, especially for young adults. Developing effective interventions for young adults is particularly important, given the plasticity of their brains,” said Dr. Akyar, who was not involved with the research.

Inability to access medication and a lack of a supportive environment, both in everyday life and in regards to therapy, are barriers to successful treatment, she noted.

“The YORS intervention aims to remove these barriers to further enhance engagement to care through a combination of medication delivery and family engagement and assertive outreach via text messaging, a modality presumed to be well received by youth,” Dr. Akyar said.

Despite having a limited sample size, the study shows how a comprehensive intervention can have a large impact on the maintenance of medication adherence and reduction of relapse in young adults, she added.

“Its early success is encouraging and warrants further study on a larger scale to determine long-term effectiveness, overall costs and feasibility, generalizability, and whether certain independent factors exist that may predict medication adherence and reduction of relapse,” she said.
 

Wraparound support

The study is also a significant reminder that the opioid crisis has affected the young adult population, who are very vulnerable to OUD, said Jose Vito, MD, child, adolescent, and addiction psychiatrist at New York University.

“The study made me realize the importance of the four components of YORS, which were the outreach, family involvement, home delivery, and monetary incentives,” Dr. Vito said in an interview.

All of these components, in addition to extended-release naltrexone or extended-release buprenorphine, “have contributed to lower rates of opioid relapse, and the relapses are much later in the course of treatment if they do occur,” he said.

Overall, the findings demonstrate the importance of not giving up on these youths, he noted.

“Programs like YORS that provide wraparound support can help alleviate the opioid health care crisis by keeping these young adults in treatment,” Dr. Vito concluded.

The study was funded by the University of Maryland Center for Addiction Research, Education, and Service. Dr. Fishman has a financial relationship with Alkermes.

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

Optical treatments for acne are emerging as promising alternatives to conventional treatments, a development that inspires clinician researchers such as Fernanda H. Sakamoto, MD, PhD.

“I love treating acne, because it can have a huge impact on our patients’ lives,” Dr. Sakamoto, a dermatologist at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, said during a virtual course on laser and aesthetic skin therapy. “Acne is the most common disease in dermatology, affecting about 80% of our patients. Eleven percent of these patients have difficult-to-treat acne, and it is also the No. 1 cause of depression and suicide among teenagers and young adults. And, even though there’s no strong evidence that optical treatments work better than conventional acne treatments, people still spend a lot on those treatments: more than 220 million in 2019.”

Early results from a pilot study suggest that use of a novel laser system known as Accure in patients with mild to moderate acne resulted in an 80% reduction in acne lesions at 12 weeks. The laser prototype, which uses a 1,726 nm wavelength and is being developed by researchers at the Wellman Center for Photomedicine, features a built-in thermal camera in the handpiece that allows the user to monitor the skin’s temperature during treatment.

In initial pilot studies of the device, Dr. Sakamoto and colleagues observed consistent damage of the sebaceous glands, with no damage to the epidermis, surrounding dermis, or other follicular structures. “But because the contrast of absorption of lipids and water is not very high, we needed to create a laser with features that we have never seen before,” she said. “One of them is a robust cooling system. The second prototype features a built-in thermal camera within the handpiece that allows us to see the temperature while we’re treating the patient. It also has built-in software that would shut down the laser if the temperature is too high. “This is the first laser with some safety features that will give the user direct feedback while treating the patient,” she said, noting that its “unique cooling system and real-time monitoring ... makes it different from any of the lasers we see on the market right now.”

Dr. Sakamoto and colleagues (Emil Tanghetti, MD, in San Diego, Roy Geronemus, MD, in New York, and Joel L. Cohen, MD, in Colorado) are conducting a clinical trial of the device, to evaluate whether Accure can selectively target sebaceous glands. As of Oct. 23, 2020, the study enrolled more than 50 patients, who are followed at 4, 8, 12, and 24 weeks post treatment, she said.

To date, 16 patients have completed the study, and the researchers have observed an average lesion reduction of 80% at 12 weeks post treatment, after four treatment sessions. This amounted to more than 12,000 trigger pulls of the device, with no unexpected adverse events. Average visual analogue scale pain scores immediately after treatment have been 1.09 out of 10.

Histologic assessment of skin samples collected from the study participants have revealed selective damage of the sebaceous glands with a normal epidermis and surrounding dermis. “Because this laser is near infrared, it is not absorbed by melanin, making it possible for a safe treatment in darker skin tones,” Dr. Sakamoto said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine.

“We have shown that it is possible to create a selective laser for acne treatment at 1,726 nm. We have proven it mathematically as well as with histological samples,” she said. “Now we are moving on to a larger clinical trial for the FDA clearance.”

Another strategy being developed for acne treatment is to make nonselective lasers selective by adding gold microparticles into the hair follicle and sebaceous glands, to allow the lasers to be absorbed. In a study that used a free electron laser, Dr. Sakamoto and colleagues demonstrated that these microparticles can stay within the sebaceous glands for selective damage of the sebaceous glands. In a subsequent pilot clinical trial they showed that the addition of the gold microparticles followed by a diode laser treatment made it possible to reduce both inflammatory and noninflammatory lesions.

More recently, an open-label European study of acne treatment with light absorbing gold microparticles and optical pulses demonstrated that the treatment led to an 80%-90% reduction of inflammatory lesions at 12 weeks, with a reduction of Investigator’s Global Assessment scale from 2 to 4.

The Food and Drug Administration cleared the treatment, Sebacia Microparticles, for the treatment of mild to moderate acne in September of 2018, but according to Dr. Sakamoto, “the company has struggled, as they were only commercializing the device in California and Washington, DC.”

Photodynamic therapy (PDT) is also being studied as an acne treatment. “PDT uses a photosensitizer that needs to be activated by a light source,” she noted. “The combination of red light and aminolevulinic acid (ALA) or methyl ester ALA has been shown to damage the sebaceous glands”.

In a recent randomized controlled trial that compared PDT to adapalene gel plus oral doxycycline, PDT showed superiority. “Because PDT induces apoptosis of the sebaceous glands, it causes a lot of pain and side effects after treatment,” Dr. Sakamoto said. “However, it can clear 80%-90% of acne in 80%-90% of patients. But because of the side effects, PDT should be limited to those patients who cannot take conventional treatments.”

Dr. Sakamoto reported having received research funding and/or consulting fees from numerous device and pharmaceutical companies.

[email protected]

Optical treatments for acne are emerging as promising alternatives to conventional treatments, a development that inspires clinician researchers such as Fernanda H. Sakamoto, MD, PhD.

“I love treating acne, because it can have a huge impact on our patients’ lives,” Dr. Sakamoto, a dermatologist at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, said during a virtual course on laser and aesthetic skin therapy. “Acne is the most common disease in dermatology, affecting about 80% of our patients. Eleven percent of these patients have difficult-to-treat acne, and it is also the No. 1 cause of depression and suicide among teenagers and young adults. And, even though there’s no strong evidence that optical treatments work better than conventional acne treatments, people still spend a lot on those treatments: more than 220 million in 2019.”

Early results from a pilot study suggest that use of a novel laser system known as Accure in patients with mild to moderate acne resulted in an 80% reduction in acne lesions at 12 weeks. The laser prototype, which uses a 1,726 nm wavelength and is being developed by researchers at the Wellman Center for Photomedicine, features a built-in thermal camera in the handpiece that allows the user to monitor the skin’s temperature during treatment.

In initial pilot studies of the device, Dr. Sakamoto and colleagues observed consistent damage of the sebaceous glands, with no damage to the epidermis, surrounding dermis, or other follicular structures. “But because the contrast of absorption of lipids and water is not very high, we needed to create a laser with features that we have never seen before,” she said. “One of them is a robust cooling system. The second prototype features a built-in thermal camera within the handpiece that allows us to see the temperature while we’re treating the patient. It also has built-in software that would shut down the laser if the temperature is too high. “This is the first laser with some safety features that will give the user direct feedback while treating the patient,” she said, noting that its “unique cooling system and real-time monitoring ... makes it different from any of the lasers we see on the market right now.”

Dr. Sakamoto and colleagues (Emil Tanghetti, MD, in San Diego, Roy Geronemus, MD, in New York, and Joel L. Cohen, MD, in Colorado) are conducting a clinical trial of the device, to evaluate whether Accure can selectively target sebaceous glands. As of Oct. 23, 2020, the study enrolled more than 50 patients, who are followed at 4, 8, 12, and 24 weeks post treatment, she said.

To date, 16 patients have completed the study, and the researchers have observed an average lesion reduction of 80% at 12 weeks post treatment, after four treatment sessions. This amounted to more than 12,000 trigger pulls of the device, with no unexpected adverse events. Average visual analogue scale pain scores immediately after treatment have been 1.09 out of 10.

Histologic assessment of skin samples collected from the study participants have revealed selective damage of the sebaceous glands with a normal epidermis and surrounding dermis. “Because this laser is near infrared, it is not absorbed by melanin, making it possible for a safe treatment in darker skin tones,” Dr. Sakamoto said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine.

“We have shown that it is possible to create a selective laser for acne treatment at 1,726 nm. We have proven it mathematically as well as with histological samples,” she said. “Now we are moving on to a larger clinical trial for the FDA clearance.”

Another strategy being developed for acne treatment is to make nonselective lasers selective by adding gold microparticles into the hair follicle and sebaceous glands, to allow the lasers to be absorbed. In a study that used a free electron laser, Dr. Sakamoto and colleagues demonstrated that these microparticles can stay within the sebaceous glands for selective damage of the sebaceous glands. In a subsequent pilot clinical trial they showed that the addition of the gold microparticles followed by a diode laser treatment made it possible to reduce both inflammatory and noninflammatory lesions.

More recently, an open-label European study of acne treatment with light absorbing gold microparticles and optical pulses demonstrated that the treatment led to an 80%-90% reduction of inflammatory lesions at 12 weeks, with a reduction of Investigator’s Global Assessment scale from 2 to 4.

The Food and Drug Administration cleared the treatment, Sebacia Microparticles, for the treatment of mild to moderate acne in September of 2018, but according to Dr. Sakamoto, “the company has struggled, as they were only commercializing the device in California and Washington, DC.”

Photodynamic therapy (PDT) is also being studied as an acne treatment. “PDT uses a photosensitizer that needs to be activated by a light source,” she noted. “The combination of red light and aminolevulinic acid (ALA) or methyl ester ALA has been shown to damage the sebaceous glands”.

In a recent randomized controlled trial that compared PDT to adapalene gel plus oral doxycycline, PDT showed superiority. “Because PDT induces apoptosis of the sebaceous glands, it causes a lot of pain and side effects after treatment,” Dr. Sakamoto said. “However, it can clear 80%-90% of acne in 80%-90% of patients. But because of the side effects, PDT should be limited to those patients who cannot take conventional treatments.”

Dr. Sakamoto reported having received research funding and/or consulting fees from numerous device and pharmaceutical companies.

[email protected]

Optical treatments for acne are emerging as promising alternatives to conventional treatments, a development that inspires clinician researchers such as Fernanda H. Sakamoto, MD, PhD.

“I love treating acne, because it can have a huge impact on our patients’ lives,” Dr. Sakamoto, a dermatologist at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, said during a virtual course on laser and aesthetic skin therapy. “Acne is the most common disease in dermatology, affecting about 80% of our patients. Eleven percent of these patients have difficult-to-treat acne, and it is also the No. 1 cause of depression and suicide among teenagers and young adults. And, even though there’s no strong evidence that optical treatments work better than conventional acne treatments, people still spend a lot on those treatments: more than 220 million in 2019.”

Early results from a pilot study suggest that use of a novel laser system known as Accure in patients with mild to moderate acne resulted in an 80% reduction in acne lesions at 12 weeks. The laser prototype, which uses a 1,726 nm wavelength and is being developed by researchers at the Wellman Center for Photomedicine, features a built-in thermal camera in the handpiece that allows the user to monitor the skin’s temperature during treatment.

In initial pilot studies of the device, Dr. Sakamoto and colleagues observed consistent damage of the sebaceous glands, with no damage to the epidermis, surrounding dermis, or other follicular structures. “But because the contrast of absorption of lipids and water is not very high, we needed to create a laser with features that we have never seen before,” she said. “One of them is a robust cooling system. The second prototype features a built-in thermal camera within the handpiece that allows us to see the temperature while we’re treating the patient. It also has built-in software that would shut down the laser if the temperature is too high. “This is the first laser with some safety features that will give the user direct feedback while treating the patient,” she said, noting that its “unique cooling system and real-time monitoring ... makes it different from any of the lasers we see on the market right now.”

Dr. Sakamoto and colleagues (Emil Tanghetti, MD, in San Diego, Roy Geronemus, MD, in New York, and Joel L. Cohen, MD, in Colorado) are conducting a clinical trial of the device, to evaluate whether Accure can selectively target sebaceous glands. As of Oct. 23, 2020, the study enrolled more than 50 patients, who are followed at 4, 8, 12, and 24 weeks post treatment, she said.

To date, 16 patients have completed the study, and the researchers have observed an average lesion reduction of 80% at 12 weeks post treatment, after four treatment sessions. This amounted to more than 12,000 trigger pulls of the device, with no unexpected adverse events. Average visual analogue scale pain scores immediately after treatment have been 1.09 out of 10.

Histologic assessment of skin samples collected from the study participants have revealed selective damage of the sebaceous glands with a normal epidermis and surrounding dermis. “Because this laser is near infrared, it is not absorbed by melanin, making it possible for a safe treatment in darker skin tones,” Dr. Sakamoto said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine.

“We have shown that it is possible to create a selective laser for acne treatment at 1,726 nm. We have proven it mathematically as well as with histological samples,” she said. “Now we are moving on to a larger clinical trial for the FDA clearance.”

Another strategy being developed for acne treatment is to make nonselective lasers selective by adding gold microparticles into the hair follicle and sebaceous glands, to allow the lasers to be absorbed. In a study that used a free electron laser, Dr. Sakamoto and colleagues demonstrated that these microparticles can stay within the sebaceous glands for selective damage of the sebaceous glands. In a subsequent pilot clinical trial they showed that the addition of the gold microparticles followed by a diode laser treatment made it possible to reduce both inflammatory and noninflammatory lesions.

More recently, an open-label European study of acne treatment with light absorbing gold microparticles and optical pulses demonstrated that the treatment led to an 80%-90% reduction of inflammatory lesions at 12 weeks, with a reduction of Investigator’s Global Assessment scale from 2 to 4.

The Food and Drug Administration cleared the treatment, Sebacia Microparticles, for the treatment of mild to moderate acne in September of 2018, but according to Dr. Sakamoto, “the company has struggled, as they were only commercializing the device in California and Washington, DC.”

Photodynamic therapy (PDT) is also being studied as an acne treatment. “PDT uses a photosensitizer that needs to be activated by a light source,” she noted. “The combination of red light and aminolevulinic acid (ALA) or methyl ester ALA has been shown to damage the sebaceous glands”.

In a recent randomized controlled trial that compared PDT to adapalene gel plus oral doxycycline, PDT showed superiority. “Because PDT induces apoptosis of the sebaceous glands, it causes a lot of pain and side effects after treatment,” Dr. Sakamoto said. “However, it can clear 80%-90% of acne in 80%-90% of patients. But because of the side effects, PDT should be limited to those patients who cannot take conventional treatments.”

Dr. Sakamoto reported having received research funding and/or consulting fees from numerous device and pharmaceutical companies.

[email protected]

Caring for LGBTQ+ pediatric patients often requires physicians to consider issues – such as preservation of fertility for transgender youth and resource allocation to sexual-minority youth in the foster-care system – that they may not think about as frequently with their other patients.

monkeybusinessimages/Getty Images

“It’s important to engage transgender and gender-diverse youth and families in fertility counseling early in their gender affirmation process,” but it does not happen as often as it should, said Jason Rafferty, MD (he/him/his), a clinical assistant professor of psychiatry and human behavior at the Warren Alpert Medical School of Brown University, Providence, R.I. Dr. Rafferty discussed two studies at the annual meeting of the American Academy of Pediatrics, held virtually this year: one on fertility outcomes among a small transgender sample and another finding that sexual-minority youth are 2.5 times more likely to be involved in the foster-care system.

“We need to recognize and address disparities in health that place sexual-minority youth at increased risk for child welfare involvement,” he told attendees.
 

Fertility preservation and counseling for transgender patients

Evidence suggests gender-affirming hormone treatment affects gonadal structures and functions in ways that may decrease fertility potential, Dr. Rafferty said. “Yet, there’s very little [research] into the reversibility or thresholds above which fertility potential is affected.”

The World Professional Association for Transgender Health (WPATH) recommends that doctors discuss the possible adverse health effects of feminizing or masculinizing treatments and the patient’s reproductive options before starting hormone therapy, although the extent to which this therapy may impair fertility isn’t known.

The first study Dr. Rafferty discussed was an assessment of semen cryopreservation outcomes among youth asserting a female identity. The researchers conducted a retrospective chart review on a convenience sample of 11 transgender and gender-diverse adolescents and young adults who had been referred for fertility preservation between January 2015 and September 2018 at the University of Pittsburgh Medical Center Children’s Hospital and the UPMC Magee-Womens Hospital in Pittsburgh.

Of the 11, 1 did not provide a sample, and another discarded their sample after 4 months. The seven patients without prior gender-affirming hormone treatment (average age 19 at time of fertility consultation) were all able to produce a semen sample, which showed normal parameters, except for some abnormal morphology. The significance of that one abnormal finding was unclear without a control group, Dr. Rafferty said. All seven began gonadotropin-releasing hormone (GnRH) agonist therapy, and four also began estradiol therapy, although Dr. Rafferty questioned why GnRH agonist therapy was started at such late ages.

Regardless, he said, the takeaway from this first group was the efficiency and effectiveness of getting a semen sample before beginning gender-affirming hormone therapy. The second group offered a different takeaway.

“What I think is probably the most unique aspect of this study is this second group of two individuals who had previously received hormones or blockers,” Dr. Rafferty told attendees. The first patient was 13 years of age at gender dysphoria onset and 18 years at the time of their fertility consultation. They had been on GnRH agonists for 6 months before semen collection. Their first sample, at 3 months after discontinuing hormones, was low-quality, but they did produce a viable sample 2 months later.

The other patient, who underwent fertility consultation at age 19, had taken estrogen and spironolactone for 26 months before semen collection and were not able to produce sperm 4 months after stopping the treatment. They did not try again because they underwent an orchiectomy.

Despite the small sample size and lack of confounding data, such as smoking and stress, the study remains the first to show successful sampling after gender-affirming hormone therapy in a teen, Dr. Rafferty said. It also shows that sampling after beginning hormone therapy may require discontinuation for several months before a successful sample is possible, thereby supporting WPATH’s recommendation for early fertility counseling.

“However, the standard of providing fertility counseling before intervention does not always occur,” Dr. Rafferty said, citing research that found low percentages of teens had received fertility counseling or discussed negative effects of therapy on fertility prior to starting it. These low numbers may result from changes in youths’ interest in fertility throughout development, but they could also relate to youths’ reluctance to discuss family planning while they feel uncomfortable in their bodies.

“My experience, and there is some empirical evidence for this, is that many transgender and gender-diverse youth feel more comfortable conceptualizing and pursuing intimate partner relationships and family planning after they start gender affirmation interventions,” Dr. Rafferty said. The stress associated with gender dysphoria can further complicate fertility discussions, and providers have to consider whether it’s more stressful to hold off on gender-affirming hormone therapy until the patient gets a successful semen sample or to start therapy and then discontinue for several months to get a sample later.

While decisions about fertility services should be fully up to the patient, in reality, multiple barriers – such as high cost, low insurance coverage, a dearth of specialists who can do the procedures, and inaccurate assumptions about transgender people’s interest in family planning – complicate the decision,.

“Systemically denying a marginalized population the ability to reproduce, or at least the ability to make a free choice about reproduction and family planning, is a reproductive justice issue that’s not getting the attention it deserves,” Dr. Rafferty said.

Clair Kronk, BSc, a session attendee from the University of Cincinnati College of Medicine and Cincinnati Children’s Hospital and Medical Center, said in an interview that she appreciated the session even while she lamented the lack of adequate evidence on transgender and gender-diverse care.

“I do feel like there are a lot of provider-based questions with no sufficient guidelines right now when it comes to transgender care,” Ms. Kronk said. “Despite being nearly a century old, treatment of trans patients is somehow still a ‘Wild West’ of medical care, which is sad to see.” She is grateful to see attention finally reaching this population.

“It is imperative that medical institutions focus on real, advanceable diversity, equity, and inclusion initiatives which center marginalized groups,” she said. “Centering minoritized and marginalized peoples in improving care is the only way lasting change will happen.”
 

Sexual-minority youth in foster care

The second study Dr. Rafferty discussed was the first nationally representative systemic assessment of the prevalence of sexual-minority youth in foster care, child welfare, and out-of-home placement. Anecdotal evidence and community samples already suggest that a disproportionately higher number of sexual-minority youth enter foster care, he said, possibly resulting in part from family conflict about sexual orientation. In addition, LGBTQ+ youth already experience higher rates of psychological and physical abuse at home – a top reason for entry into child welfare – and this population has high rates of running away, particularly around the time of coming out.

Past research has found that sexual-minority youth experience higher rates of maltreatment and discrimination than do their peers from foster parents, siblings, and agency staff, which translates to fewer support services and lower levels of reunification or adoption.

In the National Longitudinal Study of Adolescent to Adult Health involving 14,154 respondents, 6.3% reported any same-sex attraction, and 2.1% were involved in the foster-care system. The researchers determined that 4.3% of sexual-minority youth were involved in foster care, compared with just 1.9% of heterosexual youth (P = .002) – a 2.5 times greater rate – with a stronger effect among those with exclusively same-sex attraction.

In the second part of the study, the researchers looked at 1,014 youths in the foster-care system, of whom 80% had experienced an out-of-home placement. The 16% of youth in foster care reporting same sex attraction did not have a higher rate of out-of-home placement than did heterosexual youth within the system. However, there were twice as many sexual-minority youth in child welfare and four times as many in out-of-home placement, compared with their heterosexual peers, possibly suggesting that sexual-minority youth are less likely to exit the system, Dr. Rafferty said.

“Many studies have shown that family acceptance is a critical factor in building resiliency, while rejection is tied to poor physical and emotional outcomes,” he said. “It would follow that we’re identifying a critical at-risk group of sexual-minority youth lacking in fundamental and essential family support.”

This population “experiences the intersection of multiple forces of marginalization, including out-of-home placement, socioeconomic stress, sexual minority status, and likely, race,” Dr. Rafferty said.

Ms. Kronk commented during the session that fertility services and collection are extremely expensive, often forcing trans people into the absurd situation of having to choose between paying for hormone therapy or paying for fertility treatment.

“This makes a really strong argument for resource allocation based on risk” and has ramifications for the higher proportions of sexual-minority youth facing transition without adequate support services, Dr. Rafferty said.

It also suggests the need for providers to help patients feel comfortable and safe talking about their needs, Ms. Kronk said.

“Unfortunately, LGBTQIA+ health care is not taught very comprehensively in the United States [and most other countries],” she said. “Oftentimes, this leads to awkward situations where patients are more knowledgeable than their providers. Listening, learning, supporting, and being open to change are what every provider should take to heart.”

Dr. Rafferty and Ms. Kronk had no relevant financial disclosures.

Caring for LGBTQ+ pediatric patients often requires physicians to consider issues – such as preservation of fertility for transgender youth and resource allocation to sexual-minority youth in the foster-care system – that they may not think about as frequently with their other patients.

monkeybusinessimages/Getty Images

“It’s important to engage transgender and gender-diverse youth and families in fertility counseling early in their gender affirmation process,” but it does not happen as often as it should, said Jason Rafferty, MD (he/him/his), a clinical assistant professor of psychiatry and human behavior at the Warren Alpert Medical School of Brown University, Providence, R.I. Dr. Rafferty discussed two studies at the annual meeting of the American Academy of Pediatrics, held virtually this year: one on fertility outcomes among a small transgender sample and another finding that sexual-minority youth are 2.5 times more likely to be involved in the foster-care system.

“We need to recognize and address disparities in health that place sexual-minority youth at increased risk for child welfare involvement,” he told attendees.
 

Fertility preservation and counseling for transgender patients

Evidence suggests gender-affirming hormone treatment affects gonadal structures and functions in ways that may decrease fertility potential, Dr. Rafferty said. “Yet, there’s very little [research] into the reversibility or thresholds above which fertility potential is affected.”

The World Professional Association for Transgender Health (WPATH) recommends that doctors discuss the possible adverse health effects of feminizing or masculinizing treatments and the patient’s reproductive options before starting hormone therapy, although the extent to which this therapy may impair fertility isn’t known.

The first study Dr. Rafferty discussed was an assessment of semen cryopreservation outcomes among youth asserting a female identity. The researchers conducted a retrospective chart review on a convenience sample of 11 transgender and gender-diverse adolescents and young adults who had been referred for fertility preservation between January 2015 and September 2018 at the University of Pittsburgh Medical Center Children’s Hospital and the UPMC Magee-Womens Hospital in Pittsburgh.

Of the 11, 1 did not provide a sample, and another discarded their sample after 4 months. The seven patients without prior gender-affirming hormone treatment (average age 19 at time of fertility consultation) were all able to produce a semen sample, which showed normal parameters, except for some abnormal morphology. The significance of that one abnormal finding was unclear without a control group, Dr. Rafferty said. All seven began gonadotropin-releasing hormone (GnRH) agonist therapy, and four also began estradiol therapy, although Dr. Rafferty questioned why GnRH agonist therapy was started at such late ages.

Regardless, he said, the takeaway from this first group was the efficiency and effectiveness of getting a semen sample before beginning gender-affirming hormone therapy. The second group offered a different takeaway.

“What I think is probably the most unique aspect of this study is this second group of two individuals who had previously received hormones or blockers,” Dr. Rafferty told attendees. The first patient was 13 years of age at gender dysphoria onset and 18 years at the time of their fertility consultation. They had been on GnRH agonists for 6 months before semen collection. Their first sample, at 3 months after discontinuing hormones, was low-quality, but they did produce a viable sample 2 months later.

The other patient, who underwent fertility consultation at age 19, had taken estrogen and spironolactone for 26 months before semen collection and were not able to produce sperm 4 months after stopping the treatment. They did not try again because they underwent an orchiectomy.

Despite the small sample size and lack of confounding data, such as smoking and stress, the study remains the first to show successful sampling after gender-affirming hormone therapy in a teen, Dr. Rafferty said. It also shows that sampling after beginning hormone therapy may require discontinuation for several months before a successful sample is possible, thereby supporting WPATH’s recommendation for early fertility counseling.

“However, the standard of providing fertility counseling before intervention does not always occur,” Dr. Rafferty said, citing research that found low percentages of teens had received fertility counseling or discussed negative effects of therapy on fertility prior to starting it. These low numbers may result from changes in youths’ interest in fertility throughout development, but they could also relate to youths’ reluctance to discuss family planning while they feel uncomfortable in their bodies.

“My experience, and there is some empirical evidence for this, is that many transgender and gender-diverse youth feel more comfortable conceptualizing and pursuing intimate partner relationships and family planning after they start gender affirmation interventions,” Dr. Rafferty said. The stress associated with gender dysphoria can further complicate fertility discussions, and providers have to consider whether it’s more stressful to hold off on gender-affirming hormone therapy until the patient gets a successful semen sample or to start therapy and then discontinue for several months to get a sample later.

While decisions about fertility services should be fully up to the patient, in reality, multiple barriers – such as high cost, low insurance coverage, a dearth of specialists who can do the procedures, and inaccurate assumptions about transgender people’s interest in family planning – complicate the decision,.

“Systemically denying a marginalized population the ability to reproduce, or at least the ability to make a free choice about reproduction and family planning, is a reproductive justice issue that’s not getting the attention it deserves,” Dr. Rafferty said.

Clair Kronk, BSc, a session attendee from the University of Cincinnati College of Medicine and Cincinnati Children’s Hospital and Medical Center, said in an interview that she appreciated the session even while she lamented the lack of adequate evidence on transgender and gender-diverse care.

“I do feel like there are a lot of provider-based questions with no sufficient guidelines right now when it comes to transgender care,” Ms. Kronk said. “Despite being nearly a century old, treatment of trans patients is somehow still a ‘Wild West’ of medical care, which is sad to see.” She is grateful to see attention finally reaching this population.

“It is imperative that medical institutions focus on real, advanceable diversity, equity, and inclusion initiatives which center marginalized groups,” she said. “Centering minoritized and marginalized peoples in improving care is the only way lasting change will happen.”
 

Sexual-minority youth in foster care

The second study Dr. Rafferty discussed was the first nationally representative systemic assessment of the prevalence of sexual-minority youth in foster care, child welfare, and out-of-home placement. Anecdotal evidence and community samples already suggest that a disproportionately higher number of sexual-minority youth enter foster care, he said, possibly resulting in part from family conflict about sexual orientation. In addition, LGBTQ+ youth already experience higher rates of psychological and physical abuse at home – a top reason for entry into child welfare – and this population has high rates of running away, particularly around the time of coming out.

Past research has found that sexual-minority youth experience higher rates of maltreatment and discrimination than do their peers from foster parents, siblings, and agency staff, which translates to fewer support services and lower levels of reunification or adoption.

In the National Longitudinal Study of Adolescent to Adult Health involving 14,154 respondents, 6.3% reported any same-sex attraction, and 2.1% were involved in the foster-care system. The researchers determined that 4.3% of sexual-minority youth were involved in foster care, compared with just 1.9% of heterosexual youth (P = .002) – a 2.5 times greater rate – with a stronger effect among those with exclusively same-sex attraction.

In the second part of the study, the researchers looked at 1,014 youths in the foster-care system, of whom 80% had experienced an out-of-home placement. The 16% of youth in foster care reporting same sex attraction did not have a higher rate of out-of-home placement than did heterosexual youth within the system. However, there were twice as many sexual-minority youth in child welfare and four times as many in out-of-home placement, compared with their heterosexual peers, possibly suggesting that sexual-minority youth are less likely to exit the system, Dr. Rafferty said.

“Many studies have shown that family acceptance is a critical factor in building resiliency, while rejection is tied to poor physical and emotional outcomes,” he said. “It would follow that we’re identifying a critical at-risk group of sexual-minority youth lacking in fundamental and essential family support.”

This population “experiences the intersection of multiple forces of marginalization, including out-of-home placement, socioeconomic stress, sexual minority status, and likely, race,” Dr. Rafferty said.

Ms. Kronk commented during the session that fertility services and collection are extremely expensive, often forcing trans people into the absurd situation of having to choose between paying for hormone therapy or paying for fertility treatment.

“This makes a really strong argument for resource allocation based on risk” and has ramifications for the higher proportions of sexual-minority youth facing transition without adequate support services, Dr. Rafferty said.

It also suggests the need for providers to help patients feel comfortable and safe talking about their needs, Ms. Kronk said.

“Unfortunately, LGBTQIA+ health care is not taught very comprehensively in the United States [and most other countries],” she said. “Oftentimes, this leads to awkward situations where patients are more knowledgeable than their providers. Listening, learning, supporting, and being open to change are what every provider should take to heart.”

Dr. Rafferty and Ms. Kronk had no relevant financial disclosures.

Caring for LGBTQ+ pediatric patients often requires physicians to consider issues – such as preservation of fertility for transgender youth and resource allocation to sexual-minority youth in the foster-care system – that they may not think about as frequently with their other patients.

monkeybusinessimages/Getty Images

“It’s important to engage transgender and gender-diverse youth and families in fertility counseling early in their gender affirmation process,” but it does not happen as often as it should, said Jason Rafferty, MD (he/him/his), a clinical assistant professor of psychiatry and human behavior at the Warren Alpert Medical School of Brown University, Providence, R.I. Dr. Rafferty discussed two studies at the annual meeting of the American Academy of Pediatrics, held virtually this year: one on fertility outcomes among a small transgender sample and another finding that sexual-minority youth are 2.5 times more likely to be involved in the foster-care system.

“We need to recognize and address disparities in health that place sexual-minority youth at increased risk for child welfare involvement,” he told attendees.
 

Fertility preservation and counseling for transgender patients

Evidence suggests gender-affirming hormone treatment affects gonadal structures and functions in ways that may decrease fertility potential, Dr. Rafferty said. “Yet, there’s very little [research] into the reversibility or thresholds above which fertility potential is affected.”

The World Professional Association for Transgender Health (WPATH) recommends that doctors discuss the possible adverse health effects of feminizing or masculinizing treatments and the patient’s reproductive options before starting hormone therapy, although the extent to which this therapy may impair fertility isn’t known.

The first study Dr. Rafferty discussed was an assessment of semen cryopreservation outcomes among youth asserting a female identity. The researchers conducted a retrospective chart review on a convenience sample of 11 transgender and gender-diverse adolescents and young adults who had been referred for fertility preservation between January 2015 and September 2018 at the University of Pittsburgh Medical Center Children’s Hospital and the UPMC Magee-Womens Hospital in Pittsburgh.

Of the 11, 1 did not provide a sample, and another discarded their sample after 4 months. The seven patients without prior gender-affirming hormone treatment (average age 19 at time of fertility consultation) were all able to produce a semen sample, which showed normal parameters, except for some abnormal morphology. The significance of that one abnormal finding was unclear without a control group, Dr. Rafferty said. All seven began gonadotropin-releasing hormone (GnRH) agonist therapy, and four also began estradiol therapy, although Dr. Rafferty questioned why GnRH agonist therapy was started at such late ages.

Regardless, he said, the takeaway from this first group was the efficiency and effectiveness of getting a semen sample before beginning gender-affirming hormone therapy. The second group offered a different takeaway.

“What I think is probably the most unique aspect of this study is this second group of two individuals who had previously received hormones or blockers,” Dr. Rafferty told attendees. The first patient was 13 years of age at gender dysphoria onset and 18 years at the time of their fertility consultation. They had been on GnRH agonists for 6 months before semen collection. Their first sample, at 3 months after discontinuing hormones, was low-quality, but they did produce a viable sample 2 months later.

The other patient, who underwent fertility consultation at age 19, had taken estrogen and spironolactone for 26 months before semen collection and were not able to produce sperm 4 months after stopping the treatment. They did not try again because they underwent an orchiectomy.

Despite the small sample size and lack of confounding data, such as smoking and stress, the study remains the first to show successful sampling after gender-affirming hormone therapy in a teen, Dr. Rafferty said. It also shows that sampling after beginning hormone therapy may require discontinuation for several months before a successful sample is possible, thereby supporting WPATH’s recommendation for early fertility counseling.

“However, the standard of providing fertility counseling before intervention does not always occur,” Dr. Rafferty said, citing research that found low percentages of teens had received fertility counseling or discussed negative effects of therapy on fertility prior to starting it. These low numbers may result from changes in youths’ interest in fertility throughout development, but they could also relate to youths’ reluctance to discuss family planning while they feel uncomfortable in their bodies.

“My experience, and there is some empirical evidence for this, is that many transgender and gender-diverse youth feel more comfortable conceptualizing and pursuing intimate partner relationships and family planning after they start gender affirmation interventions,” Dr. Rafferty said. The stress associated with gender dysphoria can further complicate fertility discussions, and providers have to consider whether it’s more stressful to hold off on gender-affirming hormone therapy until the patient gets a successful semen sample or to start therapy and then discontinue for several months to get a sample later.

While decisions about fertility services should be fully up to the patient, in reality, multiple barriers – such as high cost, low insurance coverage, a dearth of specialists who can do the procedures, and inaccurate assumptions about transgender people’s interest in family planning – complicate the decision,.

“Systemically denying a marginalized population the ability to reproduce, or at least the ability to make a free choice about reproduction and family planning, is a reproductive justice issue that’s not getting the attention it deserves,” Dr. Rafferty said.

Clair Kronk, BSc, a session attendee from the University of Cincinnati College of Medicine and Cincinnati Children’s Hospital and Medical Center, said in an interview that she appreciated the session even while she lamented the lack of adequate evidence on transgender and gender-diverse care.

“I do feel like there are a lot of provider-based questions with no sufficient guidelines right now when it comes to transgender care,” Ms. Kronk said. “Despite being nearly a century old, treatment of trans patients is somehow still a ‘Wild West’ of medical care, which is sad to see.” She is grateful to see attention finally reaching this population.

“It is imperative that medical institutions focus on real, advanceable diversity, equity, and inclusion initiatives which center marginalized groups,” she said. “Centering minoritized and marginalized peoples in improving care is the only way lasting change will happen.”
 

Sexual-minority youth in foster care

The second study Dr. Rafferty discussed was the first nationally representative systemic assessment of the prevalence of sexual-minority youth in foster care, child welfare, and out-of-home placement. Anecdotal evidence and community samples already suggest that a disproportionately higher number of sexual-minority youth enter foster care, he said, possibly resulting in part from family conflict about sexual orientation. In addition, LGBTQ+ youth already experience higher rates of psychological and physical abuse at home – a top reason for entry into child welfare – and this population has high rates of running away, particularly around the time of coming out.

Past research has found that sexual-minority youth experience higher rates of maltreatment and discrimination than do their peers from foster parents, siblings, and agency staff, which translates to fewer support services and lower levels of reunification or adoption.

In the National Longitudinal Study of Adolescent to Adult Health involving 14,154 respondents, 6.3% reported any same-sex attraction, and 2.1% were involved in the foster-care system. The researchers determined that 4.3% of sexual-minority youth were involved in foster care, compared with just 1.9% of heterosexual youth (P = .002) – a 2.5 times greater rate – with a stronger effect among those with exclusively same-sex attraction.

In the second part of the study, the researchers looked at 1,014 youths in the foster-care system, of whom 80% had experienced an out-of-home placement. The 16% of youth in foster care reporting same sex attraction did not have a higher rate of out-of-home placement than did heterosexual youth within the system. However, there were twice as many sexual-minority youth in child welfare and four times as many in out-of-home placement, compared with their heterosexual peers, possibly suggesting that sexual-minority youth are less likely to exit the system, Dr. Rafferty said.

“Many studies have shown that family acceptance is a critical factor in building resiliency, while rejection is tied to poor physical and emotional outcomes,” he said. “It would follow that we’re identifying a critical at-risk group of sexual-minority youth lacking in fundamental and essential family support.”

This population “experiences the intersection of multiple forces of marginalization, including out-of-home placement, socioeconomic stress, sexual minority status, and likely, race,” Dr. Rafferty said.

Ms. Kronk commented during the session that fertility services and collection are extremely expensive, often forcing trans people into the absurd situation of having to choose between paying for hormone therapy or paying for fertility treatment.

“This makes a really strong argument for resource allocation based on risk” and has ramifications for the higher proportions of sexual-minority youth facing transition without adequate support services, Dr. Rafferty said.

It also suggests the need for providers to help patients feel comfortable and safe talking about their needs, Ms. Kronk said.

“Unfortunately, LGBTQIA+ health care is not taught very comprehensively in the United States [and most other countries],” she said. “Oftentimes, this leads to awkward situations where patients are more knowledgeable than their providers. Listening, learning, supporting, and being open to change are what every provider should take to heart.”

Dr. Rafferty and Ms. Kronk had no relevant financial disclosures.