Pediatrics

DENVER — The ability to provide adolescents with highly effective anti-obesity medications that now carry approvals from the US Food and Drug Administration (FDA) and support in guidelines offers reassurance of their use; however, a reality check often awaits for clinicians in terms of challenges ranging from accessing and affording the medications to managing real and rumored side effects.

Weighing in on the issues, experts at Obesity Medicine (OMA) 2024 offered some key strategies and practice hacks for overcoming those hurdles.

The incentive to provide treatment with popular glucagon-like peptide 1 (GLP-1) drugs such as semaglutide or the dual glucose-dependent insulinotropic peptide (GIP) GLP-1 tirzepatide lies in the evidence that their high efficacy in promoting weight loss, and hence preventing metabolic syndrome, has benefits that far outweigh the potential side effects, said Alaina Vidmar, MD, in presenting at the meeting.

“We can look at all the evidence and without question acknowledge that the GLP-1s/GIP agonists are the most effective agents that we currently have, with the least heterogeneity in response, and the most high responders compared with other agents,” said Dr. Vidmar, an assistant professor of clinical pediatrics at the Keck School of Medicine of University of Southern California and director of obesity medicine and bariatric surgery at Children’s Hospital Los Angeles.

The strength of the evidence is reflected in the landmark American Academy of Pediatrics (AAP) Clinical Practice Guideline for the Evaluation and Treatment of Children and Adolescents With Obesity, which recommends that “pediatricians and other primary healthcare providers should offer adolescents 12 years and older with obesity weight loss pharmacotherapy, according to medication indications, risks and may offer adolescents 8 years old with obesity weight loss pharmacotherapy, according to medication indications, risks.”

The AAP guidance echoes the recommendations of the drug makers and FDA that “a combination of specific behavioral techniques within the context of family-based behavioral treatment and the use of pharmacotherapy may be necessary to prevent life-limiting complications over time.”

However, in real-world practice, with the various challenges in providing that intensive, comprehensive care, clinicians should be prepared to get creative: “We sometimes have to do the best we can with what we have because the watchful waiting approach is not effective and leads to more harm than good,” Dr. Vidmar said.
 

Facilitating Access

The ongoing reported shortages in the highly popular anti-obesity medications, as well as insurance denials and high costs, are among the leading obstacles, for adolescents and adults alike.

Dr. Vidmar noted that key strategies at her center, Children’s Hospital Los Angeles, have been essential, however, in helping at least facilitate the authorization process.

The center’s approach began with contacting all the payers the center has contracts with to determine which of their policies cover these medications for adults and pediatrics and which agents are covered.

“This took work on the front end, but it was worth it because it helped us understand the framework for what we were going to go up against every time that we prescribed these medications,” she said.

Furthermore, the center’s specialty pharmacy set up contracts to be able to provide the drugs within the institution.

While the strategy can’t entirely mitigate the ongoing distribution concerns, “our pharmacy is now able to share with our weight management program what GLP-1s are available so that we can be more efficient in our work,” Dr. Vidmar said.

The center also created a list of contacts to provide to patients and their families, detailing local pharmacies that were most likely to have the medications.

Another strategy Dr. Vidmar’s center has utilized to allow the timely implementation of a GLP-1 treatment plan while awaiting a drug to become available is to create an alternative protocol, for instance, using liraglutide when awaiting semaglutide.

“If we are unable to get the lower doses of a weekly agent for titration, we have a standard protocol to bridge instead with liraglutide, and our patients, pharmacies, and even our authorizations are aware of the protocol,” Dr. Vidmar said.

“We often do not have a lot of control or agency over the distribution concerns; however, we can be thoughtful within our programs about how we titrate patients up to their full doses,” Dr. Vidmar said.
 

Mitigating Side Effects

When the medications are available, the common gastrointestinal (GI) side effects of nausea, vomiting, and diarrhea of the once-weekly injections are well-known, and these side effects can affect quality of life and daily function, Dr. Vidmar noted.

“We have to acknowledge that the seminal trials of these agents showed that nausea and vomiting occur in more than half of young people who take these agents during the initial titration period, and while the side effects are tolerated by many, they can be disruptive to daily life,” she said.

Encouragingly, “we also do know that for the majority of patients, those effects improve over time, and for many, they can be mitigated with nutrition changes.”

Dr. Vidmar shared a handout her center issues with key recommendations for mitigating GI effects in youth. These include:

• Eat smaller meals and eat slower
• Eat about half of what you usually eat
• Take about 15-20 minutes to eat your meal
• Aim for 60 g of protein per day
• Add fruits, vegetables, whole grains, and lean proteins to meals
• Limit foods that are spicy, greasy, or fried
• Drink water instead of sweet drinks

Consider Zofran as needed during the titration period for GI symptoms. “We’ve started using this at our institution and are teaching patients how to use it; it can really help mitigate any ER visits when there is any vomiting by educating patients and families and providing appropriate expectations, and that has been very helpful,” Dr. Vidmar said.

Regarding the GI effects, Dr. Vidmar noted she has observed that tirzepatide use (though still off-label) in youths “tends to have milder GI side effects among younger people.”
 

Mood Concerns?

Another concern that has emerged in public discussion regarding side effects is that of possible mood and suicidal ideation, raising concerns for adults and adolescents alike.

Upon investigating the reports, the FDA, in a statement, offered cautious reassurance that their review, including reports and clinical trials, “did not find an association between use of GLP-1 RAs and the occurrence of suicidal thoughts or actions.”

Noting that the agency is continuing to look into the issue, however, the FDA recommends that “healthcare professionals should monitor for and advise patients using GLP-1 RAs to report new or worsening depression, suicidal thoughts, or any unusual changes in mood or behavior.”
 

Concurrent Psychiatric Pharmacotherapy

Meanwhile, with weight gain a known and often challenging side effect of various psychiatric drugs, particularly in younger patients, obesity treatment of adolescents may commonly involve patients who are also being treated with those therapies.

Key culprits include certain antidepressants and antipsychotic medications, such as tricyclic antidepressants, and second-generation antipsychotics, such as olanzapine.

In terms of the use of GLP-1 medications for those patients, research includes a recent study of semaglutide in patients who were also being treated with antidepressants.

The study, a post hoc analysis of the STEP trials, showed “clinically meaningful weight loss regardless of baseline antidepressant use, with an adverse event profile consistent with previous studies.”

First author Robert F. Kushner, MD, said the study offers “reassurance that individuals who are taking antidepressant medications have a similar weight loss response and side-effect profile compared to individuals who are not taking these medications.”

Dr. Kushner, a professor of medicine and medicine education at Northwestern University in Chicago, and his team have not evaluated the safety profile for concomitant use with antipsychotic drugs. However, he noted that “there are studies showing that the daily GLP-1 drug liraglutide has been shown to be useful in combating antipsychotic-induced weight gain.”

“Similar studies will need to be conducted for the more effective agents, semaglutide and tirzepatide,” he said.

To counter the weight gain effects of antispychotics, metformin has long been a standard recommendation, and Dr. Vidmar noted that “I have historically always used metformin in this setting and found it very effective.”

However, the newer anti-obesity medications could prove to be important in those cases, Dr. Vidmar added.

“I do think and predict that GLP-1 agonists will be as effective, if not more, in combating the weight gain-promoting effects of these agents and act as a nice adjuvant to this treatment paradigm for psychiatrists.”

Dr. Vidmar has participated in an advisory board for Rhythm Pharmaceuticals. Dr. Kushner is on the advisory boards for Novo Nordisk, Weight Watchers, Lilly, Boehringer Ingelheim, and Altimmune.

A version of this article appeared on Medscape.com.

DENVER — The ability to provide adolescents with highly effective anti-obesity medications that now carry approvals from the US Food and Drug Administration (FDA) and support in guidelines offers reassurance of their use; however, a reality check often awaits for clinicians in terms of challenges ranging from accessing and affording the medications to managing real and rumored side effects.

Weighing in on the issues, experts at Obesity Medicine (OMA) 2024 offered some key strategies and practice hacks for overcoming those hurdles.

The incentive to provide treatment with popular glucagon-like peptide 1 (GLP-1) drugs such as semaglutide or the dual glucose-dependent insulinotropic peptide (GIP) GLP-1 tirzepatide lies in the evidence that their high efficacy in promoting weight loss, and hence preventing metabolic syndrome, has benefits that far outweigh the potential side effects, said Alaina Vidmar, MD, in presenting at the meeting.

“We can look at all the evidence and without question acknowledge that the GLP-1s/GIP agonists are the most effective agents that we currently have, with the least heterogeneity in response, and the most high responders compared with other agents,” said Dr. Vidmar, an assistant professor of clinical pediatrics at the Keck School of Medicine of University of Southern California and director of obesity medicine and bariatric surgery at Children’s Hospital Los Angeles.

The strength of the evidence is reflected in the landmark American Academy of Pediatrics (AAP) Clinical Practice Guideline for the Evaluation and Treatment of Children and Adolescents With Obesity, which recommends that “pediatricians and other primary healthcare providers should offer adolescents 12 years and older with obesity weight loss pharmacotherapy, according to medication indications, risks and may offer adolescents 8 years old with obesity weight loss pharmacotherapy, according to medication indications, risks.”

The AAP guidance echoes the recommendations of the drug makers and FDA that “a combination of specific behavioral techniques within the context of family-based behavioral treatment and the use of pharmacotherapy may be necessary to prevent life-limiting complications over time.”

However, in real-world practice, with the various challenges in providing that intensive, comprehensive care, clinicians should be prepared to get creative: “We sometimes have to do the best we can with what we have because the watchful waiting approach is not effective and leads to more harm than good,” Dr. Vidmar said.
 

Facilitating Access

The ongoing reported shortages in the highly popular anti-obesity medications, as well as insurance denials and high costs, are among the leading obstacles, for adolescents and adults alike.

Dr. Vidmar noted that key strategies at her center, Children’s Hospital Los Angeles, have been essential, however, in helping at least facilitate the authorization process.

The center’s approach began with contacting all the payers the center has contracts with to determine which of their policies cover these medications for adults and pediatrics and which agents are covered.

“This took work on the front end, but it was worth it because it helped us understand the framework for what we were going to go up against every time that we prescribed these medications,” she said.

Furthermore, the center’s specialty pharmacy set up contracts to be able to provide the drugs within the institution.

While the strategy can’t entirely mitigate the ongoing distribution concerns, “our pharmacy is now able to share with our weight management program what GLP-1s are available so that we can be more efficient in our work,” Dr. Vidmar said.

The center also created a list of contacts to provide to patients and their families, detailing local pharmacies that were most likely to have the medications.

Another strategy Dr. Vidmar’s center has utilized to allow the timely implementation of a GLP-1 treatment plan while awaiting a drug to become available is to create an alternative protocol, for instance, using liraglutide when awaiting semaglutide.

“If we are unable to get the lower doses of a weekly agent for titration, we have a standard protocol to bridge instead with liraglutide, and our patients, pharmacies, and even our authorizations are aware of the protocol,” Dr. Vidmar said.

“We often do not have a lot of control or agency over the distribution concerns; however, we can be thoughtful within our programs about how we titrate patients up to their full doses,” Dr. Vidmar said.
 

Mitigating Side Effects

When the medications are available, the common gastrointestinal (GI) side effects of nausea, vomiting, and diarrhea of the once-weekly injections are well-known, and these side effects can affect quality of life and daily function, Dr. Vidmar noted.

“We have to acknowledge that the seminal trials of these agents showed that nausea and vomiting occur in more than half of young people who take these agents during the initial titration period, and while the side effects are tolerated by many, they can be disruptive to daily life,” she said.

Encouragingly, “we also do know that for the majority of patients, those effects improve over time, and for many, they can be mitigated with nutrition changes.”

Dr. Vidmar shared a handout her center issues with key recommendations for mitigating GI effects in youth. These include:

• Eat smaller meals and eat slower
• Eat about half of what you usually eat
• Take about 15-20 minutes to eat your meal
• Aim for 60 g of protein per day
• Add fruits, vegetables, whole grains, and lean proteins to meals
• Limit foods that are spicy, greasy, or fried
• Drink water instead of sweet drinks

Consider Zofran as needed during the titration period for GI symptoms. “We’ve started using this at our institution and are teaching patients how to use it; it can really help mitigate any ER visits when there is any vomiting by educating patients and families and providing appropriate expectations, and that has been very helpful,” Dr. Vidmar said.

Regarding the GI effects, Dr. Vidmar noted she has observed that tirzepatide use (though still off-label) in youths “tends to have milder GI side effects among younger people.”
 

Mood Concerns?

Another concern that has emerged in public discussion regarding side effects is that of possible mood and suicidal ideation, raising concerns for adults and adolescents alike.

Upon investigating the reports, the FDA, in a statement, offered cautious reassurance that their review, including reports and clinical trials, “did not find an association between use of GLP-1 RAs and the occurrence of suicidal thoughts or actions.”

Noting that the agency is continuing to look into the issue, however, the FDA recommends that “healthcare professionals should monitor for and advise patients using GLP-1 RAs to report new or worsening depression, suicidal thoughts, or any unusual changes in mood or behavior.”
 

Concurrent Psychiatric Pharmacotherapy

Meanwhile, with weight gain a known and often challenging side effect of various psychiatric drugs, particularly in younger patients, obesity treatment of adolescents may commonly involve patients who are also being treated with those therapies.

Key culprits include certain antidepressants and antipsychotic medications, such as tricyclic antidepressants, and second-generation antipsychotics, such as olanzapine.

In terms of the use of GLP-1 medications for those patients, research includes a recent study of semaglutide in patients who were also being treated with antidepressants.

The study, a post hoc analysis of the STEP trials, showed “clinically meaningful weight loss regardless of baseline antidepressant use, with an adverse event profile consistent with previous studies.”

First author Robert F. Kushner, MD, said the study offers “reassurance that individuals who are taking antidepressant medications have a similar weight loss response and side-effect profile compared to individuals who are not taking these medications.”

Dr. Kushner, a professor of medicine and medicine education at Northwestern University in Chicago, and his team have not evaluated the safety profile for concomitant use with antipsychotic drugs. However, he noted that “there are studies showing that the daily GLP-1 drug liraglutide has been shown to be useful in combating antipsychotic-induced weight gain.”

“Similar studies will need to be conducted for the more effective agents, semaglutide and tirzepatide,” he said.

To counter the weight gain effects of antispychotics, metformin has long been a standard recommendation, and Dr. Vidmar noted that “I have historically always used metformin in this setting and found it very effective.”

However, the newer anti-obesity medications could prove to be important in those cases, Dr. Vidmar added.

“I do think and predict that GLP-1 agonists will be as effective, if not more, in combating the weight gain-promoting effects of these agents and act as a nice adjuvant to this treatment paradigm for psychiatrists.”

Dr. Vidmar has participated in an advisory board for Rhythm Pharmaceuticals. Dr. Kushner is on the advisory boards for Novo Nordisk, Weight Watchers, Lilly, Boehringer Ingelheim, and Altimmune.

A version of this article appeared on Medscape.com.

DENVER — The ability to provide adolescents with highly effective anti-obesity medications that now carry approvals from the US Food and Drug Administration (FDA) and support in guidelines offers reassurance of their use; however, a reality check often awaits for clinicians in terms of challenges ranging from accessing and affording the medications to managing real and rumored side effects.

Weighing in on the issues, experts at Obesity Medicine (OMA) 2024 offered some key strategies and practice hacks for overcoming those hurdles.

The incentive to provide treatment with popular glucagon-like peptide 1 (GLP-1) drugs such as semaglutide or the dual glucose-dependent insulinotropic peptide (GIP) GLP-1 tirzepatide lies in the evidence that their high efficacy in promoting weight loss, and hence preventing metabolic syndrome, has benefits that far outweigh the potential side effects, said Alaina Vidmar, MD, in presenting at the meeting.

“We can look at all the evidence and without question acknowledge that the GLP-1s/GIP agonists are the most effective agents that we currently have, with the least heterogeneity in response, and the most high responders compared with other agents,” said Dr. Vidmar, an assistant professor of clinical pediatrics at the Keck School of Medicine of University of Southern California and director of obesity medicine and bariatric surgery at Children’s Hospital Los Angeles.

The strength of the evidence is reflected in the landmark American Academy of Pediatrics (AAP) Clinical Practice Guideline for the Evaluation and Treatment of Children and Adolescents With Obesity, which recommends that “pediatricians and other primary healthcare providers should offer adolescents 12 years and older with obesity weight loss pharmacotherapy, according to medication indications, risks and may offer adolescents 8 years old with obesity weight loss pharmacotherapy, according to medication indications, risks.”

The AAP guidance echoes the recommendations of the drug makers and FDA that “a combination of specific behavioral techniques within the context of family-based behavioral treatment and the use of pharmacotherapy may be necessary to prevent life-limiting complications over time.”

However, in real-world practice, with the various challenges in providing that intensive, comprehensive care, clinicians should be prepared to get creative: “We sometimes have to do the best we can with what we have because the watchful waiting approach is not effective and leads to more harm than good,” Dr. Vidmar said.
 

Facilitating Access

The ongoing reported shortages in the highly popular anti-obesity medications, as well as insurance denials and high costs, are among the leading obstacles, for adolescents and adults alike.

Dr. Vidmar noted that key strategies at her center, Children’s Hospital Los Angeles, have been essential, however, in helping at least facilitate the authorization process.

The center’s approach began with contacting all the payers the center has contracts with to determine which of their policies cover these medications for adults and pediatrics and which agents are covered.

“This took work on the front end, but it was worth it because it helped us understand the framework for what we were going to go up against every time that we prescribed these medications,” she said.

Furthermore, the center’s specialty pharmacy set up contracts to be able to provide the drugs within the institution.

While the strategy can’t entirely mitigate the ongoing distribution concerns, “our pharmacy is now able to share with our weight management program what GLP-1s are available so that we can be more efficient in our work,” Dr. Vidmar said.

The center also created a list of contacts to provide to patients and their families, detailing local pharmacies that were most likely to have the medications.

Another strategy Dr. Vidmar’s center has utilized to allow the timely implementation of a GLP-1 treatment plan while awaiting a drug to become available is to create an alternative protocol, for instance, using liraglutide when awaiting semaglutide.

“If we are unable to get the lower doses of a weekly agent for titration, we have a standard protocol to bridge instead with liraglutide, and our patients, pharmacies, and even our authorizations are aware of the protocol,” Dr. Vidmar said.

“We often do not have a lot of control or agency over the distribution concerns; however, we can be thoughtful within our programs about how we titrate patients up to their full doses,” Dr. Vidmar said.
 

Mitigating Side Effects

When the medications are available, the common gastrointestinal (GI) side effects of nausea, vomiting, and diarrhea of the once-weekly injections are well-known, and these side effects can affect quality of life and daily function, Dr. Vidmar noted.

“We have to acknowledge that the seminal trials of these agents showed that nausea and vomiting occur in more than half of young people who take these agents during the initial titration period, and while the side effects are tolerated by many, they can be disruptive to daily life,” she said.

Encouragingly, “we also do know that for the majority of patients, those effects improve over time, and for many, they can be mitigated with nutrition changes.”

Dr. Vidmar shared a handout her center issues with key recommendations for mitigating GI effects in youth. These include:

• Eat smaller meals and eat slower
• Eat about half of what you usually eat
• Take about 15-20 minutes to eat your meal
• Aim for 60 g of protein per day
• Add fruits, vegetables, whole grains, and lean proteins to meals
• Limit foods that are spicy, greasy, or fried
• Drink water instead of sweet drinks

Consider Zofran as needed during the titration period for GI symptoms. “We’ve started using this at our institution and are teaching patients how to use it; it can really help mitigate any ER visits when there is any vomiting by educating patients and families and providing appropriate expectations, and that has been very helpful,” Dr. Vidmar said.

Regarding the GI effects, Dr. Vidmar noted she has observed that tirzepatide use (though still off-label) in youths “tends to have milder GI side effects among younger people.”
 

Mood Concerns?

Another concern that has emerged in public discussion regarding side effects is that of possible mood and suicidal ideation, raising concerns for adults and adolescents alike.

Upon investigating the reports, the FDA, in a statement, offered cautious reassurance that their review, including reports and clinical trials, “did not find an association between use of GLP-1 RAs and the occurrence of suicidal thoughts or actions.”

Noting that the agency is continuing to look into the issue, however, the FDA recommends that “healthcare professionals should monitor for and advise patients using GLP-1 RAs to report new or worsening depression, suicidal thoughts, or any unusual changes in mood or behavior.”
 

Concurrent Psychiatric Pharmacotherapy

Meanwhile, with weight gain a known and often challenging side effect of various psychiatric drugs, particularly in younger patients, obesity treatment of adolescents may commonly involve patients who are also being treated with those therapies.

Key culprits include certain antidepressants and antipsychotic medications, such as tricyclic antidepressants, and second-generation antipsychotics, such as olanzapine.

In terms of the use of GLP-1 medications for those patients, research includes a recent study of semaglutide in patients who were also being treated with antidepressants.

The study, a post hoc analysis of the STEP trials, showed “clinically meaningful weight loss regardless of baseline antidepressant use, with an adverse event profile consistent with previous studies.”

First author Robert F. Kushner, MD, said the study offers “reassurance that individuals who are taking antidepressant medications have a similar weight loss response and side-effect profile compared to individuals who are not taking these medications.”

Dr. Kushner, a professor of medicine and medicine education at Northwestern University in Chicago, and his team have not evaluated the safety profile for concomitant use with antipsychotic drugs. However, he noted that “there are studies showing that the daily GLP-1 drug liraglutide has been shown to be useful in combating antipsychotic-induced weight gain.”

“Similar studies will need to be conducted for the more effective agents, semaglutide and tirzepatide,” he said.

To counter the weight gain effects of antispychotics, metformin has long been a standard recommendation, and Dr. Vidmar noted that “I have historically always used metformin in this setting and found it very effective.”

However, the newer anti-obesity medications could prove to be important in those cases, Dr. Vidmar added.

“I do think and predict that GLP-1 agonists will be as effective, if not more, in combating the weight gain-promoting effects of these agents and act as a nice adjuvant to this treatment paradigm for psychiatrists.”

Dr. Vidmar has participated in an advisory board for Rhythm Pharmaceuticals. Dr. Kushner is on the advisory boards for Novo Nordisk, Weight Watchers, Lilly, Boehringer Ingelheim, and Altimmune.

A version of this article appeared on Medscape.com.

Targeted video games could help reduce symptoms of attention-deficit/hyperactivity disorder (ADHD) and depression in children and adolescents, results of a new review and meta-analysis suggested.

Although the video game–based or “gamified” digital mental health interventions (DMHIs) were associated with modest improvements in ADHD symptoms and depression, investigators found no significant benefit in the treatment of anxiety.

“The studies are showing these video games really do work, at least for ADHD and depression but maybe not for anxiety,” said Barry Bryant, MD, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore.

“The results may assist clinicians as they make recommendations to patients and parents regarding the efficacy of using these video games to treat mental health conditions.”

The findings were presented at the American Psychiatric Association (APA) 2024 Annual Meeting.
 

A Major Problem

Childhood mental illness is a “big problem,” with about 20% of children facing some mental health challenge such as ADHD, anxiety, or depression, said Dr. Bryant. Unfortunately, these youngsters typically have to wait a while to see a provider, he added.

DMHIs may be an option to consider in the meantime to help meet the increasing demand for treatment, he said.

Gamified DMHIs are like other video games, in that players advance in levels on digital platforms and are rewarded for progress. But they’re created specifically to target certain mental health conditions.

An ADHD game, for example, might involve users completing activities that require an increasing degree of attention. Games focused on depression might incorporate mindfulness and meditation practices or cognitive behavioral elements.

Experts in child psychiatry are involved in developing such games along with professionals in business and video game technology, said Dr. Bryant.

But the question is: Do these games really work?
 

Effective for ADHD, Depression

Investigators reviewed nearly 30 randomized controlled trials of gamified DMHIs as a treatment for anxiety, depression, and/or ADHD in people younger than 18 years that were published from January 1, 1990, to April 7, 2023.

The trials tested a wide variety of gamified DMHIs that fit the inclusion criteria: A control condition, a digital game intervention, sufficient data to calculate effect size, and available in English.

A meta-analysis was performed to examine the therapeutic effects of the gamified DMHIs for ADHD, depression, and anxiety. For all studies, the active treatment was compared with the control condition using Hedges’ g to measure effect size and 95% CIs.

Dr. Bryant noted there was significant heterogeneity of therapeutic effects between the studies and their corresponding gamified interventions.

The study found gamified DMHIs had a modest therapeutic effect for treating ADHD (pooled g = 0.280; P = .005) and depression (pooled g = 0.279; P = .005) in children and adolescents.

But games targeting anxiety didn’t seem to have the same positive impact (pooled g = 0.074; P = .197).

The results suggest the games “show potential and promise” for certain mental health conditions and could offer a “bridge” to accessing more traditional therapies, Dr. Bryant said.

“Maybe this is something that can help these children until they can get to see a psychiatrist, or it could be part of a comprehensive treatment plan,” he said.

The goal is to “make something that kids want to play and engage with” especially if they’re reluctant to sit in a therapist’s office.

The results provide clinicians with information they can actually use in their practices, said Dr. Bryant, adding that his team hopes to get their study published.
 

Gaining Traction

Commenting on the research, James Sherer, MD, medical director, Addiction Psychiatry, Overlook Medical Center, Atlantic Health System, said the study shows the literature supports video games, and these games “are gaining traction” in the field.

He noted the app for one such game, EndeavorRx, was one of the first to be approved by the US Food and Drug Administration (FDA) to treat ADHD in young people aged 8-17 years.

EndeavorRx challenges players to chase mystic creatures, race through different worlds, and use “boosts” to problem-solve while building their own universe, according to the company website.

By being incentivized to engage in certain activities, “there’s a level of executive functioning that’s being exercised and the idea is to do that repetitively,” said Dr. Sherer.

Users and their parents report improved ADHD symptoms after playing the game. One of the studies included in the review found 73% of children who played EndeavorRx reported improvement in their attention.

The company says there have been no serious adverse events seen in any clinical trial of EndeavorRx.

Dr. Sherer noted that many child psychiatrists play some sort of video game with their young patients who may be on the autism spectrum or have a learning disability.

“That may be one of the few ways to communicate with and effectively bond with the patient,” he said.

Despite their reputation of being violent and associated with “toxic subcultures,” video games can do a lot of good and be “restorative” for patients of all ages, Dr. Sherer added.

No relevant conflicts of interest were disclosed.

A version of this article appeared on Medscape.com.

Targeted video games could help reduce symptoms of attention-deficit/hyperactivity disorder (ADHD) and depression in children and adolescents, results of a new review and meta-analysis suggested.

Although the video game–based or “gamified” digital mental health interventions (DMHIs) were associated with modest improvements in ADHD symptoms and depression, investigators found no significant benefit in the treatment of anxiety.

“The studies are showing these video games really do work, at least for ADHD and depression but maybe not for anxiety,” said Barry Bryant, MD, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore.

“The results may assist clinicians as they make recommendations to patients and parents regarding the efficacy of using these video games to treat mental health conditions.”

The findings were presented at the American Psychiatric Association (APA) 2024 Annual Meeting.
 

A Major Problem

Childhood mental illness is a “big problem,” with about 20% of children facing some mental health challenge such as ADHD, anxiety, or depression, said Dr. Bryant. Unfortunately, these youngsters typically have to wait a while to see a provider, he added.

DMHIs may be an option to consider in the meantime to help meet the increasing demand for treatment, he said.

Gamified DMHIs are like other video games, in that players advance in levels on digital platforms and are rewarded for progress. But they’re created specifically to target certain mental health conditions.

An ADHD game, for example, might involve users completing activities that require an increasing degree of attention. Games focused on depression might incorporate mindfulness and meditation practices or cognitive behavioral elements.

Experts in child psychiatry are involved in developing such games along with professionals in business and video game technology, said Dr. Bryant.

But the question is: Do these games really work?
 

Effective for ADHD, Depression

Investigators reviewed nearly 30 randomized controlled trials of gamified DMHIs as a treatment for anxiety, depression, and/or ADHD in people younger than 18 years that were published from January 1, 1990, to April 7, 2023.

The trials tested a wide variety of gamified DMHIs that fit the inclusion criteria: A control condition, a digital game intervention, sufficient data to calculate effect size, and available in English.

A meta-analysis was performed to examine the therapeutic effects of the gamified DMHIs for ADHD, depression, and anxiety. For all studies, the active treatment was compared with the control condition using Hedges’ g to measure effect size and 95% CIs.

Dr. Bryant noted there was significant heterogeneity of therapeutic effects between the studies and their corresponding gamified interventions.

The study found gamified DMHIs had a modest therapeutic effect for treating ADHD (pooled g = 0.280; P = .005) and depression (pooled g = 0.279; P = .005) in children and adolescents.

But games targeting anxiety didn’t seem to have the same positive impact (pooled g = 0.074; P = .197).

The results suggest the games “show potential and promise” for certain mental health conditions and could offer a “bridge” to accessing more traditional therapies, Dr. Bryant said.

“Maybe this is something that can help these children until they can get to see a psychiatrist, or it could be part of a comprehensive treatment plan,” he said.

The goal is to “make something that kids want to play and engage with” especially if they’re reluctant to sit in a therapist’s office.

The results provide clinicians with information they can actually use in their practices, said Dr. Bryant, adding that his team hopes to get their study published.
 

Gaining Traction

Commenting on the research, James Sherer, MD, medical director, Addiction Psychiatry, Overlook Medical Center, Atlantic Health System, said the study shows the literature supports video games, and these games “are gaining traction” in the field.

He noted the app for one such game, EndeavorRx, was one of the first to be approved by the US Food and Drug Administration (FDA) to treat ADHD in young people aged 8-17 years.

EndeavorRx challenges players to chase mystic creatures, race through different worlds, and use “boosts” to problem-solve while building their own universe, according to the company website.

By being incentivized to engage in certain activities, “there’s a level of executive functioning that’s being exercised and the idea is to do that repetitively,” said Dr. Sherer.

Users and their parents report improved ADHD symptoms after playing the game. One of the studies included in the review found 73% of children who played EndeavorRx reported improvement in their attention.

The company says there have been no serious adverse events seen in any clinical trial of EndeavorRx.

Dr. Sherer noted that many child psychiatrists play some sort of video game with their young patients who may be on the autism spectrum or have a learning disability.

“That may be one of the few ways to communicate with and effectively bond with the patient,” he said.

Despite their reputation of being violent and associated with “toxic subcultures,” video games can do a lot of good and be “restorative” for patients of all ages, Dr. Sherer added.

No relevant conflicts of interest were disclosed.

A version of this article appeared on Medscape.com.

Targeted video games could help reduce symptoms of attention-deficit/hyperactivity disorder (ADHD) and depression in children and adolescents, results of a new review and meta-analysis suggested.

Although the video game–based or “gamified” digital mental health interventions (DMHIs) were associated with modest improvements in ADHD symptoms and depression, investigators found no significant benefit in the treatment of anxiety.

“The studies are showing these video games really do work, at least for ADHD and depression but maybe not for anxiety,” said Barry Bryant, MD, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore.

“The results may assist clinicians as they make recommendations to patients and parents regarding the efficacy of using these video games to treat mental health conditions.”

The findings were presented at the American Psychiatric Association (APA) 2024 Annual Meeting.
 

A Major Problem

Childhood mental illness is a “big problem,” with about 20% of children facing some mental health challenge such as ADHD, anxiety, or depression, said Dr. Bryant. Unfortunately, these youngsters typically have to wait a while to see a provider, he added.

DMHIs may be an option to consider in the meantime to help meet the increasing demand for treatment, he said.

Gamified DMHIs are like other video games, in that players advance in levels on digital platforms and are rewarded for progress. But they’re created specifically to target certain mental health conditions.

An ADHD game, for example, might involve users completing activities that require an increasing degree of attention. Games focused on depression might incorporate mindfulness and meditation practices or cognitive behavioral elements.

Experts in child psychiatry are involved in developing such games along with professionals in business and video game technology, said Dr. Bryant.

But the question is: Do these games really work?
 

Effective for ADHD, Depression

Investigators reviewed nearly 30 randomized controlled trials of gamified DMHIs as a treatment for anxiety, depression, and/or ADHD in people younger than 18 years that were published from January 1, 1990, to April 7, 2023.

The trials tested a wide variety of gamified DMHIs that fit the inclusion criteria: A control condition, a digital game intervention, sufficient data to calculate effect size, and available in English.

A meta-analysis was performed to examine the therapeutic effects of the gamified DMHIs for ADHD, depression, and anxiety. For all studies, the active treatment was compared with the control condition using Hedges’ g to measure effect size and 95% CIs.

Dr. Bryant noted there was significant heterogeneity of therapeutic effects between the studies and their corresponding gamified interventions.

The study found gamified DMHIs had a modest therapeutic effect for treating ADHD (pooled g = 0.280; P = .005) and depression (pooled g = 0.279; P = .005) in children and adolescents.

But games targeting anxiety didn’t seem to have the same positive impact (pooled g = 0.074; P = .197).

The results suggest the games “show potential and promise” for certain mental health conditions and could offer a “bridge” to accessing more traditional therapies, Dr. Bryant said.

“Maybe this is something that can help these children until they can get to see a psychiatrist, or it could be part of a comprehensive treatment plan,” he said.

The goal is to “make something that kids want to play and engage with” especially if they’re reluctant to sit in a therapist’s office.

The results provide clinicians with information they can actually use in their practices, said Dr. Bryant, adding that his team hopes to get their study published.
 

Gaining Traction

Commenting on the research, James Sherer, MD, medical director, Addiction Psychiatry, Overlook Medical Center, Atlantic Health System, said the study shows the literature supports video games, and these games “are gaining traction” in the field.

He noted the app for one such game, EndeavorRx, was one of the first to be approved by the US Food and Drug Administration (FDA) to treat ADHD in young people aged 8-17 years.

EndeavorRx challenges players to chase mystic creatures, race through different worlds, and use “boosts” to problem-solve while building their own universe, according to the company website.

By being incentivized to engage in certain activities, “there’s a level of executive functioning that’s being exercised and the idea is to do that repetitively,” said Dr. Sherer.

Users and their parents report improved ADHD symptoms after playing the game. One of the studies included in the review found 73% of children who played EndeavorRx reported improvement in their attention.

The company says there have been no serious adverse events seen in any clinical trial of EndeavorRx.

Dr. Sherer noted that many child psychiatrists play some sort of video game with their young patients who may be on the autism spectrum or have a learning disability.

“That may be one of the few ways to communicate with and effectively bond with the patient,” he said.

Despite their reputation of being violent and associated with “toxic subcultures,” video games can do a lot of good and be “restorative” for patients of all ages, Dr. Sherer added.

No relevant conflicts of interest were disclosed.

A version of this article appeared on Medscape.com.

BERLIN — To date, mRNA vaccines have had their largest global presence in combating the COVID-19 pandemic. Intensive research is underway on many other potential applications for this vaccine technology, which suggests a promising future. Martina Prelog, MD, a pediatric and adolescent medicine specialist at the University Hospital of Würzburg in Germany, reported on the principles, research status, and perspectives for these vaccines at the 25th Travel and Health Forum of the Center for Travel Medicine in Berlin.

To understand the future, the immunologist first examined the past. “The induction of cellular and humoral immune responses by externally injected mRNA was discovered in the 1990s,” she said.
 

Instability Challenge

Significant hurdles in mRNA vaccinations included the instability of mRNA and the immune system’s ability to identify foreign mRNA as a threat and destroy mRNA fragments. “The breakthrough toward vaccination came through Dr. Katalin Karikó, who, along with Dr. Drew Weissman, both of the University of Pennsylvania School of Medicine, discovered in 2005 that modifications of mRNA (replacing the nucleoside uridine with pseudouridine) enable better stability of mRNA, reduced immunogenicity, and higher translational capacity at the ribosomes,” said Dr. Prelog.

With this discovery, the two researchers paved the way for the development of mRNA vaccines against COVID-19 and other diseases. They were awarded the Nobel Prize in medicine for their discovery last year.
 

Improved Scalability

“Since 2009, mRNA vaccines have been studied as a treatment option for cancer,” said Dr. Prelog. “Since 2012, they have been studied for the influenza virus and respiratory syncytial virus [RSV].” Consequently, several mRNA vaccines are currently in development or in approval studies. “The mRNA technology offers the advantage of quickly and flexibly responding to new variants of pathogens and the ability to scale up production when there is high demand for a particular vaccine.”

Different forms and designations of mRNA vaccines are used, depending on the application and desired effect, said Dr. Prelog.

In nucleoside-modified mRNA vaccines, modifications in the mRNA sequence enable the mRNA to remain in the body longer and to induce protein synthesis more effectively.

Lipid nanoparticle (LNP)–encapsulated mRNA vaccines protect the coding mRNA sequences against degradation by the body’s enzymes and facilitate the uptake of mRNA into cells, where it then triggers the production of the desired protein. In addition, LNPs are involved in cell stimulation and support the self-adjuvant effect of mRNA vaccines, thus eliminating the need for adjuvants.

Self-amplifying mRNA vaccines include a special mRNA that replicates itself in the cell and contains a sequence for RNA replicase, in addition to the coding sequence for the protein. This composition enables increased production of the target protein without the need for a high amount of external mRNA administration. Such vaccines could trigger a longer and stronger immune response because the immune system has more time to interact with the protein.
 

Cancer Immunotherapy

Dr. Prelog also discussed personalized vaccines for cancer immunotherapy. Personalized mRNA vaccines are tailored to the patient’s genetic characteristics and antigens. They could be used in cancer immunotherapy to activate the immune system selectively against tumor cells.

Multivalent mRNA vaccines contain mRNA that codes for multiple antigens rather than just one protein to generate an immune response. These vaccines could be particularly useful in fighting pathogens with variable or changing surface structures or in eliciting protection against multiple pathogens simultaneously.

The technology of mRNA-encoded antibodies involves introducing mRNA into the cell, which creates light and heavy chains of antibodies. This step leads to the formation of antibodies targeted against toxins (eg, diphtheria and tetanus), animal venoms, infectious agents, or tumor cells.
 

Genetic Engineering

Dr. Prelog also reviewed genetic engineering techniques. In regenerative therapy or protein replacement therapy, skin fibroblasts or other cells are transfected with mRNA to enable conversion into induced pluripotent stem cells. This approach avoids the risk for DNA integration into the genome and associated mutation risks.

Another approach is making post-transcriptional modifications through RNA interference. For example, RNA structures can be used to inhibit the translation of disease-causing proteins. This technique is currently being tested against HIV and tumors such as melanoma.

In addition, mRNA technologies can be combined with CRISPR/Cas9 technology (“gene scissors”) to influence the creation of gene products even more precisely. The advantage of this technique is that mRNA is only transiently expressed, thus preventing unwanted side effects. Furthermore, mRNA is translated directly in the cytoplasm, leading to a faster initiation of gene editing.

Of the numerous ongoing clinical mRNA vaccine studies, around 70% focus on infections, about 12% on cancer, and the rest on autoimmune diseases and neurodegenerative disorders, said Dr. Prelog.
 

Research in Infections

Research in the fields of infectious diseases and oncology is the most advanced: mRNA vaccines against influenza and RSV are already in advanced clinical trials, Dr. Prelog told this news organization.

“Conventional influenza vaccines contain immunogenic surface molecules against hemagglutinin and neuraminidase in various combinations of influenza strains A and B and are produced in egg or cell cultures,” she said. “This is a time-consuming manufacturing process that takes months and, particularly with the egg-based process, bears the risk of changing the vaccine strain.”

“Additionally, influenza viruses undergo antigenic shift and drift through recombination, thus requiring annual adjustments to the vaccines. Thus, these influenza vaccines often lose accuracy in targeting circulating seasonal influenza strains.”

Several mRNA vaccines being tested contain not only coding sequences against hemagglutinin and neuraminidase but also for structural proteins of influenza viruses. “These are more conserved and mutate less easily, meaning they could serve as the basis for universal pandemic influenza vaccines,” said Dr. Prelog.

An advantage of mRNA vaccines, she added, is the strong cellular immune response that they elicit. This response is intended to provide additional protection alongside specific antibodies. An mRNA vaccine with coding sequences for the pre-fusion protein of RSV is in phase 3 trials for approval for vaccination in patients aged 60 years and older. It shows high effectiveness even in older patients and those with comorbidities.
 

Elaborate Purification Process

Bacterial origin plasmid DNA is used to produce mRNA vaccines. The mRNA vaccines for COVID-19 raised concerns that production-related DNA residues could pose a safety risk and cause autoimmune diseases.

These vaccines “typically undergo a very elaborate purification process,” said Dr. Prelog. “This involves enzymatic digestion with DNase to fragment and deplete plasmid DNA, followed by purification using chromatography columns, so that no safety-relevant DNA fragments should remain afterward.”

Thus, the Paul-Ehrlich-Institut also pointed out the very small, fragmented plasmid DNA residues of bacterial origin in mRNA COVID-19 vaccines pose no risk, unlike residual DNA from animal cell culture might pose in other vaccines.
 

Prevention and Therapy

In addition to the numerous advantages of mRNA vaccines (such as rapid adaptability to new or mutated pathogens, scalability, rapid production capability, self-adjuvant effect, strong induction of cellular immune responses, and safety), there are also challenges in RNA technology as a preventive and therapeutic measure, according to Dr. Prelog.

“Stability and storability, as well as the costs of new vaccine developments, play a role, as do the long-term effects regarding the persistence of antibody and cellular responses,” she said. The COVID-19 mRNA vaccines, for example, showed a well-maintained cellular immune response despite a tendency toward a rapid decline in humoral immune response.

“The experience with COVID-19 mRNA vaccines and the new vaccine developments based on mRNA technology give hope for an efficient and safe preventive and therapeutic use, particularly in the fields of infectious diseases and oncology,” Dr. Prelog concluded.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

BERLIN — To date, mRNA vaccines have had their largest global presence in combating the COVID-19 pandemic. Intensive research is underway on many other potential applications for this vaccine technology, which suggests a promising future. Martina Prelog, MD, a pediatric and adolescent medicine specialist at the University Hospital of Würzburg in Germany, reported on the principles, research status, and perspectives for these vaccines at the 25th Travel and Health Forum of the Center for Travel Medicine in Berlin.

To understand the future, the immunologist first examined the past. “The induction of cellular and humoral immune responses by externally injected mRNA was discovered in the 1990s,” she said.
 

Instability Challenge

Significant hurdles in mRNA vaccinations included the instability of mRNA and the immune system’s ability to identify foreign mRNA as a threat and destroy mRNA fragments. “The breakthrough toward vaccination came through Dr. Katalin Karikó, who, along with Dr. Drew Weissman, both of the University of Pennsylvania School of Medicine, discovered in 2005 that modifications of mRNA (replacing the nucleoside uridine with pseudouridine) enable better stability of mRNA, reduced immunogenicity, and higher translational capacity at the ribosomes,” said Dr. Prelog.

With this discovery, the two researchers paved the way for the development of mRNA vaccines against COVID-19 and other diseases. They were awarded the Nobel Prize in medicine for their discovery last year.
 

Improved Scalability

“Since 2009, mRNA vaccines have been studied as a treatment option for cancer,” said Dr. Prelog. “Since 2012, they have been studied for the influenza virus and respiratory syncytial virus [RSV].” Consequently, several mRNA vaccines are currently in development or in approval studies. “The mRNA technology offers the advantage of quickly and flexibly responding to new variants of pathogens and the ability to scale up production when there is high demand for a particular vaccine.”

Different forms and designations of mRNA vaccines are used, depending on the application and desired effect, said Dr. Prelog.

In nucleoside-modified mRNA vaccines, modifications in the mRNA sequence enable the mRNA to remain in the body longer and to induce protein synthesis more effectively.

Lipid nanoparticle (LNP)–encapsulated mRNA vaccines protect the coding mRNA sequences against degradation by the body’s enzymes and facilitate the uptake of mRNA into cells, where it then triggers the production of the desired protein. In addition, LNPs are involved in cell stimulation and support the self-adjuvant effect of mRNA vaccines, thus eliminating the need for adjuvants.

Self-amplifying mRNA vaccines include a special mRNA that replicates itself in the cell and contains a sequence for RNA replicase, in addition to the coding sequence for the protein. This composition enables increased production of the target protein without the need for a high amount of external mRNA administration. Such vaccines could trigger a longer and stronger immune response because the immune system has more time to interact with the protein.
 

Cancer Immunotherapy

Dr. Prelog also discussed personalized vaccines for cancer immunotherapy. Personalized mRNA vaccines are tailored to the patient’s genetic characteristics and antigens. They could be used in cancer immunotherapy to activate the immune system selectively against tumor cells.

Multivalent mRNA vaccines contain mRNA that codes for multiple antigens rather than just one protein to generate an immune response. These vaccines could be particularly useful in fighting pathogens with variable or changing surface structures or in eliciting protection against multiple pathogens simultaneously.

The technology of mRNA-encoded antibodies involves introducing mRNA into the cell, which creates light and heavy chains of antibodies. This step leads to the formation of antibodies targeted against toxins (eg, diphtheria and tetanus), animal venoms, infectious agents, or tumor cells.
 

Genetic Engineering

Dr. Prelog also reviewed genetic engineering techniques. In regenerative therapy or protein replacement therapy, skin fibroblasts or other cells are transfected with mRNA to enable conversion into induced pluripotent stem cells. This approach avoids the risk for DNA integration into the genome and associated mutation risks.

Another approach is making post-transcriptional modifications through RNA interference. For example, RNA structures can be used to inhibit the translation of disease-causing proteins. This technique is currently being tested against HIV and tumors such as melanoma.

In addition, mRNA technologies can be combined with CRISPR/Cas9 technology (“gene scissors”) to influence the creation of gene products even more precisely. The advantage of this technique is that mRNA is only transiently expressed, thus preventing unwanted side effects. Furthermore, mRNA is translated directly in the cytoplasm, leading to a faster initiation of gene editing.

Of the numerous ongoing clinical mRNA vaccine studies, around 70% focus on infections, about 12% on cancer, and the rest on autoimmune diseases and neurodegenerative disorders, said Dr. Prelog.
 

Research in Infections

Research in the fields of infectious diseases and oncology is the most advanced: mRNA vaccines against influenza and RSV are already in advanced clinical trials, Dr. Prelog told this news organization.

“Conventional influenza vaccines contain immunogenic surface molecules against hemagglutinin and neuraminidase in various combinations of influenza strains A and B and are produced in egg or cell cultures,” she said. “This is a time-consuming manufacturing process that takes months and, particularly with the egg-based process, bears the risk of changing the vaccine strain.”

“Additionally, influenza viruses undergo antigenic shift and drift through recombination, thus requiring annual adjustments to the vaccines. Thus, these influenza vaccines often lose accuracy in targeting circulating seasonal influenza strains.”

Several mRNA vaccines being tested contain not only coding sequences against hemagglutinin and neuraminidase but also for structural proteins of influenza viruses. “These are more conserved and mutate less easily, meaning they could serve as the basis for universal pandemic influenza vaccines,” said Dr. Prelog.

An advantage of mRNA vaccines, she added, is the strong cellular immune response that they elicit. This response is intended to provide additional protection alongside specific antibodies. An mRNA vaccine with coding sequences for the pre-fusion protein of RSV is in phase 3 trials for approval for vaccination in patients aged 60 years and older. It shows high effectiveness even in older patients and those with comorbidities.
 

Elaborate Purification Process

Bacterial origin plasmid DNA is used to produce mRNA vaccines. The mRNA vaccines for COVID-19 raised concerns that production-related DNA residues could pose a safety risk and cause autoimmune diseases.

These vaccines “typically undergo a very elaborate purification process,” said Dr. Prelog. “This involves enzymatic digestion with DNase to fragment and deplete plasmid DNA, followed by purification using chromatography columns, so that no safety-relevant DNA fragments should remain afterward.”

Thus, the Paul-Ehrlich-Institut also pointed out the very small, fragmented plasmid DNA residues of bacterial origin in mRNA COVID-19 vaccines pose no risk, unlike residual DNA from animal cell culture might pose in other vaccines.
 

Prevention and Therapy

In addition to the numerous advantages of mRNA vaccines (such as rapid adaptability to new or mutated pathogens, scalability, rapid production capability, self-adjuvant effect, strong induction of cellular immune responses, and safety), there are also challenges in RNA technology as a preventive and therapeutic measure, according to Dr. Prelog.

“Stability and storability, as well as the costs of new vaccine developments, play a role, as do the long-term effects regarding the persistence of antibody and cellular responses,” she said. The COVID-19 mRNA vaccines, for example, showed a well-maintained cellular immune response despite a tendency toward a rapid decline in humoral immune response.

“The experience with COVID-19 mRNA vaccines and the new vaccine developments based on mRNA technology give hope for an efficient and safe preventive and therapeutic use, particularly in the fields of infectious diseases and oncology,” Dr. Prelog concluded.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

BERLIN — To date, mRNA vaccines have had their largest global presence in combating the COVID-19 pandemic. Intensive research is underway on many other potential applications for this vaccine technology, which suggests a promising future. Martina Prelog, MD, a pediatric and adolescent medicine specialist at the University Hospital of Würzburg in Germany, reported on the principles, research status, and perspectives for these vaccines at the 25th Travel and Health Forum of the Center for Travel Medicine in Berlin.

To understand the future, the immunologist first examined the past. “The induction of cellular and humoral immune responses by externally injected mRNA was discovered in the 1990s,” she said.
 

Instability Challenge

Significant hurdles in mRNA vaccinations included the instability of mRNA and the immune system’s ability to identify foreign mRNA as a threat and destroy mRNA fragments. “The breakthrough toward vaccination came through Dr. Katalin Karikó, who, along with Dr. Drew Weissman, both of the University of Pennsylvania School of Medicine, discovered in 2005 that modifications of mRNA (replacing the nucleoside uridine with pseudouridine) enable better stability of mRNA, reduced immunogenicity, and higher translational capacity at the ribosomes,” said Dr. Prelog.

With this discovery, the two researchers paved the way for the development of mRNA vaccines against COVID-19 and other diseases. They were awarded the Nobel Prize in medicine for their discovery last year.
 

Improved Scalability

“Since 2009, mRNA vaccines have been studied as a treatment option for cancer,” said Dr. Prelog. “Since 2012, they have been studied for the influenza virus and respiratory syncytial virus [RSV].” Consequently, several mRNA vaccines are currently in development or in approval studies. “The mRNA technology offers the advantage of quickly and flexibly responding to new variants of pathogens and the ability to scale up production when there is high demand for a particular vaccine.”

Different forms and designations of mRNA vaccines are used, depending on the application and desired effect, said Dr. Prelog.

In nucleoside-modified mRNA vaccines, modifications in the mRNA sequence enable the mRNA to remain in the body longer and to induce protein synthesis more effectively.

Lipid nanoparticle (LNP)–encapsulated mRNA vaccines protect the coding mRNA sequences against degradation by the body’s enzymes and facilitate the uptake of mRNA into cells, where it then triggers the production of the desired protein. In addition, LNPs are involved in cell stimulation and support the self-adjuvant effect of mRNA vaccines, thus eliminating the need for adjuvants.

Self-amplifying mRNA vaccines include a special mRNA that replicates itself in the cell and contains a sequence for RNA replicase, in addition to the coding sequence for the protein. This composition enables increased production of the target protein without the need for a high amount of external mRNA administration. Such vaccines could trigger a longer and stronger immune response because the immune system has more time to interact with the protein.
 

Cancer Immunotherapy

Dr. Prelog also discussed personalized vaccines for cancer immunotherapy. Personalized mRNA vaccines are tailored to the patient’s genetic characteristics and antigens. They could be used in cancer immunotherapy to activate the immune system selectively against tumor cells.

Multivalent mRNA vaccines contain mRNA that codes for multiple antigens rather than just one protein to generate an immune response. These vaccines could be particularly useful in fighting pathogens with variable or changing surface structures or in eliciting protection against multiple pathogens simultaneously.

The technology of mRNA-encoded antibodies involves introducing mRNA into the cell, which creates light and heavy chains of antibodies. This step leads to the formation of antibodies targeted against toxins (eg, diphtheria and tetanus), animal venoms, infectious agents, or tumor cells.
 

Genetic Engineering

Dr. Prelog also reviewed genetic engineering techniques. In regenerative therapy or protein replacement therapy, skin fibroblasts or other cells are transfected with mRNA to enable conversion into induced pluripotent stem cells. This approach avoids the risk for DNA integration into the genome and associated mutation risks.

Another approach is making post-transcriptional modifications through RNA interference. For example, RNA structures can be used to inhibit the translation of disease-causing proteins. This technique is currently being tested against HIV and tumors such as melanoma.

In addition, mRNA technologies can be combined with CRISPR/Cas9 technology (“gene scissors”) to influence the creation of gene products even more precisely. The advantage of this technique is that mRNA is only transiently expressed, thus preventing unwanted side effects. Furthermore, mRNA is translated directly in the cytoplasm, leading to a faster initiation of gene editing.

Of the numerous ongoing clinical mRNA vaccine studies, around 70% focus on infections, about 12% on cancer, and the rest on autoimmune diseases and neurodegenerative disorders, said Dr. Prelog.
 

Research in Infections

Research in the fields of infectious diseases and oncology is the most advanced: mRNA vaccines against influenza and RSV are already in advanced clinical trials, Dr. Prelog told this news organization.

“Conventional influenza vaccines contain immunogenic surface molecules against hemagglutinin and neuraminidase in various combinations of influenza strains A and B and are produced in egg or cell cultures,” she said. “This is a time-consuming manufacturing process that takes months and, particularly with the egg-based process, bears the risk of changing the vaccine strain.”

“Additionally, influenza viruses undergo antigenic shift and drift through recombination, thus requiring annual adjustments to the vaccines. Thus, these influenza vaccines often lose accuracy in targeting circulating seasonal influenza strains.”

Several mRNA vaccines being tested contain not only coding sequences against hemagglutinin and neuraminidase but also for structural proteins of influenza viruses. “These are more conserved and mutate less easily, meaning they could serve as the basis for universal pandemic influenza vaccines,” said Dr. Prelog.

An advantage of mRNA vaccines, she added, is the strong cellular immune response that they elicit. This response is intended to provide additional protection alongside specific antibodies. An mRNA vaccine with coding sequences for the pre-fusion protein of RSV is in phase 3 trials for approval for vaccination in patients aged 60 years and older. It shows high effectiveness even in older patients and those with comorbidities.
 

Elaborate Purification Process

Bacterial origin plasmid DNA is used to produce mRNA vaccines. The mRNA vaccines for COVID-19 raised concerns that production-related DNA residues could pose a safety risk and cause autoimmune diseases.

These vaccines “typically undergo a very elaborate purification process,” said Dr. Prelog. “This involves enzymatic digestion with DNase to fragment and deplete plasmid DNA, followed by purification using chromatography columns, so that no safety-relevant DNA fragments should remain afterward.”

Thus, the Paul-Ehrlich-Institut also pointed out the very small, fragmented plasmid DNA residues of bacterial origin in mRNA COVID-19 vaccines pose no risk, unlike residual DNA from animal cell culture might pose in other vaccines.
 

Prevention and Therapy

In addition to the numerous advantages of mRNA vaccines (such as rapid adaptability to new or mutated pathogens, scalability, rapid production capability, self-adjuvant effect, strong induction of cellular immune responses, and safety), there are also challenges in RNA technology as a preventive and therapeutic measure, according to Dr. Prelog.

“Stability and storability, as well as the costs of new vaccine developments, play a role, as do the long-term effects regarding the persistence of antibody and cellular responses,” she said. The COVID-19 mRNA vaccines, for example, showed a well-maintained cellular immune response despite a tendency toward a rapid decline in humoral immune response.

“The experience with COVID-19 mRNA vaccines and the new vaccine developments based on mRNA technology give hope for an efficient and safe preventive and therapeutic use, particularly in the fields of infectious diseases and oncology,” Dr. Prelog concluded.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Cisplatin is a preferred treatment for a wide range of cancers, including breast, head and neck, lung, ovary, and more. However, its side effects — particularly nephrotoxicity — can be severe. Kidney injury on cisplatin is associated with higher mortality and can jeopardize a patient’s eligibility for other therapies.

Now, in a large study using data from six US cancer centers, researchers have developed a risk algorithm to predict acute kidney injury (AKI) after cisplatin administration.

A risk prediction calculator based on the algorithm is available online for patients and providers to determine an individual patient›s risk for kidney injury from cisplatin using readily available clinical data.

Other risk scores and risk prediction models have been developed to help clinicians assess in advance whether a patient might develop AKI after receiving cisplatin, so that more careful monitoring, dose adjustments, or an alternative treatment, if available, might be considered.

However, previous models were limited by factors such as small sample sizes, lack of external validation, older data, and liberal definitions of AKI, said Shruti Gupta, MD, MPH, director of onco-nephrology at Brigham and Women’s Hospital (BWH) and Dana-Farber Cancer Institute, and David E. Leaf, MD, MMSc, director of clinical and translational research in AKI, Division of Renal Medicine, BWH, Boston.

Dr. Gupta and Dr. Leaf believe their risk score for predicting severe AKI after intravenous (IV) cisplatin, published online in The BMJ, is “more accurate and generalizable than prior models for several reasons,” they told this news organization in a joint email.

“First, we externally validated our findings across cancer centers other than the one where it was developed,” they said. “Second, we focused on moderate to severe kidney injury, the most clinically relevant form of kidney damage, whereas prior models examined more mild forms of kidney injury. Third, we collected data on nearly 25,000 patients receiving their first dose of IV cisplatin, which is larger than all previous studies combined.”
 

‘Herculean Effort’

“We conceived of this study back in 2018, contacted collaborators at each participating cancer center, and had numerous meetings to try to gather granular data on patients treated with their first dose of intravenous (IV) cisplatin,” Dr. Gupta and Dr. Leaf explained. They also incorporated patient feedback from focus groups and surveys.

“This was truly a Herculean effort that involved physicians, programmers, research coordinators, and patients,” they said.

The multicenter study included 24,717 patients — 11,766 in the derivation cohort and 12,951 in the validation cohort. Overall, the median age was about 60 years, about 58% were men, and about 78% were White.

The primary outcome was cisplatin-induced AKI (CP-AKI), defined as a twofold or greater increase in serum creatinine or kidney replacement therapy within 14 days of a first dose of IV cisplatin.

The researchers found that the incidence of CP-AKI was 5.2% in the derivation cohort and 3.3% in the validation cohort. Their simple risk score consisting of nine covariates — age, hypertension, type 2 diabetes, hemoglobin level, white blood cell count, platelet count, serum albumin level, serum magnesium level, and cisplatin dose — predicted a higher risk for CP-AKI in both cohorts.

Notably, adding serum creatinine to the model did not change the area under the curve, and therefore, serum creatinine, though also an independent risk factor for CP-AKI, was not included in the score.

Patients in the highest risk category had 24-fold higher odds of CP-AKI in the derivation cohort and close to 18-fold higher odds in the validation cohort than those in the lowest risk category.

The primary model had a C statistic of 0.75 (95% CI, 0.73-0.76) and showed better discrimination for CP-AKI than previously published models, for which the C statistics ranged from 0.60 to 0.68. The first author of a paper on an earlier model, Shveta Motwani, MD, MMSc, of BWH and Dana-Farber Cancer Institute in Boston, is also a coauthor of the new study.

Greater severity of CP-AKI was associated with shorter 90-day survival (adjusted hazard ratio, 4.63; 95% CI, 3.56-6.02) for stage III CP-AKI vs no CP-AKI.
 

‘Definitive Work’

Joel M. Topf, MD, a nephrologist with expertise in chronic kidney disease in Detroit, who wasn’t involved in the development of the risk score, called the study “a definitive work on an important concept in oncology and nephrology.”

“While this is not the first attempt to devise a risk score, it is by far the biggest,” he told this news organization. Furthermore, the authors “used a diverse population, recruiting patients with a variety of cancers (previous attempts had often used a homogenous diagnosis, putting into question how generalizable the results were) from six different cancer centers.”

In addition, he said, “The authors did not restrict patients with chronic kidney disease or other significant comorbidities and used the geographic diversity to produce a cohort that has an age, gender, racial, and ethnic distribution, which is more representative of the US than previous, single-center attempts to risk score patients.”

An earlier model used the Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI of an increase in serum creatinine of 0.3 mg/dL, he noted. “While a sensitive definition of AKI, it captures mild, hemodynamic increases in creatinine of questionable significance,” he said.

By contrast, the new score uses KDIGO stage II and above to define AKI. “This is a better choice, as we do not want to dissuade patients and doctors from choosing chemotherapy due to a fear of insignificant kidney damage,” he said.

All that said, Dr. Topf noted that neither the current score nor the earlier model included serum creatinine. “This is curious to me and may represent the small number of patients with representative elevated creatinine in the derivation cohort (only 1.3% with an estimated glomerular filtration rate [eGFR] < 45).”

“Since the cohort is made up of people who received cis-platinum, the low prevalence of eGFRs < 45 may be due to physicians steering away from cis-platinum in this group,” he suggested. “It would be unfortunate if this risk score gave an unintentional ‘green light’ to these patients, exposing them to predictable harm.”
 

‘Certainly Useful’

Anushree Shirali, MD, an associate professor in the Section of Nephrology and consulting physician, Yale Onco-Nephrology, Yale School of Medicine, in New Haven, Connecticut, said that having a prediction score for which patients are more likely to develop AKI after a single dose of cisplatin would be helpful for oncologists, as well as nephrologists.

As a nephrologist, Dr. Shirali mostly sees patients who already have AKI, she told this news organization. But there are circumstances in which the tool could still be helpful.

“Let’s say someone has abnormal kidney function at baseline — ie, creatinine is higher than the normal range — and they were on dialysis 5 years ago for something else, and now, they have cancer and may be given cisplatin. They worry about their chances of getting AKI and needing dialysis again,” she said. “That’s just one scenario in which I might be asked to answer that question and the tool would certainly be useful.”

Other scenarios could include someone who has just one kidney because they donated a kidney for transplant years ago, and now, they have a malignancy and wonder what their actual risk is of getting kidney issues on cisplatin.

Oncologists could use the tool to determine whether a patient should be treated with cisplatin, or if they’re at high risk, whether an alternative that’s not nephrotoxic might be used. By contrast, “if somebody’s low risk and an oncologist thinks cisplatin is the best agent they have, then they might want to go ahead and use it,” Dr. Shirali said.

Future research could take into consideration that CP-AKI is dose dependent, she suggested, because a prediction score that included the number of cisplatin doses could be even more helpful to determine risk. And, even though the derivation and validation cohorts for the new tool are representative of the US population, additional research should also include more racial/ethnic diversity, she said.

Dr. Gupta and Dr. Leaf hope their tool “will be utilized immediately by patients and providers to help predict an individual’s risk of cisplatin-associated kidney damage. It is easy to use, available for free online, and incorporates readily available clinical variables.”

If a patient is at high risk, the clinical team can consider preventive measures such as administering more IV fluids before receiving cisplatin or monitoring kidney function more closely afterward, they suggested.

Dr. Gupta reported research support from the National Institutes of Health (NIH) and the National Institute of Diabetes and Digestive and Kidney Diseases. She also reported research funding from BTG International, GE HealthCare, and AstraZeneca outside the submitted work. She is a member of GlaxoSmithKline’s Global Anemia Council, a consultant for Secretome and Proletariat Therapeutics, and founder and president emeritus of the American Society of Onconephrology (unpaid). Dr. Leaf is supported by NIH grants, reported research support from BioPorto, BTG International, and Metro International Biotech, and has served as a consultant. Dr. Topf reported an ownership stake in a few DaVita-run dialysis clinics. He also runs a vascular access center and has participated in advisory boards with Cara Therapeutics, Vifor, Astra Zeneca, Bayer, Renibus Therapeutics, Travere Therapeutics, and GlaxoSmithKline. He is president of NephJC, a nonprofit educational organization with no industry support. Dr. Shirali declared no competing interests.

A version of this article appeared on Medscape.com.

Cisplatin is a preferred treatment for a wide range of cancers, including breast, head and neck, lung, ovary, and more. However, its side effects — particularly nephrotoxicity — can be severe. Kidney injury on cisplatin is associated with higher mortality and can jeopardize a patient’s eligibility for other therapies.

Now, in a large study using data from six US cancer centers, researchers have developed a risk algorithm to predict acute kidney injury (AKI) after cisplatin administration.

A risk prediction calculator based on the algorithm is available online for patients and providers to determine an individual patient›s risk for kidney injury from cisplatin using readily available clinical data.

Other risk scores and risk prediction models have been developed to help clinicians assess in advance whether a patient might develop AKI after receiving cisplatin, so that more careful monitoring, dose adjustments, or an alternative treatment, if available, might be considered.

However, previous models were limited by factors such as small sample sizes, lack of external validation, older data, and liberal definitions of AKI, said Shruti Gupta, MD, MPH, director of onco-nephrology at Brigham and Women’s Hospital (BWH) and Dana-Farber Cancer Institute, and David E. Leaf, MD, MMSc, director of clinical and translational research in AKI, Division of Renal Medicine, BWH, Boston.

Dr. Gupta and Dr. Leaf believe their risk score for predicting severe AKI after intravenous (IV) cisplatin, published online in The BMJ, is “more accurate and generalizable than prior models for several reasons,” they told this news organization in a joint email.

“First, we externally validated our findings across cancer centers other than the one where it was developed,” they said. “Second, we focused on moderate to severe kidney injury, the most clinically relevant form of kidney damage, whereas prior models examined more mild forms of kidney injury. Third, we collected data on nearly 25,000 patients receiving their first dose of IV cisplatin, which is larger than all previous studies combined.”
 

‘Herculean Effort’

“We conceived of this study back in 2018, contacted collaborators at each participating cancer center, and had numerous meetings to try to gather granular data on patients treated with their first dose of intravenous (IV) cisplatin,” Dr. Gupta and Dr. Leaf explained. They also incorporated patient feedback from focus groups and surveys.

“This was truly a Herculean effort that involved physicians, programmers, research coordinators, and patients,” they said.

The multicenter study included 24,717 patients — 11,766 in the derivation cohort and 12,951 in the validation cohort. Overall, the median age was about 60 years, about 58% were men, and about 78% were White.

The primary outcome was cisplatin-induced AKI (CP-AKI), defined as a twofold or greater increase in serum creatinine or kidney replacement therapy within 14 days of a first dose of IV cisplatin.

The researchers found that the incidence of CP-AKI was 5.2% in the derivation cohort and 3.3% in the validation cohort. Their simple risk score consisting of nine covariates — age, hypertension, type 2 diabetes, hemoglobin level, white blood cell count, platelet count, serum albumin level, serum magnesium level, and cisplatin dose — predicted a higher risk for CP-AKI in both cohorts.

Notably, adding serum creatinine to the model did not change the area under the curve, and therefore, serum creatinine, though also an independent risk factor for CP-AKI, was not included in the score.

Patients in the highest risk category had 24-fold higher odds of CP-AKI in the derivation cohort and close to 18-fold higher odds in the validation cohort than those in the lowest risk category.

The primary model had a C statistic of 0.75 (95% CI, 0.73-0.76) and showed better discrimination for CP-AKI than previously published models, for which the C statistics ranged from 0.60 to 0.68. The first author of a paper on an earlier model, Shveta Motwani, MD, MMSc, of BWH and Dana-Farber Cancer Institute in Boston, is also a coauthor of the new study.

Greater severity of CP-AKI was associated with shorter 90-day survival (adjusted hazard ratio, 4.63; 95% CI, 3.56-6.02) for stage III CP-AKI vs no CP-AKI.
 

‘Definitive Work’

Joel M. Topf, MD, a nephrologist with expertise in chronic kidney disease in Detroit, who wasn’t involved in the development of the risk score, called the study “a definitive work on an important concept in oncology and nephrology.”

“While this is not the first attempt to devise a risk score, it is by far the biggest,” he told this news organization. Furthermore, the authors “used a diverse population, recruiting patients with a variety of cancers (previous attempts had often used a homogenous diagnosis, putting into question how generalizable the results were) from six different cancer centers.”

In addition, he said, “The authors did not restrict patients with chronic kidney disease or other significant comorbidities and used the geographic diversity to produce a cohort that has an age, gender, racial, and ethnic distribution, which is more representative of the US than previous, single-center attempts to risk score patients.”

An earlier model used the Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI of an increase in serum creatinine of 0.3 mg/dL, he noted. “While a sensitive definition of AKI, it captures mild, hemodynamic increases in creatinine of questionable significance,” he said.

By contrast, the new score uses KDIGO stage II and above to define AKI. “This is a better choice, as we do not want to dissuade patients and doctors from choosing chemotherapy due to a fear of insignificant kidney damage,” he said.

All that said, Dr. Topf noted that neither the current score nor the earlier model included serum creatinine. “This is curious to me and may represent the small number of patients with representative elevated creatinine in the derivation cohort (only 1.3% with an estimated glomerular filtration rate [eGFR] < 45).”

“Since the cohort is made up of people who received cis-platinum, the low prevalence of eGFRs < 45 may be due to physicians steering away from cis-platinum in this group,” he suggested. “It would be unfortunate if this risk score gave an unintentional ‘green light’ to these patients, exposing them to predictable harm.”
 

‘Certainly Useful’

Anushree Shirali, MD, an associate professor in the Section of Nephrology and consulting physician, Yale Onco-Nephrology, Yale School of Medicine, in New Haven, Connecticut, said that having a prediction score for which patients are more likely to develop AKI after a single dose of cisplatin would be helpful for oncologists, as well as nephrologists.

As a nephrologist, Dr. Shirali mostly sees patients who already have AKI, she told this news organization. But there are circumstances in which the tool could still be helpful.

“Let’s say someone has abnormal kidney function at baseline — ie, creatinine is higher than the normal range — and they were on dialysis 5 years ago for something else, and now, they have cancer and may be given cisplatin. They worry about their chances of getting AKI and needing dialysis again,” she said. “That’s just one scenario in which I might be asked to answer that question and the tool would certainly be useful.”

Other scenarios could include someone who has just one kidney because they donated a kidney for transplant years ago, and now, they have a malignancy and wonder what their actual risk is of getting kidney issues on cisplatin.

Oncologists could use the tool to determine whether a patient should be treated with cisplatin, or if they’re at high risk, whether an alternative that’s not nephrotoxic might be used. By contrast, “if somebody’s low risk and an oncologist thinks cisplatin is the best agent they have, then they might want to go ahead and use it,” Dr. Shirali said.

Future research could take into consideration that CP-AKI is dose dependent, she suggested, because a prediction score that included the number of cisplatin doses could be even more helpful to determine risk. And, even though the derivation and validation cohorts for the new tool are representative of the US population, additional research should also include more racial/ethnic diversity, she said.

Dr. Gupta and Dr. Leaf hope their tool “will be utilized immediately by patients and providers to help predict an individual’s risk of cisplatin-associated kidney damage. It is easy to use, available for free online, and incorporates readily available clinical variables.”

If a patient is at high risk, the clinical team can consider preventive measures such as administering more IV fluids before receiving cisplatin or monitoring kidney function more closely afterward, they suggested.

Dr. Gupta reported research support from the National Institutes of Health (NIH) and the National Institute of Diabetes and Digestive and Kidney Diseases. She also reported research funding from BTG International, GE HealthCare, and AstraZeneca outside the submitted work. She is a member of GlaxoSmithKline’s Global Anemia Council, a consultant for Secretome and Proletariat Therapeutics, and founder and president emeritus of the American Society of Onconephrology (unpaid). Dr. Leaf is supported by NIH grants, reported research support from BioPorto, BTG International, and Metro International Biotech, and has served as a consultant. Dr. Topf reported an ownership stake in a few DaVita-run dialysis clinics. He also runs a vascular access center and has participated in advisory boards with Cara Therapeutics, Vifor, Astra Zeneca, Bayer, Renibus Therapeutics, Travere Therapeutics, and GlaxoSmithKline. He is president of NephJC, a nonprofit educational organization with no industry support. Dr. Shirali declared no competing interests.

A version of this article appeared on Medscape.com.

Cisplatin is a preferred treatment for a wide range of cancers, including breast, head and neck, lung, ovary, and more. However, its side effects — particularly nephrotoxicity — can be severe. Kidney injury on cisplatin is associated with higher mortality and can jeopardize a patient’s eligibility for other therapies.

Now, in a large study using data from six US cancer centers, researchers have developed a risk algorithm to predict acute kidney injury (AKI) after cisplatin administration.

A risk prediction calculator based on the algorithm is available online for patients and providers to determine an individual patient›s risk for kidney injury from cisplatin using readily available clinical data.

Other risk scores and risk prediction models have been developed to help clinicians assess in advance whether a patient might develop AKI after receiving cisplatin, so that more careful monitoring, dose adjustments, or an alternative treatment, if available, might be considered.

However, previous models were limited by factors such as small sample sizes, lack of external validation, older data, and liberal definitions of AKI, said Shruti Gupta, MD, MPH, director of onco-nephrology at Brigham and Women’s Hospital (BWH) and Dana-Farber Cancer Institute, and David E. Leaf, MD, MMSc, director of clinical and translational research in AKI, Division of Renal Medicine, BWH, Boston.

Dr. Gupta and Dr. Leaf believe their risk score for predicting severe AKI after intravenous (IV) cisplatin, published online in The BMJ, is “more accurate and generalizable than prior models for several reasons,” they told this news organization in a joint email.

“First, we externally validated our findings across cancer centers other than the one where it was developed,” they said. “Second, we focused on moderate to severe kidney injury, the most clinically relevant form of kidney damage, whereas prior models examined more mild forms of kidney injury. Third, we collected data on nearly 25,000 patients receiving their first dose of IV cisplatin, which is larger than all previous studies combined.”
 

‘Herculean Effort’

“We conceived of this study back in 2018, contacted collaborators at each participating cancer center, and had numerous meetings to try to gather granular data on patients treated with their first dose of intravenous (IV) cisplatin,” Dr. Gupta and Dr. Leaf explained. They also incorporated patient feedback from focus groups and surveys.

“This was truly a Herculean effort that involved physicians, programmers, research coordinators, and patients,” they said.

The multicenter study included 24,717 patients — 11,766 in the derivation cohort and 12,951 in the validation cohort. Overall, the median age was about 60 years, about 58% were men, and about 78% were White.

The primary outcome was cisplatin-induced AKI (CP-AKI), defined as a twofold or greater increase in serum creatinine or kidney replacement therapy within 14 days of a first dose of IV cisplatin.

The researchers found that the incidence of CP-AKI was 5.2% in the derivation cohort and 3.3% in the validation cohort. Their simple risk score consisting of nine covariates — age, hypertension, type 2 diabetes, hemoglobin level, white blood cell count, platelet count, serum albumin level, serum magnesium level, and cisplatin dose — predicted a higher risk for CP-AKI in both cohorts.

Notably, adding serum creatinine to the model did not change the area under the curve, and therefore, serum creatinine, though also an independent risk factor for CP-AKI, was not included in the score.

Patients in the highest risk category had 24-fold higher odds of CP-AKI in the derivation cohort and close to 18-fold higher odds in the validation cohort than those in the lowest risk category.

The primary model had a C statistic of 0.75 (95% CI, 0.73-0.76) and showed better discrimination for CP-AKI than previously published models, for which the C statistics ranged from 0.60 to 0.68. The first author of a paper on an earlier model, Shveta Motwani, MD, MMSc, of BWH and Dana-Farber Cancer Institute in Boston, is also a coauthor of the new study.

Greater severity of CP-AKI was associated with shorter 90-day survival (adjusted hazard ratio, 4.63; 95% CI, 3.56-6.02) for stage III CP-AKI vs no CP-AKI.
 

‘Definitive Work’

Joel M. Topf, MD, a nephrologist with expertise in chronic kidney disease in Detroit, who wasn’t involved in the development of the risk score, called the study “a definitive work on an important concept in oncology and nephrology.”

“While this is not the first attempt to devise a risk score, it is by far the biggest,” he told this news organization. Furthermore, the authors “used a diverse population, recruiting patients with a variety of cancers (previous attempts had often used a homogenous diagnosis, putting into question how generalizable the results were) from six different cancer centers.”

In addition, he said, “The authors did not restrict patients with chronic kidney disease or other significant comorbidities and used the geographic diversity to produce a cohort that has an age, gender, racial, and ethnic distribution, which is more representative of the US than previous, single-center attempts to risk score patients.”

An earlier model used the Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI of an increase in serum creatinine of 0.3 mg/dL, he noted. “While a sensitive definition of AKI, it captures mild, hemodynamic increases in creatinine of questionable significance,” he said.

By contrast, the new score uses KDIGO stage II and above to define AKI. “This is a better choice, as we do not want to dissuade patients and doctors from choosing chemotherapy due to a fear of insignificant kidney damage,” he said.

All that said, Dr. Topf noted that neither the current score nor the earlier model included serum creatinine. “This is curious to me and may represent the small number of patients with representative elevated creatinine in the derivation cohort (only 1.3% with an estimated glomerular filtration rate [eGFR] < 45).”

“Since the cohort is made up of people who received cis-platinum, the low prevalence of eGFRs < 45 may be due to physicians steering away from cis-platinum in this group,” he suggested. “It would be unfortunate if this risk score gave an unintentional ‘green light’ to these patients, exposing them to predictable harm.”
 

‘Certainly Useful’

Anushree Shirali, MD, an associate professor in the Section of Nephrology and consulting physician, Yale Onco-Nephrology, Yale School of Medicine, in New Haven, Connecticut, said that having a prediction score for which patients are more likely to develop AKI after a single dose of cisplatin would be helpful for oncologists, as well as nephrologists.

As a nephrologist, Dr. Shirali mostly sees patients who already have AKI, she told this news organization. But there are circumstances in which the tool could still be helpful.

“Let’s say someone has abnormal kidney function at baseline — ie, creatinine is higher than the normal range — and they were on dialysis 5 years ago for something else, and now, they have cancer and may be given cisplatin. They worry about their chances of getting AKI and needing dialysis again,” she said. “That’s just one scenario in which I might be asked to answer that question and the tool would certainly be useful.”

Other scenarios could include someone who has just one kidney because they donated a kidney for transplant years ago, and now, they have a malignancy and wonder what their actual risk is of getting kidney issues on cisplatin.

Oncologists could use the tool to determine whether a patient should be treated with cisplatin, or if they’re at high risk, whether an alternative that’s not nephrotoxic might be used. By contrast, “if somebody’s low risk and an oncologist thinks cisplatin is the best agent they have, then they might want to go ahead and use it,” Dr. Shirali said.

Future research could take into consideration that CP-AKI is dose dependent, she suggested, because a prediction score that included the number of cisplatin doses could be even more helpful to determine risk. And, even though the derivation and validation cohorts for the new tool are representative of the US population, additional research should also include more racial/ethnic diversity, she said.

Dr. Gupta and Dr. Leaf hope their tool “will be utilized immediately by patients and providers to help predict an individual’s risk of cisplatin-associated kidney damage. It is easy to use, available for free online, and incorporates readily available clinical variables.”

If a patient is at high risk, the clinical team can consider preventive measures such as administering more IV fluids before receiving cisplatin or monitoring kidney function more closely afterward, they suggested.

Dr. Gupta reported research support from the National Institutes of Health (NIH) and the National Institute of Diabetes and Digestive and Kidney Diseases. She also reported research funding from BTG International, GE HealthCare, and AstraZeneca outside the submitted work. She is a member of GlaxoSmithKline’s Global Anemia Council, a consultant for Secretome and Proletariat Therapeutics, and founder and president emeritus of the American Society of Onconephrology (unpaid). Dr. Leaf is supported by NIH grants, reported research support from BioPorto, BTG International, and Metro International Biotech, and has served as a consultant. Dr. Topf reported an ownership stake in a few DaVita-run dialysis clinics. He also runs a vascular access center and has participated in advisory boards with Cara Therapeutics, Vifor, Astra Zeneca, Bayer, Renibus Therapeutics, Travere Therapeutics, and GlaxoSmithKline. He is president of NephJC, a nonprofit educational organization with no industry support. Dr. Shirali declared no competing interests.

A version of this article appeared on Medscape.com.

By age 12 years, more than 14% of children have tried alcohol or tobacco, and religion, race, and income are the top predictors beginning to use these and other substances, new research suggests.

Aside from sociodemographic parameters, risk factors for substance use initiation include prenatal exposure to substances, peer use of alcohol and nicotine, and problematic school behavior, among other things, the study showed.

The results show certain modifiable risk factors may play a role in preventing youth from starting to use substances, said study author ReJoyce Green, PhD, research assistant professor, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston.

“If we’re designing, say, a prevention program or an early intervention program, these are things that could make a difference, so let’s make sure we’re bringing them into the conversation.”

The findings were presented at the annual meeting of the American Psychiatric Association American Psychiatric Association (APA) and published online in The American Journal of Psychiatry.
 

Critical Risk Factors

Use of alcohol, tobacco, and cannabis often begins during adolescence. One recent survey showed that 23% of 13-year-olds reported using alcohol, 17% reported vaping nicotine, and 8% reported vaping cannabis. Other research links younger age at substance use initiation to a more rapid transition to substance use disorders and higher rates of psychiatric disorders.

Previous studies examining predictors of substance use initiation in the Adolescent Brain Cognitive Development (ABCD) Study dataset focused primarily on self-reported measures, but the current study also looked at models that include hormones and neurocognitive factors as well as neuroimaging.

This study included 6829, 9- and 10-year-olds from the ABCD Study who had never tried substances and were followed for 3 years.

A sophisticated statistical approach was used to examine 420 variables as predictors of substance use initiation. Initiation was defined as trying any nonprescribed substance by age 12 years. “That’s including a single sip of alcohol or puff of a cigarette,” said Dr. Green.

In addition to alcohol, nicotine, and cannabis, researchers looked at initiation of synthetic cannabinoids, cocaine, methamphetamine, and ketamine, among other substances.

Self-reported measures included demographic characteristics, self and peer involvement with substance use, parenting behaviors, mental and physical health, and culture and environmental factors.

The analytical approach used machine-learning algorithms to compare the ability of domains to identify the most critical risk factors. Magnitudes of coefficients were used to assess variable importance, with positive coefficients indicating greater likelihood of substance initiation and negative coefficients indicating lower likelihood of initiation.

By age 12 years, 14.4% of the children studied reported substance initiation. Alcohol was the substance most commonly initiated (365 individuals), followed by nicotine (94 individuals) and cannabis (40 individuals), with few or no children initiating other substances.

Both those who did and did not initiate substances were similarly aged, and most participants identified as White and non-Hispanic. But the substance-use group had a lower percentage of girls and higher percentage of White participants compared with the no-substance-use group.

The model with only self-reported data had similar accuracy in predicting substance use initiation (area under the curve [AUC], 0.67) as models that added resource-intensive measures such as neurocognitive tests and hormones (AUC, 0.67) and neuroimaging (AUC, 0.66).
 

Religious Predictors

The strongest predictors of substance use initiation were related to religion: Youths whose parents reported a religious preference for Mormonism were less likely to initiate substance use (coefficient, -0.87), whereas youths whose parents reported a religious preference for Judaism were more likely to initiate substance use (coefficient, 0.32).

The third top predictor was race: Black youths were less likely to initiate substance use (coefficient, -0.32). This was followed by youths whose parents reported a religious preference for Islam who were also less likely to initiate substance use (coefficient, -0.25).

The research examined over 15 different religious categories, “so we really tried to be expansive,” noted Dr. Green.

It’s unclear why some religions appeared to have a protective impact when it comes to substance use initiation whereas others have the opposite effect. Future research could perhaps identify which components of religiosity affect substance use initiation. If so, these aspects could be developed and incorporated into prevention and intervention programs, said Dr. Green.

Next on the list of most important predictors was being a part of a household with an income of $12,000-$15,999; these youths were less likely to initiate substance use (coefficient, 0.22).

Within the culture and environment domain, a history of detention or suspension was a top predictor of substance use initiation (coefficient, 0.20). Prenatal exposure to substance use was also a robust predictor in the physical health category (coefficient, 0.15).

Other predictors included: parents with less than a high school degree or GED (coefficient, -0.14), substance use availability (coefficient, 0.12), and age at baseline (coefficient, 0.12).

The study also showed that better cognitive functioning in selected domains (eg, cognitive control, attention, and language ability) is associated with a greater likelihood of substance use initiation.
 

Shaping Future Prevention

Applying these findings in clinical settings could help tailor prevention and early intervention efforts, said the authors. It might be prudent to allocate resources to collecting data related to self-, peer-, and familial-related factors, “which were more informative in predicting substance use initiation during late childhood and early adolescence in the present study,” they wrote.

Researchers will continue to track these children through to a 10-year follow-up, said Dr. Green. “I’m really curious to see if the factors we found when they were 12 and 13, such as those related to peers and family, still hold when they’re ages 17 and 18, because there’s going to be a huge amount of brain development that’s happening throughout this phase.”

The group that initiated substance use and the group that didn’t initiate substance use were not totally balanced, and sample sizes for some religious categories were small. Another study limitation was that the analytic approach didn’t account for multilevel data within the context of site and families.

Commenting on the findings, Kathleen Brady, MD, PhD, distinguished university professor and director, South Carolina Clinical and Translational Research Institute, Medical University of South Carolina, said that the study is “critical and complex.” This, she said, is especially true as cannabis has become more accessible and potent, and as the federal government reportedly considers reclassifying it from a Schedule I drug (which includes highly dangerous, addictive substances with no medical use) to a Schedule III drug (which can be prescribed as a medication).

“The part that is the most frightening to me is the long-lasting effects that can happen when young people start using high-potency marijuana at an early age,” said Dr. Brady. “So, any information that we can give to parents, to teachers, to the public, and to doctors is important.”

She’s looking forward to getting more “incredibly important” information on substance use initiation as the study progresses and the teens get older. 

The study received support from the National Institute on Alcohol Abuse and Alcoholism and the National Institute on Drug Abuse.

A version of this article appeared on Medscape.com.

By age 12 years, more than 14% of children have tried alcohol or tobacco, and religion, race, and income are the top predictors beginning to use these and other substances, new research suggests.

Aside from sociodemographic parameters, risk factors for substance use initiation include prenatal exposure to substances, peer use of alcohol and nicotine, and problematic school behavior, among other things, the study showed.

The results show certain modifiable risk factors may play a role in preventing youth from starting to use substances, said study author ReJoyce Green, PhD, research assistant professor, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston.

“If we’re designing, say, a prevention program or an early intervention program, these are things that could make a difference, so let’s make sure we’re bringing them into the conversation.”

The findings were presented at the annual meeting of the American Psychiatric Association American Psychiatric Association (APA) and published online in The American Journal of Psychiatry.
 

Critical Risk Factors

Use of alcohol, tobacco, and cannabis often begins during adolescence. One recent survey showed that 23% of 13-year-olds reported using alcohol, 17% reported vaping nicotine, and 8% reported vaping cannabis. Other research links younger age at substance use initiation to a more rapid transition to substance use disorders and higher rates of psychiatric disorders.

Previous studies examining predictors of substance use initiation in the Adolescent Brain Cognitive Development (ABCD) Study dataset focused primarily on self-reported measures, but the current study also looked at models that include hormones and neurocognitive factors as well as neuroimaging.

This study included 6829, 9- and 10-year-olds from the ABCD Study who had never tried substances and were followed for 3 years.

A sophisticated statistical approach was used to examine 420 variables as predictors of substance use initiation. Initiation was defined as trying any nonprescribed substance by age 12 years. “That’s including a single sip of alcohol or puff of a cigarette,” said Dr. Green.

In addition to alcohol, nicotine, and cannabis, researchers looked at initiation of synthetic cannabinoids, cocaine, methamphetamine, and ketamine, among other substances.

Self-reported measures included demographic characteristics, self and peer involvement with substance use, parenting behaviors, mental and physical health, and culture and environmental factors.

The analytical approach used machine-learning algorithms to compare the ability of domains to identify the most critical risk factors. Magnitudes of coefficients were used to assess variable importance, with positive coefficients indicating greater likelihood of substance initiation and negative coefficients indicating lower likelihood of initiation.

By age 12 years, 14.4% of the children studied reported substance initiation. Alcohol was the substance most commonly initiated (365 individuals), followed by nicotine (94 individuals) and cannabis (40 individuals), with few or no children initiating other substances.

Both those who did and did not initiate substances were similarly aged, and most participants identified as White and non-Hispanic. But the substance-use group had a lower percentage of girls and higher percentage of White participants compared with the no-substance-use group.

The model with only self-reported data had similar accuracy in predicting substance use initiation (area under the curve [AUC], 0.67) as models that added resource-intensive measures such as neurocognitive tests and hormones (AUC, 0.67) and neuroimaging (AUC, 0.66).
 

Religious Predictors

The strongest predictors of substance use initiation were related to religion: Youths whose parents reported a religious preference for Mormonism were less likely to initiate substance use (coefficient, -0.87), whereas youths whose parents reported a religious preference for Judaism were more likely to initiate substance use (coefficient, 0.32).

The third top predictor was race: Black youths were less likely to initiate substance use (coefficient, -0.32). This was followed by youths whose parents reported a religious preference for Islam who were also less likely to initiate substance use (coefficient, -0.25).

The research examined over 15 different religious categories, “so we really tried to be expansive,” noted Dr. Green.

It’s unclear why some religions appeared to have a protective impact when it comes to substance use initiation whereas others have the opposite effect. Future research could perhaps identify which components of religiosity affect substance use initiation. If so, these aspects could be developed and incorporated into prevention and intervention programs, said Dr. Green.

Next on the list of most important predictors was being a part of a household with an income of $12,000-$15,999; these youths were less likely to initiate substance use (coefficient, 0.22).

Within the culture and environment domain, a history of detention or suspension was a top predictor of substance use initiation (coefficient, 0.20). Prenatal exposure to substance use was also a robust predictor in the physical health category (coefficient, 0.15).

Other predictors included: parents with less than a high school degree or GED (coefficient, -0.14), substance use availability (coefficient, 0.12), and age at baseline (coefficient, 0.12).

The study also showed that better cognitive functioning in selected domains (eg, cognitive control, attention, and language ability) is associated with a greater likelihood of substance use initiation.
 

Shaping Future Prevention

Applying these findings in clinical settings could help tailor prevention and early intervention efforts, said the authors. It might be prudent to allocate resources to collecting data related to self-, peer-, and familial-related factors, “which were more informative in predicting substance use initiation during late childhood and early adolescence in the present study,” they wrote.

Researchers will continue to track these children through to a 10-year follow-up, said Dr. Green. “I’m really curious to see if the factors we found when they were 12 and 13, such as those related to peers and family, still hold when they’re ages 17 and 18, because there’s going to be a huge amount of brain development that’s happening throughout this phase.”

The group that initiated substance use and the group that didn’t initiate substance use were not totally balanced, and sample sizes for some religious categories were small. Another study limitation was that the analytic approach didn’t account for multilevel data within the context of site and families.

Commenting on the findings, Kathleen Brady, MD, PhD, distinguished university professor and director, South Carolina Clinical and Translational Research Institute, Medical University of South Carolina, said that the study is “critical and complex.” This, she said, is especially true as cannabis has become more accessible and potent, and as the federal government reportedly considers reclassifying it from a Schedule I drug (which includes highly dangerous, addictive substances with no medical use) to a Schedule III drug (which can be prescribed as a medication).

“The part that is the most frightening to me is the long-lasting effects that can happen when young people start using high-potency marijuana at an early age,” said Dr. Brady. “So, any information that we can give to parents, to teachers, to the public, and to doctors is important.”

She’s looking forward to getting more “incredibly important” information on substance use initiation as the study progresses and the teens get older. 

The study received support from the National Institute on Alcohol Abuse and Alcoholism and the National Institute on Drug Abuse.

A version of this article appeared on Medscape.com.

By age 12 years, more than 14% of children have tried alcohol or tobacco, and religion, race, and income are the top predictors beginning to use these and other substances, new research suggests.

Aside from sociodemographic parameters, risk factors for substance use initiation include prenatal exposure to substances, peer use of alcohol and nicotine, and problematic school behavior, among other things, the study showed.

The results show certain modifiable risk factors may play a role in preventing youth from starting to use substances, said study author ReJoyce Green, PhD, research assistant professor, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston.

“If we’re designing, say, a prevention program or an early intervention program, these are things that could make a difference, so let’s make sure we’re bringing them into the conversation.”

The findings were presented at the annual meeting of the American Psychiatric Association American Psychiatric Association (APA) and published online in The American Journal of Psychiatry.
 

Critical Risk Factors

Use of alcohol, tobacco, and cannabis often begins during adolescence. One recent survey showed that 23% of 13-year-olds reported using alcohol, 17% reported vaping nicotine, and 8% reported vaping cannabis. Other research links younger age at substance use initiation to a more rapid transition to substance use disorders and higher rates of psychiatric disorders.

Previous studies examining predictors of substance use initiation in the Adolescent Brain Cognitive Development (ABCD) Study dataset focused primarily on self-reported measures, but the current study also looked at models that include hormones and neurocognitive factors as well as neuroimaging.

This study included 6829, 9- and 10-year-olds from the ABCD Study who had never tried substances and were followed for 3 years.

A sophisticated statistical approach was used to examine 420 variables as predictors of substance use initiation. Initiation was defined as trying any nonprescribed substance by age 12 years. “That’s including a single sip of alcohol or puff of a cigarette,” said Dr. Green.

In addition to alcohol, nicotine, and cannabis, researchers looked at initiation of synthetic cannabinoids, cocaine, methamphetamine, and ketamine, among other substances.

Self-reported measures included demographic characteristics, self and peer involvement with substance use, parenting behaviors, mental and physical health, and culture and environmental factors.

The analytical approach used machine-learning algorithms to compare the ability of domains to identify the most critical risk factors. Magnitudes of coefficients were used to assess variable importance, with positive coefficients indicating greater likelihood of substance initiation and negative coefficients indicating lower likelihood of initiation.

By age 12 years, 14.4% of the children studied reported substance initiation. Alcohol was the substance most commonly initiated (365 individuals), followed by nicotine (94 individuals) and cannabis (40 individuals), with few or no children initiating other substances.

Both those who did and did not initiate substances were similarly aged, and most participants identified as White and non-Hispanic. But the substance-use group had a lower percentage of girls and higher percentage of White participants compared with the no-substance-use group.

The model with only self-reported data had similar accuracy in predicting substance use initiation (area under the curve [AUC], 0.67) as models that added resource-intensive measures such as neurocognitive tests and hormones (AUC, 0.67) and neuroimaging (AUC, 0.66).
 

Religious Predictors

The strongest predictors of substance use initiation were related to religion: Youths whose parents reported a religious preference for Mormonism were less likely to initiate substance use (coefficient, -0.87), whereas youths whose parents reported a religious preference for Judaism were more likely to initiate substance use (coefficient, 0.32).

The third top predictor was race: Black youths were less likely to initiate substance use (coefficient, -0.32). This was followed by youths whose parents reported a religious preference for Islam who were also less likely to initiate substance use (coefficient, -0.25).

The research examined over 15 different religious categories, “so we really tried to be expansive,” noted Dr. Green.

It’s unclear why some religions appeared to have a protective impact when it comes to substance use initiation whereas others have the opposite effect. Future research could perhaps identify which components of religiosity affect substance use initiation. If so, these aspects could be developed and incorporated into prevention and intervention programs, said Dr. Green.

Next on the list of most important predictors was being a part of a household with an income of $12,000-$15,999; these youths were less likely to initiate substance use (coefficient, 0.22).

Within the culture and environment domain, a history of detention or suspension was a top predictor of substance use initiation (coefficient, 0.20). Prenatal exposure to substance use was also a robust predictor in the physical health category (coefficient, 0.15).

Other predictors included: parents with less than a high school degree or GED (coefficient, -0.14), substance use availability (coefficient, 0.12), and age at baseline (coefficient, 0.12).

The study also showed that better cognitive functioning in selected domains (eg, cognitive control, attention, and language ability) is associated with a greater likelihood of substance use initiation.
 

Shaping Future Prevention

Applying these findings in clinical settings could help tailor prevention and early intervention efforts, said the authors. It might be prudent to allocate resources to collecting data related to self-, peer-, and familial-related factors, “which were more informative in predicting substance use initiation during late childhood and early adolescence in the present study,” they wrote.

Researchers will continue to track these children through to a 10-year follow-up, said Dr. Green. “I’m really curious to see if the factors we found when they were 12 and 13, such as those related to peers and family, still hold when they’re ages 17 and 18, because there’s going to be a huge amount of brain development that’s happening throughout this phase.”

The group that initiated substance use and the group that didn’t initiate substance use were not totally balanced, and sample sizes for some religious categories were small. Another study limitation was that the analytic approach didn’t account for multilevel data within the context of site and families.

Commenting on the findings, Kathleen Brady, MD, PhD, distinguished university professor and director, South Carolina Clinical and Translational Research Institute, Medical University of South Carolina, said that the study is “critical and complex.” This, she said, is especially true as cannabis has become more accessible and potent, and as the federal government reportedly considers reclassifying it from a Schedule I drug (which includes highly dangerous, addictive substances with no medical use) to a Schedule III drug (which can be prescribed as a medication).

“The part that is the most frightening to me is the long-lasting effects that can happen when young people start using high-potency marijuana at an early age,” said Dr. Brady. “So, any information that we can give to parents, to teachers, to the public, and to doctors is important.”

She’s looking forward to getting more “incredibly important” information on substance use initiation as the study progresses and the teens get older. 

The study received support from the National Institute on Alcohol Abuse and Alcoholism and the National Institute on Drug Abuse.

A version of this article appeared on Medscape.com.

Diagnosis: Venous Malformation

Venous malformations are the most common type of congenital vascular malformation. Although present at birth, they are not always clinically evident early in life. They also tend to grow with the child without spontaneous regression, causing potential cosmetic concerns or complications from impingement on surrounding tissue.

Venous malformations appear with a bluish color appearing beneath the skin and can vary significantly in size and severity. Venous malformations are compressible and characterized by low to stagnant blood flow, which can spontaneously thrombose. Clinically, this may cause pain, swelling, skin changes, tissue and limb overgrowth, or functional impairment depending on location and size.

Dr. Lawence Eichenfield

Treatment

Venous malformations rarely regress spontaneously. Treatment is required if venous malformations are symptomatic, which may include pain, swelling, deformity, thrombosis, or interference with daily activities of living. Treatment plans require consideration of patient goals of care. The main categories of therapy are embolization/sclerotherapy, surgical resection, and molecular targeted therapy.

Sclerotherapy is a well-tolerated and efficacious first-line therapy. It can be used as either nonsurgical curative therapy or preoperative adjunct therapy to minimize blood loss before surgical resection. While surgical resection may cause scarring, multimodal approaches with sclerotherapy or laser therapy can decrease complications. Molecular therapies aim to reduce vascular proliferation and symptoms. Referral to hematology/oncology for evaluation and consideration of chemotherapeutic agents may be required. Sirolimus has been shown in mice models to inhibit an endothelial cell tyrosine kinase receptor that plays a role in venous malformation growth. Multiple studies have proved its efficacy in managing complicated vascular anomalies, including venous malformations. Alpelisib is an inhibitor of PI3KCA, which is part of the pathway that contributes to venous malformation formation. Dactolisib, a dual inhibitor of the PI3KA and mTOR pathways, and rebastinib, a TEK inhibitor, are being investigated.

Differential Diagnoses

The differential diagnosis includes dermal melanocytosis, nevus of Ota, hemangioma of infancy, and ashy dermatosis. In addition, venous malformations can be part of more complex vascular malformations.

Dermal melanocytosis, also known as Mongolian spots, are blue-gray patches of discoloration on the skin that appear at birth or shortly after. They result from the arrest of dermal melanocytes in the dermis during fetal life and tissue modeling. They are commonly observed in those of Asian or African descent with darker skin types. Most often, they are located in the lumbar or sacral-gluteal region. Unlike venous malformations, they are benign and do not involve vascular abnormalities. They typically fade over time.

Courtesy University of California, San Diego

Danny Lee and Samuel Le serve as research fellows and Jolina Bui as research associate in the Pediatric Dermatology Division of the Department of Dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is Distinguished Professor of Dermatology and Pediatrics and Vice-Chair of the Department of Dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. The authors have no relevant financial disclosures.

Suggested Reading

Agarwal P, Patel BC. Nevus of Ota and Ito. [Updated 2023 Jul 10]. In: StatPearls [Internet]. StatPearls Publishing; 2024.

Dompmartin A et al. The VASCERN-VASCA Working Group Diagnostic and Management Pathways for Venous Malformations. J Vasc Anom (Phila). 2023 Mar 23;4(2):e064.

Dompmartin A et al. Venous malformation: Update on aetiopathogenesis, diagnosis and management. Phlebology. 2010 Oct;25(5):224-235.

Gupta D, Thappa DM. Mongolian spots. Indian J Dermatol Venereol Leprol. 2013 Jul-Aug;79(4):469-478.

Krowchuk DP et al. Clinical Practice Guideline for the Management of Infantile Hemangiomas. Pediatrics. 2019 Jan;143(1):e20183475.

Nguyen K, Khachemoune A. Ashy dermatosis: A review. Dermatol Online J. 2019 May 15;25(5):13030/qt44f462s8.

Patel ND, Chong AT et al. Venous Malformations. Semin Intervent Radiol. 2022 Dec 20;39(5):498-507.

Diagnosis: Venous Malformation

Venous malformations are the most common type of congenital vascular malformation. Although present at birth, they are not always clinically evident early in life. They also tend to grow with the child without spontaneous regression, causing potential cosmetic concerns or complications from impingement on surrounding tissue.

Venous malformations appear with a bluish color appearing beneath the skin and can vary significantly in size and severity. Venous malformations are compressible and characterized by low to stagnant blood flow, which can spontaneously thrombose. Clinically, this may cause pain, swelling, skin changes, tissue and limb overgrowth, or functional impairment depending on location and size.

Dr. Lawence Eichenfield

Treatment

Venous malformations rarely regress spontaneously. Treatment is required if venous malformations are symptomatic, which may include pain, swelling, deformity, thrombosis, or interference with daily activities of living. Treatment plans require consideration of patient goals of care. The main categories of therapy are embolization/sclerotherapy, surgical resection, and molecular targeted therapy.

Sclerotherapy is a well-tolerated and efficacious first-line therapy. It can be used as either nonsurgical curative therapy or preoperative adjunct therapy to minimize blood loss before surgical resection. While surgical resection may cause scarring, multimodal approaches with sclerotherapy or laser therapy can decrease complications. Molecular therapies aim to reduce vascular proliferation and symptoms. Referral to hematology/oncology for evaluation and consideration of chemotherapeutic agents may be required. Sirolimus has been shown in mice models to inhibit an endothelial cell tyrosine kinase receptor that plays a role in venous malformation growth. Multiple studies have proved its efficacy in managing complicated vascular anomalies, including venous malformations. Alpelisib is an inhibitor of PI3KCA, which is part of the pathway that contributes to venous malformation formation. Dactolisib, a dual inhibitor of the PI3KA and mTOR pathways, and rebastinib, a TEK inhibitor, are being investigated.

Differential Diagnoses

The differential diagnosis includes dermal melanocytosis, nevus of Ota, hemangioma of infancy, and ashy dermatosis. In addition, venous malformations can be part of more complex vascular malformations.

Dermal melanocytosis, also known as Mongolian spots, are blue-gray patches of discoloration on the skin that appear at birth or shortly after. They result from the arrest of dermal melanocytes in the dermis during fetal life and tissue modeling. They are commonly observed in those of Asian or African descent with darker skin types. Most often, they are located in the lumbar or sacral-gluteal region. Unlike venous malformations, they are benign and do not involve vascular abnormalities. They typically fade over time.

Courtesy University of California, San Diego

Danny Lee and Samuel Le serve as research fellows and Jolina Bui as research associate in the Pediatric Dermatology Division of the Department of Dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is Distinguished Professor of Dermatology and Pediatrics and Vice-Chair of the Department of Dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. The authors have no relevant financial disclosures.

Suggested Reading

Agarwal P, Patel BC. Nevus of Ota and Ito. [Updated 2023 Jul 10]. In: StatPearls [Internet]. StatPearls Publishing; 2024.

Dompmartin A et al. The VASCERN-VASCA Working Group Diagnostic and Management Pathways for Venous Malformations. J Vasc Anom (Phila). 2023 Mar 23;4(2):e064.

Dompmartin A et al. Venous malformation: Update on aetiopathogenesis, diagnosis and management. Phlebology. 2010 Oct;25(5):224-235.

Gupta D, Thappa DM. Mongolian spots. Indian J Dermatol Venereol Leprol. 2013 Jul-Aug;79(4):469-478.

Krowchuk DP et al. Clinical Practice Guideline for the Management of Infantile Hemangiomas. Pediatrics. 2019 Jan;143(1):e20183475.

Nguyen K, Khachemoune A. Ashy dermatosis: A review. Dermatol Online J. 2019 May 15;25(5):13030/qt44f462s8.

Patel ND, Chong AT et al. Venous Malformations. Semin Intervent Radiol. 2022 Dec 20;39(5):498-507.

Diagnosis: Venous Malformation

Venous malformations are the most common type of congenital vascular malformation. Although present at birth, they are not always clinically evident early in life. They also tend to grow with the child without spontaneous regression, causing potential cosmetic concerns or complications from impingement on surrounding tissue.

Venous malformations appear with a bluish color appearing beneath the skin and can vary significantly in size and severity. Venous malformations are compressible and characterized by low to stagnant blood flow, which can spontaneously thrombose. Clinically, this may cause pain, swelling, skin changes, tissue and limb overgrowth, or functional impairment depending on location and size.

Dr. Lawence Eichenfield

Treatment

Venous malformations rarely regress spontaneously. Treatment is required if venous malformations are symptomatic, which may include pain, swelling, deformity, thrombosis, or interference with daily activities of living. Treatment plans require consideration of patient goals of care. The main categories of therapy are embolization/sclerotherapy, surgical resection, and molecular targeted therapy.

Sclerotherapy is a well-tolerated and efficacious first-line therapy. It can be used as either nonsurgical curative therapy or preoperative adjunct therapy to minimize blood loss before surgical resection. While surgical resection may cause scarring, multimodal approaches with sclerotherapy or laser therapy can decrease complications. Molecular therapies aim to reduce vascular proliferation and symptoms. Referral to hematology/oncology for evaluation and consideration of chemotherapeutic agents may be required. Sirolimus has been shown in mice models to inhibit an endothelial cell tyrosine kinase receptor that plays a role in venous malformation growth. Multiple studies have proved its efficacy in managing complicated vascular anomalies, including venous malformations. Alpelisib is an inhibitor of PI3KCA, which is part of the pathway that contributes to venous malformation formation. Dactolisib, a dual inhibitor of the PI3KA and mTOR pathways, and rebastinib, a TEK inhibitor, are being investigated.

Differential Diagnoses

The differential diagnosis includes dermal melanocytosis, nevus of Ota, hemangioma of infancy, and ashy dermatosis. In addition, venous malformations can be part of more complex vascular malformations.

Dermal melanocytosis, also known as Mongolian spots, are blue-gray patches of discoloration on the skin that appear at birth or shortly after. They result from the arrest of dermal melanocytes in the dermis during fetal life and tissue modeling. They are commonly observed in those of Asian or African descent with darker skin types. Most often, they are located in the lumbar or sacral-gluteal region. Unlike venous malformations, they are benign and do not involve vascular abnormalities. They typically fade over time.

Courtesy University of California, San Diego

Danny Lee and Samuel Le serve as research fellows and Jolina Bui as research associate in the Pediatric Dermatology Division of the Department of Dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is Distinguished Professor of Dermatology and Pediatrics and Vice-Chair of the Department of Dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. The authors have no relevant financial disclosures.

Suggested Reading

Agarwal P, Patel BC. Nevus of Ota and Ito. [Updated 2023 Jul 10]. In: StatPearls [Internet]. StatPearls Publishing; 2024.

Dompmartin A et al. The VASCERN-VASCA Working Group Diagnostic and Management Pathways for Venous Malformations. J Vasc Anom (Phila). 2023 Mar 23;4(2):e064.

Dompmartin A et al. Venous malformation: Update on aetiopathogenesis, diagnosis and management. Phlebology. 2010 Oct;25(5):224-235.

Gupta D, Thappa DM. Mongolian spots. Indian J Dermatol Venereol Leprol. 2013 Jul-Aug;79(4):469-478.

Krowchuk DP et al. Clinical Practice Guideline for the Management of Infantile Hemangiomas. Pediatrics. 2019 Jan;143(1):e20183475.

Nguyen K, Khachemoune A. Ashy dermatosis: A review. Dermatol Online J. 2019 May 15;25(5):13030/qt44f462s8.

Patel ND, Chong AT et al. Venous Malformations. Semin Intervent Radiol. 2022 Dec 20;39(5):498-507.

TORONTO — Misinformation in pediatric medicine, like other areas of medicine, is widely regarded as a major public health threat, but the good news is that a new survey reveals that pediatricians still believe their counsel is respected by patients and families.

Despite acknowledging that health misinformation is on the rise, “nearly all the pediatricians we surveyed agreed or strongly agreed that their patients consider them a trusted information source,” reported Elizabeth A. Gottschlich, MA, a senior research associate with the American Academy of Pediatrics, Itasca, Illinois.

These data were generated by an ongoing cohort analysis called the Pediatricians Life and Career Experience Study (PLACES). Each year, two surveys are conducted with three groups of pediatricians in this cohort. They are defined by years in which they graduated from residency (2002-2004, 2009-2011, or 2016-2018).

While the longer survey of the two captures an array of issues regarding life and practice, the shorter “checkpoint” survey addresses a high-priority topic. In 2023, it was health misinformation. The data from this survey were presented at the Pediatric Academic Societies annual meeting.

About 40% of the 2706 pediatricians who completed this particular survey (just over 65% of the participants in PLACES) were general pediatricians, 50% were pediatric subspecialists, and 10% were hospitalists.

Almost all of the survey questions were answered on a five-point Likert scale.
 

A Matter of Trust

According to Ms. Gottschlich, approximately 80% of pediatricians agreed or strongly agreed that misinformation is a clinical issue for them. About one third of these strongly agreed, and only 6% disagreed.

There was also strong consensus that the problem has grown worse since the start of the COVID-19 epidemic. To this statement, 70% agreed or strongly agreed and 24% did not agree or disagree. Only 4% disagreed.

However, relatively few respondents appeared to be concerned about the ability of pediatricians to address the problem of misinformation, Ms. Gottschlich reported.

When asked to respond to the statement that the “community recognizes and uses pediatricians as trusted source for health information,” 87% agreed or strongly agreed. Of the remaining, 9% did not agree or disagree, leaving just 4% that disagreed or strongly disagreed.

For a similar but slightly different question, the consensus was even greater. To the statement “patients/families in your practice seek your input as a trusted source for health information,” 94% agreed or strongly agreed.
 

Encountering Misinformation

The survey went on to ask pediatricians about encounters with misinformation for seven specific issues. On the five-point Likert scale, the choices ranged from a few times per year to every day.

For reproductive health, gender-affirming care, and firearm injury prevention, about 80% of respondents answered at the very low end of the scale, meaning no more than about once per month. Encounters with misinformation was slightly greater with autism; nearly one third responded that they encountered misinformation once a week or more frequently.

For all three questions regarding vaccines, the proportions climbed substantially. Of these, the COVID-19 vaccine was the most common topic of misinformation, with more than half reporting that they addressed incorrect information once a week or more. Seven percent reported this occurs daily.

Nearly 40% of pediatricians responded that they dealt with misinformation about the HPV vaccine once per week or more, while 35% reported that they encountered misinformation this frequently about routine childhood vaccines. There was a small but not necessarily trivial proportion for each of these categories of vaccine who reported that they encountered misinformation on a daily basis.

When stratified by clinical focus, the encounters varied. For the COVID-19 vaccine, general pediatricians (67%) were far more likely to report addressing misinformation on a weekly or more frequent basis than hospitalists (39%) or subspecialists (46%). They were more than twice as likely to encounter misinformation about the HPV vaccine than hospitalists or pediatric subspecialists (46%, 17%, and 19%, respectively).

When stratified by urban, suburban, or rural practice areas, differences were relatively modest. Pediatricians in urban practices were less likely to face misinformation about HPV vaccine (29% vs 44% and 48% for suburban and rural areas, respectively), while pediatricians in rural practice were more likely to face misinformation about routine childhood vaccines (60% vs 33% and 35% for urban and suburban practices, respectively).

Differences were even narrower when misinformation encounters were compared among the West, Midwest, South, and Northeast. For the threshold of once per week or more commonly, misinformation about the COVID-19 vaccine was less common in the South (50% vs 55%-58% in the other areas), while misinformation about routine childhood vaccines was more commonly encountered in the West (41% vs 32%-35% in the other areas).
 

A Growing Problem

The confidence among pediatricians that their knowledge is valued is reassuring, according to Ms. Gottschlich, who noted that the U.S. Surgeon General declared health misinformation a serious threat to public health in 2021, but the problem of misinformation is growing, according to several sources.

One of these sources, at least in regard to adolescent health, appears to be social media, according to a recently published review article in JAMA Pediatrics. The lead author of that article, Monica L. Wang, DSc, has dual academic appointments at the Boston University School of Public Health and Harvard University’s T.H. Chan School of Public Health, Boston. Asked for a comment on this issue, she suggested that it might not be enough to just respond to misinformation but rather might be better to develop a dialogue that will reveal misconceptions.

“Just as they screen for preventive issues like seat belt use, sunscreen, and safe sex practices, [pediatricians should integrate] questions about health misinformation into visits, which can be a natural and effective way to encourage dialogue, proactively share accurate information, and promote well-being,” she said.

Agreeing with the premise that pediatricians are a credible source of information for parents and children, Dr. Wang very much endorses the principle that “pediatricians can play a critical role in addressing health misinformation.”

Ms. Gottschlich and Dr. Wang report no potential conflicts of interest.
 

TORONTO — Misinformation in pediatric medicine, like other areas of medicine, is widely regarded as a major public health threat, but the good news is that a new survey reveals that pediatricians still believe their counsel is respected by patients and families.

Despite acknowledging that health misinformation is on the rise, “nearly all the pediatricians we surveyed agreed or strongly agreed that their patients consider them a trusted information source,” reported Elizabeth A. Gottschlich, MA, a senior research associate with the American Academy of Pediatrics, Itasca, Illinois.

These data were generated by an ongoing cohort analysis called the Pediatricians Life and Career Experience Study (PLACES). Each year, two surveys are conducted with three groups of pediatricians in this cohort. They are defined by years in which they graduated from residency (2002-2004, 2009-2011, or 2016-2018).

While the longer survey of the two captures an array of issues regarding life and practice, the shorter “checkpoint” survey addresses a high-priority topic. In 2023, it was health misinformation. The data from this survey were presented at the Pediatric Academic Societies annual meeting.

About 40% of the 2706 pediatricians who completed this particular survey (just over 65% of the participants in PLACES) were general pediatricians, 50% were pediatric subspecialists, and 10% were hospitalists.

Almost all of the survey questions were answered on a five-point Likert scale.
 

A Matter of Trust

According to Ms. Gottschlich, approximately 80% of pediatricians agreed or strongly agreed that misinformation is a clinical issue for them. About one third of these strongly agreed, and only 6% disagreed.

There was also strong consensus that the problem has grown worse since the start of the COVID-19 epidemic. To this statement, 70% agreed or strongly agreed and 24% did not agree or disagree. Only 4% disagreed.

However, relatively few respondents appeared to be concerned about the ability of pediatricians to address the problem of misinformation, Ms. Gottschlich reported.

When asked to respond to the statement that the “community recognizes and uses pediatricians as trusted source for health information,” 87% agreed or strongly agreed. Of the remaining, 9% did not agree or disagree, leaving just 4% that disagreed or strongly disagreed.

For a similar but slightly different question, the consensus was even greater. To the statement “patients/families in your practice seek your input as a trusted source for health information,” 94% agreed or strongly agreed.
 

Encountering Misinformation

The survey went on to ask pediatricians about encounters with misinformation for seven specific issues. On the five-point Likert scale, the choices ranged from a few times per year to every day.

For reproductive health, gender-affirming care, and firearm injury prevention, about 80% of respondents answered at the very low end of the scale, meaning no more than about once per month. Encounters with misinformation was slightly greater with autism; nearly one third responded that they encountered misinformation once a week or more frequently.

For all three questions regarding vaccines, the proportions climbed substantially. Of these, the COVID-19 vaccine was the most common topic of misinformation, with more than half reporting that they addressed incorrect information once a week or more. Seven percent reported this occurs daily.

Nearly 40% of pediatricians responded that they dealt with misinformation about the HPV vaccine once per week or more, while 35% reported that they encountered misinformation this frequently about routine childhood vaccines. There was a small but not necessarily trivial proportion for each of these categories of vaccine who reported that they encountered misinformation on a daily basis.

When stratified by clinical focus, the encounters varied. For the COVID-19 vaccine, general pediatricians (67%) were far more likely to report addressing misinformation on a weekly or more frequent basis than hospitalists (39%) or subspecialists (46%). They were more than twice as likely to encounter misinformation about the HPV vaccine than hospitalists or pediatric subspecialists (46%, 17%, and 19%, respectively).

When stratified by urban, suburban, or rural practice areas, differences were relatively modest. Pediatricians in urban practices were less likely to face misinformation about HPV vaccine (29% vs 44% and 48% for suburban and rural areas, respectively), while pediatricians in rural practice were more likely to face misinformation about routine childhood vaccines (60% vs 33% and 35% for urban and suburban practices, respectively).

Differences were even narrower when misinformation encounters were compared among the West, Midwest, South, and Northeast. For the threshold of once per week or more commonly, misinformation about the COVID-19 vaccine was less common in the South (50% vs 55%-58% in the other areas), while misinformation about routine childhood vaccines was more commonly encountered in the West (41% vs 32%-35% in the other areas).
 

A Growing Problem

The confidence among pediatricians that their knowledge is valued is reassuring, according to Ms. Gottschlich, who noted that the U.S. Surgeon General declared health misinformation a serious threat to public health in 2021, but the problem of misinformation is growing, according to several sources.

One of these sources, at least in regard to adolescent health, appears to be social media, according to a recently published review article in JAMA Pediatrics. The lead author of that article, Monica L. Wang, DSc, has dual academic appointments at the Boston University School of Public Health and Harvard University’s T.H. Chan School of Public Health, Boston. Asked for a comment on this issue, she suggested that it might not be enough to just respond to misinformation but rather might be better to develop a dialogue that will reveal misconceptions.

“Just as they screen for preventive issues like seat belt use, sunscreen, and safe sex practices, [pediatricians should integrate] questions about health misinformation into visits, which can be a natural and effective way to encourage dialogue, proactively share accurate information, and promote well-being,” she said.

Agreeing with the premise that pediatricians are a credible source of information for parents and children, Dr. Wang very much endorses the principle that “pediatricians can play a critical role in addressing health misinformation.”

Ms. Gottschlich and Dr. Wang report no potential conflicts of interest.
 

TORONTO — Misinformation in pediatric medicine, like other areas of medicine, is widely regarded as a major public health threat, but the good news is that a new survey reveals that pediatricians still believe their counsel is respected by patients and families.

Despite acknowledging that health misinformation is on the rise, “nearly all the pediatricians we surveyed agreed or strongly agreed that their patients consider them a trusted information source,” reported Elizabeth A. Gottschlich, MA, a senior research associate with the American Academy of Pediatrics, Itasca, Illinois.

These data were generated by an ongoing cohort analysis called the Pediatricians Life and Career Experience Study (PLACES). Each year, two surveys are conducted with three groups of pediatricians in this cohort. They are defined by years in which they graduated from residency (2002-2004, 2009-2011, or 2016-2018).

While the longer survey of the two captures an array of issues regarding life and practice, the shorter “checkpoint” survey addresses a high-priority topic. In 2023, it was health misinformation. The data from this survey were presented at the Pediatric Academic Societies annual meeting.

About 40% of the 2706 pediatricians who completed this particular survey (just over 65% of the participants in PLACES) were general pediatricians, 50% were pediatric subspecialists, and 10% were hospitalists.

Almost all of the survey questions were answered on a five-point Likert scale.
 

A Matter of Trust

According to Ms. Gottschlich, approximately 80% of pediatricians agreed or strongly agreed that misinformation is a clinical issue for them. About one third of these strongly agreed, and only 6% disagreed.

There was also strong consensus that the problem has grown worse since the start of the COVID-19 epidemic. To this statement, 70% agreed or strongly agreed and 24% did not agree or disagree. Only 4% disagreed.

However, relatively few respondents appeared to be concerned about the ability of pediatricians to address the problem of misinformation, Ms. Gottschlich reported.

When asked to respond to the statement that the “community recognizes and uses pediatricians as trusted source for health information,” 87% agreed or strongly agreed. Of the remaining, 9% did not agree or disagree, leaving just 4% that disagreed or strongly disagreed.

For a similar but slightly different question, the consensus was even greater. To the statement “patients/families in your practice seek your input as a trusted source for health information,” 94% agreed or strongly agreed.
 

Encountering Misinformation

The survey went on to ask pediatricians about encounters with misinformation for seven specific issues. On the five-point Likert scale, the choices ranged from a few times per year to every day.

For reproductive health, gender-affirming care, and firearm injury prevention, about 80% of respondents answered at the very low end of the scale, meaning no more than about once per month. Encounters with misinformation was slightly greater with autism; nearly one third responded that they encountered misinformation once a week or more frequently.

For all three questions regarding vaccines, the proportions climbed substantially. Of these, the COVID-19 vaccine was the most common topic of misinformation, with more than half reporting that they addressed incorrect information once a week or more. Seven percent reported this occurs daily.

Nearly 40% of pediatricians responded that they dealt with misinformation about the HPV vaccine once per week or more, while 35% reported that they encountered misinformation this frequently about routine childhood vaccines. There was a small but not necessarily trivial proportion for each of these categories of vaccine who reported that they encountered misinformation on a daily basis.

When stratified by clinical focus, the encounters varied. For the COVID-19 vaccine, general pediatricians (67%) were far more likely to report addressing misinformation on a weekly or more frequent basis than hospitalists (39%) or subspecialists (46%). They were more than twice as likely to encounter misinformation about the HPV vaccine than hospitalists or pediatric subspecialists (46%, 17%, and 19%, respectively).

When stratified by urban, suburban, or rural practice areas, differences were relatively modest. Pediatricians in urban practices were less likely to face misinformation about HPV vaccine (29% vs 44% and 48% for suburban and rural areas, respectively), while pediatricians in rural practice were more likely to face misinformation about routine childhood vaccines (60% vs 33% and 35% for urban and suburban practices, respectively).

Differences were even narrower when misinformation encounters were compared among the West, Midwest, South, and Northeast. For the threshold of once per week or more commonly, misinformation about the COVID-19 vaccine was less common in the South (50% vs 55%-58% in the other areas), while misinformation about routine childhood vaccines was more commonly encountered in the West (41% vs 32%-35% in the other areas).
 

A Growing Problem

The confidence among pediatricians that their knowledge is valued is reassuring, according to Ms. Gottschlich, who noted that the U.S. Surgeon General declared health misinformation a serious threat to public health in 2021, but the problem of misinformation is growing, according to several sources.

One of these sources, at least in regard to adolescent health, appears to be social media, according to a recently published review article in JAMA Pediatrics. The lead author of that article, Monica L. Wang, DSc, has dual academic appointments at the Boston University School of Public Health and Harvard University’s T.H. Chan School of Public Health, Boston. Asked for a comment on this issue, she suggested that it might not be enough to just respond to misinformation but rather might be better to develop a dialogue that will reveal misconceptions.

“Just as they screen for preventive issues like seat belt use, sunscreen, and safe sex practices, [pediatricians should integrate] questions about health misinformation into visits, which can be a natural and effective way to encourage dialogue, proactively share accurate information, and promote well-being,” she said.

Agreeing with the premise that pediatricians are a credible source of information for parents and children, Dr. Wang very much endorses the principle that “pediatricians can play a critical role in addressing health misinformation.”

Ms. Gottschlich and Dr. Wang report no potential conflicts of interest.
 

Recent newspaper headlines have focused almost exclusively on gender-affirming medical interventions for transgender youth (eg, puberty blockers and gender-affirming hormones like estrogen and testosterone). It is true that these are important treatments that are consistently tied to improvements in mental health. However, an additional powerful predictor of good mental health outcomes for transgender youth is parental support and acceptance.

It is essential that clinicians consider this when creating treatment plans for transgender youth. While transgender young people are struggling with gender dysphoria, their parents are often struggling as well. Sadly, they are often afraid to share their own struggles, despite working through these being essential for their children’s thriving and well-being. I have a few key tips for combating this issue. My upcoming book Free to Be: Understanding Kids & Gender Identity provides much more context for parents and providers, but I will highlight a few big takeaways here.

Stanford Lucille Packard Children&#039;s Hospital.

Give Parents Their Own Space

Many parents have never encountered a transgender person in their life and have a lot of questions. At times, they may be “thinking out loud” and say things in passing that aren’t their final thoughts or opinions on a matter. This can, unfortunately, be damaging to their children. I often speak with adult transgender people whose parents said something they no longer believe (eg, “being trans is just a mental illness – you need therapy to fix it”), but these comments stick in the person’s mind and drive shame and self-esteem challenges later in life, sometimes for decades. Parents need to have a safe space, with a trained professional with expertise in gender, to work through their concerns and questions away from their children, so that when they talk to their kids about gender, they are presenting their fully formed thoughts.

Validate Parents’ Difficult Experiences

As pediatric providers, we are often focused on the difficult experiences of our transgender pediatric patients. However, their parents tend to be struggling as well, and that struggling predicts adverse mental health outcomes for their children.

The most common reaction a parent has upon learning their child is transgender is fear. It’s important to validate this fear (and other feelings that come out), so that parents know they can share with you what’s really going on in their minds.

There are some common themes we see for parents. Some are big fears: fear that their child will be victimized or fear that their child will later regret taking gender-affirming hormones and blame the parents for giving permission to take them. Parents often say they had a gendered vision for what their child’s future would be like, and their child coming out as transgender changes that (it can be helpful to gently remind parents that children almost never grow up exactly how we predict).

Some themes are more mundane but nonetheless distressing for parents, such as not wanting to throw away meaningful souvenirs from past vacations that have their child’s birth name on them. Clinicians can and should validate these thoughts and feelings, while also providing additional context and education. I often recommend the book Found in Transition by Pariah Hassouri, a pediatrician who goes through many of these common struggles after her daughter comes out as transgender.

 

Take a Three-Stage Approach When Adolescents Are Considering Gender-Affirming Medical Interventions

We recently outlined our process for conducting a biopsychosocial assessment for adolescents considering pubertal suppression for adolescent gender dysphoria in The Journal of the American Academy of Child & Adolescent Psychiatry, for those who want more detail on how to conduct these assessments. On the theme of supporting parents, I would highlight the value of taking a three-stage approach. In the first stage, a clinician meets with an adolescent alone to collect their gender history and discuss important considerations regarding the medical intervention. In stage two, the same information about the medical intervention is shared with parents, along with a summary of what the adolescent shared with the clinician (with the adolescent’s consent, of course). Often there will be some areas of disconnect. We make a list of these areas of disconnect that are addressed in stage three, in which the full family is brought together to get everyone on the same page and understanding each other’s perspectives.

Common disconnects include gender dysphoria seeming to “come out of nowhere” from the parents’ perspective, necessitating the young person to recount an early life experience in which they were harassed for expressing gender nonconformity, leading them to act stereotypically in line with their sex assigned at birth for years to avoid being “outed” and harassed more. Conversations around fertility preservation can be particularly complex. Young people and their parents also sometimes have different conceptualizations of gender identity and require a shared framework for talking about gender identity (which I offer in my forthcoming book). This list of family therapy topics can be diverse and highly dependent on the family. An additional resource for this phase of the family therapy is The Family Acceptance Project, which has created culturally tailored materials to help parents understand their sexual and gender minority children.

In summary, fostering healthy family functioning is essential for the care of transgender and gender diverse youth, and parents require support in addition to their children needing support. I encourage all gender providers to incorporate the vital element of family therapy into their practice.

 

Dr. Turban is director of the Gender Psychiatry Program at the University of California, San Francisco, where he is an assistant professor of child & adolescent psychiatry and affiliate faculty at the Philip R. Lee Institute for Health Policy Studies. He is on X @jack_turban.

Recent newspaper headlines have focused almost exclusively on gender-affirming medical interventions for transgender youth (eg, puberty blockers and gender-affirming hormones like estrogen and testosterone). It is true that these are important treatments that are consistently tied to improvements in mental health. However, an additional powerful predictor of good mental health outcomes for transgender youth is parental support and acceptance.

It is essential that clinicians consider this when creating treatment plans for transgender youth. While transgender young people are struggling with gender dysphoria, their parents are often struggling as well. Sadly, they are often afraid to share their own struggles, despite working through these being essential for their children’s thriving and well-being. I have a few key tips for combating this issue. My upcoming book Free to Be: Understanding Kids & Gender Identity provides much more context for parents and providers, but I will highlight a few big takeaways here.

Stanford Lucille Packard Children&#039;s Hospital.

Give Parents Their Own Space

Many parents have never encountered a transgender person in their life and have a lot of questions. At times, they may be “thinking out loud” and say things in passing that aren’t their final thoughts or opinions on a matter. This can, unfortunately, be damaging to their children. I often speak with adult transgender people whose parents said something they no longer believe (eg, “being trans is just a mental illness – you need therapy to fix it”), but these comments stick in the person’s mind and drive shame and self-esteem challenges later in life, sometimes for decades. Parents need to have a safe space, with a trained professional with expertise in gender, to work through their concerns and questions away from their children, so that when they talk to their kids about gender, they are presenting their fully formed thoughts.

Validate Parents’ Difficult Experiences

As pediatric providers, we are often focused on the difficult experiences of our transgender pediatric patients. However, their parents tend to be struggling as well, and that struggling predicts adverse mental health outcomes for their children.

The most common reaction a parent has upon learning their child is transgender is fear. It’s important to validate this fear (and other feelings that come out), so that parents know they can share with you what’s really going on in their minds.

There are some common themes we see for parents. Some are big fears: fear that their child will be victimized or fear that their child will later regret taking gender-affirming hormones and blame the parents for giving permission to take them. Parents often say they had a gendered vision for what their child’s future would be like, and their child coming out as transgender changes that (it can be helpful to gently remind parents that children almost never grow up exactly how we predict).

Some themes are more mundane but nonetheless distressing for parents, such as not wanting to throw away meaningful souvenirs from past vacations that have their child’s birth name on them. Clinicians can and should validate these thoughts and feelings, while also providing additional context and education. I often recommend the book Found in Transition by Pariah Hassouri, a pediatrician who goes through many of these common struggles after her daughter comes out as transgender.

 

Take a Three-Stage Approach When Adolescents Are Considering Gender-Affirming Medical Interventions

We recently outlined our process for conducting a biopsychosocial assessment for adolescents considering pubertal suppression for adolescent gender dysphoria in The Journal of the American Academy of Child & Adolescent Psychiatry, for those who want more detail on how to conduct these assessments. On the theme of supporting parents, I would highlight the value of taking a three-stage approach. In the first stage, a clinician meets with an adolescent alone to collect their gender history and discuss important considerations regarding the medical intervention. In stage two, the same information about the medical intervention is shared with parents, along with a summary of what the adolescent shared with the clinician (with the adolescent’s consent, of course). Often there will be some areas of disconnect. We make a list of these areas of disconnect that are addressed in stage three, in which the full family is brought together to get everyone on the same page and understanding each other’s perspectives.

Common disconnects include gender dysphoria seeming to “come out of nowhere” from the parents’ perspective, necessitating the young person to recount an early life experience in which they were harassed for expressing gender nonconformity, leading them to act stereotypically in line with their sex assigned at birth for years to avoid being “outed” and harassed more. Conversations around fertility preservation can be particularly complex. Young people and their parents also sometimes have different conceptualizations of gender identity and require a shared framework for talking about gender identity (which I offer in my forthcoming book). This list of family therapy topics can be diverse and highly dependent on the family. An additional resource for this phase of the family therapy is The Family Acceptance Project, which has created culturally tailored materials to help parents understand their sexual and gender minority children.

In summary, fostering healthy family functioning is essential for the care of transgender and gender diverse youth, and parents require support in addition to their children needing support. I encourage all gender providers to incorporate the vital element of family therapy into their practice.

 

Dr. Turban is director of the Gender Psychiatry Program at the University of California, San Francisco, where he is an assistant professor of child & adolescent psychiatry and affiliate faculty at the Philip R. Lee Institute for Health Policy Studies. He is on X @jack_turban.

Recent newspaper headlines have focused almost exclusively on gender-affirming medical interventions for transgender youth (eg, puberty blockers and gender-affirming hormones like estrogen and testosterone). It is true that these are important treatments that are consistently tied to improvements in mental health. However, an additional powerful predictor of good mental health outcomes for transgender youth is parental support and acceptance.

It is essential that clinicians consider this when creating treatment plans for transgender youth. While transgender young people are struggling with gender dysphoria, their parents are often struggling as well. Sadly, they are often afraid to share their own struggles, despite working through these being essential for their children’s thriving and well-being. I have a few key tips for combating this issue. My upcoming book Free to Be: Understanding Kids & Gender Identity provides much more context for parents and providers, but I will highlight a few big takeaways here.

Stanford Lucille Packard Children&#039;s Hospital.

Give Parents Their Own Space

Many parents have never encountered a transgender person in their life and have a lot of questions. At times, they may be “thinking out loud” and say things in passing that aren’t their final thoughts or opinions on a matter. This can, unfortunately, be damaging to their children. I often speak with adult transgender people whose parents said something they no longer believe (eg, “being trans is just a mental illness – you need therapy to fix it”), but these comments stick in the person’s mind and drive shame and self-esteem challenges later in life, sometimes for decades. Parents need to have a safe space, with a trained professional with expertise in gender, to work through their concerns and questions away from their children, so that when they talk to their kids about gender, they are presenting their fully formed thoughts.

Validate Parents’ Difficult Experiences

As pediatric providers, we are often focused on the difficult experiences of our transgender pediatric patients. However, their parents tend to be struggling as well, and that struggling predicts adverse mental health outcomes for their children.

The most common reaction a parent has upon learning their child is transgender is fear. It’s important to validate this fear (and other feelings that come out), so that parents know they can share with you what’s really going on in their minds.

There are some common themes we see for parents. Some are big fears: fear that their child will be victimized or fear that their child will later regret taking gender-affirming hormones and blame the parents for giving permission to take them. Parents often say they had a gendered vision for what their child’s future would be like, and their child coming out as transgender changes that (it can be helpful to gently remind parents that children almost never grow up exactly how we predict).

Some themes are more mundane but nonetheless distressing for parents, such as not wanting to throw away meaningful souvenirs from past vacations that have their child’s birth name on them. Clinicians can and should validate these thoughts and feelings, while also providing additional context and education. I often recommend the book Found in Transition by Pariah Hassouri, a pediatrician who goes through many of these common struggles after her daughter comes out as transgender.

 

Take a Three-Stage Approach When Adolescents Are Considering Gender-Affirming Medical Interventions

We recently outlined our process for conducting a biopsychosocial assessment for adolescents considering pubertal suppression for adolescent gender dysphoria in The Journal of the American Academy of Child & Adolescent Psychiatry, for those who want more detail on how to conduct these assessments. On the theme of supporting parents, I would highlight the value of taking a three-stage approach. In the first stage, a clinician meets with an adolescent alone to collect their gender history and discuss important considerations regarding the medical intervention. In stage two, the same information about the medical intervention is shared with parents, along with a summary of what the adolescent shared with the clinician (with the adolescent’s consent, of course). Often there will be some areas of disconnect. We make a list of these areas of disconnect that are addressed in stage three, in which the full family is brought together to get everyone on the same page and understanding each other’s perspectives.

Common disconnects include gender dysphoria seeming to “come out of nowhere” from the parents’ perspective, necessitating the young person to recount an early life experience in which they were harassed for expressing gender nonconformity, leading them to act stereotypically in line with their sex assigned at birth for years to avoid being “outed” and harassed more. Conversations around fertility preservation can be particularly complex. Young people and their parents also sometimes have different conceptualizations of gender identity and require a shared framework for talking about gender identity (which I offer in my forthcoming book). This list of family therapy topics can be diverse and highly dependent on the family. An additional resource for this phase of the family therapy is The Family Acceptance Project, which has created culturally tailored materials to help parents understand their sexual and gender minority children.

In summary, fostering healthy family functioning is essential for the care of transgender and gender diverse youth, and parents require support in addition to their children needing support. I encourage all gender providers to incorporate the vital element of family therapy into their practice.

 

Dr. Turban is director of the Gender Psychiatry Program at the University of California, San Francisco, where he is an assistant professor of child & adolescent psychiatry and affiliate faculty at the Philip R. Lee Institute for Health Policy Studies. He is on X @jack_turban.

DENVER — A retrospective analysis of pediatric patients with Lennox-Gastaut syndrome (LGS) suggests that the antiseizure medication cenobamate (SK Life Sciences) in combination with existing lines of therapy may be associated with fewer hospital in-patient days and emergency room visits. The conclusions were reached by comparing outcomes to patient historical data, though they were not analyzed statistically.

A Proof-of-Concept Study

In an interview, Karen Keough, MD, who presented the study during a poster session at the 2024 annual meeting of the American Academy of Neurology, conceded the key limitation was that the researchers were not able to perform statistical analysis due to the nature of the data. “It’s just showing trends. It’s proof of concept that cenobamate can be effective in one of the most refractory forms of epilepsy, which always includes focal seizures. That’s what led to the initial FDA indication, but we also know that this medication has a lot of promise and is probably going to be effective in other forms of epilepsy and probably in other seizure types,” said Dr. Keough, who is a neurologist at Pediatrix Child Neurology Consultants of Austin, Texas.

Although she has seen significant improvements in many patients, Dr. Keough reported that most patients become refractory again. “Unfortunately, honeymoons are probably real in cenobamate. Continuing to follow those patients as I do, since they’re my own patients, I have quite a few who had more than a year of seizure freedom, [but] their seizures are back, though not as bad as they were before cenobamate. I just can’t get them back to that 100% control category. I do have a few that are still in the 100% control category, but not very many,” she said.

She also presented a retrospective chart review of 36 LGS patients between the ages of 1 and 27 years at the American Epilepsy Society in December 2023, which showed that addition of cenobamate was associated with a reduction in seizure frequency in 85% of patients. “It was a profound number of patients who had long periods of seizure freedom,” she said.
 

A Promising Treatment Option

Dr. Keough is considering moving cenobamate up in the treatment sequence of new LGS patients. “I don’t use cenobamate first line in anyone because we have good first-line agents for simple epilepsy in Lennox-Gastaut, but I’m bringing out cenobamate pretty early in the course, because I do think it has superior efficacy compared with most other drugs that we have available. Most of my patients are very established and they’ve seen lots of other drugs. For many patients, there are only a couple of drugs left on the list that [they] have never tried, but we’re going to put cenobamate at the top of that. For my newer diagnoses, I’m going to bring it out much earlier,” she said, though other drugs such as clobazam (Onfi) would still rank ahead of cenobamate.

The study was drawn from records of the HealthVerity Marketplace Database, which includes more than 150 commercial, Medicare, and Medicaid payers. It included 76 patients aged 17 or under who took at least one antiseizure medication between May 2020 and December 2022, and who had filled at least two prescriptions of cenobamate and had 180 or more days of medical and pharmacy enrollment. The mean age was 13.4 years (5.3% 0-5 years, 15.8% 6-11 years, 78.9% 12-17 years), and 40.8% were female. Seizure types included absence (17.1%), focal (75.0%), and generalized tonic-clonic (86.8%). All patients had a history of intractable seizures, 80.3% had a history of status epilepticus, and 28.9% had a history of infantile seizures. A little more than one fourth (27.6%) of patients had commercial insurance. In the previous 90 days, 21.1% had had an emergency room visit or in-patient hospital stay.

Common antiseizure medications taken with cenobamate included cannabidiol (n = 14), clobazam (n = 8), and levetiracetam (n = 18).

During the cenobamate treatment period, patients had a lower incidence of epilepsy-related inpatient days per year (3.36 vs 3.94), epilepsy-related ER visits per year (0.66 vs 1.19), and likelihood of requiring a new line of epilepsy therapy (35.5% vs 100%).
 

‘Promising’ Results, but More Research Is Needed

The fact that cenobamate was used in combination with other therapies, plus the lack of a control group, makes it difficult to determine if cenobamate was actually responsible for the improvements, according to Nassim Zecavati, MD, who was asked for comment on the study. “I think the results are promising, but there’s obviously a need for a randomized, controlled trial to understand whether it was this medication or the combination of cenobamate with [other medications]. How do we know that this isn’t a compound effect, that it’s multifactorial, and a combination of multiple medications versus the cenobamate?” she said.

Still, she noted that LGS patients are highly vulnerable to hospital admissions and status epilepticus, making the parameters examined in the study valid and important. “I think that this drug likely has a role in the treatment of patients with LGS, particularly pediatric patients. I think we just need more data,” said Dr. Zecavati, who is director of Epilepsy at the Children’s Hospital of Richmond in Virginia and associate professor of Neurology at Virginia Commonwealth University.

Dr. Keough is a speaker for SK Life Sciences. Dr. Zecavati has no relevant financial disclosures.

DENVER — A retrospective analysis of pediatric patients with Lennox-Gastaut syndrome (LGS) suggests that the antiseizure medication cenobamate (SK Life Sciences) in combination with existing lines of therapy may be associated with fewer hospital in-patient days and emergency room visits. The conclusions were reached by comparing outcomes to patient historical data, though they were not analyzed statistically.

A Proof-of-Concept Study

In an interview, Karen Keough, MD, who presented the study during a poster session at the 2024 annual meeting of the American Academy of Neurology, conceded the key limitation was that the researchers were not able to perform statistical analysis due to the nature of the data. “It’s just showing trends. It’s proof of concept that cenobamate can be effective in one of the most refractory forms of epilepsy, which always includes focal seizures. That’s what led to the initial FDA indication, but we also know that this medication has a lot of promise and is probably going to be effective in other forms of epilepsy and probably in other seizure types,” said Dr. Keough, who is a neurologist at Pediatrix Child Neurology Consultants of Austin, Texas.

Although she has seen significant improvements in many patients, Dr. Keough reported that most patients become refractory again. “Unfortunately, honeymoons are probably real in cenobamate. Continuing to follow those patients as I do, since they’re my own patients, I have quite a few who had more than a year of seizure freedom, [but] their seizures are back, though not as bad as they were before cenobamate. I just can’t get them back to that 100% control category. I do have a few that are still in the 100% control category, but not very many,” she said.

She also presented a retrospective chart review of 36 LGS patients between the ages of 1 and 27 years at the American Epilepsy Society in December 2023, which showed that addition of cenobamate was associated with a reduction in seizure frequency in 85% of patients. “It was a profound number of patients who had long periods of seizure freedom,” she said.
 

A Promising Treatment Option

Dr. Keough is considering moving cenobamate up in the treatment sequence of new LGS patients. “I don’t use cenobamate first line in anyone because we have good first-line agents for simple epilepsy in Lennox-Gastaut, but I’m bringing out cenobamate pretty early in the course, because I do think it has superior efficacy compared with most other drugs that we have available. Most of my patients are very established and they’ve seen lots of other drugs. For many patients, there are only a couple of drugs left on the list that [they] have never tried, but we’re going to put cenobamate at the top of that. For my newer diagnoses, I’m going to bring it out much earlier,” she said, though other drugs such as clobazam (Onfi) would still rank ahead of cenobamate.

The study was drawn from records of the HealthVerity Marketplace Database, which includes more than 150 commercial, Medicare, and Medicaid payers. It included 76 patients aged 17 or under who took at least one antiseizure medication between May 2020 and December 2022, and who had filled at least two prescriptions of cenobamate and had 180 or more days of medical and pharmacy enrollment. The mean age was 13.4 years (5.3% 0-5 years, 15.8% 6-11 years, 78.9% 12-17 years), and 40.8% were female. Seizure types included absence (17.1%), focal (75.0%), and generalized tonic-clonic (86.8%). All patients had a history of intractable seizures, 80.3% had a history of status epilepticus, and 28.9% had a history of infantile seizures. A little more than one fourth (27.6%) of patients had commercial insurance. In the previous 90 days, 21.1% had had an emergency room visit or in-patient hospital stay.

Common antiseizure medications taken with cenobamate included cannabidiol (n = 14), clobazam (n = 8), and levetiracetam (n = 18).

During the cenobamate treatment period, patients had a lower incidence of epilepsy-related inpatient days per year (3.36 vs 3.94), epilepsy-related ER visits per year (0.66 vs 1.19), and likelihood of requiring a new line of epilepsy therapy (35.5% vs 100%).
 

‘Promising’ Results, but More Research Is Needed

The fact that cenobamate was used in combination with other therapies, plus the lack of a control group, makes it difficult to determine if cenobamate was actually responsible for the improvements, according to Nassim Zecavati, MD, who was asked for comment on the study. “I think the results are promising, but there’s obviously a need for a randomized, controlled trial to understand whether it was this medication or the combination of cenobamate with [other medications]. How do we know that this isn’t a compound effect, that it’s multifactorial, and a combination of multiple medications versus the cenobamate?” she said.

Still, she noted that LGS patients are highly vulnerable to hospital admissions and status epilepticus, making the parameters examined in the study valid and important. “I think that this drug likely has a role in the treatment of patients with LGS, particularly pediatric patients. I think we just need more data,” said Dr. Zecavati, who is director of Epilepsy at the Children’s Hospital of Richmond in Virginia and associate professor of Neurology at Virginia Commonwealth University.

Dr. Keough is a speaker for SK Life Sciences. Dr. Zecavati has no relevant financial disclosures.

DENVER — A retrospective analysis of pediatric patients with Lennox-Gastaut syndrome (LGS) suggests that the antiseizure medication cenobamate (SK Life Sciences) in combination with existing lines of therapy may be associated with fewer hospital in-patient days and emergency room visits. The conclusions were reached by comparing outcomes to patient historical data, though they were not analyzed statistically.

A Proof-of-Concept Study

In an interview, Karen Keough, MD, who presented the study during a poster session at the 2024 annual meeting of the American Academy of Neurology, conceded the key limitation was that the researchers were not able to perform statistical analysis due to the nature of the data. “It’s just showing trends. It’s proof of concept that cenobamate can be effective in one of the most refractory forms of epilepsy, which always includes focal seizures. That’s what led to the initial FDA indication, but we also know that this medication has a lot of promise and is probably going to be effective in other forms of epilepsy and probably in other seizure types,” said Dr. Keough, who is a neurologist at Pediatrix Child Neurology Consultants of Austin, Texas.

Although she has seen significant improvements in many patients, Dr. Keough reported that most patients become refractory again. “Unfortunately, honeymoons are probably real in cenobamate. Continuing to follow those patients as I do, since they’re my own patients, I have quite a few who had more than a year of seizure freedom, [but] their seizures are back, though not as bad as they were before cenobamate. I just can’t get them back to that 100% control category. I do have a few that are still in the 100% control category, but not very many,” she said.

She also presented a retrospective chart review of 36 LGS patients between the ages of 1 and 27 years at the American Epilepsy Society in December 2023, which showed that addition of cenobamate was associated with a reduction in seizure frequency in 85% of patients. “It was a profound number of patients who had long periods of seizure freedom,” she said.
 

A Promising Treatment Option

Dr. Keough is considering moving cenobamate up in the treatment sequence of new LGS patients. “I don’t use cenobamate first line in anyone because we have good first-line agents for simple epilepsy in Lennox-Gastaut, but I’m bringing out cenobamate pretty early in the course, because I do think it has superior efficacy compared with most other drugs that we have available. Most of my patients are very established and they’ve seen lots of other drugs. For many patients, there are only a couple of drugs left on the list that [they] have never tried, but we’re going to put cenobamate at the top of that. For my newer diagnoses, I’m going to bring it out much earlier,” she said, though other drugs such as clobazam (Onfi) would still rank ahead of cenobamate.

The study was drawn from records of the HealthVerity Marketplace Database, which includes more than 150 commercial, Medicare, and Medicaid payers. It included 76 patients aged 17 or under who took at least one antiseizure medication between May 2020 and December 2022, and who had filled at least two prescriptions of cenobamate and had 180 or more days of medical and pharmacy enrollment. The mean age was 13.4 years (5.3% 0-5 years, 15.8% 6-11 years, 78.9% 12-17 years), and 40.8% were female. Seizure types included absence (17.1%), focal (75.0%), and generalized tonic-clonic (86.8%). All patients had a history of intractable seizures, 80.3% had a history of status epilepticus, and 28.9% had a history of infantile seizures. A little more than one fourth (27.6%) of patients had commercial insurance. In the previous 90 days, 21.1% had had an emergency room visit or in-patient hospital stay.

Common antiseizure medications taken with cenobamate included cannabidiol (n = 14), clobazam (n = 8), and levetiracetam (n = 18).

During the cenobamate treatment period, patients had a lower incidence of epilepsy-related inpatient days per year (3.36 vs 3.94), epilepsy-related ER visits per year (0.66 vs 1.19), and likelihood of requiring a new line of epilepsy therapy (35.5% vs 100%).
 

‘Promising’ Results, but More Research Is Needed

The fact that cenobamate was used in combination with other therapies, plus the lack of a control group, makes it difficult to determine if cenobamate was actually responsible for the improvements, according to Nassim Zecavati, MD, who was asked for comment on the study. “I think the results are promising, but there’s obviously a need for a randomized, controlled trial to understand whether it was this medication or the combination of cenobamate with [other medications]. How do we know that this isn’t a compound effect, that it’s multifactorial, and a combination of multiple medications versus the cenobamate?” she said.

Still, she noted that LGS patients are highly vulnerable to hospital admissions and status epilepticus, making the parameters examined in the study valid and important. “I think that this drug likely has a role in the treatment of patients with LGS, particularly pediatric patients. I think we just need more data,” said Dr. Zecavati, who is director of Epilepsy at the Children’s Hospital of Richmond in Virginia and associate professor of Neurology at Virginia Commonwealth University.

Dr. Keough is a speaker for SK Life Sciences. Dr. Zecavati has no relevant financial disclosures.

SAN DIEGO — In the clinical experience of Kelly M. Cordoro, MD, many pediatric dermatology encounters involve shared decision-making (SDM): a collaborative model in which physicians and patients work together to make health care decisions based on the best evidence and on the patient’s values, priorities, and preferences.

“SDM is a cornerstone of person-centered care,” Dr. Cordoro, professor of dermatology and pediatrics at the University of California, San Francisco, said at the Society for Pediatric Dermatology meeting, held in advance of the annual meeting of the American Academy of Dermatology. “We do it all the time. It can be patient-led, clinician-led, or a patient/family dyad approach. If we do it well, it can improve outcomes. Patients report more satisfying interactions with their care team. It brings adolescent patients especially a sense of independence and they adapt faster to their illness.”

Dr. Cordoro

AHRQ’s Five-Step Approach

The Agency for Healthcare Research and Quality developed a five-step approach to SDM known as SHARE: Seek your patient’s participation; Help your patient explore and compare treatment options; Assess your patient’s values and preferences; Reach a decision with your patient, and Evaluate your patient’s decision. “We do this all the time in practice with adult patients, but may not label it as SDM,” said Dr. Cordoro, chief and fellowship director of pediatric dermatology at UCSF.

“Where it gets a little murkier is in pediatric decision-making, which is a complex type of surrogate decision-making.” In this situation the patient — a minor — does not have full autonomy. The challenge for caregivers is that giving or withholding permission for interventions is a difficult role. “Their job is to protect the patient’s well-being while empowering them toward independence,” she said. “It can be hard for caregivers to understand complex information.” The challenge for clinicians, she continued, is to know when to invite SDM. This requires relational and sharp communication skills. “We must consider our patient’s/family’s health literacy and be sure the information we share is understood,” she said. “What are the social and structural determinants of health that are going to influence decision-making? You want to move into a relationship like this with cultural humility so you can understand what their preferences are and how they’re seeing the problem. Because there’s no universal agreement on the age at which minors should be deemed decision-making competent in health care, the approach is nuanced and depends on each individual patient and family.”

Dr. Cordoro proposed the following four-step approach to SDM to use in pediatric dermatology:

Step 1: Share relevant information about the condition and treatment options in a clear and understandable manner. The average US resident is at the seventh-to eighth-grade level, “so we have to avoid medical jargon and use plain language,” Dr. Cordoro said. Then, use the teach-back approach to assess their understanding. “Ask, ‘What is your understanding of the most important points that we talked about?’ Or, ‘Please share with me what you heard so I’m sure we all understand the plan.’ Using these techniques will reduce the barriers to care such as health literacy.”

Step 2: Solicit and understand patient/patient family perspectives, preferences and priorities. The goal here is to uncover their beliefs, concerns, and assumptions that may influence their decisions. “Be mindful of power asymmetry,” she noted. “Many families still believe the doctor is the boss and they are there to be told what to do. Be clear that the patient has a say. Talk directly to the patient about their interests if developmentally appropriate.”

Step 3: Invite patients/family into a shared decision-making conversation. Consider statements like, “There are many reasonable options here. Let’s work together to come up with the decision that’s right for you.” Or, “Let’s start by exploring your specific goals and concerns. As you think about the options I just talked to you about, what’s important to you?” Or, “Do you want to think about this decision with anyone else?”

Step 4: Check back in frequently. Pause between significant points and check in. “See how they’re doing during the conversation,” she said. “At future appointments, remember to solicit their input on additional decisions.”

In Dr. Cordoro’s opinion, one potential pitfall of SDM is an over-reliance on patient decision aids. “Very few are available in dermatology,” she said. “Some are relevant but none specifically to pediatric dermatology. They are often complex and require a high reading comprehension level. This disadvantages patients and families with low health literacy. Keep it clear and simple. Your patients will appreciate it.”

Dr. Cordoro reported having no relevant disclosures.

SAN DIEGO — In the clinical experience of Kelly M. Cordoro, MD, many pediatric dermatology encounters involve shared decision-making (SDM): a collaborative model in which physicians and patients work together to make health care decisions based on the best evidence and on the patient’s values, priorities, and preferences.

“SDM is a cornerstone of person-centered care,” Dr. Cordoro, professor of dermatology and pediatrics at the University of California, San Francisco, said at the Society for Pediatric Dermatology meeting, held in advance of the annual meeting of the American Academy of Dermatology. “We do it all the time. It can be patient-led, clinician-led, or a patient/family dyad approach. If we do it well, it can improve outcomes. Patients report more satisfying interactions with their care team. It brings adolescent patients especially a sense of independence and they adapt faster to their illness.”

Dr. Cordoro

AHRQ’s Five-Step Approach

The Agency for Healthcare Research and Quality developed a five-step approach to SDM known as SHARE: Seek your patient’s participation; Help your patient explore and compare treatment options; Assess your patient’s values and preferences; Reach a decision with your patient, and Evaluate your patient’s decision. “We do this all the time in practice with adult patients, but may not label it as SDM,” said Dr. Cordoro, chief and fellowship director of pediatric dermatology at UCSF.

“Where it gets a little murkier is in pediatric decision-making, which is a complex type of surrogate decision-making.” In this situation the patient — a minor — does not have full autonomy. The challenge for caregivers is that giving or withholding permission for interventions is a difficult role. “Their job is to protect the patient’s well-being while empowering them toward independence,” she said. “It can be hard for caregivers to understand complex information.” The challenge for clinicians, she continued, is to know when to invite SDM. This requires relational and sharp communication skills. “We must consider our patient’s/family’s health literacy and be sure the information we share is understood,” she said. “What are the social and structural determinants of health that are going to influence decision-making? You want to move into a relationship like this with cultural humility so you can understand what their preferences are and how they’re seeing the problem. Because there’s no universal agreement on the age at which minors should be deemed decision-making competent in health care, the approach is nuanced and depends on each individual patient and family.”

Dr. Cordoro proposed the following four-step approach to SDM to use in pediatric dermatology:

Step 1: Share relevant information about the condition and treatment options in a clear and understandable manner. The average US resident is at the seventh-to eighth-grade level, “so we have to avoid medical jargon and use plain language,” Dr. Cordoro said. Then, use the teach-back approach to assess their understanding. “Ask, ‘What is your understanding of the most important points that we talked about?’ Or, ‘Please share with me what you heard so I’m sure we all understand the plan.’ Using these techniques will reduce the barriers to care such as health literacy.”

Step 2: Solicit and understand patient/patient family perspectives, preferences and priorities. The goal here is to uncover their beliefs, concerns, and assumptions that may influence their decisions. “Be mindful of power asymmetry,” she noted. “Many families still believe the doctor is the boss and they are there to be told what to do. Be clear that the patient has a say. Talk directly to the patient about their interests if developmentally appropriate.”

Step 3: Invite patients/family into a shared decision-making conversation. Consider statements like, “There are many reasonable options here. Let’s work together to come up with the decision that’s right for you.” Or, “Let’s start by exploring your specific goals and concerns. As you think about the options I just talked to you about, what’s important to you?” Or, “Do you want to think about this decision with anyone else?”

Step 4: Check back in frequently. Pause between significant points and check in. “See how they’re doing during the conversation,” she said. “At future appointments, remember to solicit their input on additional decisions.”

In Dr. Cordoro’s opinion, one potential pitfall of SDM is an over-reliance on patient decision aids. “Very few are available in dermatology,” she said. “Some are relevant but none specifically to pediatric dermatology. They are often complex and require a high reading comprehension level. This disadvantages patients and families with low health literacy. Keep it clear and simple. Your patients will appreciate it.”

Dr. Cordoro reported having no relevant disclosures.

SAN DIEGO — In the clinical experience of Kelly M. Cordoro, MD, many pediatric dermatology encounters involve shared decision-making (SDM): a collaborative model in which physicians and patients work together to make health care decisions based on the best evidence and on the patient’s values, priorities, and preferences.

“SDM is a cornerstone of person-centered care,” Dr. Cordoro, professor of dermatology and pediatrics at the University of California, San Francisco, said at the Society for Pediatric Dermatology meeting, held in advance of the annual meeting of the American Academy of Dermatology. “We do it all the time. It can be patient-led, clinician-led, or a patient/family dyad approach. If we do it well, it can improve outcomes. Patients report more satisfying interactions with their care team. It brings adolescent patients especially a sense of independence and they adapt faster to their illness.”

Dr. Cordoro

AHRQ’s Five-Step Approach

The Agency for Healthcare Research and Quality developed a five-step approach to SDM known as SHARE: Seek your patient’s participation; Help your patient explore and compare treatment options; Assess your patient’s values and preferences; Reach a decision with your patient, and Evaluate your patient’s decision. “We do this all the time in practice with adult patients, but may not label it as SDM,” said Dr. Cordoro, chief and fellowship director of pediatric dermatology at UCSF.

“Where it gets a little murkier is in pediatric decision-making, which is a complex type of surrogate decision-making.” In this situation the patient — a minor — does not have full autonomy. The challenge for caregivers is that giving or withholding permission for interventions is a difficult role. “Their job is to protect the patient’s well-being while empowering them toward independence,” she said. “It can be hard for caregivers to understand complex information.” The challenge for clinicians, she continued, is to know when to invite SDM. This requires relational and sharp communication skills. “We must consider our patient’s/family’s health literacy and be sure the information we share is understood,” she said. “What are the social and structural determinants of health that are going to influence decision-making? You want to move into a relationship like this with cultural humility so you can understand what their preferences are and how they’re seeing the problem. Because there’s no universal agreement on the age at which minors should be deemed decision-making competent in health care, the approach is nuanced and depends on each individual patient and family.”

Dr. Cordoro proposed the following four-step approach to SDM to use in pediatric dermatology:

Step 1: Share relevant information about the condition and treatment options in a clear and understandable manner. The average US resident is at the seventh-to eighth-grade level, “so we have to avoid medical jargon and use plain language,” Dr. Cordoro said. Then, use the teach-back approach to assess their understanding. “Ask, ‘What is your understanding of the most important points that we talked about?’ Or, ‘Please share with me what you heard so I’m sure we all understand the plan.’ Using these techniques will reduce the barriers to care such as health literacy.”

Step 2: Solicit and understand patient/patient family perspectives, preferences and priorities. The goal here is to uncover their beliefs, concerns, and assumptions that may influence their decisions. “Be mindful of power asymmetry,” she noted. “Many families still believe the doctor is the boss and they are there to be told what to do. Be clear that the patient has a say. Talk directly to the patient about their interests if developmentally appropriate.”

Step 3: Invite patients/family into a shared decision-making conversation. Consider statements like, “There are many reasonable options here. Let’s work together to come up with the decision that’s right for you.” Or, “Let’s start by exploring your specific goals and concerns. As you think about the options I just talked to you about, what’s important to you?” Or, “Do you want to think about this decision with anyone else?”

Step 4: Check back in frequently. Pause between significant points and check in. “See how they’re doing during the conversation,” she said. “At future appointments, remember to solicit their input on additional decisions.”

In Dr. Cordoro’s opinion, one potential pitfall of SDM is an over-reliance on patient decision aids. “Very few are available in dermatology,” she said. “Some are relevant but none specifically to pediatric dermatology. They are often complex and require a high reading comprehension level. This disadvantages patients and families with low health literacy. Keep it clear and simple. Your patients will appreciate it.”

Dr. Cordoro reported having no relevant disclosures.