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Customized Video Games Promising for ADHD, Depression, in Children
, 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.
, 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.
, 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.
FROM APA 2024
New mRNA Vaccines in Development for Cancer and Infections
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.
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.
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.
Can a Risk Score Predict Kidney Injury After Cisplatin?
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.
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.
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.
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.
FROM THE BMJ
Top Predictors of Substance Initiation in Youth Flagged
, 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.
, 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.
, 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.
FROM APA 2024
A 6-Year-Old Female Presents With a Bruise-Like Lesion on the Lip, Tongue, and Chin Area Present Since Birth
Diagnosis: Venous 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.
Venous malformations result from disorganized angiogenesis secondary to sporadic mutations in somatic cells. The most common implicated gene is TEK, a receptor tyrosine kinase. PIK3CA has also been involved. Both genes are involved in the PI3K/AKT/mTOR pathway, which regulates cell growth, proliferation, and angiogenesis. In venous endothelial cells, abnormal angiogenesis and vessel maturation may lead to venous malformation formation. Dysplastic vessels frequently separate from normal veins but may be contiguous with the deep venous system.
Diagnosis involves clinical history and physical examination. Imaging with ultrasound and magnetic resonance imaging (MRI) may be utilized. While ultrasound may be preferred for superficial venous malformations, MRI or MRI with MR angiography (MRA) is the preferred method for venous malformation assessment. Genetic testing may be appropriate for complex malformations, as classification of lesions by underlying mutation may allow targeted therapy.
This patient’s past MRI and MRA findings were consistent with a venous malformation.
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.
Nevus of Ota is a benign congenital condition that presents with blue-gray or brown patches of pigmentation on the skin around the eyes, cheeks, and forehead. They are dermal melanocytes with a speckled instead of uniform appearance. Nevus of Ota primarily affects individuals of Asian descent and typically presents in the trigeminal nerve distribution region. Treatment can be done to minimize deformity, generally with pigmented laser surgery.
Hemangiomas of infancy are common benign tumors of infancy caused by endothelial cell proliferation. They are characterized by rapid growth followed by spontaneous involution within the first year of life and for several years. Hemangiomas can be superficial, deep, or mixed with features of both superficial and deep. Superficial hemangiomas present as raised, lobulated, and bright red while deep hemangiomas present as a bluish-hued nodule, plaque, or tumor. They are diagnosed clinically but skin biopsies and imaging can confirm the suspected diagnosis. While hemangiomas may self-resolve, complicated hemangiomas can be treated with topical timolol, oral propranolol, topical and intralesional corticosteroids, pulsed-dye laser, and surgical resection.
Ashy dermatosis is a term for asymptomatic, gray-blue or ashy patches distributed symmetrically on the trunk, head, neck, and upper extremities. It primarily affects individuals with darker skin types (Fitzpatrick III-V), and is more common in patients with Hispanic, Asian, or African backgrounds. The direct cause of ashy dermatosis is unknown but it is thought to be linked to drug ingestion, genetics, infection, and immune-mediated mechanisms. The general treatment includes topical corticosteroids, clofazimine, topical calcineurin inhibitors, oral dapsone, phototherapy, topical retinoids, or isotretinoin to reduce inflammation and pigmentation.
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
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.
Venous malformations result from disorganized angiogenesis secondary to sporadic mutations in somatic cells. The most common implicated gene is TEK, a receptor tyrosine kinase. PIK3CA has also been involved. Both genes are involved in the PI3K/AKT/mTOR pathway, which regulates cell growth, proliferation, and angiogenesis. In venous endothelial cells, abnormal angiogenesis and vessel maturation may lead to venous malformation formation. Dysplastic vessels frequently separate from normal veins but may be contiguous with the deep venous system.
Diagnosis involves clinical history and physical examination. Imaging with ultrasound and magnetic resonance imaging (MRI) may be utilized. While ultrasound may be preferred for superficial venous malformations, MRI or MRI with MR angiography (MRA) is the preferred method for venous malformation assessment. Genetic testing may be appropriate for complex malformations, as classification of lesions by underlying mutation may allow targeted therapy.
This patient’s past MRI and MRA findings were consistent with a venous malformation.
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.
Nevus of Ota is a benign congenital condition that presents with blue-gray or brown patches of pigmentation on the skin around the eyes, cheeks, and forehead. They are dermal melanocytes with a speckled instead of uniform appearance. Nevus of Ota primarily affects individuals of Asian descent and typically presents in the trigeminal nerve distribution region. Treatment can be done to minimize deformity, generally with pigmented laser surgery.
Hemangiomas of infancy are common benign tumors of infancy caused by endothelial cell proliferation. They are characterized by rapid growth followed by spontaneous involution within the first year of life and for several years. Hemangiomas can be superficial, deep, or mixed with features of both superficial and deep. Superficial hemangiomas present as raised, lobulated, and bright red while deep hemangiomas present as a bluish-hued nodule, plaque, or tumor. They are diagnosed clinically but skin biopsies and imaging can confirm the suspected diagnosis. While hemangiomas may self-resolve, complicated hemangiomas can be treated with topical timolol, oral propranolol, topical and intralesional corticosteroids, pulsed-dye laser, and surgical resection.
Ashy dermatosis is a term for asymptomatic, gray-blue or ashy patches distributed symmetrically on the trunk, head, neck, and upper extremities. It primarily affects individuals with darker skin types (Fitzpatrick III-V), and is more common in patients with Hispanic, Asian, or African backgrounds. The direct cause of ashy dermatosis is unknown but it is thought to be linked to drug ingestion, genetics, infection, and immune-mediated mechanisms. The general treatment includes topical corticosteroids, clofazimine, topical calcineurin inhibitors, oral dapsone, phototherapy, topical retinoids, or isotretinoin to reduce inflammation and pigmentation.
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
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.
Venous malformations result from disorganized angiogenesis secondary to sporadic mutations in somatic cells. The most common implicated gene is TEK, a receptor tyrosine kinase. PIK3CA has also been involved. Both genes are involved in the PI3K/AKT/mTOR pathway, which regulates cell growth, proliferation, and angiogenesis. In venous endothelial cells, abnormal angiogenesis and vessel maturation may lead to venous malformation formation. Dysplastic vessels frequently separate from normal veins but may be contiguous with the deep venous system.
Diagnosis involves clinical history and physical examination. Imaging with ultrasound and magnetic resonance imaging (MRI) may be utilized. While ultrasound may be preferred for superficial venous malformations, MRI or MRI with MR angiography (MRA) is the preferred method for venous malformation assessment. Genetic testing may be appropriate for complex malformations, as classification of lesions by underlying mutation may allow targeted therapy.
This patient’s past MRI and MRA findings were consistent with a venous malformation.
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.
Nevus of Ota is a benign congenital condition that presents with blue-gray or brown patches of pigmentation on the skin around the eyes, cheeks, and forehead. They are dermal melanocytes with a speckled instead of uniform appearance. Nevus of Ota primarily affects individuals of Asian descent and typically presents in the trigeminal nerve distribution region. Treatment can be done to minimize deformity, generally with pigmented laser surgery.
Hemangiomas of infancy are common benign tumors of infancy caused by endothelial cell proliferation. They are characterized by rapid growth followed by spontaneous involution within the first year of life and for several years. Hemangiomas can be superficial, deep, or mixed with features of both superficial and deep. Superficial hemangiomas present as raised, lobulated, and bright red while deep hemangiomas present as a bluish-hued nodule, plaque, or tumor. They are diagnosed clinically but skin biopsies and imaging can confirm the suspected diagnosis. While hemangiomas may self-resolve, complicated hemangiomas can be treated with topical timolol, oral propranolol, topical and intralesional corticosteroids, pulsed-dye laser, and surgical resection.
Ashy dermatosis is a term for asymptomatic, gray-blue or ashy patches distributed symmetrically on the trunk, head, neck, and upper extremities. It primarily affects individuals with darker skin types (Fitzpatrick III-V), and is more common in patients with Hispanic, Asian, or African backgrounds. The direct cause of ashy dermatosis is unknown but it is thought to be linked to drug ingestion, genetics, infection, and immune-mediated mechanisms. The general treatment includes topical corticosteroids, clofazimine, topical calcineurin inhibitors, oral dapsone, phototherapy, topical retinoids, or isotretinoin to reduce inflammation and pigmentation.
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.
A 6-year-old girl presents with a bruise-like lesion on the lip, tongue, and chin area present since birth. The family states that her tongue has been increasing in size and is painful. On physical exam, she presents with left lower mucosal lip fullness and an overlying violaceous hue extending into the oral mucosa and onto the left tongue. The left portion of the dorsal tongue displays an increased thickness and bluish discoloration and there is a pink, smooth papule on the left anterolateral tongue.
Pediatrician Credibility Remains Intact in Midst of Health Misinformation
TORONTO —
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 —
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 —
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.
FROM PAS 2024
The Importance of Family Therapy for Transgender Youth
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. 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.
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. 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.
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. 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.
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.
For Pediatric LGS, Cenobamate Shows Promise
DENVER — 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 — 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 — 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.
FROM AAN 2024
Consider a Four-Step Approach to Shared Decision-Making in Pediatric Dermatology
SAN DIEGO — In the clinical experience of Kelly M. Cordoro, MD, .
“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.”
Conditions such as acne, psoriasis, and atopic dermatitis have multiple treatment options, often without a single best choice. The ideal treatment depends on disease characteristics (extent, sites affected, symptoms, and natural history), the patient (age, comorbidities, overall disease burden), therapies (safety, efficacy, duration, and adverse events), and preferences (logistics, time, shots vs. pills, etc.). “These factors vary between patients and within the same patient over time, and at each step along the course of the condition, SDM approaches are relevant,” she said.
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, .
“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.”
Conditions such as acne, psoriasis, and atopic dermatitis have multiple treatment options, often without a single best choice. The ideal treatment depends on disease characteristics (extent, sites affected, symptoms, and natural history), the patient (age, comorbidities, overall disease burden), therapies (safety, efficacy, duration, and adverse events), and preferences (logistics, time, shots vs. pills, etc.). “These factors vary between patients and within the same patient over time, and at each step along the course of the condition, SDM approaches are relevant,” she said.
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, .
“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.”
Conditions such as acne, psoriasis, and atopic dermatitis have multiple treatment options, often without a single best choice. The ideal treatment depends on disease characteristics (extent, sites affected, symptoms, and natural history), the patient (age, comorbidities, overall disease burden), therapies (safety, efficacy, duration, and adverse events), and preferences (logistics, time, shots vs. pills, etc.). “These factors vary between patients and within the same patient over time, and at each step along the course of the condition, SDM approaches are relevant,” she said.
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.
FROM AAD 2024
High-Quality Diet in Early Life May Ward Off Later IBD
, prospective pooled data from two Scandinavian birth cohorts suggested.
It appears important to feed children a quality diet at a very young age, in particular one rich in vegetables and fish, since by age three, only dietary fish intake had any impact on IBD risk.
Although high intakes of these two food categories in very early life correlated with lower IBD risk, exposure to sugar-sweetened beverages (SSBs) was associated with an increased risk. “While non-causal explanations for our results cannot be ruled out, these novel findings are consistent with the hypothesis that early-life diet, possibly mediated through changes in the gut microbiome, may affect the risk of developing IBD,” wrote lead author Annie Guo, a PhD candidate in the Department of Pediatrics, University of Gothenburg, Sweden, and colleagues. The report was published in Gut.
“This is a population-based study investigating the risk for IBD, rather than the specific effect of diet,” Ms. Guo said in an interview. “Therefore, the results are not enough on their own to be translated into individual advice that can be applicable in the clinic. However, the study supports current dietary guidelines for small children, that is, the intake of sugar should be limited and a higher intake of fish and vegetables is beneficial for overall health.”
Two-Cohort Study
The investigators prospectively recorded food-group information on children (just under half were female) from the All Babies in Southeast Sweden and The Norwegian Mother, Father and Child Cohort Study to assess the diet quality using a Healthy Eating Index and intake frequency. Parents answered questions about their offspring’s diet at ages 12-18 months and 30-36 months. Quality of diet was measured by intake of meat, fish, fruit, vegetables, dairy, sweets, snacks, and drinks.
The Swedish cohort included 21,700 children born between October 1997 and October 1999, while the Norwegian analysis included 114,500 children, 95,200 mothers, and 75,200 fathers recruited from across Norway from 1999 to 2008. In 1,304,433 person-years of follow-up, the researchers tracked 81,280 participants from birth to childhood and adolescence, with median follow-ups in the two cohorts ranging from 1 year of age to 21.3 years (Sweden) and to 15.2 years of age (Norway). Of these children, 307 were diagnosed with IBD: Crohn’s disease (CD; n = 131); ulcerative colitis (UC; n = 97); and IBD unclassified (n = 79).
Adjusting for parental IBD history, sex, origin, education, and maternal comorbidities, the study found:
- Compared with low-quality diet, both medium- and high-quality diets at 1 year were associated with a roughly 25% reduced risk for IBD (pooled adjusted hazard ratio [aHR], 0.75 [95% CI, 0.58-0.98] and 0.75 [0.56-1.0], respectively).
- The pooled aHR per increase of category was 0.86 (95% CI, 0.74-0.99). The pooled aHR for IBD in 1-year-olds with high vs low fish intake was 0.70 (95% CI, 0.49-1.0), and this diet showed an association with a reduced risk for UC (pooled aHR, 0.46; 95% CI, 0.21-0.99). Higher vegetable intake at 1 year was also associated with a risk reduction in IBD (HR, 0.72; 95% CI, 0.55-0.95). It has been hypothesized that intake of vegetables and vegetable fibers may have programming effects on the immune system.
- AutoWith 72% of children reportedly consuming SSBs at age 1, pooled aHRs showed that some vs no intake of SSBs was associated with an increased risk for later IBD (pooled aHR, 1.42; 95% CI, 1.05-1.90).
- There were no obvious associations between overall IBD or CD/UC risk and meat, dairy, fruit, grains, potatoes, and foods high in sugar and/or fat. Diet at age 3 years was not associated with incident IBD (pooled aHR, 1.02; 95% CI, 0.76-1.37), suggesting that the risk impact of diet is greatest on very young and vulnerable microbiomes.
Ms. Guo noted that a Swedish national survey among 4-year-olds found a mean SSB consumption of 187 g/d with a mean frequency of once daily. The most desired changes in food habits are a lower intake of soft drinks, sweets, crisps, cakes, and biscuits and an increase in the intake of fruits and vegetables. A similar Norwegian survey among 2-year-olds showed that SSBs were consumed by 36% of all children with a mean intake of 40 g/d.
The exact mechanism by which sugar affects the intestinal microbiota is not established. “However, what we do know is that an excessive intake of sugar can disrupt the balance of the gut microbiome,” Ms. Guo said. “And if the child has a high intake of foods with high in sugar, that also increases the chances that the child’s overall diet has a lower intake of other foods that contribute to a diverse microbiome such as fruits and vegetables.”
An ‘Elegant’ Study
In an accompanying editorial, gastroenterologist Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, of Mass General Brigham and the Mass General Research Institute, Boston, cautioned that accurately measuring food intake in very young children is difficult, and dietary questionnaires in this study did not address food additives and emulsifiers common in commercial baby food, which may play a role in the pathogenesis of IBD.
Another study limitation is that the dietary questionnaire used has not been qualitatively or quantitatively validated against other more conventional methods, said Dr. Ananthakrishnan, who was not involved in the research.
Nevertheless, he called the study “elegant” and expanding of the data on the importance of this period in IBD development. “Although in the present study there was no association between diet at 3 years and development of IBD (in contrast to the association observed for dietary intake at 1 year), other prospective cohorts of adult-onset IBD have demonstrated an inverse association between vegetable or fish intake and reduced risk for CD while sugar-sweetened beverages have been linked to a higher risk for IBD.”
As to the question of recommending early preventive diet for IBD, “thus far, data on the impact of diet very early in childhood, outside of breastfeeding, on the risk for IBD has been lacking,” Dr. Ananthakrishnan said in an interview. “This important study highlights that diet as early as 1 year can modify subsequent risk for IBD. This raises the intriguing possibility of whether early changes in diet could be used, particularly in those at higher risk, to reduce or even prevent future development of IBD. Of course, more works needs to be done to define modifiability of diet as a risk factor, but this is an important supportive data.”
In his editorial, Dr. Ananthakrishnan stated that despite the absence of gold-standard interventional data demonstrating a benefit of dietary interventions, “in my opinion, it may still be reasonable to suggest such interventions to motivate individuals who incorporate several of the dietary patterns associated with lower risk for IBD from this and other studies. This includes ensuring adequate dietary fiber, particularly from fruits and vegetables, intake of fish, minimizing sugar-sweetened beverages and preferring fresh over processed and ultra-processed foods and snacks.” According to the study authors, their novel findings support further research on the role of childhood diet in the prevention of IBD.
The All Babies in Southeast Sweden Study is supported by Barndiabetesfonden (Swedish Child Diabetes Foundation), the Swedish Council for Working Life and Social Research, the Swedish Research Council, the Medical Research Council of Southeast Sweden, the JDRF Wallenberg Foundation, ALF and LFoU grants from Region Östergötland and Linköping University, and the Joanna Cocozza Foundation.
The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research.
Ms. Guo received grants from the Swedish Society for Medical Research and the Henning and Johan Throne-Holst Foundation to conduct this study. Co-author Karl Mårild has received funding from the Swedish Society for Medical Research, the Swedish Research Council, and ALF, Sweden’s medical research and education co-ordinating body. The authors declared no competing interests. Dr. Ananthakrishnan is supported by the National Institutes of Health, the Leona M. and Harry B. Helmsley Charitable Trust, and the Chleck Family Foundation. He has served on the scientific advisory board for Geneoscopy.
, prospective pooled data from two Scandinavian birth cohorts suggested.
It appears important to feed children a quality diet at a very young age, in particular one rich in vegetables and fish, since by age three, only dietary fish intake had any impact on IBD risk.
Although high intakes of these two food categories in very early life correlated with lower IBD risk, exposure to sugar-sweetened beverages (SSBs) was associated with an increased risk. “While non-causal explanations for our results cannot be ruled out, these novel findings are consistent with the hypothesis that early-life diet, possibly mediated through changes in the gut microbiome, may affect the risk of developing IBD,” wrote lead author Annie Guo, a PhD candidate in the Department of Pediatrics, University of Gothenburg, Sweden, and colleagues. The report was published in Gut.
“This is a population-based study investigating the risk for IBD, rather than the specific effect of diet,” Ms. Guo said in an interview. “Therefore, the results are not enough on their own to be translated into individual advice that can be applicable in the clinic. However, the study supports current dietary guidelines for small children, that is, the intake of sugar should be limited and a higher intake of fish and vegetables is beneficial for overall health.”
Two-Cohort Study
The investigators prospectively recorded food-group information on children (just under half were female) from the All Babies in Southeast Sweden and The Norwegian Mother, Father and Child Cohort Study to assess the diet quality using a Healthy Eating Index and intake frequency. Parents answered questions about their offspring’s diet at ages 12-18 months and 30-36 months. Quality of diet was measured by intake of meat, fish, fruit, vegetables, dairy, sweets, snacks, and drinks.
The Swedish cohort included 21,700 children born between October 1997 and October 1999, while the Norwegian analysis included 114,500 children, 95,200 mothers, and 75,200 fathers recruited from across Norway from 1999 to 2008. In 1,304,433 person-years of follow-up, the researchers tracked 81,280 participants from birth to childhood and adolescence, with median follow-ups in the two cohorts ranging from 1 year of age to 21.3 years (Sweden) and to 15.2 years of age (Norway). Of these children, 307 were diagnosed with IBD: Crohn’s disease (CD; n = 131); ulcerative colitis (UC; n = 97); and IBD unclassified (n = 79).
Adjusting for parental IBD history, sex, origin, education, and maternal comorbidities, the study found:
- Compared with low-quality diet, both medium- and high-quality diets at 1 year were associated with a roughly 25% reduced risk for IBD (pooled adjusted hazard ratio [aHR], 0.75 [95% CI, 0.58-0.98] and 0.75 [0.56-1.0], respectively).
- The pooled aHR per increase of category was 0.86 (95% CI, 0.74-0.99). The pooled aHR for IBD in 1-year-olds with high vs low fish intake was 0.70 (95% CI, 0.49-1.0), and this diet showed an association with a reduced risk for UC (pooled aHR, 0.46; 95% CI, 0.21-0.99). Higher vegetable intake at 1 year was also associated with a risk reduction in IBD (HR, 0.72; 95% CI, 0.55-0.95). It has been hypothesized that intake of vegetables and vegetable fibers may have programming effects on the immune system.
- AutoWith 72% of children reportedly consuming SSBs at age 1, pooled aHRs showed that some vs no intake of SSBs was associated with an increased risk for later IBD (pooled aHR, 1.42; 95% CI, 1.05-1.90).
- There were no obvious associations between overall IBD or CD/UC risk and meat, dairy, fruit, grains, potatoes, and foods high in sugar and/or fat. Diet at age 3 years was not associated with incident IBD (pooled aHR, 1.02; 95% CI, 0.76-1.37), suggesting that the risk impact of diet is greatest on very young and vulnerable microbiomes.
Ms. Guo noted that a Swedish national survey among 4-year-olds found a mean SSB consumption of 187 g/d with a mean frequency of once daily. The most desired changes in food habits are a lower intake of soft drinks, sweets, crisps, cakes, and biscuits and an increase in the intake of fruits and vegetables. A similar Norwegian survey among 2-year-olds showed that SSBs were consumed by 36% of all children with a mean intake of 40 g/d.
The exact mechanism by which sugar affects the intestinal microbiota is not established. “However, what we do know is that an excessive intake of sugar can disrupt the balance of the gut microbiome,” Ms. Guo said. “And if the child has a high intake of foods with high in sugar, that also increases the chances that the child’s overall diet has a lower intake of other foods that contribute to a diverse microbiome such as fruits and vegetables.”
An ‘Elegant’ Study
In an accompanying editorial, gastroenterologist Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, of Mass General Brigham and the Mass General Research Institute, Boston, cautioned that accurately measuring food intake in very young children is difficult, and dietary questionnaires in this study did not address food additives and emulsifiers common in commercial baby food, which may play a role in the pathogenesis of IBD.
Another study limitation is that the dietary questionnaire used has not been qualitatively or quantitatively validated against other more conventional methods, said Dr. Ananthakrishnan, who was not involved in the research.
Nevertheless, he called the study “elegant” and expanding of the data on the importance of this period in IBD development. “Although in the present study there was no association between diet at 3 years and development of IBD (in contrast to the association observed for dietary intake at 1 year), other prospective cohorts of adult-onset IBD have demonstrated an inverse association between vegetable or fish intake and reduced risk for CD while sugar-sweetened beverages have been linked to a higher risk for IBD.”
As to the question of recommending early preventive diet for IBD, “thus far, data on the impact of diet very early in childhood, outside of breastfeeding, on the risk for IBD has been lacking,” Dr. Ananthakrishnan said in an interview. “This important study highlights that diet as early as 1 year can modify subsequent risk for IBD. This raises the intriguing possibility of whether early changes in diet could be used, particularly in those at higher risk, to reduce or even prevent future development of IBD. Of course, more works needs to be done to define modifiability of diet as a risk factor, but this is an important supportive data.”
In his editorial, Dr. Ananthakrishnan stated that despite the absence of gold-standard interventional data demonstrating a benefit of dietary interventions, “in my opinion, it may still be reasonable to suggest such interventions to motivate individuals who incorporate several of the dietary patterns associated with lower risk for IBD from this and other studies. This includes ensuring adequate dietary fiber, particularly from fruits and vegetables, intake of fish, minimizing sugar-sweetened beverages and preferring fresh over processed and ultra-processed foods and snacks.” According to the study authors, their novel findings support further research on the role of childhood diet in the prevention of IBD.
The All Babies in Southeast Sweden Study is supported by Barndiabetesfonden (Swedish Child Diabetes Foundation), the Swedish Council for Working Life and Social Research, the Swedish Research Council, the Medical Research Council of Southeast Sweden, the JDRF Wallenberg Foundation, ALF and LFoU grants from Region Östergötland and Linköping University, and the Joanna Cocozza Foundation.
The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research.
Ms. Guo received grants from the Swedish Society for Medical Research and the Henning and Johan Throne-Holst Foundation to conduct this study. Co-author Karl Mårild has received funding from the Swedish Society for Medical Research, the Swedish Research Council, and ALF, Sweden’s medical research and education co-ordinating body. The authors declared no competing interests. Dr. Ananthakrishnan is supported by the National Institutes of Health, the Leona M. and Harry B. Helmsley Charitable Trust, and the Chleck Family Foundation. He has served on the scientific advisory board for Geneoscopy.
, prospective pooled data from two Scandinavian birth cohorts suggested.
It appears important to feed children a quality diet at a very young age, in particular one rich in vegetables and fish, since by age three, only dietary fish intake had any impact on IBD risk.
Although high intakes of these two food categories in very early life correlated with lower IBD risk, exposure to sugar-sweetened beverages (SSBs) was associated with an increased risk. “While non-causal explanations for our results cannot be ruled out, these novel findings are consistent with the hypothesis that early-life diet, possibly mediated through changes in the gut microbiome, may affect the risk of developing IBD,” wrote lead author Annie Guo, a PhD candidate in the Department of Pediatrics, University of Gothenburg, Sweden, and colleagues. The report was published in Gut.
“This is a population-based study investigating the risk for IBD, rather than the specific effect of diet,” Ms. Guo said in an interview. “Therefore, the results are not enough on their own to be translated into individual advice that can be applicable in the clinic. However, the study supports current dietary guidelines for small children, that is, the intake of sugar should be limited and a higher intake of fish and vegetables is beneficial for overall health.”
Two-Cohort Study
The investigators prospectively recorded food-group information on children (just under half were female) from the All Babies in Southeast Sweden and The Norwegian Mother, Father and Child Cohort Study to assess the diet quality using a Healthy Eating Index and intake frequency. Parents answered questions about their offspring’s diet at ages 12-18 months and 30-36 months. Quality of diet was measured by intake of meat, fish, fruit, vegetables, dairy, sweets, snacks, and drinks.
The Swedish cohort included 21,700 children born between October 1997 and October 1999, while the Norwegian analysis included 114,500 children, 95,200 mothers, and 75,200 fathers recruited from across Norway from 1999 to 2008. In 1,304,433 person-years of follow-up, the researchers tracked 81,280 participants from birth to childhood and adolescence, with median follow-ups in the two cohorts ranging from 1 year of age to 21.3 years (Sweden) and to 15.2 years of age (Norway). Of these children, 307 were diagnosed with IBD: Crohn’s disease (CD; n = 131); ulcerative colitis (UC; n = 97); and IBD unclassified (n = 79).
Adjusting for parental IBD history, sex, origin, education, and maternal comorbidities, the study found:
- Compared with low-quality diet, both medium- and high-quality diets at 1 year were associated with a roughly 25% reduced risk for IBD (pooled adjusted hazard ratio [aHR], 0.75 [95% CI, 0.58-0.98] and 0.75 [0.56-1.0], respectively).
- The pooled aHR per increase of category was 0.86 (95% CI, 0.74-0.99). The pooled aHR for IBD in 1-year-olds with high vs low fish intake was 0.70 (95% CI, 0.49-1.0), and this diet showed an association with a reduced risk for UC (pooled aHR, 0.46; 95% CI, 0.21-0.99). Higher vegetable intake at 1 year was also associated with a risk reduction in IBD (HR, 0.72; 95% CI, 0.55-0.95). It has been hypothesized that intake of vegetables and vegetable fibers may have programming effects on the immune system.
- AutoWith 72% of children reportedly consuming SSBs at age 1, pooled aHRs showed that some vs no intake of SSBs was associated with an increased risk for later IBD (pooled aHR, 1.42; 95% CI, 1.05-1.90).
- There were no obvious associations between overall IBD or CD/UC risk and meat, dairy, fruit, grains, potatoes, and foods high in sugar and/or fat. Diet at age 3 years was not associated with incident IBD (pooled aHR, 1.02; 95% CI, 0.76-1.37), suggesting that the risk impact of diet is greatest on very young and vulnerable microbiomes.
Ms. Guo noted that a Swedish national survey among 4-year-olds found a mean SSB consumption of 187 g/d with a mean frequency of once daily. The most desired changes in food habits are a lower intake of soft drinks, sweets, crisps, cakes, and biscuits and an increase in the intake of fruits and vegetables. A similar Norwegian survey among 2-year-olds showed that SSBs were consumed by 36% of all children with a mean intake of 40 g/d.
The exact mechanism by which sugar affects the intestinal microbiota is not established. “However, what we do know is that an excessive intake of sugar can disrupt the balance of the gut microbiome,” Ms. Guo said. “And if the child has a high intake of foods with high in sugar, that also increases the chances that the child’s overall diet has a lower intake of other foods that contribute to a diverse microbiome such as fruits and vegetables.”
An ‘Elegant’ Study
In an accompanying editorial, gastroenterologist Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, of Mass General Brigham and the Mass General Research Institute, Boston, cautioned that accurately measuring food intake in very young children is difficult, and dietary questionnaires in this study did not address food additives and emulsifiers common in commercial baby food, which may play a role in the pathogenesis of IBD.
Another study limitation is that the dietary questionnaire used has not been qualitatively or quantitatively validated against other more conventional methods, said Dr. Ananthakrishnan, who was not involved in the research.
Nevertheless, he called the study “elegant” and expanding of the data on the importance of this period in IBD development. “Although in the present study there was no association between diet at 3 years and development of IBD (in contrast to the association observed for dietary intake at 1 year), other prospective cohorts of adult-onset IBD have demonstrated an inverse association between vegetable or fish intake and reduced risk for CD while sugar-sweetened beverages have been linked to a higher risk for IBD.”
As to the question of recommending early preventive diet for IBD, “thus far, data on the impact of diet very early in childhood, outside of breastfeeding, on the risk for IBD has been lacking,” Dr. Ananthakrishnan said in an interview. “This important study highlights that diet as early as 1 year can modify subsequent risk for IBD. This raises the intriguing possibility of whether early changes in diet could be used, particularly in those at higher risk, to reduce or even prevent future development of IBD. Of course, more works needs to be done to define modifiability of diet as a risk factor, but this is an important supportive data.”
In his editorial, Dr. Ananthakrishnan stated that despite the absence of gold-standard interventional data demonstrating a benefit of dietary interventions, “in my opinion, it may still be reasonable to suggest such interventions to motivate individuals who incorporate several of the dietary patterns associated with lower risk for IBD from this and other studies. This includes ensuring adequate dietary fiber, particularly from fruits and vegetables, intake of fish, minimizing sugar-sweetened beverages and preferring fresh over processed and ultra-processed foods and snacks.” According to the study authors, their novel findings support further research on the role of childhood diet in the prevention of IBD.
The All Babies in Southeast Sweden Study is supported by Barndiabetesfonden (Swedish Child Diabetes Foundation), the Swedish Council for Working Life and Social Research, the Swedish Research Council, the Medical Research Council of Southeast Sweden, the JDRF Wallenberg Foundation, ALF and LFoU grants from Region Östergötland and Linköping University, and the Joanna Cocozza Foundation.
The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research.
Ms. Guo received grants from the Swedish Society for Medical Research and the Henning and Johan Throne-Holst Foundation to conduct this study. Co-author Karl Mårild has received funding from the Swedish Society for Medical Research, the Swedish Research Council, and ALF, Sweden’s medical research and education co-ordinating body. The authors declared no competing interests. Dr. Ananthakrishnan is supported by the National Institutes of Health, the Leona M. and Harry B. Helmsley Charitable Trust, and the Chleck Family Foundation. He has served on the scientific advisory board for Geneoscopy.
FROM GUT