Jennifer Lubell

Attention-deficit/hyperactivity disorder and autism spectrum disorder (ASD) often coexist in children and adults, but the range of cognitive abilities can vary widely in these patients. Researchers from around the world are leveraging symptom, cognitive assessment, and neurobiological measures to gain insights on how individuals with ADHD/ASD approach and solve problems.

Several experts discussed the progress of their research during the session, “Overlap and differences of ADHD and autism – new findings of functional imaging and cognition studies” at the World Congress on ADHD – Virtual Event.

“The overlap of these two disorders is a critical issue for our field,” said Sarah Karalunas, PhD, assistant professor of clinical psychology at Purdue University, West Lafayette, Ind., who moderated the session. Clinicians are often asked to make differential diagnoses between these two disorders. Only recently has the DSM-5 allowed their codiagnosis. “There’s increasing recognition that there may be shared cognitive and physiological features that reflect their shared risk and account for the high levels of symptom overlap,” said Dr. Karalunas.
 

Shared cognitive markers

Under the DSM’s change, “it’s now recognized that an estimated 20%-60% of children with ASD have comorbidities with ADHD, and around 20%-40% of children with ADHD have ASD symptoms,” said Beth Johnson, PhD, a research fellow with the Turner Institute for Brain and Mental Health at Monash University, Melbourne.

The shared overlap on genetic traits and comorbidities such as intellectual disability, anxiety, depression, and oppositional defiant disorder, make it difficult for clinicians to predict clinical outcomes, noted Dr. Johnson.

“We’re now understanding that they’re likely to be multiple autisms and ADHDs, that these symptoms exist on a spectrum of severity or ability,” she said. Dr. Johnson discussed a data-driven subtyping approach based on neurocognitive and symptom profiles in children with ADHD. The aim was to better understand how symptoms are managed across ADHD, ASD and comorbid ASD-ADHD.

As part of this research, her team recruited 295 controls and 117 children with ADHD who underwent clinical phenotyping and also completed working memory tasks, stop signal, and sustained attention tasks.

The researchers divided the children into four stable clusters based on the ADHD rating scale and autism questionnaire data: high ASD/ADHD traits, high ADHD/low ASD, low ADHD/moderate ASD, and low ADHD/ASD. Approximately half of the children with ADHD showed moderate to high ASD symptoms. Looking at neurocognition across the tasks, unsurprisingly, performance was lowest among the high-ASD/ADHD children, with performance on the stop signal being the most pronounced. “Notably, performance on the working memory task worsened with increasing ADHD symptoms,” she reported.
 

Drift model identifies information processing

Dr. Karalunas has also compared subgroups of ADHD and ASD children. “Our analysis examined whether cognitive impairments in ASD reflect a shared risk mechanism or co-occurring ADHD symptoms and why we see an overlap in these types of impairments,” she said.

Her study included 509 children with ADHD, 97 with ASD, and 301 controls (typical development). All three groups underwent a full cognitive assessment battery that measured attention arousal, basic processing speed, and working memory. Those tasks were collapsed into a series of variables as well as a set of tasks measuring response inhibition, switching, interference control, reward discounting, and measure of reaction time variability.

Four cognitive profiles emerged: a typically developing group, an ADHD group, an ASD group with low levels of ADHD symptoms and an ASD group with high levels of ADHD symptoms.

The ADHD group did worse on many of the tasks than the control group, and the ASD group with low ADHD levels also did poorly relative to the typically developing sample. This shows that autism – even in absence of co-occurring ADHD – demonstrates more cognitive impairment than typically developing kids. The ADHD group with high levels of autism did the most poorly across all of the tasks.

The findings also revealed a symptom severity pattern: the group with fewer symptoms did the best and the group with the most symptoms did the worst. “Overall, this reflects severity of impairment,” said Dr. Karalunas.

To identify measures more specific to either ADHD or autism, Dr. Karalunas and colleagues did a follow-up analysis to characterize cognitive performance. To accomplish this, they applied a drift-diffusion model to the same four cognitive profiles. The model assessed three parameters: drift rate, which relates to the speed or efficiency of information processing, boundary separation or speed accuracy trade-offs (impulsivity), and nondecision time such as motor preparation.

Using the same four cognitive profiles, they found that the ADHD group had slower drift rate relative to the control, although the two groups did not differ on boundary separation, which meant there were no differences on waiting to need to respond. The ADHD group had faster nondecision times. “This is a classic pattern, shown in the literature,” said Dr. Karalunas.
 

In other results, an interesting pattern began to evolve

Both ASD groups, for example, had much wider boundary separations, which meant they were waiting to be sure before they responded than the ADHD or typically developing groups. In contrast, the two ADHD groups had much faster non-decision times, whereas the two non-ADHD groups had similar nondecisions times.

Unlike the previous analysis, which saw a symptom severity pattern develop, “we’re getting two parameters that seem to track much more specifically to specific symptom domains,” observed Dr. Karalunas.

The results suggest there’s a substantial overlap in cognitive impairments in ADHD/ASD. “But we have pretty strong evidence at this point that these similarities are not accounted for by symptom overlap, especially for things like response and inhibition, working memory and processing speed. These seem to be independently related to ADHD and autism, regardless of the level of comorbid ADHD symptoms in the autism group,” said Dr. Karalunas.

The hope is to expand on these types of analyses to address the interaction of cognition-emotion and social cognition, and empirically define groups based on cognitive performance, she said.
 

Neurocognitive studies

Researchers have also been studying neural networks to assess ASD and ADHD. Roselyne Chauvin, PhD, a postdoctoral associate at Washington University, St. Louis, discussed the concept of “a task generic connectome,” in which researchers look for a common network between targeted task paradigms to get closer to a common alteration across impairments.

In her research, Dr. Chauvin and colleagues looked at connectivity modulations across three tasks: working memory, reward processing tasks, and stop signal tasks, comparing ADHD patients to siblings and controls. The ADHD group showed reduced sensitivity or a smaller number of connections modulated in the tasks compared with the other groups. Researchers wondered where those missed connections were located.

Dividing the cohorts into task generic and task specific groups, Dr. Chauvin and colleagues found that the ADHD group lacked common processing skills. They were also able to identify reproducible missing circuits in the ADHD participants. Among the cohorts, there was a higher modulation of task-specific edges in the ADHD group.

The ADHD patients seemed to be using more task-tailored alternative strategies that were more challenging and suboptimal.

She also previewed her ongoing work with the EU-AIMS Longitudinal European Autism Project (LEAP) database to study ASD-ADHD comorbidity. In this project, she and her colleagues looked at several tasks: probing emotion processing, inhibitory control, theory of mind, and reward anticipation. Comparing ASD groups with or without ADHD comorbidity or a shared connection, she and her team were able to devise a functional profile predictive of ADHD severity. As an example, “for the connection only used by the ASD with ADHD comorbidity, the more they were using those connections of higher amplitude in the modulation, inside this subset of connection, the higher they would have ADHD severity,” said Dr. Chauvin.

Neural correlates of different behavioral and cognitive profiles haven’t been widely studied, according to Charlotte Tye, PhD, who’s based at the Institute of Psychiatry, Psychology & Neuroscience, King’s College, London. Electroencephalography is a useful technique for understanding the neural correlates of cognitive impairments and teasing apart different models of co-occurrence in ASD and ADHD. 

Dr. Tye and colleagues tested this approach in a cohort of boys aged 8-13 years diagnosed with ASD and/or ADHD, measuring EEG while the children did various continuous performance tasks to assess changes in brain activity. Examining P3 amplitude (event-related potential components) they found that children with ADHD or ADHD+ASD showed an attenuated amplitude of the P3, compared with typically developing children and those with ASD.

“This suggests children with an ADHD diagnosis exhibited reduced inhibitory control,” said Dr. Tye. In contrast, children with ASD showed reduced conflict monitoring as indexed by altered N2 amplitude across task conditions.

These, and other studies conducted by Dr. Tye and colleagues indicate that children with ADHD show reduced neural responses during attentional processing, whereas autistic children show typical neural responses, supporting specific profiles.

“Autistic children with a diagnosis of ADHD appear to show the unique patterns of neural responses of autism and ADHD, supporting an additive co-occurrence rather than a distinct condition. This contributes to identification of transdiagnostic subgroups within neurodevelopmental conditions for targeting of personalized intervention, and suggests that children with co-occurring autism and ADHD require support for both conditions,” said Dr. Tye.

An important takeaway from all of these findings is “we can’t look just at how someone does overall on a single test,” said Dr. Karalunas in an interview. “There is a tremendous amount of variability between people who have the same diagnosis, and our research really needs to account for this.”

Attention-deficit/hyperactivity disorder and autism spectrum disorder (ASD) often coexist in children and adults, but the range of cognitive abilities can vary widely in these patients. Researchers from around the world are leveraging symptom, cognitive assessment, and neurobiological measures to gain insights on how individuals with ADHD/ASD approach and solve problems.

Several experts discussed the progress of their research during the session, “Overlap and differences of ADHD and autism – new findings of functional imaging and cognition studies” at the World Congress on ADHD – Virtual Event.

“The overlap of these two disorders is a critical issue for our field,” said Sarah Karalunas, PhD, assistant professor of clinical psychology at Purdue University, West Lafayette, Ind., who moderated the session. Clinicians are often asked to make differential diagnoses between these two disorders. Only recently has the DSM-5 allowed their codiagnosis. “There’s increasing recognition that there may be shared cognitive and physiological features that reflect their shared risk and account for the high levels of symptom overlap,” said Dr. Karalunas.
 

Shared cognitive markers

Under the DSM’s change, “it’s now recognized that an estimated 20%-60% of children with ASD have comorbidities with ADHD, and around 20%-40% of children with ADHD have ASD symptoms,” said Beth Johnson, PhD, a research fellow with the Turner Institute for Brain and Mental Health at Monash University, Melbourne.

The shared overlap on genetic traits and comorbidities such as intellectual disability, anxiety, depression, and oppositional defiant disorder, make it difficult for clinicians to predict clinical outcomes, noted Dr. Johnson.

“We’re now understanding that they’re likely to be multiple autisms and ADHDs, that these symptoms exist on a spectrum of severity or ability,” she said. Dr. Johnson discussed a data-driven subtyping approach based on neurocognitive and symptom profiles in children with ADHD. The aim was to better understand how symptoms are managed across ADHD, ASD and comorbid ASD-ADHD.

As part of this research, her team recruited 295 controls and 117 children with ADHD who underwent clinical phenotyping and also completed working memory tasks, stop signal, and sustained attention tasks.

The researchers divided the children into four stable clusters based on the ADHD rating scale and autism questionnaire data: high ASD/ADHD traits, high ADHD/low ASD, low ADHD/moderate ASD, and low ADHD/ASD. Approximately half of the children with ADHD showed moderate to high ASD symptoms. Looking at neurocognition across the tasks, unsurprisingly, performance was lowest among the high-ASD/ADHD children, with performance on the stop signal being the most pronounced. “Notably, performance on the working memory task worsened with increasing ADHD symptoms,” she reported.
 

Drift model identifies information processing

Dr. Karalunas has also compared subgroups of ADHD and ASD children. “Our analysis examined whether cognitive impairments in ASD reflect a shared risk mechanism or co-occurring ADHD symptoms and why we see an overlap in these types of impairments,” she said.

Her study included 509 children with ADHD, 97 with ASD, and 301 controls (typical development). All three groups underwent a full cognitive assessment battery that measured attention arousal, basic processing speed, and working memory. Those tasks were collapsed into a series of variables as well as a set of tasks measuring response inhibition, switching, interference control, reward discounting, and measure of reaction time variability.

Four cognitive profiles emerged: a typically developing group, an ADHD group, an ASD group with low levels of ADHD symptoms and an ASD group with high levels of ADHD symptoms.

The ADHD group did worse on many of the tasks than the control group, and the ASD group with low ADHD levels also did poorly relative to the typically developing sample. This shows that autism – even in absence of co-occurring ADHD – demonstrates more cognitive impairment than typically developing kids. The ADHD group with high levels of autism did the most poorly across all of the tasks.

The findings also revealed a symptom severity pattern: the group with fewer symptoms did the best and the group with the most symptoms did the worst. “Overall, this reflects severity of impairment,” said Dr. Karalunas.

To identify measures more specific to either ADHD or autism, Dr. Karalunas and colleagues did a follow-up analysis to characterize cognitive performance. To accomplish this, they applied a drift-diffusion model to the same four cognitive profiles. The model assessed three parameters: drift rate, which relates to the speed or efficiency of information processing, boundary separation or speed accuracy trade-offs (impulsivity), and nondecision time such as motor preparation.

Using the same four cognitive profiles, they found that the ADHD group had slower drift rate relative to the control, although the two groups did not differ on boundary separation, which meant there were no differences on waiting to need to respond. The ADHD group had faster nondecision times. “This is a classic pattern, shown in the literature,” said Dr. Karalunas.
 

In other results, an interesting pattern began to evolve

Both ASD groups, for example, had much wider boundary separations, which meant they were waiting to be sure before they responded than the ADHD or typically developing groups. In contrast, the two ADHD groups had much faster non-decision times, whereas the two non-ADHD groups had similar nondecisions times.

Unlike the previous analysis, which saw a symptom severity pattern develop, “we’re getting two parameters that seem to track much more specifically to specific symptom domains,” observed Dr. Karalunas.

The results suggest there’s a substantial overlap in cognitive impairments in ADHD/ASD. “But we have pretty strong evidence at this point that these similarities are not accounted for by symptom overlap, especially for things like response and inhibition, working memory and processing speed. These seem to be independently related to ADHD and autism, regardless of the level of comorbid ADHD symptoms in the autism group,” said Dr. Karalunas.

The hope is to expand on these types of analyses to address the interaction of cognition-emotion and social cognition, and empirically define groups based on cognitive performance, she said.
 

Neurocognitive studies

Researchers have also been studying neural networks to assess ASD and ADHD. Roselyne Chauvin, PhD, a postdoctoral associate at Washington University, St. Louis, discussed the concept of “a task generic connectome,” in which researchers look for a common network between targeted task paradigms to get closer to a common alteration across impairments.

In her research, Dr. Chauvin and colleagues looked at connectivity modulations across three tasks: working memory, reward processing tasks, and stop signal tasks, comparing ADHD patients to siblings and controls. The ADHD group showed reduced sensitivity or a smaller number of connections modulated in the tasks compared with the other groups. Researchers wondered where those missed connections were located.

Dividing the cohorts into task generic and task specific groups, Dr. Chauvin and colleagues found that the ADHD group lacked common processing skills. They were also able to identify reproducible missing circuits in the ADHD participants. Among the cohorts, there was a higher modulation of task-specific edges in the ADHD group.

The ADHD patients seemed to be using more task-tailored alternative strategies that were more challenging and suboptimal.

She also previewed her ongoing work with the EU-AIMS Longitudinal European Autism Project (LEAP) database to study ASD-ADHD comorbidity. In this project, she and her colleagues looked at several tasks: probing emotion processing, inhibitory control, theory of mind, and reward anticipation. Comparing ASD groups with or without ADHD comorbidity or a shared connection, she and her team were able to devise a functional profile predictive of ADHD severity. As an example, “for the connection only used by the ASD with ADHD comorbidity, the more they were using those connections of higher amplitude in the modulation, inside this subset of connection, the higher they would have ADHD severity,” said Dr. Chauvin.

Neural correlates of different behavioral and cognitive profiles haven’t been widely studied, according to Charlotte Tye, PhD, who’s based at the Institute of Psychiatry, Psychology & Neuroscience, King’s College, London. Electroencephalography is a useful technique for understanding the neural correlates of cognitive impairments and teasing apart different models of co-occurrence in ASD and ADHD. 

Dr. Tye and colleagues tested this approach in a cohort of boys aged 8-13 years diagnosed with ASD and/or ADHD, measuring EEG while the children did various continuous performance tasks to assess changes in brain activity. Examining P3 amplitude (event-related potential components) they found that children with ADHD or ADHD+ASD showed an attenuated amplitude of the P3, compared with typically developing children and those with ASD.

“This suggests children with an ADHD diagnosis exhibited reduced inhibitory control,” said Dr. Tye. In contrast, children with ASD showed reduced conflict monitoring as indexed by altered N2 amplitude across task conditions.

These, and other studies conducted by Dr. Tye and colleagues indicate that children with ADHD show reduced neural responses during attentional processing, whereas autistic children show typical neural responses, supporting specific profiles.

“Autistic children with a diagnosis of ADHD appear to show the unique patterns of neural responses of autism and ADHD, supporting an additive co-occurrence rather than a distinct condition. This contributes to identification of transdiagnostic subgroups within neurodevelopmental conditions for targeting of personalized intervention, and suggests that children with co-occurring autism and ADHD require support for both conditions,” said Dr. Tye.

An important takeaway from all of these findings is “we can’t look just at how someone does overall on a single test,” said Dr. Karalunas in an interview. “There is a tremendous amount of variability between people who have the same diagnosis, and our research really needs to account for this.”

Attention-deficit/hyperactivity disorder and autism spectrum disorder (ASD) often coexist in children and adults, but the range of cognitive abilities can vary widely in these patients. Researchers from around the world are leveraging symptom, cognitive assessment, and neurobiological measures to gain insights on how individuals with ADHD/ASD approach and solve problems.

Several experts discussed the progress of their research during the session, “Overlap and differences of ADHD and autism – new findings of functional imaging and cognition studies” at the World Congress on ADHD – Virtual Event.

“The overlap of these two disorders is a critical issue for our field,” said Sarah Karalunas, PhD, assistant professor of clinical psychology at Purdue University, West Lafayette, Ind., who moderated the session. Clinicians are often asked to make differential diagnoses between these two disorders. Only recently has the DSM-5 allowed their codiagnosis. “There’s increasing recognition that there may be shared cognitive and physiological features that reflect their shared risk and account for the high levels of symptom overlap,” said Dr. Karalunas.
 

Shared cognitive markers

Under the DSM’s change, “it’s now recognized that an estimated 20%-60% of children with ASD have comorbidities with ADHD, and around 20%-40% of children with ADHD have ASD symptoms,” said Beth Johnson, PhD, a research fellow with the Turner Institute for Brain and Mental Health at Monash University, Melbourne.

The shared overlap on genetic traits and comorbidities such as intellectual disability, anxiety, depression, and oppositional defiant disorder, make it difficult for clinicians to predict clinical outcomes, noted Dr. Johnson.

“We’re now understanding that they’re likely to be multiple autisms and ADHDs, that these symptoms exist on a spectrum of severity or ability,” she said. Dr. Johnson discussed a data-driven subtyping approach based on neurocognitive and symptom profiles in children with ADHD. The aim was to better understand how symptoms are managed across ADHD, ASD and comorbid ASD-ADHD.

As part of this research, her team recruited 295 controls and 117 children with ADHD who underwent clinical phenotyping and also completed working memory tasks, stop signal, and sustained attention tasks.

The researchers divided the children into four stable clusters based on the ADHD rating scale and autism questionnaire data: high ASD/ADHD traits, high ADHD/low ASD, low ADHD/moderate ASD, and low ADHD/ASD. Approximately half of the children with ADHD showed moderate to high ASD symptoms. Looking at neurocognition across the tasks, unsurprisingly, performance was lowest among the high-ASD/ADHD children, with performance on the stop signal being the most pronounced. “Notably, performance on the working memory task worsened with increasing ADHD symptoms,” she reported.
 

Drift model identifies information processing

Dr. Karalunas has also compared subgroups of ADHD and ASD children. “Our analysis examined whether cognitive impairments in ASD reflect a shared risk mechanism or co-occurring ADHD symptoms and why we see an overlap in these types of impairments,” she said.

Her study included 509 children with ADHD, 97 with ASD, and 301 controls (typical development). All three groups underwent a full cognitive assessment battery that measured attention arousal, basic processing speed, and working memory. Those tasks were collapsed into a series of variables as well as a set of tasks measuring response inhibition, switching, interference control, reward discounting, and measure of reaction time variability.

Four cognitive profiles emerged: a typically developing group, an ADHD group, an ASD group with low levels of ADHD symptoms and an ASD group with high levels of ADHD symptoms.

The ADHD group did worse on many of the tasks than the control group, and the ASD group with low ADHD levels also did poorly relative to the typically developing sample. This shows that autism – even in absence of co-occurring ADHD – demonstrates more cognitive impairment than typically developing kids. The ADHD group with high levels of autism did the most poorly across all of the tasks.

The findings also revealed a symptom severity pattern: the group with fewer symptoms did the best and the group with the most symptoms did the worst. “Overall, this reflects severity of impairment,” said Dr. Karalunas.

To identify measures more specific to either ADHD or autism, Dr. Karalunas and colleagues did a follow-up analysis to characterize cognitive performance. To accomplish this, they applied a drift-diffusion model to the same four cognitive profiles. The model assessed three parameters: drift rate, which relates to the speed or efficiency of information processing, boundary separation or speed accuracy trade-offs (impulsivity), and nondecision time such as motor preparation.

Using the same four cognitive profiles, they found that the ADHD group had slower drift rate relative to the control, although the two groups did not differ on boundary separation, which meant there were no differences on waiting to need to respond. The ADHD group had faster nondecision times. “This is a classic pattern, shown in the literature,” said Dr. Karalunas.
 

In other results, an interesting pattern began to evolve

Both ASD groups, for example, had much wider boundary separations, which meant they were waiting to be sure before they responded than the ADHD or typically developing groups. In contrast, the two ADHD groups had much faster non-decision times, whereas the two non-ADHD groups had similar nondecisions times.

Unlike the previous analysis, which saw a symptom severity pattern develop, “we’re getting two parameters that seem to track much more specifically to specific symptom domains,” observed Dr. Karalunas.

The results suggest there’s a substantial overlap in cognitive impairments in ADHD/ASD. “But we have pretty strong evidence at this point that these similarities are not accounted for by symptom overlap, especially for things like response and inhibition, working memory and processing speed. These seem to be independently related to ADHD and autism, regardless of the level of comorbid ADHD symptoms in the autism group,” said Dr. Karalunas.

The hope is to expand on these types of analyses to address the interaction of cognition-emotion and social cognition, and empirically define groups based on cognitive performance, she said.
 

Neurocognitive studies

Researchers have also been studying neural networks to assess ASD and ADHD. Roselyne Chauvin, PhD, a postdoctoral associate at Washington University, St. Louis, discussed the concept of “a task generic connectome,” in which researchers look for a common network between targeted task paradigms to get closer to a common alteration across impairments.

In her research, Dr. Chauvin and colleagues looked at connectivity modulations across three tasks: working memory, reward processing tasks, and stop signal tasks, comparing ADHD patients to siblings and controls. The ADHD group showed reduced sensitivity or a smaller number of connections modulated in the tasks compared with the other groups. Researchers wondered where those missed connections were located.

Dividing the cohorts into task generic and task specific groups, Dr. Chauvin and colleagues found that the ADHD group lacked common processing skills. They were also able to identify reproducible missing circuits in the ADHD participants. Among the cohorts, there was a higher modulation of task-specific edges in the ADHD group.

The ADHD patients seemed to be using more task-tailored alternative strategies that were more challenging and suboptimal.

She also previewed her ongoing work with the EU-AIMS Longitudinal European Autism Project (LEAP) database to study ASD-ADHD comorbidity. In this project, she and her colleagues looked at several tasks: probing emotion processing, inhibitory control, theory of mind, and reward anticipation. Comparing ASD groups with or without ADHD comorbidity or a shared connection, she and her team were able to devise a functional profile predictive of ADHD severity. As an example, “for the connection only used by the ASD with ADHD comorbidity, the more they were using those connections of higher amplitude in the modulation, inside this subset of connection, the higher they would have ADHD severity,” said Dr. Chauvin.

Neural correlates of different behavioral and cognitive profiles haven’t been widely studied, according to Charlotte Tye, PhD, who’s based at the Institute of Psychiatry, Psychology & Neuroscience, King’s College, London. Electroencephalography is a useful technique for understanding the neural correlates of cognitive impairments and teasing apart different models of co-occurrence in ASD and ADHD. 

Dr. Tye and colleagues tested this approach in a cohort of boys aged 8-13 years diagnosed with ASD and/or ADHD, measuring EEG while the children did various continuous performance tasks to assess changes in brain activity. Examining P3 amplitude (event-related potential components) they found that children with ADHD or ADHD+ASD showed an attenuated amplitude of the P3, compared with typically developing children and those with ASD.

“This suggests children with an ADHD diagnosis exhibited reduced inhibitory control,” said Dr. Tye. In contrast, children with ASD showed reduced conflict monitoring as indexed by altered N2 amplitude across task conditions.

These, and other studies conducted by Dr. Tye and colleagues indicate that children with ADHD show reduced neural responses during attentional processing, whereas autistic children show typical neural responses, supporting specific profiles.

“Autistic children with a diagnosis of ADHD appear to show the unique patterns of neural responses of autism and ADHD, supporting an additive co-occurrence rather than a distinct condition. This contributes to identification of transdiagnostic subgroups within neurodevelopmental conditions for targeting of personalized intervention, and suggests that children with co-occurring autism and ADHD require support for both conditions,” said Dr. Tye.

An important takeaway from all of these findings is “we can’t look just at how someone does overall on a single test,” said Dr. Karalunas in an interview. “There is a tremendous amount of variability between people who have the same diagnosis, and our research really needs to account for this.”

While it’s possible that residual effects of SARS-CoV-2 could lead to an eruption of attention-deficit/hyperactivity disorder (ADHD) cases, a debate at the World Congress on ADHD – Virtual Event underscored the fact that this is still a hypothesis. The bottom line is there needs to be more data, said Luis Augusto Rohde, MD, PhD, cochair of the congress’ scientific program committee and moderator of the session, “Residual effects of the 2019 pandemic will mirror the 1918 pandemic: Will we have lots of new ADHD cases?”

Considering the current pattern of the pandemic, there is not enough evidence for this to be a concern, Dr. Rohde said in an interview.

James Swanson, PhD, professor of pediatrics at the University of California, Irvine, opined that biological co-effects of COVID-19 are likely to have selective effects in children that may produce symptoms representative of ADHD. Using the 1918 Spanish flu pandemic as a historical reference, he estimated that COVID-19 would produce 5 million individuals with new-onset symptoms related to ADHD. “If these cases meet DSM-5 or ICD-11 criteria, there will be lots of new ADHD cases,” he predicted.

David Coghill, MD, a professor of child adolescent mental health at the University of Melbourne, observed that the sums Dr. Swanson presented “are based on maxing out the potential rather than looking at the sums more realistically.”
 

Could the 1918 pandemic offer clues?

In a commentary, Dr. Swanson and Nora D. Volkow, MD, wrote about “lessons learned” from the 1918 pandemic, and how residual sequelae in that era led to a condition labeled hyperkinetic syndrome in children. “It may be worthwhile to consider the hypothesis that the COVID-19 pandemic may result in a novel etiologic subtype of ADHD that clinicians may recognize in patients in the future,” wrote the commentators. 

In survivors of the 1918 pandemic, brain inflammation or encephalitis sometimes emerged as residual sequelae, said Dr. Swanson. In some adult cases, these symptoms were diagnosed as “encephalitis lethargica” (EL) and were associated with Parkinson’s disease. In 1930, based on patients evaluated after 1918, researchers Franz Kramer and Hans Pollnow at Charité Hospital in Berlin described the behavioral manifestation of EL in children as hyperkinetic syndrome, a condition that was characterized by symptoms similar to the properties of ADHD: lack of concentration, insufficient goal orientation, and increased distractibility. “They even reported on autopsy cases that described brain regions that we now know are associated with ADHD from decades of brain imaging studies,” said Dr. Swanson.

COVID-19 rarely results in severe respiratory problems in children but the absolute number requiring hospitalization has accumulated and is now relatively large, said Dr. Swanson. One study of 1,695 severe COVID-19 cases in children and adolescents used MRI and detected neural effects in specific brain regions such as basal ganglia and frontal lobes that previous research had associated with ADHD. Approximately 22% of these rare but severe cases had documented neurologic involvement, and studies of affected children with mild or none of the initial respiratory symptoms of COVID-19 also detected similar selective effects in these brain regions.

A recent survey of medical records of 80 million people that identified 240,000 COVID cases (mostly adults) revealed that a third had neurological and psychiatric sequelae. Dr. Swanson also mentioned an article he wrote more than a decade ago on environmental as well as genetic factors that resulted in etiologic subtypes of ADHD, which provided a model for the impact of COVID-19 on specific brain regions that are associated with ADHD.

So far, the COVID-19 pandemic has produced 150 million cases worldwide and there are about 100 million survivors, setting an estimate of a maximum number of cases with residual sequelae. “I think that severe COVID-19 will probably be related to severe residual sequelae, and that mild or asymptomatic COVID-19 may be associated with less severe residual sequelae, which may resemble ADHD” said Dr. Swanson. If one-third of the cases manifest in some neurologic or psychiatric systems, this means 27 million would have residual sequelae. If 20% have impaired concentration or brain fog, this could result in about 5 million ADHD cases, he said. 
 

Estimates aren’t evidence

The Swanson/Volkow commentary contains a lot of references to “might, could, and may,” said Dr. Coghill. While it’s true that COVID-19 could produce a novel etiologic subtype of ADHD, “the point here is at the moment, all of this is based on hypotheses,” he said.

The Spanish flu did produce mental health consequences – survivors reported depression, sleep disturbances, mental distraction, dizziness, and difficulties coping at work. In the United States, flu death rates from 1918 to 1920 were directly attributed to suicide rates. Unfortunately, these impacts weren’t widely researched, said Dr. Coghill.

It also seems clear that the 1918 Spanish flu outbreak was associated with significant neurological consequences, said Dr. Coghill. By 1919 and 1920, physicians and researchers in the United Kingdom were reporting increases in a variety of symptoms among some patients recovering from flu, such as neuropathy, neurasthenia, meningitis, degenerative changes in nerve cells, and a decline in visual acuity.

The EL cases Dr. Swanson mentioned did coincide with and reach epidemic proportions alongside the Spanish flu. “But still, a causal relationship is far from proven,” said Dr. Coghill.

Sol Levy, MD, described a “disease of criminals” following the 1918 pandemic, in which patients exhibited a high degree of general hyperkinesis, a difficulty in maintaining quiet attitudes, abruptness and clumsiness, and “explosive motor release of all voluntarily inhibited activities.”

However, these impairments suggest a much broader presentation typically seen in ADHD, noted Dr. Coghill.

Neurological complications occur more commonly than initially thought in severe COVID-19, with estimates ranging from 36% to 84%. But in a systematic review of neuropsychiatric complications of severe coronavirus infection, researchers found few psychiatric sequelae of these infections. While they did mention impaired concentration and difficulties with emotional ability, it’s very important to remember that these conditions “are cardinal symptoms of a wide range of psychiatric disorders,” said Dr. Coghill.

Overall, more neurological and neuropsychiatric symptoms largely confine to those with severe COVID-19, meaning they’re much less likely to occur in children and young adults, he said.

If there are severe effects of COVID-19, Dr. Swanson countered that “they might have more ADHD than the complex residual effects [Dr. Coghill] described. I hope that he’s right, but I do think there will be biological co-effects of COVID-19 that will produce symptoms that are more ADHD than other neurological disorders.”
 

Epigenetic effects

Researchers are now seeing transgenerational and intergenerational effects of potential infection. “So I certainly back high-quality studies looking at the effects of maternal and paternal infection on offspring,” said Dr. Coghill. Establishing clinical cohort studies to follow up on this population would be essential in understanding the risks of SARS-CoV-2. “That might be one way we’ll see an increase in ADHD,” said Dr. Coghill.

The reality is COVID-19 hasn’t been around for that long, and current knowledge about it is limited, he said. Rapid publications, cross-sectional or retrospective data, and poor methodological quality and rigor make generalizability difficult. In addition, limited testing and detection probably underestimate prevalence of neurological and neuropsychiatric complications.

“If history teaches us anything, it is that we should always be measured in how we glean lessons from the past. So let’s not get ahead of ourselves,” he cautioned.

An informal, post-discussion survey of session participants revealed that a slight majority – 55%-60% – expected residual effects of COVID-19 to lead to more ADHD, compared to 40%-45% who didn’t think this would happen.

Dr. Swanson has two patents: (PIXA4), which uses a “time-of-flight” camera to measure growth on infants, and a provisional patent on the mechanism of tolerance to stimulant medication (PATSMTA). Dr. Coghill worked for several pharmaceutical companies but had no disclosures relevant to this debate.

While it’s possible that residual effects of SARS-CoV-2 could lead to an eruption of attention-deficit/hyperactivity disorder (ADHD) cases, a debate at the World Congress on ADHD – Virtual Event underscored the fact that this is still a hypothesis. The bottom line is there needs to be more data, said Luis Augusto Rohde, MD, PhD, cochair of the congress’ scientific program committee and moderator of the session, “Residual effects of the 2019 pandemic will mirror the 1918 pandemic: Will we have lots of new ADHD cases?”

Considering the current pattern of the pandemic, there is not enough evidence for this to be a concern, Dr. Rohde said in an interview.

James Swanson, PhD, professor of pediatrics at the University of California, Irvine, opined that biological co-effects of COVID-19 are likely to have selective effects in children that may produce symptoms representative of ADHD. Using the 1918 Spanish flu pandemic as a historical reference, he estimated that COVID-19 would produce 5 million individuals with new-onset symptoms related to ADHD. “If these cases meet DSM-5 or ICD-11 criteria, there will be lots of new ADHD cases,” he predicted.

David Coghill, MD, a professor of child adolescent mental health at the University of Melbourne, observed that the sums Dr. Swanson presented “are based on maxing out the potential rather than looking at the sums more realistically.”
 

Could the 1918 pandemic offer clues?

In a commentary, Dr. Swanson and Nora D. Volkow, MD, wrote about “lessons learned” from the 1918 pandemic, and how residual sequelae in that era led to a condition labeled hyperkinetic syndrome in children. “It may be worthwhile to consider the hypothesis that the COVID-19 pandemic may result in a novel etiologic subtype of ADHD that clinicians may recognize in patients in the future,” wrote the commentators. 

In survivors of the 1918 pandemic, brain inflammation or encephalitis sometimes emerged as residual sequelae, said Dr. Swanson. In some adult cases, these symptoms were diagnosed as “encephalitis lethargica” (EL) and were associated with Parkinson’s disease. In 1930, based on patients evaluated after 1918, researchers Franz Kramer and Hans Pollnow at Charité Hospital in Berlin described the behavioral manifestation of EL in children as hyperkinetic syndrome, a condition that was characterized by symptoms similar to the properties of ADHD: lack of concentration, insufficient goal orientation, and increased distractibility. “They even reported on autopsy cases that described brain regions that we now know are associated with ADHD from decades of brain imaging studies,” said Dr. Swanson.

COVID-19 rarely results in severe respiratory problems in children but the absolute number requiring hospitalization has accumulated and is now relatively large, said Dr. Swanson. One study of 1,695 severe COVID-19 cases in children and adolescents used MRI and detected neural effects in specific brain regions such as basal ganglia and frontal lobes that previous research had associated with ADHD. Approximately 22% of these rare but severe cases had documented neurologic involvement, and studies of affected children with mild or none of the initial respiratory symptoms of COVID-19 also detected similar selective effects in these brain regions.

A recent survey of medical records of 80 million people that identified 240,000 COVID cases (mostly adults) revealed that a third had neurological and psychiatric sequelae. Dr. Swanson also mentioned an article he wrote more than a decade ago on environmental as well as genetic factors that resulted in etiologic subtypes of ADHD, which provided a model for the impact of COVID-19 on specific brain regions that are associated with ADHD.

So far, the COVID-19 pandemic has produced 150 million cases worldwide and there are about 100 million survivors, setting an estimate of a maximum number of cases with residual sequelae. “I think that severe COVID-19 will probably be related to severe residual sequelae, and that mild or asymptomatic COVID-19 may be associated with less severe residual sequelae, which may resemble ADHD” said Dr. Swanson. If one-third of the cases manifest in some neurologic or psychiatric systems, this means 27 million would have residual sequelae. If 20% have impaired concentration or brain fog, this could result in about 5 million ADHD cases, he said. 
 

Estimates aren’t evidence

The Swanson/Volkow commentary contains a lot of references to “might, could, and may,” said Dr. Coghill. While it’s true that COVID-19 could produce a novel etiologic subtype of ADHD, “the point here is at the moment, all of this is based on hypotheses,” he said.

The Spanish flu did produce mental health consequences – survivors reported depression, sleep disturbances, mental distraction, dizziness, and difficulties coping at work. In the United States, flu death rates from 1918 to 1920 were directly attributed to suicide rates. Unfortunately, these impacts weren’t widely researched, said Dr. Coghill.

It also seems clear that the 1918 Spanish flu outbreak was associated with significant neurological consequences, said Dr. Coghill. By 1919 and 1920, physicians and researchers in the United Kingdom were reporting increases in a variety of symptoms among some patients recovering from flu, such as neuropathy, neurasthenia, meningitis, degenerative changes in nerve cells, and a decline in visual acuity.

The EL cases Dr. Swanson mentioned did coincide with and reach epidemic proportions alongside the Spanish flu. “But still, a causal relationship is far from proven,” said Dr. Coghill.

Sol Levy, MD, described a “disease of criminals” following the 1918 pandemic, in which patients exhibited a high degree of general hyperkinesis, a difficulty in maintaining quiet attitudes, abruptness and clumsiness, and “explosive motor release of all voluntarily inhibited activities.”

However, these impairments suggest a much broader presentation typically seen in ADHD, noted Dr. Coghill.

Neurological complications occur more commonly than initially thought in severe COVID-19, with estimates ranging from 36% to 84%. But in a systematic review of neuropsychiatric complications of severe coronavirus infection, researchers found few psychiatric sequelae of these infections. While they did mention impaired concentration and difficulties with emotional ability, it’s very important to remember that these conditions “are cardinal symptoms of a wide range of psychiatric disorders,” said Dr. Coghill.

Overall, more neurological and neuropsychiatric symptoms largely confine to those with severe COVID-19, meaning they’re much less likely to occur in children and young adults, he said.

If there are severe effects of COVID-19, Dr. Swanson countered that “they might have more ADHD than the complex residual effects [Dr. Coghill] described. I hope that he’s right, but I do think there will be biological co-effects of COVID-19 that will produce symptoms that are more ADHD than other neurological disorders.”
 

Epigenetic effects

Researchers are now seeing transgenerational and intergenerational effects of potential infection. “So I certainly back high-quality studies looking at the effects of maternal and paternal infection on offspring,” said Dr. Coghill. Establishing clinical cohort studies to follow up on this population would be essential in understanding the risks of SARS-CoV-2. “That might be one way we’ll see an increase in ADHD,” said Dr. Coghill.

The reality is COVID-19 hasn’t been around for that long, and current knowledge about it is limited, he said. Rapid publications, cross-sectional or retrospective data, and poor methodological quality and rigor make generalizability difficult. In addition, limited testing and detection probably underestimate prevalence of neurological and neuropsychiatric complications.

“If history teaches us anything, it is that we should always be measured in how we glean lessons from the past. So let’s not get ahead of ourselves,” he cautioned.

An informal, post-discussion survey of session participants revealed that a slight majority – 55%-60% – expected residual effects of COVID-19 to lead to more ADHD, compared to 40%-45% who didn’t think this would happen.

Dr. Swanson has two patents: (PIXA4), which uses a “time-of-flight” camera to measure growth on infants, and a provisional patent on the mechanism of tolerance to stimulant medication (PATSMTA). Dr. Coghill worked for several pharmaceutical companies but had no disclosures relevant to this debate.

While it’s possible that residual effects of SARS-CoV-2 could lead to an eruption of attention-deficit/hyperactivity disorder (ADHD) cases, a debate at the World Congress on ADHD – Virtual Event underscored the fact that this is still a hypothesis. The bottom line is there needs to be more data, said Luis Augusto Rohde, MD, PhD, cochair of the congress’ scientific program committee and moderator of the session, “Residual effects of the 2019 pandemic will mirror the 1918 pandemic: Will we have lots of new ADHD cases?”

Considering the current pattern of the pandemic, there is not enough evidence for this to be a concern, Dr. Rohde said in an interview.

James Swanson, PhD, professor of pediatrics at the University of California, Irvine, opined that biological co-effects of COVID-19 are likely to have selective effects in children that may produce symptoms representative of ADHD. Using the 1918 Spanish flu pandemic as a historical reference, he estimated that COVID-19 would produce 5 million individuals with new-onset symptoms related to ADHD. “If these cases meet DSM-5 or ICD-11 criteria, there will be lots of new ADHD cases,” he predicted.

David Coghill, MD, a professor of child adolescent mental health at the University of Melbourne, observed that the sums Dr. Swanson presented “are based on maxing out the potential rather than looking at the sums more realistically.”
 

Could the 1918 pandemic offer clues?

In a commentary, Dr. Swanson and Nora D. Volkow, MD, wrote about “lessons learned” from the 1918 pandemic, and how residual sequelae in that era led to a condition labeled hyperkinetic syndrome in children. “It may be worthwhile to consider the hypothesis that the COVID-19 pandemic may result in a novel etiologic subtype of ADHD that clinicians may recognize in patients in the future,” wrote the commentators. 

In survivors of the 1918 pandemic, brain inflammation or encephalitis sometimes emerged as residual sequelae, said Dr. Swanson. In some adult cases, these symptoms were diagnosed as “encephalitis lethargica” (EL) and were associated with Parkinson’s disease. In 1930, based on patients evaluated after 1918, researchers Franz Kramer and Hans Pollnow at Charité Hospital in Berlin described the behavioral manifestation of EL in children as hyperkinetic syndrome, a condition that was characterized by symptoms similar to the properties of ADHD: lack of concentration, insufficient goal orientation, and increased distractibility. “They even reported on autopsy cases that described brain regions that we now know are associated with ADHD from decades of brain imaging studies,” said Dr. Swanson.

COVID-19 rarely results in severe respiratory problems in children but the absolute number requiring hospitalization has accumulated and is now relatively large, said Dr. Swanson. One study of 1,695 severe COVID-19 cases in children and adolescents used MRI and detected neural effects in specific brain regions such as basal ganglia and frontal lobes that previous research had associated with ADHD. Approximately 22% of these rare but severe cases had documented neurologic involvement, and studies of affected children with mild or none of the initial respiratory symptoms of COVID-19 also detected similar selective effects in these brain regions.

A recent survey of medical records of 80 million people that identified 240,000 COVID cases (mostly adults) revealed that a third had neurological and psychiatric sequelae. Dr. Swanson also mentioned an article he wrote more than a decade ago on environmental as well as genetic factors that resulted in etiologic subtypes of ADHD, which provided a model for the impact of COVID-19 on specific brain regions that are associated with ADHD.

So far, the COVID-19 pandemic has produced 150 million cases worldwide and there are about 100 million survivors, setting an estimate of a maximum number of cases with residual sequelae. “I think that severe COVID-19 will probably be related to severe residual sequelae, and that mild or asymptomatic COVID-19 may be associated with less severe residual sequelae, which may resemble ADHD” said Dr. Swanson. If one-third of the cases manifest in some neurologic or psychiatric systems, this means 27 million would have residual sequelae. If 20% have impaired concentration or brain fog, this could result in about 5 million ADHD cases, he said. 
 

Estimates aren’t evidence

The Swanson/Volkow commentary contains a lot of references to “might, could, and may,” said Dr. Coghill. While it’s true that COVID-19 could produce a novel etiologic subtype of ADHD, “the point here is at the moment, all of this is based on hypotheses,” he said.

The Spanish flu did produce mental health consequences – survivors reported depression, sleep disturbances, mental distraction, dizziness, and difficulties coping at work. In the United States, flu death rates from 1918 to 1920 were directly attributed to suicide rates. Unfortunately, these impacts weren’t widely researched, said Dr. Coghill.

It also seems clear that the 1918 Spanish flu outbreak was associated with significant neurological consequences, said Dr. Coghill. By 1919 and 1920, physicians and researchers in the United Kingdom were reporting increases in a variety of symptoms among some patients recovering from flu, such as neuropathy, neurasthenia, meningitis, degenerative changes in nerve cells, and a decline in visual acuity.

The EL cases Dr. Swanson mentioned did coincide with and reach epidemic proportions alongside the Spanish flu. “But still, a causal relationship is far from proven,” said Dr. Coghill.

Sol Levy, MD, described a “disease of criminals” following the 1918 pandemic, in which patients exhibited a high degree of general hyperkinesis, a difficulty in maintaining quiet attitudes, abruptness and clumsiness, and “explosive motor release of all voluntarily inhibited activities.”

However, these impairments suggest a much broader presentation typically seen in ADHD, noted Dr. Coghill.

Neurological complications occur more commonly than initially thought in severe COVID-19, with estimates ranging from 36% to 84%. But in a systematic review of neuropsychiatric complications of severe coronavirus infection, researchers found few psychiatric sequelae of these infections. While they did mention impaired concentration and difficulties with emotional ability, it’s very important to remember that these conditions “are cardinal symptoms of a wide range of psychiatric disorders,” said Dr. Coghill.

Overall, more neurological and neuropsychiatric symptoms largely confine to those with severe COVID-19, meaning they’re much less likely to occur in children and young adults, he said.

If there are severe effects of COVID-19, Dr. Swanson countered that “they might have more ADHD than the complex residual effects [Dr. Coghill] described. I hope that he’s right, but I do think there will be biological co-effects of COVID-19 that will produce symptoms that are more ADHD than other neurological disorders.”
 

Epigenetic effects

Researchers are now seeing transgenerational and intergenerational effects of potential infection. “So I certainly back high-quality studies looking at the effects of maternal and paternal infection on offspring,” said Dr. Coghill. Establishing clinical cohort studies to follow up on this population would be essential in understanding the risks of SARS-CoV-2. “That might be one way we’ll see an increase in ADHD,” said Dr. Coghill.

The reality is COVID-19 hasn’t been around for that long, and current knowledge about it is limited, he said. Rapid publications, cross-sectional or retrospective data, and poor methodological quality and rigor make generalizability difficult. In addition, limited testing and detection probably underestimate prevalence of neurological and neuropsychiatric complications.

“If history teaches us anything, it is that we should always be measured in how we glean lessons from the past. So let’s not get ahead of ourselves,” he cautioned.

An informal, post-discussion survey of session participants revealed that a slight majority – 55%-60% – expected residual effects of COVID-19 to lead to more ADHD, compared to 40%-45% who didn’t think this would happen.

Dr. Swanson has two patents: (PIXA4), which uses a “time-of-flight” camera to measure growth on infants, and a provisional patent on the mechanism of tolerance to stimulant medication (PATSMTA). Dr. Coghill worked for several pharmaceutical companies but had no disclosures relevant to this debate.

For children with attention-deficit/hyperactivity disorder, taking a weekend or summer break from methylphenidate may have some benefits. A drug “holiday” can help assess whether a drug is still useful and possibly help with drug tolerance, weight gain, and growth suppression. But drug holidays are not without their problems, Lily Hechtman, MD, FRCP, professor at the department of psychiatry, McGill University, Montreal, said during a session at the World Congress on ADHD – Virtual Event.

Ceasing a medication can have repercussions from a health and social standpoint, cautioned Dr. Hechtman, a presenter and moderator of the session, “Unsolved mysteries in the treatment of ADHD with psychostimulants.”

The rate of drug holidays is somewhere between 30% and 40% in ADHD patients. Patients have multiple reasons for taking them, said Dr. Hechtman. The American Academy of Child & Adolescent Psychology as well as the National Institute for Health and Clinical Excellence recommend this method to assess whether a medication is still necessary. Parents may opt for a drug holiday because most would prefer their children to take less medication.

A drug holiday can counteract some of the key side effects of stimulant medication such as decreased appetite and weight loss, and the moodiness and irritability that accompanies the medication, as well as sleep problems.

It may also be used to avoid drug tolerance, the need to increase dosage as medication continues. A 2002 study of 166 children and adolescents treated with methylphenidate revealed that 60% had developed drug tolerance. Drug tolerance increases with duration. “So, the longer the child is on medication, the more likely he or she will develop some drug tolerance,” said Dr. Hechtman.

It is hypothesized that a drug holiday results in the resensitization of the neurons in the brain because they aren’t exposed to the stimulation of dopamine release and dopamine exposure.

The minimum time a patient needs a drug holiday to deal with some drug tolerance is about a month. “Even if you have a drug holiday and your drug tolerance has been decreased, it can reoccur with increasing dosages, once medication resumes” after the holiday, said Dr. Hechtman.
 

The growth factor

A drug holiday can also address concerns about growth suppression. “Some studies show that drug holidays help with growth suppression and others do not,” said Dr. Hechtman.

The Multimodal Treatment of ADHD (MTA) study, which followed children with ADHD from childhood to adolescence into adulthood, offers some key insights on the effects of treatment on growth.

Over a 10-year period, “you could see that the rate of medication use decreased significantly with time” among participants, said Dr. Hechtman, a coauthor of the MTA research. Only 10% who began the study aged 7-9 years were still using stimulants 10 years later. Looking at short-term effects on growth among these children, those who never went on stimulants to begin with had no growth suppression at all, whereas those who underwent early and consistent treatment experienced the greatest growth suppression.

Comparatively, inconsistently medicated participants had less growth suppression than those who remained on medication. “They were pretty close to the controls,” said Dr. Hechtman.

These patterns continued in a 16-year follow-up, as these patients became adults. Based on the results in the inconsistently treated group, this suggests that drug holidays can limit the effects of growth suppression, at least to a certain extent, said Dr. Hechtman.

Other studies have yielded varying results on the impact of drug holidays on height and weight. “The evidence for the utility of drug holidays for medication side effects is there for decreased appetite and weight, but not so much for decreased height,” summarized Dr. Hechtman.

One recent study of 230 children by James Waxmonsky and colleagues that examined drug holidays on weekends and summers showed that drug holidays did increase weight but interestingly, not height. Older studies Dr. Hechtman cited had inconsistent results on height and weight gain and loss. A 2012 study suggested that drug holidays resulted in a slight improvement in appetite for both weekend and school holidays. But only 9% of the children in the sample (n = 51) saw their appetite return to normal levels.
 

‘Negative things can happen’

The downside of drug holidays is parents may rationalize that their child is doing fine without the medication, and discontinue it. The process of stopping and starting medication can lead to other problems. “Negative things can happen during drug holidays,” said Dr. Hechtman.

The large variability of doses over the weekend can result in rebound and side effects.

A child may go from a full dose, which could be 50-60 mg of stimulant to zero from Friday to Saturday. As a result they have a lot of rebound on that Saturday. Similarly, they go from zero on Sunday to full dose on the Monday, causing lots of side effects. “Also, they will never have a stable effective dose because of the roller-coaster effect of being on and off the drugs,” she noted.

The lack of consistency and accommodation to the side effects can lead to discontinuation of the medication.

Off medication, the child may be more accident prone or have more injuries. “Their behavior off the medication may be such that it leads to social problems,” Dr. Hechtman continued. Weekend activities that require medication such as homework or school projects, family or religious gatherings, or sports and social activities with family and peers may be affected. If the child is behaving poorly off the medication, they may be expelled from such activities. If it’s a summer drug holiday, they may get kicked out of camp or the swimming pool.

If the child’s condition is already worsening, and a drug holiday takes place on top of this, the child may experience a rebound or relapse, in which the condition looks a lot worse than it did with the drugs.
 

Do drug holidays matter?

Another session speaker, James Swanson, PhD, who noted that the “emergence of tolerance may limit and eventually undermine initial relative benefit” of stimulants, said there may be instances in which drug holidays may be impractical.

Given the poor adherence to ADHD medication, “most treated ADHD cases stop medication anyway and these patients do not have an opportunity for drug holidays,” he said in an interview.

“If tolerance does emerge, then for long-term treatment the concept of drug holiday seems difficult to evaluate to me,” said Dr. Swanson, director of the Child Development Center at the University of California, Irvine.

Planned medication breaks may not be a good way to evaluate efficacy unless it is performed under “double-blind” conditions, he offered. The MTA used an approach of switching between short periods of time, with and without medication. “We did this to compare medication to placebo and to compare doses of medication to optimize the short-term benefit,” said Dr. Swanson, a coauthor of the MTA study.

Dr. Hechtman receives funding from The Canadian Institutes of Health Research. Dr. Swanson has two patents: (PIXA4), which uses a “time-of-flight” camera to measure growth on infants, and a provisional patent on the mechanism of tolerance to stimulant medication (PATSMTA).

For children with attention-deficit/hyperactivity disorder, taking a weekend or summer break from methylphenidate may have some benefits. A drug “holiday” can help assess whether a drug is still useful and possibly help with drug tolerance, weight gain, and growth suppression. But drug holidays are not without their problems, Lily Hechtman, MD, FRCP, professor at the department of psychiatry, McGill University, Montreal, said during a session at the World Congress on ADHD – Virtual Event.

Ceasing a medication can have repercussions from a health and social standpoint, cautioned Dr. Hechtman, a presenter and moderator of the session, “Unsolved mysteries in the treatment of ADHD with psychostimulants.”

The rate of drug holidays is somewhere between 30% and 40% in ADHD patients. Patients have multiple reasons for taking them, said Dr. Hechtman. The American Academy of Child & Adolescent Psychology as well as the National Institute for Health and Clinical Excellence recommend this method to assess whether a medication is still necessary. Parents may opt for a drug holiday because most would prefer their children to take less medication.

A drug holiday can counteract some of the key side effects of stimulant medication such as decreased appetite and weight loss, and the moodiness and irritability that accompanies the medication, as well as sleep problems.

It may also be used to avoid drug tolerance, the need to increase dosage as medication continues. A 2002 study of 166 children and adolescents treated with methylphenidate revealed that 60% had developed drug tolerance. Drug tolerance increases with duration. “So, the longer the child is on medication, the more likely he or she will develop some drug tolerance,” said Dr. Hechtman.

It is hypothesized that a drug holiday results in the resensitization of the neurons in the brain because they aren’t exposed to the stimulation of dopamine release and dopamine exposure.

The minimum time a patient needs a drug holiday to deal with some drug tolerance is about a month. “Even if you have a drug holiday and your drug tolerance has been decreased, it can reoccur with increasing dosages, once medication resumes” after the holiday, said Dr. Hechtman.
 

The growth factor

A drug holiday can also address concerns about growth suppression. “Some studies show that drug holidays help with growth suppression and others do not,” said Dr. Hechtman.

The Multimodal Treatment of ADHD (MTA) study, which followed children with ADHD from childhood to adolescence into adulthood, offers some key insights on the effects of treatment on growth.

Over a 10-year period, “you could see that the rate of medication use decreased significantly with time” among participants, said Dr. Hechtman, a coauthor of the MTA research. Only 10% who began the study aged 7-9 years were still using stimulants 10 years later. Looking at short-term effects on growth among these children, those who never went on stimulants to begin with had no growth suppression at all, whereas those who underwent early and consistent treatment experienced the greatest growth suppression.

Comparatively, inconsistently medicated participants had less growth suppression than those who remained on medication. “They were pretty close to the controls,” said Dr. Hechtman.

These patterns continued in a 16-year follow-up, as these patients became adults. Based on the results in the inconsistently treated group, this suggests that drug holidays can limit the effects of growth suppression, at least to a certain extent, said Dr. Hechtman.

Other studies have yielded varying results on the impact of drug holidays on height and weight. “The evidence for the utility of drug holidays for medication side effects is there for decreased appetite and weight, but not so much for decreased height,” summarized Dr. Hechtman.

One recent study of 230 children by James Waxmonsky and colleagues that examined drug holidays on weekends and summers showed that drug holidays did increase weight but interestingly, not height. Older studies Dr. Hechtman cited had inconsistent results on height and weight gain and loss. A 2012 study suggested that drug holidays resulted in a slight improvement in appetite for both weekend and school holidays. But only 9% of the children in the sample (n = 51) saw their appetite return to normal levels.
 

‘Negative things can happen’

The downside of drug holidays is parents may rationalize that their child is doing fine without the medication, and discontinue it. The process of stopping and starting medication can lead to other problems. “Negative things can happen during drug holidays,” said Dr. Hechtman.

The large variability of doses over the weekend can result in rebound and side effects.

A child may go from a full dose, which could be 50-60 mg of stimulant to zero from Friday to Saturday. As a result they have a lot of rebound on that Saturday. Similarly, they go from zero on Sunday to full dose on the Monday, causing lots of side effects. “Also, they will never have a stable effective dose because of the roller-coaster effect of being on and off the drugs,” she noted.

The lack of consistency and accommodation to the side effects can lead to discontinuation of the medication.

Off medication, the child may be more accident prone or have more injuries. “Their behavior off the medication may be such that it leads to social problems,” Dr. Hechtman continued. Weekend activities that require medication such as homework or school projects, family or religious gatherings, or sports and social activities with family and peers may be affected. If the child is behaving poorly off the medication, they may be expelled from such activities. If it’s a summer drug holiday, they may get kicked out of camp or the swimming pool.

If the child’s condition is already worsening, and a drug holiday takes place on top of this, the child may experience a rebound or relapse, in which the condition looks a lot worse than it did with the drugs.
 

Do drug holidays matter?

Another session speaker, James Swanson, PhD, who noted that the “emergence of tolerance may limit and eventually undermine initial relative benefit” of stimulants, said there may be instances in which drug holidays may be impractical.

Given the poor adherence to ADHD medication, “most treated ADHD cases stop medication anyway and these patients do not have an opportunity for drug holidays,” he said in an interview.

“If tolerance does emerge, then for long-term treatment the concept of drug holiday seems difficult to evaluate to me,” said Dr. Swanson, director of the Child Development Center at the University of California, Irvine.

Planned medication breaks may not be a good way to evaluate efficacy unless it is performed under “double-blind” conditions, he offered. The MTA used an approach of switching between short periods of time, with and without medication. “We did this to compare medication to placebo and to compare doses of medication to optimize the short-term benefit,” said Dr. Swanson, a coauthor of the MTA study.

Dr. Hechtman receives funding from The Canadian Institutes of Health Research. Dr. Swanson has two patents: (PIXA4), which uses a “time-of-flight” camera to measure growth on infants, and a provisional patent on the mechanism of tolerance to stimulant medication (PATSMTA).

For children with attention-deficit/hyperactivity disorder, taking a weekend or summer break from methylphenidate may have some benefits. A drug “holiday” can help assess whether a drug is still useful and possibly help with drug tolerance, weight gain, and growth suppression. But drug holidays are not without their problems, Lily Hechtman, MD, FRCP, professor at the department of psychiatry, McGill University, Montreal, said during a session at the World Congress on ADHD – Virtual Event.

Ceasing a medication can have repercussions from a health and social standpoint, cautioned Dr. Hechtman, a presenter and moderator of the session, “Unsolved mysteries in the treatment of ADHD with psychostimulants.”

The rate of drug holidays is somewhere between 30% and 40% in ADHD patients. Patients have multiple reasons for taking them, said Dr. Hechtman. The American Academy of Child & Adolescent Psychology as well as the National Institute for Health and Clinical Excellence recommend this method to assess whether a medication is still necessary. Parents may opt for a drug holiday because most would prefer their children to take less medication.

A drug holiday can counteract some of the key side effects of stimulant medication such as decreased appetite and weight loss, and the moodiness and irritability that accompanies the medication, as well as sleep problems.

It may also be used to avoid drug tolerance, the need to increase dosage as medication continues. A 2002 study of 166 children and adolescents treated with methylphenidate revealed that 60% had developed drug tolerance. Drug tolerance increases with duration. “So, the longer the child is on medication, the more likely he or she will develop some drug tolerance,” said Dr. Hechtman.

It is hypothesized that a drug holiday results in the resensitization of the neurons in the brain because they aren’t exposed to the stimulation of dopamine release and dopamine exposure.

The minimum time a patient needs a drug holiday to deal with some drug tolerance is about a month. “Even if you have a drug holiday and your drug tolerance has been decreased, it can reoccur with increasing dosages, once medication resumes” after the holiday, said Dr. Hechtman.
 

The growth factor

A drug holiday can also address concerns about growth suppression. “Some studies show that drug holidays help with growth suppression and others do not,” said Dr. Hechtman.

The Multimodal Treatment of ADHD (MTA) study, which followed children with ADHD from childhood to adolescence into adulthood, offers some key insights on the effects of treatment on growth.

Over a 10-year period, “you could see that the rate of medication use decreased significantly with time” among participants, said Dr. Hechtman, a coauthor of the MTA research. Only 10% who began the study aged 7-9 years were still using stimulants 10 years later. Looking at short-term effects on growth among these children, those who never went on stimulants to begin with had no growth suppression at all, whereas those who underwent early and consistent treatment experienced the greatest growth suppression.

Comparatively, inconsistently medicated participants had less growth suppression than those who remained on medication. “They were pretty close to the controls,” said Dr. Hechtman.

These patterns continued in a 16-year follow-up, as these patients became adults. Based on the results in the inconsistently treated group, this suggests that drug holidays can limit the effects of growth suppression, at least to a certain extent, said Dr. Hechtman.

Other studies have yielded varying results on the impact of drug holidays on height and weight. “The evidence for the utility of drug holidays for medication side effects is there for decreased appetite and weight, but not so much for decreased height,” summarized Dr. Hechtman.

One recent study of 230 children by James Waxmonsky and colleagues that examined drug holidays on weekends and summers showed that drug holidays did increase weight but interestingly, not height. Older studies Dr. Hechtman cited had inconsistent results on height and weight gain and loss. A 2012 study suggested that drug holidays resulted in a slight improvement in appetite for both weekend and school holidays. But only 9% of the children in the sample (n = 51) saw their appetite return to normal levels.
 

‘Negative things can happen’

The downside of drug holidays is parents may rationalize that their child is doing fine without the medication, and discontinue it. The process of stopping and starting medication can lead to other problems. “Negative things can happen during drug holidays,” said Dr. Hechtman.

The large variability of doses over the weekend can result in rebound and side effects.

A child may go from a full dose, which could be 50-60 mg of stimulant to zero from Friday to Saturday. As a result they have a lot of rebound on that Saturday. Similarly, they go from zero on Sunday to full dose on the Monday, causing lots of side effects. “Also, they will never have a stable effective dose because of the roller-coaster effect of being on and off the drugs,” she noted.

The lack of consistency and accommodation to the side effects can lead to discontinuation of the medication.

Off medication, the child may be more accident prone or have more injuries. “Their behavior off the medication may be such that it leads to social problems,” Dr. Hechtman continued. Weekend activities that require medication such as homework or school projects, family or religious gatherings, or sports and social activities with family and peers may be affected. If the child is behaving poorly off the medication, they may be expelled from such activities. If it’s a summer drug holiday, they may get kicked out of camp or the swimming pool.

If the child’s condition is already worsening, and a drug holiday takes place on top of this, the child may experience a rebound or relapse, in which the condition looks a lot worse than it did with the drugs.
 

Do drug holidays matter?

Another session speaker, James Swanson, PhD, who noted that the “emergence of tolerance may limit and eventually undermine initial relative benefit” of stimulants, said there may be instances in which drug holidays may be impractical.

Given the poor adherence to ADHD medication, “most treated ADHD cases stop medication anyway and these patients do not have an opportunity for drug holidays,” he said in an interview.

“If tolerance does emerge, then for long-term treatment the concept of drug holiday seems difficult to evaluate to me,” said Dr. Swanson, director of the Child Development Center at the University of California, Irvine.

Planned medication breaks may not be a good way to evaluate efficacy unless it is performed under “double-blind” conditions, he offered. The MTA used an approach of switching between short periods of time, with and without medication. “We did this to compare medication to placebo and to compare doses of medication to optimize the short-term benefit,” said Dr. Swanson, a coauthor of the MTA study.

Dr. Hechtman receives funding from The Canadian Institutes of Health Research. Dr. Swanson has two patents: (PIXA4), which uses a “time-of-flight” camera to measure growth on infants, and a provisional patent on the mechanism of tolerance to stimulant medication (PATSMTA).

New digital tools are on the horizon to help patients with attention-deficit/hyperactivity disorder (ADHD) manage the condition.

Rostislav_Sedlacek/Thinkstock

Speakers at the World Congress on ADHD – Virtual Event described innovations aimed at improving medication compliance or reducing symptoms through the use of smartphone technology such as apps and text messaging, and video games. Some of these technologies have shown promising results in clinical trials, but the experts called for additional studies to further vet their efficacy.

An explosion in technology

ADHD, the most common neurodevelopmental disorder, has global prevalence rates ranging from 5% to 7%, said Dr. Kirk. Digital technology and digital health “have been heralded as having enormous potential to improve early access and to improve the increasing demand in child support services,” she said.

The world has seen an explosion of digital technology innovation in the last decade, spurred on most recently by the COVID-19 pandemic. New demand exists for tools in educational and health care settings to provide information and support through websites, apps, SMS, video conferencing, and wearable devices, Dr. Kirk said.

Looking at the landscape of ADHD digital therapeutics, “there are probably tens of thousands of apps and other digital products to treat and manage conditions across the spectrum,” said Scott H. Kollins, PhD, MS, a clinical psychologist at Duke Health’s ADHD Clinic in Durham, N.C.

Video game interventions

AKL-T01, a tool that pairs continuous fine motor tasks and perceptual reaction time tasks, went through several rounds of clinical trials to achieve federal approval as a digital therapeutic.

“This not just another video game,” said Dr. Kollins, who helped developed it. The tool’s adaptive algorithms adjust and monitor task difficulty based on performance, using a video game format and rewards to engage users.

Two phase 3 trials provided the basis for the Food and Drug Administration’s approval of AKL-T01, also known as EndeavorRx, in 2020. The first trial, published in The Lancet, randomized 348 children 1:1 to receive either the AKL-T01 treatment or a controlled intervention, which was a word game. Participating children aged 8-12 with a confirmed ADHD diagnosis were asked to play the game for about 25 minutes a day, 5 days a week over 4 weeks. The study excluded children who were taking medicine.

The researchers reported statistically significant improvements in attentional functioning in the AKL-T01 group as rated by test of variables of attention. The trial reported no serious adverse events, although one child in the AKL-T01 group withdrew from the study.

“As kids go through this treatment, it’s challenging and the difficulty levels increase, so it’s not surprising that kids get frustrated with that, or have emotional outbursts,” Dr. Kollins said. Those reactions suggest that the intervention was working, he added.

A follow-up study, published in npj Digital Medicine, broadened the scope. That study included children who had taken medication and extended the study period. Overall, 206 children aged 8-14 (130 on stimulants and 76 on no medication) played the game for 28 days, taking a pause for another 28 days, then reinitiating the treatment.

As in the first trial, AKL-T01 significantly improved ADHD-related impairment, a metric that continued to improve in the second round of treatment. Looking at secondary outcomes, the proportion of children deemed as clinical responders on the Impairment Rating Scale, 68.3% of all of the participants were responders by the end of the study on the ADHD ratings scale, meaning there was a greater than 30% improvement in symptoms. Upward of 50% of participants at the end of the second round of treatment showed substantial improvement in their ADHD ratings scale scores.

“This was really a substantial move ... the first-ever app-based video game approved by the FDA,” noted Dr. Kollins, who is affiliated with the Duke Clinical Research Institute. Some skeptics have called this a marketing ploy or have questioned the integrity of the FDA approval process.

“I would submit and argue that the rigor of the trial speaks for itself,” he said. “But it’s not surprising that there’s skepticism in the clinical community about something like this – a brand new treatment modality.”

In her own research, Dr. Kirk has studied game-based interventions aimed at assessing ADHD and improving cognitive training. In 2018, her team developed a touch screen game–based intervention for early evaluation of attention skills, using six activities. In a visual search task, children were asked to locate red lobsters on a screen that showed a variety of underwater creatures. In another selection attention task, children were asked to scan the screen for a particular target, such as a yellow star, and to indicate whether that target was absent or present on the screen. Other tasks assessed for sustained attention abilities and information processing speed.

She and her colleagues recruited 340 children aged 4-7 years to evaluate whether the tool produced consistent results over time, and compared favorably to existing measures of attention. None of the participants had been diagnosed with ADHD. To assess reliability, a subset of children completed another assessment 2 weeks after the first one. The study showed varying results according to activity. The visual search task had high test-retest reliability and the strongest validity, compared with the other tasks. The sustained attention tasks exhibited the weakest validity.

The next steps are to assess whether this tool is sensitive enough to detect differences between children with or without clinical attention difficulties such as ADHD, Dr. Kirk said.

Apps improve adherence

As some technologies focus on reducing symptoms through games, others seek to improve medication compliance through SMS and smartphone apps.

Studies have shown that medication can decrease incidence of smoking, mood disorders, traumatic brain injuries, car crashes, and educational outcomes. However, risk decreases only if compliance is good, said Joseph Biederman, MD. Right now, “there’s extremely poor adherence to stimulant medications in ADHD” across the world, said Dr. Biederman, chief of clinical and research programs in pediatric psychopharmacology and adult ADHD at Massachusetts General Hospital in Boston.

“This is a problem that’s driven by ADHD itself,” he continued. Prescribers don’t always have the time to educate the patient on medications, deal with misconceptions, or provide support for management of daily activities.

Text reminders may offer a solution. Partnering with a Canadian technology company, MEMOTEXT, Dr. Biederman and colleagues at Massachusetts General Hospital developed an SMS-based disease management intervention for ADHD.

The tool aims to manage work, home life, and social relationships by supporting the timely renewal of medications. It doesn’t just remind people to take their ADHD medication, it reminds them to take any other medication they need, and provides the reasons why it’s important to take these drugs. Through interactive questions, it also assesses the progress and knowledge of patients and families about ADHD.

Testing this app in pediatric settings, Dr. Biederman and colleagues published a study in the Journal of Psychopharmacology showing a dramatic increase in compliance – from 60% to 90%.

In another study, this one published in the Journal of Clinical Psychopharmacology, Dr. Biederman and colleagues found that compliance improved, from 35% to 70% in adults. The SMS program in these settings not only improved adherence, but it also reduced costs of ADHD-associated complications while adding beneficial support and value to patients, families, and prescribers, Dr. Biederman said.

Promising findings about the power of apps to increase ADHD medication adherence led Luis Augusto Rohde, MD, PhD, and colleagues to develop the FOCUS app in 2016, for use in his home country of Brazil. The app objectively monitors symptoms of ADHD and establishes cooperative relationships between the patient, their families, and caregivers, said Dr. Rohde, professor of child and adolescent psychiatry at the Federal University of Rio Grande do Sul’s department of psychiatry, Porto Alegre, Brazil.

Digital tech pros and cons

The accessibility of digital technology to children living in remote areas is one of its biggest assets, Dr. Kirk said.

Digital technologies capture real time data, are easy to use, are suitable for young children with developmental disorders, have few adverse effects, and can be easily updated. However, there are some limitations, she added. Attitudes toward technology, time required to supervise their use, and funding to facilitate the use of such technology can hinder implementation. Given that digital technology is increasingly being used to collect sensitive medical data and assess clinical conditions, it’s crucial for these new technologies to be compliant with HIPAA requirements, Dr. Kirk said.

“We are at the front end of a revolution, and much more of this is coming down the pike,” Dr. Kollins predicted. Developers need to be thoughtful and deliberate in how they design clinical evidence strategies for digital therapeutics for ADHD.

“There’s much work that needs to be done from a clinical, statistical, regulatory, and policy perspective, but this journey illustrates this can be done with ADHD and other mental health conditions.”

Dr. Kirk disclosed working previously for a small technology company in Melbourne that developed medical technologies for children. Dr. Kollins’ work has been supported by numerous U.S. agencies, including the National Institute of Mental Health. He has served as a consultant to numerous pharmaceutical companies tied to ADHD clinical psychopharmacology. Dr. Biederman has provided research support to Genentech, Headspace, Pfizer, Roche Translational & Clinical Research Center, and other pharmaceutical companies. Also, Dr. Biederman has a partnership with MEMOTEXT through Partners Healthcare Innovation. Dr. Rohde has received grant or research support from, and served as a consultant to, several companies, including Bial, Novartis, Pfizer, and Shire/Takeda. He has received authorship royalties from Oxford University Press and ArtMed, and travel grants from Shire.

New digital tools are on the horizon to help patients with attention-deficit/hyperactivity disorder (ADHD) manage the condition.

Rostislav_Sedlacek/Thinkstock

Speakers at the World Congress on ADHD – Virtual Event described innovations aimed at improving medication compliance or reducing symptoms through the use of smartphone technology such as apps and text messaging, and video games. Some of these technologies have shown promising results in clinical trials, but the experts called for additional studies to further vet their efficacy.

An explosion in technology

ADHD, the most common neurodevelopmental disorder, has global prevalence rates ranging from 5% to 7%, said Dr. Kirk. Digital technology and digital health “have been heralded as having enormous potential to improve early access and to improve the increasing demand in child support services,” she said.

The world has seen an explosion of digital technology innovation in the last decade, spurred on most recently by the COVID-19 pandemic. New demand exists for tools in educational and health care settings to provide information and support through websites, apps, SMS, video conferencing, and wearable devices, Dr. Kirk said.

Looking at the landscape of ADHD digital therapeutics, “there are probably tens of thousands of apps and other digital products to treat and manage conditions across the spectrum,” said Scott H. Kollins, PhD, MS, a clinical psychologist at Duke Health’s ADHD Clinic in Durham, N.C.

Video game interventions

AKL-T01, a tool that pairs continuous fine motor tasks and perceptual reaction time tasks, went through several rounds of clinical trials to achieve federal approval as a digital therapeutic.

“This not just another video game,” said Dr. Kollins, who helped developed it. The tool’s adaptive algorithms adjust and monitor task difficulty based on performance, using a video game format and rewards to engage users.

Two phase 3 trials provided the basis for the Food and Drug Administration’s approval of AKL-T01, also known as EndeavorRx, in 2020. The first trial, published in The Lancet, randomized 348 children 1:1 to receive either the AKL-T01 treatment or a controlled intervention, which was a word game. Participating children aged 8-12 with a confirmed ADHD diagnosis were asked to play the game for about 25 minutes a day, 5 days a week over 4 weeks. The study excluded children who were taking medicine.

The researchers reported statistically significant improvements in attentional functioning in the AKL-T01 group as rated by test of variables of attention. The trial reported no serious adverse events, although one child in the AKL-T01 group withdrew from the study.

“As kids go through this treatment, it’s challenging and the difficulty levels increase, so it’s not surprising that kids get frustrated with that, or have emotional outbursts,” Dr. Kollins said. Those reactions suggest that the intervention was working, he added.

A follow-up study, published in npj Digital Medicine, broadened the scope. That study included children who had taken medication and extended the study period. Overall, 206 children aged 8-14 (130 on stimulants and 76 on no medication) played the game for 28 days, taking a pause for another 28 days, then reinitiating the treatment.

As in the first trial, AKL-T01 significantly improved ADHD-related impairment, a metric that continued to improve in the second round of treatment. Looking at secondary outcomes, the proportion of children deemed as clinical responders on the Impairment Rating Scale, 68.3% of all of the participants were responders by the end of the study on the ADHD ratings scale, meaning there was a greater than 30% improvement in symptoms. Upward of 50% of participants at the end of the second round of treatment showed substantial improvement in their ADHD ratings scale scores.

“This was really a substantial move ... the first-ever app-based video game approved by the FDA,” noted Dr. Kollins, who is affiliated with the Duke Clinical Research Institute. Some skeptics have called this a marketing ploy or have questioned the integrity of the FDA approval process.

“I would submit and argue that the rigor of the trial speaks for itself,” he said. “But it’s not surprising that there’s skepticism in the clinical community about something like this – a brand new treatment modality.”

In her own research, Dr. Kirk has studied game-based interventions aimed at assessing ADHD and improving cognitive training. In 2018, her team developed a touch screen game–based intervention for early evaluation of attention skills, using six activities. In a visual search task, children were asked to locate red lobsters on a screen that showed a variety of underwater creatures. In another selection attention task, children were asked to scan the screen for a particular target, such as a yellow star, and to indicate whether that target was absent or present on the screen. Other tasks assessed for sustained attention abilities and information processing speed.

She and her colleagues recruited 340 children aged 4-7 years to evaluate whether the tool produced consistent results over time, and compared favorably to existing measures of attention. None of the participants had been diagnosed with ADHD. To assess reliability, a subset of children completed another assessment 2 weeks after the first one. The study showed varying results according to activity. The visual search task had high test-retest reliability and the strongest validity, compared with the other tasks. The sustained attention tasks exhibited the weakest validity.

The next steps are to assess whether this tool is sensitive enough to detect differences between children with or without clinical attention difficulties such as ADHD, Dr. Kirk said.

Apps improve adherence

As some technologies focus on reducing symptoms through games, others seek to improve medication compliance through SMS and smartphone apps.

Studies have shown that medication can decrease incidence of smoking, mood disorders, traumatic brain injuries, car crashes, and educational outcomes. However, risk decreases only if compliance is good, said Joseph Biederman, MD. Right now, “there’s extremely poor adherence to stimulant medications in ADHD” across the world, said Dr. Biederman, chief of clinical and research programs in pediatric psychopharmacology and adult ADHD at Massachusetts General Hospital in Boston.

“This is a problem that’s driven by ADHD itself,” he continued. Prescribers don’t always have the time to educate the patient on medications, deal with misconceptions, or provide support for management of daily activities.

Text reminders may offer a solution. Partnering with a Canadian technology company, MEMOTEXT, Dr. Biederman and colleagues at Massachusetts General Hospital developed an SMS-based disease management intervention for ADHD.

The tool aims to manage work, home life, and social relationships by supporting the timely renewal of medications. It doesn’t just remind people to take their ADHD medication, it reminds them to take any other medication they need, and provides the reasons why it’s important to take these drugs. Through interactive questions, it also assesses the progress and knowledge of patients and families about ADHD.

Testing this app in pediatric settings, Dr. Biederman and colleagues published a study in the Journal of Psychopharmacology showing a dramatic increase in compliance – from 60% to 90%.

In another study, this one published in the Journal of Clinical Psychopharmacology, Dr. Biederman and colleagues found that compliance improved, from 35% to 70% in adults. The SMS program in these settings not only improved adherence, but it also reduced costs of ADHD-associated complications while adding beneficial support and value to patients, families, and prescribers, Dr. Biederman said.

Promising findings about the power of apps to increase ADHD medication adherence led Luis Augusto Rohde, MD, PhD, and colleagues to develop the FOCUS app in 2016, for use in his home country of Brazil. The app objectively monitors symptoms of ADHD and establishes cooperative relationships between the patient, their families, and caregivers, said Dr. Rohde, professor of child and adolescent psychiatry at the Federal University of Rio Grande do Sul’s department of psychiatry, Porto Alegre, Brazil.

Digital tech pros and cons

The accessibility of digital technology to children living in remote areas is one of its biggest assets, Dr. Kirk said.

Digital technologies capture real time data, are easy to use, are suitable for young children with developmental disorders, have few adverse effects, and can be easily updated. However, there are some limitations, she added. Attitudes toward technology, time required to supervise their use, and funding to facilitate the use of such technology can hinder implementation. Given that digital technology is increasingly being used to collect sensitive medical data and assess clinical conditions, it’s crucial for these new technologies to be compliant with HIPAA requirements, Dr. Kirk said.

“We are at the front end of a revolution, and much more of this is coming down the pike,” Dr. Kollins predicted. Developers need to be thoughtful and deliberate in how they design clinical evidence strategies for digital therapeutics for ADHD.

“There’s much work that needs to be done from a clinical, statistical, regulatory, and policy perspective, but this journey illustrates this can be done with ADHD and other mental health conditions.”

Dr. Kirk disclosed working previously for a small technology company in Melbourne that developed medical technologies for children. Dr. Kollins’ work has been supported by numerous U.S. agencies, including the National Institute of Mental Health. He has served as a consultant to numerous pharmaceutical companies tied to ADHD clinical psychopharmacology. Dr. Biederman has provided research support to Genentech, Headspace, Pfizer, Roche Translational & Clinical Research Center, and other pharmaceutical companies. Also, Dr. Biederman has a partnership with MEMOTEXT through Partners Healthcare Innovation. Dr. Rohde has received grant or research support from, and served as a consultant to, several companies, including Bial, Novartis, Pfizer, and Shire/Takeda. He has received authorship royalties from Oxford University Press and ArtMed, and travel grants from Shire.

New digital tools are on the horizon to help patients with attention-deficit/hyperactivity disorder (ADHD) manage the condition.

Rostislav_Sedlacek/Thinkstock

Speakers at the World Congress on ADHD – Virtual Event described innovations aimed at improving medication compliance or reducing symptoms through the use of smartphone technology such as apps and text messaging, and video games. Some of these technologies have shown promising results in clinical trials, but the experts called for additional studies to further vet their efficacy.

An explosion in technology

ADHD, the most common neurodevelopmental disorder, has global prevalence rates ranging from 5% to 7%, said Dr. Kirk. Digital technology and digital health “have been heralded as having enormous potential to improve early access and to improve the increasing demand in child support services,” she said.

The world has seen an explosion of digital technology innovation in the last decade, spurred on most recently by the COVID-19 pandemic. New demand exists for tools in educational and health care settings to provide information and support through websites, apps, SMS, video conferencing, and wearable devices, Dr. Kirk said.

Looking at the landscape of ADHD digital therapeutics, “there are probably tens of thousands of apps and other digital products to treat and manage conditions across the spectrum,” said Scott H. Kollins, PhD, MS, a clinical psychologist at Duke Health’s ADHD Clinic in Durham, N.C.

Video game interventions

AKL-T01, a tool that pairs continuous fine motor tasks and perceptual reaction time tasks, went through several rounds of clinical trials to achieve federal approval as a digital therapeutic.

“This not just another video game,” said Dr. Kollins, who helped developed it. The tool’s adaptive algorithms adjust and monitor task difficulty based on performance, using a video game format and rewards to engage users.

Two phase 3 trials provided the basis for the Food and Drug Administration’s approval of AKL-T01, also known as EndeavorRx, in 2020. The first trial, published in The Lancet, randomized 348 children 1:1 to receive either the AKL-T01 treatment or a controlled intervention, which was a word game. Participating children aged 8-12 with a confirmed ADHD diagnosis were asked to play the game for about 25 minutes a day, 5 days a week over 4 weeks. The study excluded children who were taking medicine.

The researchers reported statistically significant improvements in attentional functioning in the AKL-T01 group as rated by test of variables of attention. The trial reported no serious adverse events, although one child in the AKL-T01 group withdrew from the study.

“As kids go through this treatment, it’s challenging and the difficulty levels increase, so it’s not surprising that kids get frustrated with that, or have emotional outbursts,” Dr. Kollins said. Those reactions suggest that the intervention was working, he added.

A follow-up study, published in npj Digital Medicine, broadened the scope. That study included children who had taken medication and extended the study period. Overall, 206 children aged 8-14 (130 on stimulants and 76 on no medication) played the game for 28 days, taking a pause for another 28 days, then reinitiating the treatment.

As in the first trial, AKL-T01 significantly improved ADHD-related impairment, a metric that continued to improve in the second round of treatment. Looking at secondary outcomes, the proportion of children deemed as clinical responders on the Impairment Rating Scale, 68.3% of all of the participants were responders by the end of the study on the ADHD ratings scale, meaning there was a greater than 30% improvement in symptoms. Upward of 50% of participants at the end of the second round of treatment showed substantial improvement in their ADHD ratings scale scores.

“This was really a substantial move ... the first-ever app-based video game approved by the FDA,” noted Dr. Kollins, who is affiliated with the Duke Clinical Research Institute. Some skeptics have called this a marketing ploy or have questioned the integrity of the FDA approval process.

“I would submit and argue that the rigor of the trial speaks for itself,” he said. “But it’s not surprising that there’s skepticism in the clinical community about something like this – a brand new treatment modality.”

In her own research, Dr. Kirk has studied game-based interventions aimed at assessing ADHD and improving cognitive training. In 2018, her team developed a touch screen game–based intervention for early evaluation of attention skills, using six activities. In a visual search task, children were asked to locate red lobsters on a screen that showed a variety of underwater creatures. In another selection attention task, children were asked to scan the screen for a particular target, such as a yellow star, and to indicate whether that target was absent or present on the screen. Other tasks assessed for sustained attention abilities and information processing speed.

She and her colleagues recruited 340 children aged 4-7 years to evaluate whether the tool produced consistent results over time, and compared favorably to existing measures of attention. None of the participants had been diagnosed with ADHD. To assess reliability, a subset of children completed another assessment 2 weeks after the first one. The study showed varying results according to activity. The visual search task had high test-retest reliability and the strongest validity, compared with the other tasks. The sustained attention tasks exhibited the weakest validity.

The next steps are to assess whether this tool is sensitive enough to detect differences between children with or without clinical attention difficulties such as ADHD, Dr. Kirk said.

Apps improve adherence

As some technologies focus on reducing symptoms through games, others seek to improve medication compliance through SMS and smartphone apps.

Studies have shown that medication can decrease incidence of smoking, mood disorders, traumatic brain injuries, car crashes, and educational outcomes. However, risk decreases only if compliance is good, said Joseph Biederman, MD. Right now, “there’s extremely poor adherence to stimulant medications in ADHD” across the world, said Dr. Biederman, chief of clinical and research programs in pediatric psychopharmacology and adult ADHD at Massachusetts General Hospital in Boston.

“This is a problem that’s driven by ADHD itself,” he continued. Prescribers don’t always have the time to educate the patient on medications, deal with misconceptions, or provide support for management of daily activities.

Text reminders may offer a solution. Partnering with a Canadian technology company, MEMOTEXT, Dr. Biederman and colleagues at Massachusetts General Hospital developed an SMS-based disease management intervention for ADHD.

The tool aims to manage work, home life, and social relationships by supporting the timely renewal of medications. It doesn’t just remind people to take their ADHD medication, it reminds them to take any other medication they need, and provides the reasons why it’s important to take these drugs. Through interactive questions, it also assesses the progress and knowledge of patients and families about ADHD.

Testing this app in pediatric settings, Dr. Biederman and colleagues published a study in the Journal of Psychopharmacology showing a dramatic increase in compliance – from 60% to 90%.

In another study, this one published in the Journal of Clinical Psychopharmacology, Dr. Biederman and colleagues found that compliance improved, from 35% to 70% in adults. The SMS program in these settings not only improved adherence, but it also reduced costs of ADHD-associated complications while adding beneficial support and value to patients, families, and prescribers, Dr. Biederman said.

Promising findings about the power of apps to increase ADHD medication adherence led Luis Augusto Rohde, MD, PhD, and colleagues to develop the FOCUS app in 2016, for use in his home country of Brazil. The app objectively monitors symptoms of ADHD and establishes cooperative relationships between the patient, their families, and caregivers, said Dr. Rohde, professor of child and adolescent psychiatry at the Federal University of Rio Grande do Sul’s department of psychiatry, Porto Alegre, Brazil.

Digital tech pros and cons

The accessibility of digital technology to children living in remote areas is one of its biggest assets, Dr. Kirk said.

Digital technologies capture real time data, are easy to use, are suitable for young children with developmental disorders, have few adverse effects, and can be easily updated. However, there are some limitations, she added. Attitudes toward technology, time required to supervise their use, and funding to facilitate the use of such technology can hinder implementation. Given that digital technology is increasingly being used to collect sensitive medical data and assess clinical conditions, it’s crucial for these new technologies to be compliant with HIPAA requirements, Dr. Kirk said.

“We are at the front end of a revolution, and much more of this is coming down the pike,” Dr. Kollins predicted. Developers need to be thoughtful and deliberate in how they design clinical evidence strategies for digital therapeutics for ADHD.

“There’s much work that needs to be done from a clinical, statistical, regulatory, and policy perspective, but this journey illustrates this can be done with ADHD and other mental health conditions.”

Dr. Kirk disclosed working previously for a small technology company in Melbourne that developed medical technologies for children. Dr. Kollins’ work has been supported by numerous U.S. agencies, including the National Institute of Mental Health. He has served as a consultant to numerous pharmaceutical companies tied to ADHD clinical psychopharmacology. Dr. Biederman has provided research support to Genentech, Headspace, Pfizer, Roche Translational & Clinical Research Center, and other pharmaceutical companies. Also, Dr. Biederman has a partnership with MEMOTEXT through Partners Healthcare Innovation. Dr. Rohde has received grant or research support from, and served as a consultant to, several companies, including Bial, Novartis, Pfizer, and Shire/Takeda. He has received authorship royalties from Oxford University Press and ArtMed, and travel grants from Shire.

A large study of adolescent soccer players in Michigan revealed key differences in concussion injury metrics among males and females, underscoring a need to develop sex-specific approaches to managing injury in the sport.

Sport-related concussion (SRC) is a specific concern in young female athletes, study authors Abigail C. Bretzin, PhD, and colleagues noted in their paper, which appears in JAMA Network Open. Previous surveillance studies on SRC at the high school and college level have reported higher rates of injury risk and longer recovery outcomes in female soccer athletes. Taking a deeper dive into these trends, the investigators explored whether sex-associated differences existed in SRC, addressing the mechanics, management, and recovery from SRC.

“This is an area that is remarkably underresearched,” William Stewart, MBChB, PhD, the study’s corresponding author, said in an interview. Prior studies of males and females have shown that female axons are thinner, with fewer microtubules or internal scaffolding than male axons. This potentially increases risk of shear injury in females. Limited research has also cited differences in concussion risk across the menstrual cycle in female athletes.
 

Reporting system targets four injury areas

The investigators conducted a high school injury surveillance project in 43,741 male and 39,637 female soccer athletes participating in the Michigan High School Athletic Association (MHSAA) Head Injury Reporting System. The study included students from 9th to 12th grade, spanning from the beginning of academic year 2016-2017 to the end of academic year 2018-2019. Since 2015, the state has mandated high schools to submit data to MHSAA.

MHSAA captures data on four categories: person-to-person contact, person-to-object contact, person-to-playing surface contact, or uncertain about cause of the event. Study outcomes included details regarding injury mechanism, immediate management, and return-to-play time for each documented SRC.

Investigators reported notable differences among male and female players. Documented SRC risk was 1.88 times higher among adolescent girls than boys across all academic years (RR, 1.88; 95% CI, 1.69-2.09; P < .001). They also cited inconsistencies in distribution of injury mechanisms among the sexes. Females were most likely to suffer injury from equipment contact such as heading a ball (41.9%), whereas male players commonly sustained SRC from contact with another player (48.4%). The authors suggested that “female soccer athletes have lower neck strength and girth, compared with male athletes, with these variables inversely associated with linear and rotational head acceleration after soccer ball heading.”

Boys had greater odds of immediate removal from play and but also returned to the sport 2 days sooner than girls. “The possibility exists, therefore, that this longer recovery time might, in part, be reflective of our observed differences in immediate care, in particular removal from play,” the authors wrote. Immediate removal from play was also more common in cases where an athletic trainer played a part in evaluating players for SRC.
 

Eliminating the one-size-fits-all approach

Current concussion management is based on a “one-size-fits-all” model, said Dr. Stewart. Male and female athletes are treated following a common concussion management protocol, covering concussion detection through to rehabilitation. “This model of management is based on research that is almost exclusively in male athletes.”

What the study showed is this one-size-fits-all approach may be flawed, letting down female athletes. “We should be pursuing more research in sex differences in concussion and, importantly, putting these into practice in sex-specific concussion management protocols,” he suggested.

Future studies should also look at the effects of athletic trainer employment on SRC metrics. “Although this was a large, statewide epidemiological study of reported SRC in adolescent soccer athletes, inclusive of high schools with and without access to athletic trainers, the Head Injury Reporting System did not include information on the whether there were athletic trainer services available at each school, including specific athletic training services for soccer,” wrote the investigators, in citing the study’s limitations.
 

Girls report symptoms more often

“The researchers are to be commended for taking a prospective approach to address this common observation in high school sports,” said Keith J. Loud, MD, MSc, FAAP, a sports pediatrician at Children’s Hospital at Dartmouth-Hitchcock in Manchester, N.H. The results are “entirely believable,” said Dr. Loud, who was not affiliated with the study. “We have long postulated differences in neurophysiology, neck strength, style of play, and tendency to report as explanations for the observation that girls in high school soccer are diagnosed with more concussions than boys.”

The findings suggest that boys play more aggressively, but sustain fewer concussions, he added. Girls in the meantime, are more likely to speak up about their injury.

“Concussion diagnosis still relies to a large degree on the athlete to report symptoms, which is one of our hypotheses as to why girls seem to sustain more concussions – they report symptoms more often. That could also be why they have a prolonged recovery,” offered Dr. Loud. A main limitation of this study is it can’t overcome this reporting bias.

Dr. Loud was also concerned that girls were less likely to be removed from game play, even though they apparently sustained more concussions. “Perhaps that is because their injuries are less obvious on the field, and they are diagnosed when reported after the games.”

Dr. Stewart reported receiving grants from The Football Association and National Health Service Research Scotland during the study. He also served as a nonremunerated member of the Fédération Internationale de Football Association Independent Football Concussion Advisory Group and the Football Association Expert Panel on Concussion and Head Injury in Football. None of the other authors had disclosures.

A large study of adolescent soccer players in Michigan revealed key differences in concussion injury metrics among males and females, underscoring a need to develop sex-specific approaches to managing injury in the sport.

Sport-related concussion (SRC) is a specific concern in young female athletes, study authors Abigail C. Bretzin, PhD, and colleagues noted in their paper, which appears in JAMA Network Open. Previous surveillance studies on SRC at the high school and college level have reported higher rates of injury risk and longer recovery outcomes in female soccer athletes. Taking a deeper dive into these trends, the investigators explored whether sex-associated differences existed in SRC, addressing the mechanics, management, and recovery from SRC.

“This is an area that is remarkably underresearched,” William Stewart, MBChB, PhD, the study’s corresponding author, said in an interview. Prior studies of males and females have shown that female axons are thinner, with fewer microtubules or internal scaffolding than male axons. This potentially increases risk of shear injury in females. Limited research has also cited differences in concussion risk across the menstrual cycle in female athletes.
 

Reporting system targets four injury areas

The investigators conducted a high school injury surveillance project in 43,741 male and 39,637 female soccer athletes participating in the Michigan High School Athletic Association (MHSAA) Head Injury Reporting System. The study included students from 9th to 12th grade, spanning from the beginning of academic year 2016-2017 to the end of academic year 2018-2019. Since 2015, the state has mandated high schools to submit data to MHSAA.

MHSAA captures data on four categories: person-to-person contact, person-to-object contact, person-to-playing surface contact, or uncertain about cause of the event. Study outcomes included details regarding injury mechanism, immediate management, and return-to-play time for each documented SRC.

Investigators reported notable differences among male and female players. Documented SRC risk was 1.88 times higher among adolescent girls than boys across all academic years (RR, 1.88; 95% CI, 1.69-2.09; P < .001). They also cited inconsistencies in distribution of injury mechanisms among the sexes. Females were most likely to suffer injury from equipment contact such as heading a ball (41.9%), whereas male players commonly sustained SRC from contact with another player (48.4%). The authors suggested that “female soccer athletes have lower neck strength and girth, compared with male athletes, with these variables inversely associated with linear and rotational head acceleration after soccer ball heading.”

Boys had greater odds of immediate removal from play and but also returned to the sport 2 days sooner than girls. “The possibility exists, therefore, that this longer recovery time might, in part, be reflective of our observed differences in immediate care, in particular removal from play,” the authors wrote. Immediate removal from play was also more common in cases where an athletic trainer played a part in evaluating players for SRC.
 

Eliminating the one-size-fits-all approach

Current concussion management is based on a “one-size-fits-all” model, said Dr. Stewart. Male and female athletes are treated following a common concussion management protocol, covering concussion detection through to rehabilitation. “This model of management is based on research that is almost exclusively in male athletes.”

What the study showed is this one-size-fits-all approach may be flawed, letting down female athletes. “We should be pursuing more research in sex differences in concussion and, importantly, putting these into practice in sex-specific concussion management protocols,” he suggested.

Future studies should also look at the effects of athletic trainer employment on SRC metrics. “Although this was a large, statewide epidemiological study of reported SRC in adolescent soccer athletes, inclusive of high schools with and without access to athletic trainers, the Head Injury Reporting System did not include information on the whether there were athletic trainer services available at each school, including specific athletic training services for soccer,” wrote the investigators, in citing the study’s limitations.
 

Girls report symptoms more often

“The researchers are to be commended for taking a prospective approach to address this common observation in high school sports,” said Keith J. Loud, MD, MSc, FAAP, a sports pediatrician at Children’s Hospital at Dartmouth-Hitchcock in Manchester, N.H. The results are “entirely believable,” said Dr. Loud, who was not affiliated with the study. “We have long postulated differences in neurophysiology, neck strength, style of play, and tendency to report as explanations for the observation that girls in high school soccer are diagnosed with more concussions than boys.”

The findings suggest that boys play more aggressively, but sustain fewer concussions, he added. Girls in the meantime, are more likely to speak up about their injury.

“Concussion diagnosis still relies to a large degree on the athlete to report symptoms, which is one of our hypotheses as to why girls seem to sustain more concussions – they report symptoms more often. That could also be why they have a prolonged recovery,” offered Dr. Loud. A main limitation of this study is it can’t overcome this reporting bias.

Dr. Loud was also concerned that girls were less likely to be removed from game play, even though they apparently sustained more concussions. “Perhaps that is because their injuries are less obvious on the field, and they are diagnosed when reported after the games.”

Dr. Stewart reported receiving grants from The Football Association and National Health Service Research Scotland during the study. He also served as a nonremunerated member of the Fédération Internationale de Football Association Independent Football Concussion Advisory Group and the Football Association Expert Panel on Concussion and Head Injury in Football. None of the other authors had disclosures.

A large study of adolescent soccer players in Michigan revealed key differences in concussion injury metrics among males and females, underscoring a need to develop sex-specific approaches to managing injury in the sport.

Sport-related concussion (SRC) is a specific concern in young female athletes, study authors Abigail C. Bretzin, PhD, and colleagues noted in their paper, which appears in JAMA Network Open. Previous surveillance studies on SRC at the high school and college level have reported higher rates of injury risk and longer recovery outcomes in female soccer athletes. Taking a deeper dive into these trends, the investigators explored whether sex-associated differences existed in SRC, addressing the mechanics, management, and recovery from SRC.

“This is an area that is remarkably underresearched,” William Stewart, MBChB, PhD, the study’s corresponding author, said in an interview. Prior studies of males and females have shown that female axons are thinner, with fewer microtubules or internal scaffolding than male axons. This potentially increases risk of shear injury in females. Limited research has also cited differences in concussion risk across the menstrual cycle in female athletes.
 

Reporting system targets four injury areas

The investigators conducted a high school injury surveillance project in 43,741 male and 39,637 female soccer athletes participating in the Michigan High School Athletic Association (MHSAA) Head Injury Reporting System. The study included students from 9th to 12th grade, spanning from the beginning of academic year 2016-2017 to the end of academic year 2018-2019. Since 2015, the state has mandated high schools to submit data to MHSAA.

MHSAA captures data on four categories: person-to-person contact, person-to-object contact, person-to-playing surface contact, or uncertain about cause of the event. Study outcomes included details regarding injury mechanism, immediate management, and return-to-play time for each documented SRC.

Investigators reported notable differences among male and female players. Documented SRC risk was 1.88 times higher among adolescent girls than boys across all academic years (RR, 1.88; 95% CI, 1.69-2.09; P < .001). They also cited inconsistencies in distribution of injury mechanisms among the sexes. Females were most likely to suffer injury from equipment contact such as heading a ball (41.9%), whereas male players commonly sustained SRC from contact with another player (48.4%). The authors suggested that “female soccer athletes have lower neck strength and girth, compared with male athletes, with these variables inversely associated with linear and rotational head acceleration after soccer ball heading.”

Boys had greater odds of immediate removal from play and but also returned to the sport 2 days sooner than girls. “The possibility exists, therefore, that this longer recovery time might, in part, be reflective of our observed differences in immediate care, in particular removal from play,” the authors wrote. Immediate removal from play was also more common in cases where an athletic trainer played a part in evaluating players for SRC.
 

Eliminating the one-size-fits-all approach

Current concussion management is based on a “one-size-fits-all” model, said Dr. Stewart. Male and female athletes are treated following a common concussion management protocol, covering concussion detection through to rehabilitation. “This model of management is based on research that is almost exclusively in male athletes.”

What the study showed is this one-size-fits-all approach may be flawed, letting down female athletes. “We should be pursuing more research in sex differences in concussion and, importantly, putting these into practice in sex-specific concussion management protocols,” he suggested.

Future studies should also look at the effects of athletic trainer employment on SRC metrics. “Although this was a large, statewide epidemiological study of reported SRC in adolescent soccer athletes, inclusive of high schools with and without access to athletic trainers, the Head Injury Reporting System did not include information on the whether there were athletic trainer services available at each school, including specific athletic training services for soccer,” wrote the investigators, in citing the study’s limitations.
 

Girls report symptoms more often

“The researchers are to be commended for taking a prospective approach to address this common observation in high school sports,” said Keith J. Loud, MD, MSc, FAAP, a sports pediatrician at Children’s Hospital at Dartmouth-Hitchcock in Manchester, N.H. The results are “entirely believable,” said Dr. Loud, who was not affiliated with the study. “We have long postulated differences in neurophysiology, neck strength, style of play, and tendency to report as explanations for the observation that girls in high school soccer are diagnosed with more concussions than boys.”

The findings suggest that boys play more aggressively, but sustain fewer concussions, he added. Girls in the meantime, are more likely to speak up about their injury.

“Concussion diagnosis still relies to a large degree on the athlete to report symptoms, which is one of our hypotheses as to why girls seem to sustain more concussions – they report symptoms more often. That could also be why they have a prolonged recovery,” offered Dr. Loud. A main limitation of this study is it can’t overcome this reporting bias.

Dr. Loud was also concerned that girls were less likely to be removed from game play, even though they apparently sustained more concussions. “Perhaps that is because their injuries are less obvious on the field, and they are diagnosed when reported after the games.”

Dr. Stewart reported receiving grants from The Football Association and National Health Service Research Scotland during the study. He also served as a nonremunerated member of the Fédération Internationale de Football Association Independent Football Concussion Advisory Group and the Football Association Expert Panel on Concussion and Head Injury in Football. None of the other authors had disclosures.

A study of U.S. children across ethnic and racial groups found that Asians were least likely to receive therapy for ADHD, compared with White children – who had the highest odds of getting some kind of treatment over other groups.

Other studies have identified disparity problems in ADHD diagnosis, although results have varied on inequality metrics. Few studies have looked at Asians separately, according to the study’s lead author, Yu Shi, MD, MPH. “They were usually just classified as ‘other’ or as non-White,” Dr. Shi, a consultant with the Mayo Clinic’s division of pediatric anesthesia in Rochester, Minn., said in an interview.

Disparities might stem from cultural and socioeconomic factors, and the way in which clinicians interpret behavior and apply diagnostic criteria.

“Further understanding of how treatment patterns for ADHD may differ based on race, at the time of initial diagnosis and in the early stages of treatment, may help all children receive appropriate evidence-based care,” Dr. Shi and colleagues reported in JAMA Network Open.
 

Researchers develop large birth cohort

Dr. Shi and colleagues hypothesized that non-Hispanic White children had a greater chance of getting diagnosed and treated within the first year of diagnosis than that of other ethnic and racial cohorts. Using administrative claims data with socioeconomic status information from a national commercial insurance warehouse, they constructed a retrospective birth cohort of children born between Jan. 1, 2006, and Dec. 31, 2012. The children had continuous insurance coverage for at least 4 years, and represented non-Hispanic Whites, Blacks, Hispanics, and Asians. Self-reporting identified the race/ethnicity groups.

Investigators analyzed ADHD diagnosis and treatment data on 238,011 children between October 2019 and December 2020, using a multivariate Cox regression model to adjust for sex, region, and household income. Primary and secondary outcomes included ADHD diagnosis as defined by recent ICD codes, ADHD behavior, and medication therapies in the clinical setting after initial diagnosis, respectively.

Whites made up most of the cohort (72.7%), followed by Hispanics (9.8%), Asians (6.7%), and Blacks (6.2%). Nearly half the population was female (48.8%). During the follow-up period with these children, 11,401, or 4.8%, had received an ADHD diagnosis. Mean age of diagnosis was 6.5 years, and overall incidence of ADHD was 69 per 10,000 person years (95% confidence interval, 68-70).

Pediatricians were most likely to make an ADHD diagnosis, although the study cited other clinicians, such as psychiatrists, neurologists, psychologists, and family practice clinicians, as responsible for these decisions.

Children diagnosed with ADHD had more years of coverage in the data set, and were more likely to be White and male. The Southern census region had a higher representation of diagnoses (50.6%) than did the Northeast region (11.8%).
 

Asians at highest odds for no treatment

Taking a closer look at race and ethnicity, Whites had the highest cumulative incidence of ADHD (14.19%), versus Asian children, who had lowest incidence (6.08%). “The curves for Black and Hispanic children were similar in shape and slightly lower than that for White children,” reported the investigators.

White children had higher odds of receiving some kind of treatment, compared with the other groups.

Incidence of medication treatment was lower among Asians and Hispanics. In a striking finding, Asians were most likely to receive no treatment at all (odds ratio compared with White children, 0.54; 95% confidence interval, 0.42-0.70). “However, the percentage of Asian children receiving psychotherapy was not significantly lower than other groups, which is different than a 2013 study finding that Asian children with ADHD were less likely to use mental health services,” they noted.

Most of the patients received medication (32.4%) in the first year after diagnosis, whereas (19.4%) received behavioral therapy only. Nineteen percent had both. More than 29% of these cases had no claims associated with either treatment. Among school-aged children, 65.5% were prescribed medications, compared with just 14.4% who received therapy. Twenty percent had no treatment.

Diagnosis with another disorder often preceded ADHD diagnosis. Results varied among racial groups. White children were more likely than were Black children to be diagnosed with an anxiety or adjustment disorder. Relative to White children, Asians were more likely to be diagnosed with autism spectrum disorder, speech sound disorders, or unspecified neurodevelopmental disorders. Even after an ADHD diagnosis, clinicians were more likely to diagnose Asian children with autism.
 

Parents may influence treatment decisions

Parental views and preferences may explain some of the variations in diagnosis and treatment among the racial/ethnic groups.

“In order for a diagnosis of ADHD to happen, a parent has first to recognize a problem and bring a child for clinical evaluation,” said Dr. Shi. “A certain behavior could be viewed as normal or a problem depending on a person’s cultural or racial background.” It’s unclear whether clinicians played any role in diagnosis disparities, he added. Patients’ concerns about racism might also influence the desire to get treated in health care systems.

Overall, the findings underscore the presence of racial and ethnic disparities in ADHD diagnosis and treatment. Future research should explore the underlying mechanisms, Dr. Shi suggested. While he and his colleagues have no immediate plans to do another ADHD study, “we’re planning on research to understand disparities in surgery in children,” he said.

The authors cited numerous limitations with their study. Use of ICD codes to identify cases might not have represented true clinical diagnosis, since the data were collected for billing, not research purposes. Investigators drew participants from a commercial insurance database, which did not necessarily reflect all U.S. children. The results might not represent a large number of children covered by Medicaid, for example, noted Dr. Shi. “It is more difficult to work with Medicaid data because there’s no national-level Medicaid data for research. Only state-level data is available.”

Because of other data gaps, Dr. Shi and colleagues might have underestimated the number of children in therapy.
 

A need for ‘culturally sensitive care’

The findings “ultimately demonstrate the need for culturally sensitive care in the diagnosis and treatment of children and adolescents,” said Tiffani L. Bell, MD, a psychiatrist in Winston-Salem, N.C., who was not involved with the study. She specializes in child and adolescent psychiatry.

The exact cause for racial disparity in diagnosis and treatment of ADHD is unknown and likely multifaceted, she continued. “It may be due to differences in the way that disruptive behaviors are interrupted based on factors such as race. This study found that Asian parents often brought their children in for evaluation for reasons other than ADHD. Concerns surrounding the stigma of mental health treatment and racism also could contribute to the disparity in diagnosis and treatment,” she said.

Dr. Bell said she hopes to see future studies that address the impact of social determinants of health on mental illness and investigate underlying causes that contribute to disparities in treatment and diagnosis.

The Mayo Clinic supported the study but had no role in its design or research methods. The authors reported no conflicts of interest.

A study of U.S. children across ethnic and racial groups found that Asians were least likely to receive therapy for ADHD, compared with White children – who had the highest odds of getting some kind of treatment over other groups.

Other studies have identified disparity problems in ADHD diagnosis, although results have varied on inequality metrics. Few studies have looked at Asians separately, according to the study’s lead author, Yu Shi, MD, MPH. “They were usually just classified as ‘other’ or as non-White,” Dr. Shi, a consultant with the Mayo Clinic’s division of pediatric anesthesia in Rochester, Minn., said in an interview.

Disparities might stem from cultural and socioeconomic factors, and the way in which clinicians interpret behavior and apply diagnostic criteria.

“Further understanding of how treatment patterns for ADHD may differ based on race, at the time of initial diagnosis and in the early stages of treatment, may help all children receive appropriate evidence-based care,” Dr. Shi and colleagues reported in JAMA Network Open.
 

Researchers develop large birth cohort

Dr. Shi and colleagues hypothesized that non-Hispanic White children had a greater chance of getting diagnosed and treated within the first year of diagnosis than that of other ethnic and racial cohorts. Using administrative claims data with socioeconomic status information from a national commercial insurance warehouse, they constructed a retrospective birth cohort of children born between Jan. 1, 2006, and Dec. 31, 2012. The children had continuous insurance coverage for at least 4 years, and represented non-Hispanic Whites, Blacks, Hispanics, and Asians. Self-reporting identified the race/ethnicity groups.

Investigators analyzed ADHD diagnosis and treatment data on 238,011 children between October 2019 and December 2020, using a multivariate Cox regression model to adjust for sex, region, and household income. Primary and secondary outcomes included ADHD diagnosis as defined by recent ICD codes, ADHD behavior, and medication therapies in the clinical setting after initial diagnosis, respectively.

Whites made up most of the cohort (72.7%), followed by Hispanics (9.8%), Asians (6.7%), and Blacks (6.2%). Nearly half the population was female (48.8%). During the follow-up period with these children, 11,401, or 4.8%, had received an ADHD diagnosis. Mean age of diagnosis was 6.5 years, and overall incidence of ADHD was 69 per 10,000 person years (95% confidence interval, 68-70).

Pediatricians were most likely to make an ADHD diagnosis, although the study cited other clinicians, such as psychiatrists, neurologists, psychologists, and family practice clinicians, as responsible for these decisions.

Children diagnosed with ADHD had more years of coverage in the data set, and were more likely to be White and male. The Southern census region had a higher representation of diagnoses (50.6%) than did the Northeast region (11.8%).
 

Asians at highest odds for no treatment

Taking a closer look at race and ethnicity, Whites had the highest cumulative incidence of ADHD (14.19%), versus Asian children, who had lowest incidence (6.08%). “The curves for Black and Hispanic children were similar in shape and slightly lower than that for White children,” reported the investigators.

White children had higher odds of receiving some kind of treatment, compared with the other groups.

Incidence of medication treatment was lower among Asians and Hispanics. In a striking finding, Asians were most likely to receive no treatment at all (odds ratio compared with White children, 0.54; 95% confidence interval, 0.42-0.70). “However, the percentage of Asian children receiving psychotherapy was not significantly lower than other groups, which is different than a 2013 study finding that Asian children with ADHD were less likely to use mental health services,” they noted.

Most of the patients received medication (32.4%) in the first year after diagnosis, whereas (19.4%) received behavioral therapy only. Nineteen percent had both. More than 29% of these cases had no claims associated with either treatment. Among school-aged children, 65.5% were prescribed medications, compared with just 14.4% who received therapy. Twenty percent had no treatment.

Diagnosis with another disorder often preceded ADHD diagnosis. Results varied among racial groups. White children were more likely than were Black children to be diagnosed with an anxiety or adjustment disorder. Relative to White children, Asians were more likely to be diagnosed with autism spectrum disorder, speech sound disorders, or unspecified neurodevelopmental disorders. Even after an ADHD diagnosis, clinicians were more likely to diagnose Asian children with autism.
 

Parents may influence treatment decisions

Parental views and preferences may explain some of the variations in diagnosis and treatment among the racial/ethnic groups.

“In order for a diagnosis of ADHD to happen, a parent has first to recognize a problem and bring a child for clinical evaluation,” said Dr. Shi. “A certain behavior could be viewed as normal or a problem depending on a person’s cultural or racial background.” It’s unclear whether clinicians played any role in diagnosis disparities, he added. Patients’ concerns about racism might also influence the desire to get treated in health care systems.

Overall, the findings underscore the presence of racial and ethnic disparities in ADHD diagnosis and treatment. Future research should explore the underlying mechanisms, Dr. Shi suggested. While he and his colleagues have no immediate plans to do another ADHD study, “we’re planning on research to understand disparities in surgery in children,” he said.

The authors cited numerous limitations with their study. Use of ICD codes to identify cases might not have represented true clinical diagnosis, since the data were collected for billing, not research purposes. Investigators drew participants from a commercial insurance database, which did not necessarily reflect all U.S. children. The results might not represent a large number of children covered by Medicaid, for example, noted Dr. Shi. “It is more difficult to work with Medicaid data because there’s no national-level Medicaid data for research. Only state-level data is available.”

Because of other data gaps, Dr. Shi and colleagues might have underestimated the number of children in therapy.
 

A need for ‘culturally sensitive care’

The findings “ultimately demonstrate the need for culturally sensitive care in the diagnosis and treatment of children and adolescents,” said Tiffani L. Bell, MD, a psychiatrist in Winston-Salem, N.C., who was not involved with the study. She specializes in child and adolescent psychiatry.

The exact cause for racial disparity in diagnosis and treatment of ADHD is unknown and likely multifaceted, she continued. “It may be due to differences in the way that disruptive behaviors are interrupted based on factors such as race. This study found that Asian parents often brought their children in for evaluation for reasons other than ADHD. Concerns surrounding the stigma of mental health treatment and racism also could contribute to the disparity in diagnosis and treatment,” she said.

Dr. Bell said she hopes to see future studies that address the impact of social determinants of health on mental illness and investigate underlying causes that contribute to disparities in treatment and diagnosis.

The Mayo Clinic supported the study but had no role in its design or research methods. The authors reported no conflicts of interest.

A study of U.S. children across ethnic and racial groups found that Asians were least likely to receive therapy for ADHD, compared with White children – who had the highest odds of getting some kind of treatment over other groups.

Other studies have identified disparity problems in ADHD diagnosis, although results have varied on inequality metrics. Few studies have looked at Asians separately, according to the study’s lead author, Yu Shi, MD, MPH. “They were usually just classified as ‘other’ or as non-White,” Dr. Shi, a consultant with the Mayo Clinic’s division of pediatric anesthesia in Rochester, Minn., said in an interview.

Disparities might stem from cultural and socioeconomic factors, and the way in which clinicians interpret behavior and apply diagnostic criteria.

“Further understanding of how treatment patterns for ADHD may differ based on race, at the time of initial diagnosis and in the early stages of treatment, may help all children receive appropriate evidence-based care,” Dr. Shi and colleagues reported in JAMA Network Open.
 

Researchers develop large birth cohort

Dr. Shi and colleagues hypothesized that non-Hispanic White children had a greater chance of getting diagnosed and treated within the first year of diagnosis than that of other ethnic and racial cohorts. Using administrative claims data with socioeconomic status information from a national commercial insurance warehouse, they constructed a retrospective birth cohort of children born between Jan. 1, 2006, and Dec. 31, 2012. The children had continuous insurance coverage for at least 4 years, and represented non-Hispanic Whites, Blacks, Hispanics, and Asians. Self-reporting identified the race/ethnicity groups.

Investigators analyzed ADHD diagnosis and treatment data on 238,011 children between October 2019 and December 2020, using a multivariate Cox regression model to adjust for sex, region, and household income. Primary and secondary outcomes included ADHD diagnosis as defined by recent ICD codes, ADHD behavior, and medication therapies in the clinical setting after initial diagnosis, respectively.

Whites made up most of the cohort (72.7%), followed by Hispanics (9.8%), Asians (6.7%), and Blacks (6.2%). Nearly half the population was female (48.8%). During the follow-up period with these children, 11,401, or 4.8%, had received an ADHD diagnosis. Mean age of diagnosis was 6.5 years, and overall incidence of ADHD was 69 per 10,000 person years (95% confidence interval, 68-70).

Pediatricians were most likely to make an ADHD diagnosis, although the study cited other clinicians, such as psychiatrists, neurologists, psychologists, and family practice clinicians, as responsible for these decisions.

Children diagnosed with ADHD had more years of coverage in the data set, and were more likely to be White and male. The Southern census region had a higher representation of diagnoses (50.6%) than did the Northeast region (11.8%).
 

Asians at highest odds for no treatment

Taking a closer look at race and ethnicity, Whites had the highest cumulative incidence of ADHD (14.19%), versus Asian children, who had lowest incidence (6.08%). “The curves for Black and Hispanic children were similar in shape and slightly lower than that for White children,” reported the investigators.

White children had higher odds of receiving some kind of treatment, compared with the other groups.

Incidence of medication treatment was lower among Asians and Hispanics. In a striking finding, Asians were most likely to receive no treatment at all (odds ratio compared with White children, 0.54; 95% confidence interval, 0.42-0.70). “However, the percentage of Asian children receiving psychotherapy was not significantly lower than other groups, which is different than a 2013 study finding that Asian children with ADHD were less likely to use mental health services,” they noted.

Most of the patients received medication (32.4%) in the first year after diagnosis, whereas (19.4%) received behavioral therapy only. Nineteen percent had both. More than 29% of these cases had no claims associated with either treatment. Among school-aged children, 65.5% were prescribed medications, compared with just 14.4% who received therapy. Twenty percent had no treatment.

Diagnosis with another disorder often preceded ADHD diagnosis. Results varied among racial groups. White children were more likely than were Black children to be diagnosed with an anxiety or adjustment disorder. Relative to White children, Asians were more likely to be diagnosed with autism spectrum disorder, speech sound disorders, or unspecified neurodevelopmental disorders. Even after an ADHD diagnosis, clinicians were more likely to diagnose Asian children with autism.
 

Parents may influence treatment decisions

Parental views and preferences may explain some of the variations in diagnosis and treatment among the racial/ethnic groups.

“In order for a diagnosis of ADHD to happen, a parent has first to recognize a problem and bring a child for clinical evaluation,” said Dr. Shi. “A certain behavior could be viewed as normal or a problem depending on a person’s cultural or racial background.” It’s unclear whether clinicians played any role in diagnosis disparities, he added. Patients’ concerns about racism might also influence the desire to get treated in health care systems.

Overall, the findings underscore the presence of racial and ethnic disparities in ADHD diagnosis and treatment. Future research should explore the underlying mechanisms, Dr. Shi suggested. While he and his colleagues have no immediate plans to do another ADHD study, “we’re planning on research to understand disparities in surgery in children,” he said.

The authors cited numerous limitations with their study. Use of ICD codes to identify cases might not have represented true clinical diagnosis, since the data were collected for billing, not research purposes. Investigators drew participants from a commercial insurance database, which did not necessarily reflect all U.S. children. The results might not represent a large number of children covered by Medicaid, for example, noted Dr. Shi. “It is more difficult to work with Medicaid data because there’s no national-level Medicaid data for research. Only state-level data is available.”

Because of other data gaps, Dr. Shi and colleagues might have underestimated the number of children in therapy.
 

A need for ‘culturally sensitive care’

The findings “ultimately demonstrate the need for culturally sensitive care in the diagnosis and treatment of children and adolescents,” said Tiffani L. Bell, MD, a psychiatrist in Winston-Salem, N.C., who was not involved with the study. She specializes in child and adolescent psychiatry.

The exact cause for racial disparity in diagnosis and treatment of ADHD is unknown and likely multifaceted, she continued. “It may be due to differences in the way that disruptive behaviors are interrupted based on factors such as race. This study found that Asian parents often brought their children in for evaluation for reasons other than ADHD. Concerns surrounding the stigma of mental health treatment and racism also could contribute to the disparity in diagnosis and treatment,” she said.

Dr. Bell said she hopes to see future studies that address the impact of social determinants of health on mental illness and investigate underlying causes that contribute to disparities in treatment and diagnosis.

The Mayo Clinic supported the study but had no role in its design or research methods. The authors reported no conflicts of interest.

Studies are flagging racial and ethnic disparities in rheumatology training materials, pointing to a need to boost representation of darker skin tones and better educate physicians in evaluating this cohort.

AndreyPopov/Getty Images

Not enough is known about these disparities in rheumatology education, despite the fact that minorities make up 40% of the population in the United States.

The problem starts with books and references used in medical schools, Lynn McKinley-Grant, MD, immediate past president of the Skin of Color Society and associate professor of dermatology at Howard University, Washington, said in an interview. “In the medical literature there has been a dearth of images in skin of color in all specialties,” she said. With an increased diversity in the U.S. population, there is a need for health care providers to be able to recognize disease patterns in all skin types.” If a physician is training at an institution where there are not many patients of color in the community, the rheumatologists are even more limited in terms of their clinical experience.

This lack of training in diagnosis of disease has serious clinical repercussions, as seen in COVID cases, Dr. McKinley-Grant noted. “You end up not being able to recognize early erythema, jaundice, anemia, or hypoxemia because those conditions are a different color or pattern in the darker skin types. This can lead to errors in treatment, diagnosis, and medical care, resulting in increased morbidity and mortality.”

Studies point to education gaps

A team of researchers from Washington University in St. Louis called attention to this issue at the American College of Rhematology’s Convergence 2020 conference.

“Patients of color with lupus are especially vulnerable as they often carry a greater disease burden, yet studies show that individuals with darker skin tones are underrepresented in medical educational materials,” Vijay Kannuthurai, MD, and colleagues wrote in their study abstract. The team surveyed 132 providers in St. Louis, Mo., on their confidence in evaluating any rash, and rashes in patients with lupus and varied skin tones.

Participating clinicians, mostly rheumatologists, dermatologists, or internists, had a higher confidence level in diagnosing any rash versus lupus rashes, but were considerably less confident in diagnosing lupus rash on darker skin, compared with those on fair skin. This represents “a disparity between provider confidence and the patient population lupus traditionally affects,” the investigators concluded.

Another recent study found evidence of disparities in clinical education resources. “The lack of dark skin representation among rheumatology educational materials contributes to the implicit bias and structural racism present in medical education by promoting White-only models of disease,” lead author Adrienne Strait, a medical student at the University of California, San Francisco, said in an interview. “Given that rheumatic diseases disproportionately impact racial and ethnic minorities, we felt it was important to examine the representation of these groups within rheumatology training resources.”

She and her colleagues gathered images of rheumatic diseases from four major databases: the American College of Rheumatology’s Image Library, UpToDate, the New England Journal of Medicine Images in Clinical Medicine and Clinical Cases filtered by “Rheumatology,” and the 9th edition of Kelley’s Textbook of Rheumatology. They used Fitzpatrick’s skin phototypes to independently code images depicting skin as “light” (skin types I-IV), “dark” (skin types V-VI), or “indeterminate,” focusing on systemic lupus erythematosus (SLE) and rheumatoid arthritis, two conditions with a known connection to racial and ethnic health disparities.

Taking into account the high incidence of sarcoidosis and SLE in Black patients when compared with White patients, the investigators did a secondary analysis that excluded these cases.

Among 1,043 patient images studied, just 13.4% represented dark skin, compared with 84% that represented light skin. More than 2% represented an indeterminate skin color. Comparing dark-skin representation in the clinical images and SLE images with the representation of Asian, Native American, and Black individuals in the United States and within lupus cases nationally, the investigators found significant underrepresentation of dark skin.

Only 4.2% of RA images had dark-skin representation, making RA one of the diseases with the lowest representation in the study, along with juvenile idiopathic arthritis, the spondyloarthropathies, and Kawasaki disease. “Representation of dark skin in SLE was also lower than the proportion of Black individuals in SLE studies,” the investigators noted. Overall, representation of dark skin in SLE images was just 22.6%. Sarcoidosis comparatively had the largest representation of dark-skin images (69.6%, n = 32).

“Excluding sarcoidosis and SLE images, the overall representation of dark skin was 9.4% (n = 84), which was significantly lower than the proportion of Asian, Native American, and Black individuals within the U.S. Census population,” according to Ms. Strait and her associates. UpToDate contained the largest proportion of images of dark skin respective to other databases, whereas Kelley’s Textbook had the smallest.
 

Actionable steps

Many physicians are willing to improve upon their skills in identifying conditions on darker skin, as the study by Dr. Kannuthurai and associates suggests. Overall, 93% of the survey’s participants wanted to learn more about rashes in patients of color. “Future educational interventions may help practitioners improve their confidence when diagnosing rashes in lupus patients” with darker skin, they suggested.

Ms. Strait and her colleagues recommended a series of actionable steps to improve diversity and equity of dark skin tone representation in rheumatology curricula.

Editors of educational resources, for example, should make image diversity a priority for those diseases that are most commonly associated with cutaneous manifestations, such as SLE, vasculitis, inflammatory myopathies, systemic sclerosis, sarcoidosis, and psoriasis. They also called for educators in academic rheumatology programs to collaborate to improve diversity in resources used at the undergraduate and graduate medical education level.

Efforts should take place at the local, regional, and national level to publicly discuss and educate clinicians about rheumatic diseases in individuals of color. Speakers at rheumatology conferences should strive to educate learners about presentations of rheumatic diseases in individuals of color. The ACR in the meantime could establish a task force to enhance racial and ethnic diversity in their image library and other published resources.

“These steps may improve provider recognition and diagnosis of rheumatic disease manifestations in skin of color, which may in turn reduce health disparities among racial and ethnic minority groups,” Ms. Strait said.

Beth L. Jonas, MD, chair of the ACR’s Committee on Rheumatology Training and Workforce Issues, called the findings of this study “timely and important.” The researchers highlighted a deficiency in rheumatology training materials that needs addressing, she said in an interview. “I definitely agree that ACR needs to be mindful of this. There’s no doubt that we need to take these recommendations and move along these lines.”

The ACR took a first step in 2020 with the creation of a diversity, equity, and inclusion committee. “We are undergoing a college-wide look at what we do, with an eye toward inclusion. There is a strong interest in addressing health disparities and being an equitable and inclusive community of rheumatology health care professionals,” said Dr. Jonas, chief of the University of North Carolina at Chapel Hill’s division of rheumatology, allergy, and immunology.

The American Academy of Dermatology is also working to improve the image library with images of disease in skin of color. “Everyone’s jumping on this now,” Dr. McKinley-Grant observed. The medical profession can’t afford not to. It’s a life-threatening issue when rheumatoid arthritis and other diseases in people of color aren’t diagnosed early and correctly, she added.

Technologies seek to reduce bias

While many organizations are taking steps to improve representation of darker skin images, VisualDx has taken the lead on this, she said. “They’ve been doing this for years now. There are over 14,000 images of disease in skin of color, including all the rheumatologic diseases. There’s a mobile app and desktop decision support system, and it is very popular. A majority of medical schools have this as a library resource, and hospital systems license it for EHR integration.” Doctors can also get it individually. This enables them to share images and handouts of a diagnosis and select images of patients of color, said Dr. McKinley-Grant, who uses the VisualDx smartphone app DermExpert, which is an app for nondermatologists that features an image library of skin lesions, including darker-skin images.

ProjectIMPACT, powered by VisualDx, is another effort to support reducing health care bias in darker skin. The project is a collaboration between the New England Journal of Medicine Group and the Skin Of Color Society. According to Dr. McKinley-Grant, the organizers are building awareness of the importance of reducing the educational and clinical gaps in diagnosing patients of color and trying to get students and educators to pledge to take meaningful steps and to have real-world impact.

This isn’t just exclusive to dermatology and rheumatology – it involves all medical specialties, she stressed.

ProjectIMPACT isn’t just a resource for physicians, she continued. Librarians can also use it to develop more resources on skin of color.

The Skin Of Color Society and VisualDx have also partnered with the NEJM Group to develop a comprehensive virtual series on the impact of skin color and ethnicity on clinical research. The four-part series addresses structural racism and racial bias in medicine, hair disorders in people of color, pigmentary disorders, keloids, COVID-19 comorbidities, and cutaneous manifestations of systemic diseases in children and adults.

Nuances of recognizing disease

As a medical student, Dr. McKinley-Grant said she was fortunate to attend the Albert Schweitzer Hospital in Lambarene, Gabon, on a fellowship. For 3 months, she gained a wealth of experience examining only African patients with brown skin.

In her other training in medicine, “I’ve been at institutions with diverse populations, in Boston, New York, and Washington,” learning more about all different skin pigments.

This type of training should be more widely available, especially now, with COVID-19 producing new manifestations of skin lesions, she emphasized. Such efforts involve a diversification of images physicians are being trained on so that they can recognize the same disease in a person of color.

“Doctors have to be able to recognize different colors, different shades of brown and shades of white. Not all white skin is the same color,” she noted. In looking at a rash or lesion, “you have to learn how to discern differences in the background color of the skin, which is determined by melanin in the skin (Fitzpatrick skin types I-VI) and by what’s going on in the blood, such as how much oxygen and hemoglobin the patient has in their blood.” Inflammation and infection (erythema) will appear more violaceous in IV-VI skin types, for example.

At the University of North Carolina at Chapel Hill, a group of students and faculty have created a dermatology image library to address the deficiency in the availability of images for teaching purposes. “Our medical students recognized the gap and started this,” Dr. Jonas said. Julie Mervak, MD, assistant professor of dermatology, is spearheading this effort, with students Linnea Westerkam and Anuj Pranav Sanghvi.

“I understand that others around the country are working on similar initiatives,” Dr. Jonas said.

None of the sources for this story had any relevant disclosures.

Studies are flagging racial and ethnic disparities in rheumatology training materials, pointing to a need to boost representation of darker skin tones and better educate physicians in evaluating this cohort.

AndreyPopov/Getty Images

Not enough is known about these disparities in rheumatology education, despite the fact that minorities make up 40% of the population in the United States.

The problem starts with books and references used in medical schools, Lynn McKinley-Grant, MD, immediate past president of the Skin of Color Society and associate professor of dermatology at Howard University, Washington, said in an interview. “In the medical literature there has been a dearth of images in skin of color in all specialties,” she said. With an increased diversity in the U.S. population, there is a need for health care providers to be able to recognize disease patterns in all skin types.” If a physician is training at an institution where there are not many patients of color in the community, the rheumatologists are even more limited in terms of their clinical experience.

This lack of training in diagnosis of disease has serious clinical repercussions, as seen in COVID cases, Dr. McKinley-Grant noted. “You end up not being able to recognize early erythema, jaundice, anemia, or hypoxemia because those conditions are a different color or pattern in the darker skin types. This can lead to errors in treatment, diagnosis, and medical care, resulting in increased morbidity and mortality.”

Studies point to education gaps

A team of researchers from Washington University in St. Louis called attention to this issue at the American College of Rhematology’s Convergence 2020 conference.

“Patients of color with lupus are especially vulnerable as they often carry a greater disease burden, yet studies show that individuals with darker skin tones are underrepresented in medical educational materials,” Vijay Kannuthurai, MD, and colleagues wrote in their study abstract. The team surveyed 132 providers in St. Louis, Mo., on their confidence in evaluating any rash, and rashes in patients with lupus and varied skin tones.

Participating clinicians, mostly rheumatologists, dermatologists, or internists, had a higher confidence level in diagnosing any rash versus lupus rashes, but were considerably less confident in diagnosing lupus rash on darker skin, compared with those on fair skin. This represents “a disparity between provider confidence and the patient population lupus traditionally affects,” the investigators concluded.

Another recent study found evidence of disparities in clinical education resources. “The lack of dark skin representation among rheumatology educational materials contributes to the implicit bias and structural racism present in medical education by promoting White-only models of disease,” lead author Adrienne Strait, a medical student at the University of California, San Francisco, said in an interview. “Given that rheumatic diseases disproportionately impact racial and ethnic minorities, we felt it was important to examine the representation of these groups within rheumatology training resources.”

She and her colleagues gathered images of rheumatic diseases from four major databases: the American College of Rheumatology’s Image Library, UpToDate, the New England Journal of Medicine Images in Clinical Medicine and Clinical Cases filtered by “Rheumatology,” and the 9th edition of Kelley’s Textbook of Rheumatology. They used Fitzpatrick’s skin phototypes to independently code images depicting skin as “light” (skin types I-IV), “dark” (skin types V-VI), or “indeterminate,” focusing on systemic lupus erythematosus (SLE) and rheumatoid arthritis, two conditions with a known connection to racial and ethnic health disparities.

Taking into account the high incidence of sarcoidosis and SLE in Black patients when compared with White patients, the investigators did a secondary analysis that excluded these cases.

Among 1,043 patient images studied, just 13.4% represented dark skin, compared with 84% that represented light skin. More than 2% represented an indeterminate skin color. Comparing dark-skin representation in the clinical images and SLE images with the representation of Asian, Native American, and Black individuals in the United States and within lupus cases nationally, the investigators found significant underrepresentation of dark skin.

Only 4.2% of RA images had dark-skin representation, making RA one of the diseases with the lowest representation in the study, along with juvenile idiopathic arthritis, the spondyloarthropathies, and Kawasaki disease. “Representation of dark skin in SLE was also lower than the proportion of Black individuals in SLE studies,” the investigators noted. Overall, representation of dark skin in SLE images was just 22.6%. Sarcoidosis comparatively had the largest representation of dark-skin images (69.6%, n = 32).

“Excluding sarcoidosis and SLE images, the overall representation of dark skin was 9.4% (n = 84), which was significantly lower than the proportion of Asian, Native American, and Black individuals within the U.S. Census population,” according to Ms. Strait and her associates. UpToDate contained the largest proportion of images of dark skin respective to other databases, whereas Kelley’s Textbook had the smallest.
 

Actionable steps

Many physicians are willing to improve upon their skills in identifying conditions on darker skin, as the study by Dr. Kannuthurai and associates suggests. Overall, 93% of the survey’s participants wanted to learn more about rashes in patients of color. “Future educational interventions may help practitioners improve their confidence when diagnosing rashes in lupus patients” with darker skin, they suggested.

Ms. Strait and her colleagues recommended a series of actionable steps to improve diversity and equity of dark skin tone representation in rheumatology curricula.

Editors of educational resources, for example, should make image diversity a priority for those diseases that are most commonly associated with cutaneous manifestations, such as SLE, vasculitis, inflammatory myopathies, systemic sclerosis, sarcoidosis, and psoriasis. They also called for educators in academic rheumatology programs to collaborate to improve diversity in resources used at the undergraduate and graduate medical education level.

Efforts should take place at the local, regional, and national level to publicly discuss and educate clinicians about rheumatic diseases in individuals of color. Speakers at rheumatology conferences should strive to educate learners about presentations of rheumatic diseases in individuals of color. The ACR in the meantime could establish a task force to enhance racial and ethnic diversity in their image library and other published resources.

“These steps may improve provider recognition and diagnosis of rheumatic disease manifestations in skin of color, which may in turn reduce health disparities among racial and ethnic minority groups,” Ms. Strait said.

Beth L. Jonas, MD, chair of the ACR’s Committee on Rheumatology Training and Workforce Issues, called the findings of this study “timely and important.” The researchers highlighted a deficiency in rheumatology training materials that needs addressing, she said in an interview. “I definitely agree that ACR needs to be mindful of this. There’s no doubt that we need to take these recommendations and move along these lines.”

The ACR took a first step in 2020 with the creation of a diversity, equity, and inclusion committee. “We are undergoing a college-wide look at what we do, with an eye toward inclusion. There is a strong interest in addressing health disparities and being an equitable and inclusive community of rheumatology health care professionals,” said Dr. Jonas, chief of the University of North Carolina at Chapel Hill’s division of rheumatology, allergy, and immunology.

The American Academy of Dermatology is also working to improve the image library with images of disease in skin of color. “Everyone’s jumping on this now,” Dr. McKinley-Grant observed. The medical profession can’t afford not to. It’s a life-threatening issue when rheumatoid arthritis and other diseases in people of color aren’t diagnosed early and correctly, she added.

Technologies seek to reduce bias

While many organizations are taking steps to improve representation of darker skin images, VisualDx has taken the lead on this, she said. “They’ve been doing this for years now. There are over 14,000 images of disease in skin of color, including all the rheumatologic diseases. There’s a mobile app and desktop decision support system, and it is very popular. A majority of medical schools have this as a library resource, and hospital systems license it for EHR integration.” Doctors can also get it individually. This enables them to share images and handouts of a diagnosis and select images of patients of color, said Dr. McKinley-Grant, who uses the VisualDx smartphone app DermExpert, which is an app for nondermatologists that features an image library of skin lesions, including darker-skin images.

ProjectIMPACT, powered by VisualDx, is another effort to support reducing health care bias in darker skin. The project is a collaboration between the New England Journal of Medicine Group and the Skin Of Color Society. According to Dr. McKinley-Grant, the organizers are building awareness of the importance of reducing the educational and clinical gaps in diagnosing patients of color and trying to get students and educators to pledge to take meaningful steps and to have real-world impact.

This isn’t just exclusive to dermatology and rheumatology – it involves all medical specialties, she stressed.

ProjectIMPACT isn’t just a resource for physicians, she continued. Librarians can also use it to develop more resources on skin of color.

The Skin Of Color Society and VisualDx have also partnered with the NEJM Group to develop a comprehensive virtual series on the impact of skin color and ethnicity on clinical research. The four-part series addresses structural racism and racial bias in medicine, hair disorders in people of color, pigmentary disorders, keloids, COVID-19 comorbidities, and cutaneous manifestations of systemic diseases in children and adults.

Nuances of recognizing disease

As a medical student, Dr. McKinley-Grant said she was fortunate to attend the Albert Schweitzer Hospital in Lambarene, Gabon, on a fellowship. For 3 months, she gained a wealth of experience examining only African patients with brown skin.

In her other training in medicine, “I’ve been at institutions with diverse populations, in Boston, New York, and Washington,” learning more about all different skin pigments.

This type of training should be more widely available, especially now, with COVID-19 producing new manifestations of skin lesions, she emphasized. Such efforts involve a diversification of images physicians are being trained on so that they can recognize the same disease in a person of color.

“Doctors have to be able to recognize different colors, different shades of brown and shades of white. Not all white skin is the same color,” she noted. In looking at a rash or lesion, “you have to learn how to discern differences in the background color of the skin, which is determined by melanin in the skin (Fitzpatrick skin types I-VI) and by what’s going on in the blood, such as how much oxygen and hemoglobin the patient has in their blood.” Inflammation and infection (erythema) will appear more violaceous in IV-VI skin types, for example.

At the University of North Carolina at Chapel Hill, a group of students and faculty have created a dermatology image library to address the deficiency in the availability of images for teaching purposes. “Our medical students recognized the gap and started this,” Dr. Jonas said. Julie Mervak, MD, assistant professor of dermatology, is spearheading this effort, with students Linnea Westerkam and Anuj Pranav Sanghvi.

“I understand that others around the country are working on similar initiatives,” Dr. Jonas said.

None of the sources for this story had any relevant disclosures.

Studies are flagging racial and ethnic disparities in rheumatology training materials, pointing to a need to boost representation of darker skin tones and better educate physicians in evaluating this cohort.

AndreyPopov/Getty Images

Not enough is known about these disparities in rheumatology education, despite the fact that minorities make up 40% of the population in the United States.

The problem starts with books and references used in medical schools, Lynn McKinley-Grant, MD, immediate past president of the Skin of Color Society and associate professor of dermatology at Howard University, Washington, said in an interview. “In the medical literature there has been a dearth of images in skin of color in all specialties,” she said. With an increased diversity in the U.S. population, there is a need for health care providers to be able to recognize disease patterns in all skin types.” If a physician is training at an institution where there are not many patients of color in the community, the rheumatologists are even more limited in terms of their clinical experience.

This lack of training in diagnosis of disease has serious clinical repercussions, as seen in COVID cases, Dr. McKinley-Grant noted. “You end up not being able to recognize early erythema, jaundice, anemia, or hypoxemia because those conditions are a different color or pattern in the darker skin types. This can lead to errors in treatment, diagnosis, and medical care, resulting in increased morbidity and mortality.”

Studies point to education gaps

A team of researchers from Washington University in St. Louis called attention to this issue at the American College of Rhematology’s Convergence 2020 conference.

“Patients of color with lupus are especially vulnerable as they often carry a greater disease burden, yet studies show that individuals with darker skin tones are underrepresented in medical educational materials,” Vijay Kannuthurai, MD, and colleagues wrote in their study abstract. The team surveyed 132 providers in St. Louis, Mo., on their confidence in evaluating any rash, and rashes in patients with lupus and varied skin tones.

Participating clinicians, mostly rheumatologists, dermatologists, or internists, had a higher confidence level in diagnosing any rash versus lupus rashes, but were considerably less confident in diagnosing lupus rash on darker skin, compared with those on fair skin. This represents “a disparity between provider confidence and the patient population lupus traditionally affects,” the investigators concluded.

Another recent study found evidence of disparities in clinical education resources. “The lack of dark skin representation among rheumatology educational materials contributes to the implicit bias and structural racism present in medical education by promoting White-only models of disease,” lead author Adrienne Strait, a medical student at the University of California, San Francisco, said in an interview. “Given that rheumatic diseases disproportionately impact racial and ethnic minorities, we felt it was important to examine the representation of these groups within rheumatology training resources.”

She and her colleagues gathered images of rheumatic diseases from four major databases: the American College of Rheumatology’s Image Library, UpToDate, the New England Journal of Medicine Images in Clinical Medicine and Clinical Cases filtered by “Rheumatology,” and the 9th edition of Kelley’s Textbook of Rheumatology. They used Fitzpatrick’s skin phototypes to independently code images depicting skin as “light” (skin types I-IV), “dark” (skin types V-VI), or “indeterminate,” focusing on systemic lupus erythematosus (SLE) and rheumatoid arthritis, two conditions with a known connection to racial and ethnic health disparities.

Taking into account the high incidence of sarcoidosis and SLE in Black patients when compared with White patients, the investigators did a secondary analysis that excluded these cases.

Among 1,043 patient images studied, just 13.4% represented dark skin, compared with 84% that represented light skin. More than 2% represented an indeterminate skin color. Comparing dark-skin representation in the clinical images and SLE images with the representation of Asian, Native American, and Black individuals in the United States and within lupus cases nationally, the investigators found significant underrepresentation of dark skin.

Only 4.2% of RA images had dark-skin representation, making RA one of the diseases with the lowest representation in the study, along with juvenile idiopathic arthritis, the spondyloarthropathies, and Kawasaki disease. “Representation of dark skin in SLE was also lower than the proportion of Black individuals in SLE studies,” the investigators noted. Overall, representation of dark skin in SLE images was just 22.6%. Sarcoidosis comparatively had the largest representation of dark-skin images (69.6%, n = 32).

“Excluding sarcoidosis and SLE images, the overall representation of dark skin was 9.4% (n = 84), which was significantly lower than the proportion of Asian, Native American, and Black individuals within the U.S. Census population,” according to Ms. Strait and her associates. UpToDate contained the largest proportion of images of dark skin respective to other databases, whereas Kelley’s Textbook had the smallest.
 

Actionable steps

Many physicians are willing to improve upon their skills in identifying conditions on darker skin, as the study by Dr. Kannuthurai and associates suggests. Overall, 93% of the survey’s participants wanted to learn more about rashes in patients of color. “Future educational interventions may help practitioners improve their confidence when diagnosing rashes in lupus patients” with darker skin, they suggested.

Ms. Strait and her colleagues recommended a series of actionable steps to improve diversity and equity of dark skin tone representation in rheumatology curricula.

Editors of educational resources, for example, should make image diversity a priority for those diseases that are most commonly associated with cutaneous manifestations, such as SLE, vasculitis, inflammatory myopathies, systemic sclerosis, sarcoidosis, and psoriasis. They also called for educators in academic rheumatology programs to collaborate to improve diversity in resources used at the undergraduate and graduate medical education level.

Efforts should take place at the local, regional, and national level to publicly discuss and educate clinicians about rheumatic diseases in individuals of color. Speakers at rheumatology conferences should strive to educate learners about presentations of rheumatic diseases in individuals of color. The ACR in the meantime could establish a task force to enhance racial and ethnic diversity in their image library and other published resources.

“These steps may improve provider recognition and diagnosis of rheumatic disease manifestations in skin of color, which may in turn reduce health disparities among racial and ethnic minority groups,” Ms. Strait said.

Beth L. Jonas, MD, chair of the ACR’s Committee on Rheumatology Training and Workforce Issues, called the findings of this study “timely and important.” The researchers highlighted a deficiency in rheumatology training materials that needs addressing, she said in an interview. “I definitely agree that ACR needs to be mindful of this. There’s no doubt that we need to take these recommendations and move along these lines.”

The ACR took a first step in 2020 with the creation of a diversity, equity, and inclusion committee. “We are undergoing a college-wide look at what we do, with an eye toward inclusion. There is a strong interest in addressing health disparities and being an equitable and inclusive community of rheumatology health care professionals,” said Dr. Jonas, chief of the University of North Carolina at Chapel Hill’s division of rheumatology, allergy, and immunology.

The American Academy of Dermatology is also working to improve the image library with images of disease in skin of color. “Everyone’s jumping on this now,” Dr. McKinley-Grant observed. The medical profession can’t afford not to. It’s a life-threatening issue when rheumatoid arthritis and other diseases in people of color aren’t diagnosed early and correctly, she added.

Technologies seek to reduce bias

While many organizations are taking steps to improve representation of darker skin images, VisualDx has taken the lead on this, she said. “They’ve been doing this for years now. There are over 14,000 images of disease in skin of color, including all the rheumatologic diseases. There’s a mobile app and desktop decision support system, and it is very popular. A majority of medical schools have this as a library resource, and hospital systems license it for EHR integration.” Doctors can also get it individually. This enables them to share images and handouts of a diagnosis and select images of patients of color, said Dr. McKinley-Grant, who uses the VisualDx smartphone app DermExpert, which is an app for nondermatologists that features an image library of skin lesions, including darker-skin images.

ProjectIMPACT, powered by VisualDx, is another effort to support reducing health care bias in darker skin. The project is a collaboration between the New England Journal of Medicine Group and the Skin Of Color Society. According to Dr. McKinley-Grant, the organizers are building awareness of the importance of reducing the educational and clinical gaps in diagnosing patients of color and trying to get students and educators to pledge to take meaningful steps and to have real-world impact.

This isn’t just exclusive to dermatology and rheumatology – it involves all medical specialties, she stressed.

ProjectIMPACT isn’t just a resource for physicians, she continued. Librarians can also use it to develop more resources on skin of color.

The Skin Of Color Society and VisualDx have also partnered with the NEJM Group to develop a comprehensive virtual series on the impact of skin color and ethnicity on clinical research. The four-part series addresses structural racism and racial bias in medicine, hair disorders in people of color, pigmentary disorders, keloids, COVID-19 comorbidities, and cutaneous manifestations of systemic diseases in children and adults.

Nuances of recognizing disease

As a medical student, Dr. McKinley-Grant said she was fortunate to attend the Albert Schweitzer Hospital in Lambarene, Gabon, on a fellowship. For 3 months, she gained a wealth of experience examining only African patients with brown skin.

In her other training in medicine, “I’ve been at institutions with diverse populations, in Boston, New York, and Washington,” learning more about all different skin pigments.

This type of training should be more widely available, especially now, with COVID-19 producing new manifestations of skin lesions, she emphasized. Such efforts involve a diversification of images physicians are being trained on so that they can recognize the same disease in a person of color.

“Doctors have to be able to recognize different colors, different shades of brown and shades of white. Not all white skin is the same color,” she noted. In looking at a rash or lesion, “you have to learn how to discern differences in the background color of the skin, which is determined by melanin in the skin (Fitzpatrick skin types I-VI) and by what’s going on in the blood, such as how much oxygen and hemoglobin the patient has in their blood.” Inflammation and infection (erythema) will appear more violaceous in IV-VI skin types, for example.

At the University of North Carolina at Chapel Hill, a group of students and faculty have created a dermatology image library to address the deficiency in the availability of images for teaching purposes. “Our medical students recognized the gap and started this,” Dr. Jonas said. Julie Mervak, MD, assistant professor of dermatology, is spearheading this effort, with students Linnea Westerkam and Anuj Pranav Sanghvi.

“I understand that others around the country are working on similar initiatives,” Dr. Jonas said.

None of the sources for this story had any relevant disclosures.

An investigational vaginal gel significantly reduced urogenital chlamydia and gonorrhea in women at high risk for infection, compared with placebo, opening up new possibilities for an on-demand prevention option. Investigators of a randomized trial reported these findings in the American Journal of Obstetrics and Gynecology.

Rates of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) are on the rise in the United States, despite wide availability of male and female condoms to prevent sexually transmitted infections. This suggests that women need a more discrete method that they can better control. Other vaginal microbicides developed over the last few decades haven’t performed well in protecting against STIs or HIV in clinical trials.

The slightly alkaline nature of human semen has the potential to neutralize vaginal pH after intercourse, creating a more vulnerable environment for STIs. EVO100 is an investigational antimicrobial, bioadhesive vaginal gel that contains L-lactic acid, citric acid, and potassium bitartrate. In preclinical studies, it was highly effective at buffering the alkaline properties of human semen and maintaining vaginal pH levels. Patients generally tolerated it well, aside from some reports of vaginal itching and burning.

An investigational vaginal gel significantly reduced urogenital chlamydia and gonorrhea in women at high risk for infection, compared with placebo, opening up new possibilities for an on-demand prevention option. Investigators of a randomized trial reported these findings in the American Journal of Obstetrics and Gynecology.

Rates of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) are on the rise in the United States, despite wide availability of male and female condoms to prevent sexually transmitted infections. This suggests that women need a more discrete method that they can better control. Other vaginal microbicides developed over the last few decades haven’t performed well in protecting against STIs or HIV in clinical trials.

The slightly alkaline nature of human semen has the potential to neutralize vaginal pH after intercourse, creating a more vulnerable environment for STIs. EVO100 is an investigational antimicrobial, bioadhesive vaginal gel that contains L-lactic acid, citric acid, and potassium bitartrate. In preclinical studies, it was highly effective at buffering the alkaline properties of human semen and maintaining vaginal pH levels. Patients generally tolerated it well, aside from some reports of vaginal itching and burning.

An investigational vaginal gel significantly reduced urogenital chlamydia and gonorrhea in women at high risk for infection, compared with placebo, opening up new possibilities for an on-demand prevention option. Investigators of a randomized trial reported these findings in the American Journal of Obstetrics and Gynecology.

Rates of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) are on the rise in the United States, despite wide availability of male and female condoms to prevent sexually transmitted infections. This suggests that women need a more discrete method that they can better control. Other vaginal microbicides developed over the last few decades haven’t performed well in protecting against STIs or HIV in clinical trials.

The slightly alkaline nature of human semen has the potential to neutralize vaginal pH after intercourse, creating a more vulnerable environment for STIs. EVO100 is an investigational antimicrobial, bioadhesive vaginal gel that contains L-lactic acid, citric acid, and potassium bitartrate. In preclinical studies, it was highly effective at buffering the alkaline properties of human semen and maintaining vaginal pH levels. Patients generally tolerated it well, aside from some reports of vaginal itching and burning.

A new genetic mutation in schizophrenia that blocks neuron communication in the brain may lead to novel treatment strategies and improve understanding of the mechanics of this disease.

The discovery of this new gene, PCDHA3, could enhance the development of genetic-risk calculators “that may help us understand vulnerability to schizophrenia in high-risk individuals and identify individuals with schizophrenia who have a greater risk for poor outcomes,” said Todd Lencz, PhD, a professor at the Feinstein Institutes for Medical Research in New York, and lead author of this research. Dr. Lencz and associates reported on this new finding in the journal Neuron.

Schizophrenia affects 20 million people worldwide. Previous research has identified the important role genes play in the disease, but isolating individual genes to better understand schizophrenia has proven to be a challenge. This is a very heterogeneous disorder, with many hundreds if not thousands of genes involved, Dr. Lencz explained in an interview. “It is very different from single-gene disorders like Huntington disease, for example. For this reason, we need very large sample sizes to find any one gene that seems to be common to many cases in a sample.”
 

Study focused on homogeneous population

To enhance the power of finding rare variants in a heterogeneous disease with large numbers of genes, Dr. Lencz and colleagues chose a homogeneous “founder” population, a cohort of Ashkenazi Jews, to examine genomes from schizophrenia patients and controls. “As we have reported in prior work over the last decade, the 10 million or so Ashkenazi Jews living worldwide today all are descended from just a few hundred people who lived approximately 750 years ago, and moved into Central and Eastern Europe,” said Dr. Lencz. The study included 786 cases of schizophrenia and 463 controls from this Ashkenazi population. This is considered to be an extremely small sample for a genetic study. However, because this population evolved from a few hundred individuals to a massive explosion in a historically short period of time, it had enhanced statistical power, said Dr. Lencz.

“We showed that just a few thousand Ashkenazi Jewish cases would have the statistical power of a regular population that was 5-10 times larger, from a genetic discovery perspective,” he added.
 

Search for ultrarare variants

The investigators used whole-genome sequencing to conduct their analysis, using public databases to filter out any variants that had been previously observed in healthy individuals worldwide. “We were looking for ultrarare variants that might have a very powerful effect on the disease,” Dr. Lencz said. Such individual mutations are very rarely seen in the general population.

Because of the disease’s ultraheterogeneity, it’s extremely unusual to find a recurrent, ultrarare variant. “In some ways, the genetics of schizophrenia is so complex that every patient worldwide is unique in the genetics that led to his or her disorder.” The goal was to find individual mutations that might be observed multiple times across the schizophrenia group, Dr. Lencz said.
 

Rare gene found in five cases

Dr. Lencz and colleagues accomplished this with their unique Ashkenazi Jewish population. “We identified one particular mutation that was repeatedly observed in our cases that has not been observed in healthy individuals that we’re aware of,” he said. The PCDHA3 mutation was identified in 3 out of the 786 schizophrenia cases.

In another dataset, they examined from the Schizophrenia Exome Sequencing Meta-analysis (SCHEMA) consortium, they found it two additional times, bringing the total to five cases. SCHEMA is a large international consortium of genetics studies in schizophrenia that contains thousands of cases and controls, some of which are Ashkenazi Jewish cases.

“Importantly, the mutation was not observed in any controls, in either our Ashkenazi dataset, the SCHEMA dataset, or more than 100,000 other controls reported in several publicly available genetics databases,” Dr. Lencz said.
 

How the gene leads to schizophrenia

PCDHA3 derives from the protocadherin gene family, which generates a unique bar code that enables neurons to recognize and communicate with other neurons. This communication creates a scaffolding of sorts that enables normal brain function. Dr. Lencz and colleagues discovered that the PCDHA3 variant blocks this normal protocadherin function.

Among the 786 cases, the investigators found several other genes in the broad cadherin family that had implications in schizophrenia development.

Much of the genetics of schizophrenia in recent years has focused on the synapse as the point of abnormality underlying the disorder. “We think our paper demonstrates in multiple ways the synaptic scaffolding role the cadherins superfamily of genes play in schizophrenia pathophysiology. This is novel – it has never been described before,” said Dr. Lencz. The discovery of the PCDHA3 variant adds a level of detail and resolution to this process, pointing researchers toward a specific aspect of synaptic formation that may be aberrant. “So the hope is we’re not just learning about these five individuals and their synapses. This result is perhaps telling us to look very carefully at this aspect of synaptic formation.”
 

Implications for clinical practice

Dr. Lencz and colleagues plan to expand upon and enhance their existing Ashkenazi sample to take advantage of the founder effect in this population. “Of course, there are many large-scale efforts to recruit ethnically diverse patients with schizophrenia to study around the world. We encourage that. Our expectation is that the biology is not in any way unique to Ashkenazi individuals. This is just the approach we took to enhance our power,” he said.

The PCDHA3 discovery won’t have an immediate impact on clinical practice. In the longer term, “we are aware of certain pharmacologic approaches that might be able to manipulate the cadherins. That would be a worthy focus for future research,” Dr. Lencz said.

Additional studies will be critical to see how current medications in schizophrenia treatment could mitigate and improve any changes caused by this genetic mutation, noted Anthony T. Ng, MD, who was not involved with the study. More specifically, studies would help assess the impact of a schizophrenia patient with this mutation in areas of functioning, “so that psychosocial and rehabilitation treatment models of schizophrenia can provide more targeted treatment,” said Dr. Ng, medical director of community services and director of neuromodulation services at Northern Light Acadia Hospital in Bangor, Maine.

The work of Dr. Lencz and associates is significant in that “it started to identify a very specific genetic change that can help focus treatment of schizophrenia,” Dr. Ng said.

Neither Dr. Lencz nor his associates had any conflicts of interest. Dr. Ng had no disclosures.

A new genetic mutation in schizophrenia that blocks neuron communication in the brain may lead to novel treatment strategies and improve understanding of the mechanics of this disease.

The discovery of this new gene, PCDHA3, could enhance the development of genetic-risk calculators “that may help us understand vulnerability to schizophrenia in high-risk individuals and identify individuals with schizophrenia who have a greater risk for poor outcomes,” said Todd Lencz, PhD, a professor at the Feinstein Institutes for Medical Research in New York, and lead author of this research. Dr. Lencz and associates reported on this new finding in the journal Neuron.

Schizophrenia affects 20 million people worldwide. Previous research has identified the important role genes play in the disease, but isolating individual genes to better understand schizophrenia has proven to be a challenge. This is a very heterogeneous disorder, with many hundreds if not thousands of genes involved, Dr. Lencz explained in an interview. “It is very different from single-gene disorders like Huntington disease, for example. For this reason, we need very large sample sizes to find any one gene that seems to be common to many cases in a sample.”
 

Study focused on homogeneous population

To enhance the power of finding rare variants in a heterogeneous disease with large numbers of genes, Dr. Lencz and colleagues chose a homogeneous “founder” population, a cohort of Ashkenazi Jews, to examine genomes from schizophrenia patients and controls. “As we have reported in prior work over the last decade, the 10 million or so Ashkenazi Jews living worldwide today all are descended from just a few hundred people who lived approximately 750 years ago, and moved into Central and Eastern Europe,” said Dr. Lencz. The study included 786 cases of schizophrenia and 463 controls from this Ashkenazi population. This is considered to be an extremely small sample for a genetic study. However, because this population evolved from a few hundred individuals to a massive explosion in a historically short period of time, it had enhanced statistical power, said Dr. Lencz.

“We showed that just a few thousand Ashkenazi Jewish cases would have the statistical power of a regular population that was 5-10 times larger, from a genetic discovery perspective,” he added.
 

Search for ultrarare variants

The investigators used whole-genome sequencing to conduct their analysis, using public databases to filter out any variants that had been previously observed in healthy individuals worldwide. “We were looking for ultrarare variants that might have a very powerful effect on the disease,” Dr. Lencz said. Such individual mutations are very rarely seen in the general population.

Because of the disease’s ultraheterogeneity, it’s extremely unusual to find a recurrent, ultrarare variant. “In some ways, the genetics of schizophrenia is so complex that every patient worldwide is unique in the genetics that led to his or her disorder.” The goal was to find individual mutations that might be observed multiple times across the schizophrenia group, Dr. Lencz said.
 

Rare gene found in five cases

Dr. Lencz and colleagues accomplished this with their unique Ashkenazi Jewish population. “We identified one particular mutation that was repeatedly observed in our cases that has not been observed in healthy individuals that we’re aware of,” he said. The PCDHA3 mutation was identified in 3 out of the 786 schizophrenia cases.

In another dataset, they examined from the Schizophrenia Exome Sequencing Meta-analysis (SCHEMA) consortium, they found it two additional times, bringing the total to five cases. SCHEMA is a large international consortium of genetics studies in schizophrenia that contains thousands of cases and controls, some of which are Ashkenazi Jewish cases.

“Importantly, the mutation was not observed in any controls, in either our Ashkenazi dataset, the SCHEMA dataset, or more than 100,000 other controls reported in several publicly available genetics databases,” Dr. Lencz said.
 

How the gene leads to schizophrenia

PCDHA3 derives from the protocadherin gene family, which generates a unique bar code that enables neurons to recognize and communicate with other neurons. This communication creates a scaffolding of sorts that enables normal brain function. Dr. Lencz and colleagues discovered that the PCDHA3 variant blocks this normal protocadherin function.

Among the 786 cases, the investigators found several other genes in the broad cadherin family that had implications in schizophrenia development.

Much of the genetics of schizophrenia in recent years has focused on the synapse as the point of abnormality underlying the disorder. “We think our paper demonstrates in multiple ways the synaptic scaffolding role the cadherins superfamily of genes play in schizophrenia pathophysiology. This is novel – it has never been described before,” said Dr. Lencz. The discovery of the PCDHA3 variant adds a level of detail and resolution to this process, pointing researchers toward a specific aspect of synaptic formation that may be aberrant. “So the hope is we’re not just learning about these five individuals and their synapses. This result is perhaps telling us to look very carefully at this aspect of synaptic formation.”
 

Implications for clinical practice

Dr. Lencz and colleagues plan to expand upon and enhance their existing Ashkenazi sample to take advantage of the founder effect in this population. “Of course, there are many large-scale efforts to recruit ethnically diverse patients with schizophrenia to study around the world. We encourage that. Our expectation is that the biology is not in any way unique to Ashkenazi individuals. This is just the approach we took to enhance our power,” he said.

The PCDHA3 discovery won’t have an immediate impact on clinical practice. In the longer term, “we are aware of certain pharmacologic approaches that might be able to manipulate the cadherins. That would be a worthy focus for future research,” Dr. Lencz said.

Additional studies will be critical to see how current medications in schizophrenia treatment could mitigate and improve any changes caused by this genetic mutation, noted Anthony T. Ng, MD, who was not involved with the study. More specifically, studies would help assess the impact of a schizophrenia patient with this mutation in areas of functioning, “so that psychosocial and rehabilitation treatment models of schizophrenia can provide more targeted treatment,” said Dr. Ng, medical director of community services and director of neuromodulation services at Northern Light Acadia Hospital in Bangor, Maine.

The work of Dr. Lencz and associates is significant in that “it started to identify a very specific genetic change that can help focus treatment of schizophrenia,” Dr. Ng said.

Neither Dr. Lencz nor his associates had any conflicts of interest. Dr. Ng had no disclosures.

A new genetic mutation in schizophrenia that blocks neuron communication in the brain may lead to novel treatment strategies and improve understanding of the mechanics of this disease.

The discovery of this new gene, PCDHA3, could enhance the development of genetic-risk calculators “that may help us understand vulnerability to schizophrenia in high-risk individuals and identify individuals with schizophrenia who have a greater risk for poor outcomes,” said Todd Lencz, PhD, a professor at the Feinstein Institutes for Medical Research in New York, and lead author of this research. Dr. Lencz and associates reported on this new finding in the journal Neuron.

Schizophrenia affects 20 million people worldwide. Previous research has identified the important role genes play in the disease, but isolating individual genes to better understand schizophrenia has proven to be a challenge. This is a very heterogeneous disorder, with many hundreds if not thousands of genes involved, Dr. Lencz explained in an interview. “It is very different from single-gene disorders like Huntington disease, for example. For this reason, we need very large sample sizes to find any one gene that seems to be common to many cases in a sample.”
 

Study focused on homogeneous population

To enhance the power of finding rare variants in a heterogeneous disease with large numbers of genes, Dr. Lencz and colleagues chose a homogeneous “founder” population, a cohort of Ashkenazi Jews, to examine genomes from schizophrenia patients and controls. “As we have reported in prior work over the last decade, the 10 million or so Ashkenazi Jews living worldwide today all are descended from just a few hundred people who lived approximately 750 years ago, and moved into Central and Eastern Europe,” said Dr. Lencz. The study included 786 cases of schizophrenia and 463 controls from this Ashkenazi population. This is considered to be an extremely small sample for a genetic study. However, because this population evolved from a few hundred individuals to a massive explosion in a historically short period of time, it had enhanced statistical power, said Dr. Lencz.

“We showed that just a few thousand Ashkenazi Jewish cases would have the statistical power of a regular population that was 5-10 times larger, from a genetic discovery perspective,” he added.
 

Search for ultrarare variants

The investigators used whole-genome sequencing to conduct their analysis, using public databases to filter out any variants that had been previously observed in healthy individuals worldwide. “We were looking for ultrarare variants that might have a very powerful effect on the disease,” Dr. Lencz said. Such individual mutations are very rarely seen in the general population.

Because of the disease’s ultraheterogeneity, it’s extremely unusual to find a recurrent, ultrarare variant. “In some ways, the genetics of schizophrenia is so complex that every patient worldwide is unique in the genetics that led to his or her disorder.” The goal was to find individual mutations that might be observed multiple times across the schizophrenia group, Dr. Lencz said.
 

Rare gene found in five cases

Dr. Lencz and colleagues accomplished this with their unique Ashkenazi Jewish population. “We identified one particular mutation that was repeatedly observed in our cases that has not been observed in healthy individuals that we’re aware of,” he said. The PCDHA3 mutation was identified in 3 out of the 786 schizophrenia cases.

In another dataset, they examined from the Schizophrenia Exome Sequencing Meta-analysis (SCHEMA) consortium, they found it two additional times, bringing the total to five cases. SCHEMA is a large international consortium of genetics studies in schizophrenia that contains thousands of cases and controls, some of which are Ashkenazi Jewish cases.

“Importantly, the mutation was not observed in any controls, in either our Ashkenazi dataset, the SCHEMA dataset, or more than 100,000 other controls reported in several publicly available genetics databases,” Dr. Lencz said.
 

How the gene leads to schizophrenia

PCDHA3 derives from the protocadherin gene family, which generates a unique bar code that enables neurons to recognize and communicate with other neurons. This communication creates a scaffolding of sorts that enables normal brain function. Dr. Lencz and colleagues discovered that the PCDHA3 variant blocks this normal protocadherin function.

Among the 786 cases, the investigators found several other genes in the broad cadherin family that had implications in schizophrenia development.

Much of the genetics of schizophrenia in recent years has focused on the synapse as the point of abnormality underlying the disorder. “We think our paper demonstrates in multiple ways the synaptic scaffolding role the cadherins superfamily of genes play in schizophrenia pathophysiology. This is novel – it has never been described before,” said Dr. Lencz. The discovery of the PCDHA3 variant adds a level of detail and resolution to this process, pointing researchers toward a specific aspect of synaptic formation that may be aberrant. “So the hope is we’re not just learning about these five individuals and their synapses. This result is perhaps telling us to look very carefully at this aspect of synaptic formation.”
 

Implications for clinical practice

Dr. Lencz and colleagues plan to expand upon and enhance their existing Ashkenazi sample to take advantage of the founder effect in this population. “Of course, there are many large-scale efforts to recruit ethnically diverse patients with schizophrenia to study around the world. We encourage that. Our expectation is that the biology is not in any way unique to Ashkenazi individuals. This is just the approach we took to enhance our power,” he said.

The PCDHA3 discovery won’t have an immediate impact on clinical practice. In the longer term, “we are aware of certain pharmacologic approaches that might be able to manipulate the cadherins. That would be a worthy focus for future research,” Dr. Lencz said.

Additional studies will be critical to see how current medications in schizophrenia treatment could mitigate and improve any changes caused by this genetic mutation, noted Anthony T. Ng, MD, who was not involved with the study. More specifically, studies would help assess the impact of a schizophrenia patient with this mutation in areas of functioning, “so that psychosocial and rehabilitation treatment models of schizophrenia can provide more targeted treatment,” said Dr. Ng, medical director of community services and director of neuromodulation services at Northern Light Acadia Hospital in Bangor, Maine.

The work of Dr. Lencz and associates is significant in that “it started to identify a very specific genetic change that can help focus treatment of schizophrenia,” Dr. Ng said.

Neither Dr. Lencz nor his associates had any conflicts of interest. Dr. Ng had no disclosures.

Broadening the diagnosis of gestational diabetes mellitus (GDM) with a one-step screening approach does not lead to significant differences in maternal or perinatal outcomes, compared with a two-step approach. Investigators reported these findings in the New England Journal of Medicine after testing the two screening methods in more than 23,000 pregnant women.

GDM affects 6%-25% of pregnant women, increasing the risk of neonatal death and stillborn births. It can also lead to serious complications such as fetal overgrowth. Clinical guidelines recommend GDM screening between 24 and 28 weeks’ gestation to improve outcomes in mothers and infants. However, the scientific community has struggled to reach a consensus on testing approach.

For decades, clinicians used a two-step screening approach: a nonfasting 1-hour glucose challenge test and a longer 3-hour fasting oral glucose tolerance test to diagnose GDM; roughly 20% who test positive on this glucose challenge test require the second step. Results of a large study led to new diagnostic criteria on a one-step 75-g oral glucose tolerance test. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study “found a linear relationship with hyperglycemia and outcomes – the higher the glucose, the worse the outcomes,” said Teresa Hillier, MD, MS, an endocrinologist and investigator with Kaiser Permanente Center for Health Research Northwest and CHR-Hawaii. The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) made a clinical recommendation on the one-step approach, now a common screening tool in the United States.
 

A focus on rare GDM outcomes

The IADPSG fasting one-step criteria typically identifies women with milder symptoms as having gestational diabetes, a factor expected to increase diagnosis rates by two- or threefold, said Dr. Hillier. “The unknown question was whether diagnosing and treating more women would be associated with any differences in any of the multiple GDM-associated outcomes for mother and baby.”

She and her colleagues conducted a large-scale randomized trial at two Kaiser sites to assess multiple maternal and perinatal outcomes including rare but important GDM-associated outcomes such as stillbirth and neonatal death between the two screening methods.

They randomized 23,792 pregnant women 1:1 to the one- or two-step gestational diabetes test at their first prenatal visit. Primary outcomes included diagnosis of gestational diabetes; large-for-gestational-age infants; primary cesarean section, and gestational hypertension or preeclampsia; and a composite perinatal outcome of any stillbirth, neonatal death, shoulder dystocia, bone fracture, or arm or hand nerve palsy related to birth injury.

Most participants (94%) completed screening, although there was lower adherence to screening in the one-step approach. The reasons for this aren’t entirely clear, said Dr. Hillier. Convenience may be a factor; patients have to fast for several hours to complete the one-step test, whereas the first test of the two-step screening approach can be done at any time of day, and most patients pass this test.

Corroborating HAPO’s results, twice as many women in the one-step group (16.5%) received a GDM diagnosis, compared with 8.5% in the two-step group (unadjusted relative risk, 1.94; 97.5% confidence interval, 1.79-2.11). However, for the other primary outcomes, investigators found no significant differences in incidences or unadjusted risks. Perinatal composite outcomes for the one- and two-step groups were 3.1% and 3.0%, respectively, and primary cesarean section outcomes were 24.0% and 24.6%.

In the one-step group, 8.9% experienced large-for-gestational-age infants outcomes, compared with 9.2% in the two-step group (RR, 0.95; 97.5% CI, 0.87-1.05). Among those diagnosed with gestational diabetes, similar percentages of women in the one- and two-step groups received insulin or hypoglycemic medication (42.6% and 45.6%, respectively).

Dr. Hillier and colleagues also reported comparable results among the two groups on safety outcomes and secondary outcomes such as macrosomia incidence, small-for-gestational-age infants, and factors such as neonatal hypoglycemia and respiratory distress.

“Although we did not find increased harms associated with the diagnosis and treatment of gestational diabetes in many more women with the one-step approach, some retrospective observational cohort studies have shown higher incidences of primary cesarean delivery and neonatal hypoglycemia with one-step screening after conversion from two-step protocols, with no substantive improvement in outcomes,” Dr. Hillier and colleagues noted.

The trial had several limitations. Adjustments made to address lower adherence to the one-step approach might not have accounted for all nonadherence differences. Another issue is the two sites didn’t use identical thresholds for the glucose challenge test in the two-step cohort. Demographically, the study lacked Black and American Indian representation.

“Moreover, the potential long-term benefits of increased diagnoses of gestational diabetes – such as the identification of more women at high risk for subsequent diabetes who might benefit from risk-reduction strategies – were not addressed by the trial,” Brian Casey, MD, wrote in a related editorial. Based on the study’s findings, “the perinatal benefits of the diagnosis of gestational diabetes with the use of the IADPSG single-step approach appear to be insufficient to justify the associated patient and health care costs of broadening the diagnosis” of GDM, added Dr. Casey, a professor with the department of obstetrics and gynecology at the University of Alabama at Birmingham.
 

U.S. doctors unlikely to change behaviors

Most U.S. physicians favor the two-step method. This has been a huge controversy worldwide, with other countries pushing the United States to use the one-step method, Vincenzo Berghella, MD, a professor with Thomas Jefferson University, Philadelphia, said in an interview. “I expect this study will increase the divide between the U.S. and the rest of the world,” since U.S. physicians will see no benefit to the one-step method, and continue to use the two-step method. 

It’s not surprising that GDM diagnosis incidence went up to 16.5% with the inclusion of the one-step test, compared with 8.5% with the two-step test, Dr. Berghella continued. What’s less clear, are the details of treatment among the 8% diagnosed to have GDM with the one-step test, but not the two-step test. 

These women were likely to have milder degrees of insulin resistance or GDM. Dr. Berghella, who has advocated in the past for the one-step approach, said it would be important to find out if these women, who test positive at the one-step test but would test negative at the two-step test, were treated properly with diet, exercise, and possibly insulin or other hypoglycemic agents for their mild degree of insulin resistance. The researchers concluded that expanding the definition of GDM through the one-step test didn’t make a difference. However, “it’s not just the test that will make the difference in maternal and baby outcomes, but the aggressive management of diabetes with diet, exercise, and medications as needed once that test comes back abnormal,” he said.

The randomized trial was a massive undertaking, said Dr. Hillier.

“We are still evaluating our future plans,” she added. Forthcoming subgroup analyses from the trial could further help inform clinical practice guidelines.

Dr. Hillier received a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development to support this study. The investigators reported no potential conflict of interest relevant to this article.

Broadening the diagnosis of gestational diabetes mellitus (GDM) with a one-step screening approach does not lead to significant differences in maternal or perinatal outcomes, compared with a two-step approach. Investigators reported these findings in the New England Journal of Medicine after testing the two screening methods in more than 23,000 pregnant women.

GDM affects 6%-25% of pregnant women, increasing the risk of neonatal death and stillborn births. It can also lead to serious complications such as fetal overgrowth. Clinical guidelines recommend GDM screening between 24 and 28 weeks’ gestation to improve outcomes in mothers and infants. However, the scientific community has struggled to reach a consensus on testing approach.

For decades, clinicians used a two-step screening approach: a nonfasting 1-hour glucose challenge test and a longer 3-hour fasting oral glucose tolerance test to diagnose GDM; roughly 20% who test positive on this glucose challenge test require the second step. Results of a large study led to new diagnostic criteria on a one-step 75-g oral glucose tolerance test. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study “found a linear relationship with hyperglycemia and outcomes – the higher the glucose, the worse the outcomes,” said Teresa Hillier, MD, MS, an endocrinologist and investigator with Kaiser Permanente Center for Health Research Northwest and CHR-Hawaii. The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) made a clinical recommendation on the one-step approach, now a common screening tool in the United States.
 

A focus on rare GDM outcomes

The IADPSG fasting one-step criteria typically identifies women with milder symptoms as having gestational diabetes, a factor expected to increase diagnosis rates by two- or threefold, said Dr. Hillier. “The unknown question was whether diagnosing and treating more women would be associated with any differences in any of the multiple GDM-associated outcomes for mother and baby.”

She and her colleagues conducted a large-scale randomized trial at two Kaiser sites to assess multiple maternal and perinatal outcomes including rare but important GDM-associated outcomes such as stillbirth and neonatal death between the two screening methods.

They randomized 23,792 pregnant women 1:1 to the one- or two-step gestational diabetes test at their first prenatal visit. Primary outcomes included diagnosis of gestational diabetes; large-for-gestational-age infants; primary cesarean section, and gestational hypertension or preeclampsia; and a composite perinatal outcome of any stillbirth, neonatal death, shoulder dystocia, bone fracture, or arm or hand nerve palsy related to birth injury.

Most participants (94%) completed screening, although there was lower adherence to screening in the one-step approach. The reasons for this aren’t entirely clear, said Dr. Hillier. Convenience may be a factor; patients have to fast for several hours to complete the one-step test, whereas the first test of the two-step screening approach can be done at any time of day, and most patients pass this test.

Corroborating HAPO’s results, twice as many women in the one-step group (16.5%) received a GDM diagnosis, compared with 8.5% in the two-step group (unadjusted relative risk, 1.94; 97.5% confidence interval, 1.79-2.11). However, for the other primary outcomes, investigators found no significant differences in incidences or unadjusted risks. Perinatal composite outcomes for the one- and two-step groups were 3.1% and 3.0%, respectively, and primary cesarean section outcomes were 24.0% and 24.6%.

In the one-step group, 8.9% experienced large-for-gestational-age infants outcomes, compared with 9.2% in the two-step group (RR, 0.95; 97.5% CI, 0.87-1.05). Among those diagnosed with gestational diabetes, similar percentages of women in the one- and two-step groups received insulin or hypoglycemic medication (42.6% and 45.6%, respectively).

Dr. Hillier and colleagues also reported comparable results among the two groups on safety outcomes and secondary outcomes such as macrosomia incidence, small-for-gestational-age infants, and factors such as neonatal hypoglycemia and respiratory distress.

“Although we did not find increased harms associated with the diagnosis and treatment of gestational diabetes in many more women with the one-step approach, some retrospective observational cohort studies have shown higher incidences of primary cesarean delivery and neonatal hypoglycemia with one-step screening after conversion from two-step protocols, with no substantive improvement in outcomes,” Dr. Hillier and colleagues noted.

The trial had several limitations. Adjustments made to address lower adherence to the one-step approach might not have accounted for all nonadherence differences. Another issue is the two sites didn’t use identical thresholds for the glucose challenge test in the two-step cohort. Demographically, the study lacked Black and American Indian representation.

“Moreover, the potential long-term benefits of increased diagnoses of gestational diabetes – such as the identification of more women at high risk for subsequent diabetes who might benefit from risk-reduction strategies – were not addressed by the trial,” Brian Casey, MD, wrote in a related editorial. Based on the study’s findings, “the perinatal benefits of the diagnosis of gestational diabetes with the use of the IADPSG single-step approach appear to be insufficient to justify the associated patient and health care costs of broadening the diagnosis” of GDM, added Dr. Casey, a professor with the department of obstetrics and gynecology at the University of Alabama at Birmingham.
 

U.S. doctors unlikely to change behaviors

Most U.S. physicians favor the two-step method. This has been a huge controversy worldwide, with other countries pushing the United States to use the one-step method, Vincenzo Berghella, MD, a professor with Thomas Jefferson University, Philadelphia, said in an interview. “I expect this study will increase the divide between the U.S. and the rest of the world,” since U.S. physicians will see no benefit to the one-step method, and continue to use the two-step method. 

It’s not surprising that GDM diagnosis incidence went up to 16.5% with the inclusion of the one-step test, compared with 8.5% with the two-step test, Dr. Berghella continued. What’s less clear, are the details of treatment among the 8% diagnosed to have GDM with the one-step test, but not the two-step test. 

These women were likely to have milder degrees of insulin resistance or GDM. Dr. Berghella, who has advocated in the past for the one-step approach, said it would be important to find out if these women, who test positive at the one-step test but would test negative at the two-step test, were treated properly with diet, exercise, and possibly insulin or other hypoglycemic agents for their mild degree of insulin resistance. The researchers concluded that expanding the definition of GDM through the one-step test didn’t make a difference. However, “it’s not just the test that will make the difference in maternal and baby outcomes, but the aggressive management of diabetes with diet, exercise, and medications as needed once that test comes back abnormal,” he said.

The randomized trial was a massive undertaking, said Dr. Hillier.

“We are still evaluating our future plans,” she added. Forthcoming subgroup analyses from the trial could further help inform clinical practice guidelines.

Dr. Hillier received a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development to support this study. The investigators reported no potential conflict of interest relevant to this article.

Broadening the diagnosis of gestational diabetes mellitus (GDM) with a one-step screening approach does not lead to significant differences in maternal or perinatal outcomes, compared with a two-step approach. Investigators reported these findings in the New England Journal of Medicine after testing the two screening methods in more than 23,000 pregnant women.

GDM affects 6%-25% of pregnant women, increasing the risk of neonatal death and stillborn births. It can also lead to serious complications such as fetal overgrowth. Clinical guidelines recommend GDM screening between 24 and 28 weeks’ gestation to improve outcomes in mothers and infants. However, the scientific community has struggled to reach a consensus on testing approach.

For decades, clinicians used a two-step screening approach: a nonfasting 1-hour glucose challenge test and a longer 3-hour fasting oral glucose tolerance test to diagnose GDM; roughly 20% who test positive on this glucose challenge test require the second step. Results of a large study led to new diagnostic criteria on a one-step 75-g oral glucose tolerance test. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study “found a linear relationship with hyperglycemia and outcomes – the higher the glucose, the worse the outcomes,” said Teresa Hillier, MD, MS, an endocrinologist and investigator with Kaiser Permanente Center for Health Research Northwest and CHR-Hawaii. The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) made a clinical recommendation on the one-step approach, now a common screening tool in the United States.
 

A focus on rare GDM outcomes

The IADPSG fasting one-step criteria typically identifies women with milder symptoms as having gestational diabetes, a factor expected to increase diagnosis rates by two- or threefold, said Dr. Hillier. “The unknown question was whether diagnosing and treating more women would be associated with any differences in any of the multiple GDM-associated outcomes for mother and baby.”

She and her colleagues conducted a large-scale randomized trial at two Kaiser sites to assess multiple maternal and perinatal outcomes including rare but important GDM-associated outcomes such as stillbirth and neonatal death between the two screening methods.

They randomized 23,792 pregnant women 1:1 to the one- or two-step gestational diabetes test at their first prenatal visit. Primary outcomes included diagnosis of gestational diabetes; large-for-gestational-age infants; primary cesarean section, and gestational hypertension or preeclampsia; and a composite perinatal outcome of any stillbirth, neonatal death, shoulder dystocia, bone fracture, or arm or hand nerve palsy related to birth injury.

Most participants (94%) completed screening, although there was lower adherence to screening in the one-step approach. The reasons for this aren’t entirely clear, said Dr. Hillier. Convenience may be a factor; patients have to fast for several hours to complete the one-step test, whereas the first test of the two-step screening approach can be done at any time of day, and most patients pass this test.

Corroborating HAPO’s results, twice as many women in the one-step group (16.5%) received a GDM diagnosis, compared with 8.5% in the two-step group (unadjusted relative risk, 1.94; 97.5% confidence interval, 1.79-2.11). However, for the other primary outcomes, investigators found no significant differences in incidences or unadjusted risks. Perinatal composite outcomes for the one- and two-step groups were 3.1% and 3.0%, respectively, and primary cesarean section outcomes were 24.0% and 24.6%.

In the one-step group, 8.9% experienced large-for-gestational-age infants outcomes, compared with 9.2% in the two-step group (RR, 0.95; 97.5% CI, 0.87-1.05). Among those diagnosed with gestational diabetes, similar percentages of women in the one- and two-step groups received insulin or hypoglycemic medication (42.6% and 45.6%, respectively).

Dr. Hillier and colleagues also reported comparable results among the two groups on safety outcomes and secondary outcomes such as macrosomia incidence, small-for-gestational-age infants, and factors such as neonatal hypoglycemia and respiratory distress.

“Although we did not find increased harms associated with the diagnosis and treatment of gestational diabetes in many more women with the one-step approach, some retrospective observational cohort studies have shown higher incidences of primary cesarean delivery and neonatal hypoglycemia with one-step screening after conversion from two-step protocols, with no substantive improvement in outcomes,” Dr. Hillier and colleagues noted.

The trial had several limitations. Adjustments made to address lower adherence to the one-step approach might not have accounted for all nonadherence differences. Another issue is the two sites didn’t use identical thresholds for the glucose challenge test in the two-step cohort. Demographically, the study lacked Black and American Indian representation.

“Moreover, the potential long-term benefits of increased diagnoses of gestational diabetes – such as the identification of more women at high risk for subsequent diabetes who might benefit from risk-reduction strategies – were not addressed by the trial,” Brian Casey, MD, wrote in a related editorial. Based on the study’s findings, “the perinatal benefits of the diagnosis of gestational diabetes with the use of the IADPSG single-step approach appear to be insufficient to justify the associated patient and health care costs of broadening the diagnosis” of GDM, added Dr. Casey, a professor with the department of obstetrics and gynecology at the University of Alabama at Birmingham.
 

U.S. doctors unlikely to change behaviors

Most U.S. physicians favor the two-step method. This has been a huge controversy worldwide, with other countries pushing the United States to use the one-step method, Vincenzo Berghella, MD, a professor with Thomas Jefferson University, Philadelphia, said in an interview. “I expect this study will increase the divide between the U.S. and the rest of the world,” since U.S. physicians will see no benefit to the one-step method, and continue to use the two-step method. 

It’s not surprising that GDM diagnosis incidence went up to 16.5% with the inclusion of the one-step test, compared with 8.5% with the two-step test, Dr. Berghella continued. What’s less clear, are the details of treatment among the 8% diagnosed to have GDM with the one-step test, but not the two-step test. 

These women were likely to have milder degrees of insulin resistance or GDM. Dr. Berghella, who has advocated in the past for the one-step approach, said it would be important to find out if these women, who test positive at the one-step test but would test negative at the two-step test, were treated properly with diet, exercise, and possibly insulin or other hypoglycemic agents for their mild degree of insulin resistance. The researchers concluded that expanding the definition of GDM through the one-step test didn’t make a difference. However, “it’s not just the test that will make the difference in maternal and baby outcomes, but the aggressive management of diabetes with diet, exercise, and medications as needed once that test comes back abnormal,” he said.

The randomized trial was a massive undertaking, said Dr. Hillier.

“We are still evaluating our future plans,” she added. Forthcoming subgroup analyses from the trial could further help inform clinical practice guidelines.

Dr. Hillier received a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development to support this study. The investigators reported no potential conflict of interest relevant to this article.