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Shift Needed in Research, Treatment, Care for Aging MS Population
NASHVILLE, TENNESSEE — a phenomenon that’s driving a shift in priorities including the creation of MS aging centers and a push for more clinical trials aimed at this growing patient population.
Given typical patterns of MS onset and its rate of progression, disease duration has long been thought to be the key variable driving disability, but Jennifer Graves, MD, PhD, director of the neuroimmunology research program at the University of California, San Diego, said she now believes that “patient age is actually more important.”
Speaking at the annual meeting of the Consortium of Multiple Sclerosis Centers (CMSC), Dr. Graves noted that it is well known that key MS symptoms increase over time, particularly during the transition from a relapsing to a progressive phenotype.
However, she maintains that, independent of disease progression, the impact of aging on MS has been underappreciated. She cited research showing that, relative to chronological age, biologic age is more robustly correlated with MS outcomes.
In studies evaluating variables such as telomere length, various markers of senescence, and DNA methylation patterns, Dr. Graves and others have shown that biologic versus chronological aging is more rapid in patients with MS than those without the disease. In addition, within the population with MS, there are also data supporting the premise that disease progression is slower in those with a younger versus older biologic age.
“This raises the question of whether biologic age is a driver of MS and whether we can slow the disease trajectory if we slow [biologic] aging,” Dr. Graves said. While she acknowledged that genetics play an important role in the aging process, she pointed to evidence showing exposure to toxins and other biological stressors, as well as poor lifestyle choices, such as lack of exercise and smoking, are modifiable aging variables.
There are already many avenues of research regarding aging processes and their interaction with MS. Dr. Graves spoke briefly about current research into the relationship between declining ovarian function, declining telomere length, and how this might relate to the transition to progressive MS and advancing disability. To date, her research has revealed a correlation between declining ovarian function and increasing MS disability.
Shifting Priorities
The rapid aging of the population with MS in the United States makes research into slowing biologic aging a priority, said Robert Motl, PhD, professor in the department of physical therapy, University of Alabama at Birmingham Multiple Sclerosis Center. He reported he was able to secure funding from the National MS Society for the Healthy Aging through LifesTyle MS Research Center 10 years ago.
“We are the first and, so far, the only research center devoted to the study of aging in MS,” said Dr. Motl, another participant in the CMSC aging symposium. Dr. Motl said he and a colleague have been evaluating specific strategies to meet the varied needs of aging patients with MS with a key focus on physical therapy and preserving function.
Yinan Zhang, MD, an assistant professor of neurology at the Ohio State University Wexner Medical Center in Columbus, recently started a multidisciplinary clinic for the management of older patients with MS and said he hopes these types of clinics will help shed light on the unmet needs of older adults with MS — particularly the need for better therapies to address common types of neurodegeneration in this population.
“We need to move away from immunomodulatory agents [in older patients],” Dr. Zhang said. Older patients are typically excluded from therapeutic MS trials for a number of reasons, not least because trials have been traditionally targeted at relapsing disease, which is less common in older patients with MS. He believes older patients are particularly appropriate candidates for MS therapy trials aimed at progressive neurodegeneration, which is characteristic of late-stage disease. Therapies with the potential to slow, or even reverse, demyelination are among the novel strategies being pursued in progressive MS.
Multidisciplinary Approach
Dr. Zhang acknowledged that his recently established MS clinic is still in the early phases and is largely focused on comprehensive care designed to meet the diverse needs of older individuals who often have advanced disabilities and comorbidities.
Currently, each patient that attends the clinic consults with six different types of providers, including a psychologist, a pharmacist, and a physical therapist — all in a single appointment.
Dr. Zhang said his decision to open a clinic was motivated by the increased volume of older patients with MS and was inspired by similar clinics for other disease states in older individuals.
“The need is already strong and growing,” said Dr. Zhang, who speculated that these types of clinics will become widespread as the need for this care is more broadly recognized and accepted.
As the clinic evolves and matures, Dr. Zhang anticipates there will be a research component to better characterize cell senescence and aging processes that might eventually be modifiable or even reversible. He also speculated that aging in MS might eventually become a subspecialty.
Dr. Graves reported financial relationships with Horizon Therapeutics. Dr. Zhang reported no potential conflicts of interest. Dr. Motl reported financial relationships with Bristol-Myers Squibb.
A version of this article appeared on Medscape.com.
NASHVILLE, TENNESSEE — a phenomenon that’s driving a shift in priorities including the creation of MS aging centers and a push for more clinical trials aimed at this growing patient population.
Given typical patterns of MS onset and its rate of progression, disease duration has long been thought to be the key variable driving disability, but Jennifer Graves, MD, PhD, director of the neuroimmunology research program at the University of California, San Diego, said she now believes that “patient age is actually more important.”
Speaking at the annual meeting of the Consortium of Multiple Sclerosis Centers (CMSC), Dr. Graves noted that it is well known that key MS symptoms increase over time, particularly during the transition from a relapsing to a progressive phenotype.
However, she maintains that, independent of disease progression, the impact of aging on MS has been underappreciated. She cited research showing that, relative to chronological age, biologic age is more robustly correlated with MS outcomes.
In studies evaluating variables such as telomere length, various markers of senescence, and DNA methylation patterns, Dr. Graves and others have shown that biologic versus chronological aging is more rapid in patients with MS than those without the disease. In addition, within the population with MS, there are also data supporting the premise that disease progression is slower in those with a younger versus older biologic age.
“This raises the question of whether biologic age is a driver of MS and whether we can slow the disease trajectory if we slow [biologic] aging,” Dr. Graves said. While she acknowledged that genetics play an important role in the aging process, she pointed to evidence showing exposure to toxins and other biological stressors, as well as poor lifestyle choices, such as lack of exercise and smoking, are modifiable aging variables.
There are already many avenues of research regarding aging processes and their interaction with MS. Dr. Graves spoke briefly about current research into the relationship between declining ovarian function, declining telomere length, and how this might relate to the transition to progressive MS and advancing disability. To date, her research has revealed a correlation between declining ovarian function and increasing MS disability.
Shifting Priorities
The rapid aging of the population with MS in the United States makes research into slowing biologic aging a priority, said Robert Motl, PhD, professor in the department of physical therapy, University of Alabama at Birmingham Multiple Sclerosis Center. He reported he was able to secure funding from the National MS Society for the Healthy Aging through LifesTyle MS Research Center 10 years ago.
“We are the first and, so far, the only research center devoted to the study of aging in MS,” said Dr. Motl, another participant in the CMSC aging symposium. Dr. Motl said he and a colleague have been evaluating specific strategies to meet the varied needs of aging patients with MS with a key focus on physical therapy and preserving function.
Yinan Zhang, MD, an assistant professor of neurology at the Ohio State University Wexner Medical Center in Columbus, recently started a multidisciplinary clinic for the management of older patients with MS and said he hopes these types of clinics will help shed light on the unmet needs of older adults with MS — particularly the need for better therapies to address common types of neurodegeneration in this population.
“We need to move away from immunomodulatory agents [in older patients],” Dr. Zhang said. Older patients are typically excluded from therapeutic MS trials for a number of reasons, not least because trials have been traditionally targeted at relapsing disease, which is less common in older patients with MS. He believes older patients are particularly appropriate candidates for MS therapy trials aimed at progressive neurodegeneration, which is characteristic of late-stage disease. Therapies with the potential to slow, or even reverse, demyelination are among the novel strategies being pursued in progressive MS.
Multidisciplinary Approach
Dr. Zhang acknowledged that his recently established MS clinic is still in the early phases and is largely focused on comprehensive care designed to meet the diverse needs of older individuals who often have advanced disabilities and comorbidities.
Currently, each patient that attends the clinic consults with six different types of providers, including a psychologist, a pharmacist, and a physical therapist — all in a single appointment.
Dr. Zhang said his decision to open a clinic was motivated by the increased volume of older patients with MS and was inspired by similar clinics for other disease states in older individuals.
“The need is already strong and growing,” said Dr. Zhang, who speculated that these types of clinics will become widespread as the need for this care is more broadly recognized and accepted.
As the clinic evolves and matures, Dr. Zhang anticipates there will be a research component to better characterize cell senescence and aging processes that might eventually be modifiable or even reversible. He also speculated that aging in MS might eventually become a subspecialty.
Dr. Graves reported financial relationships with Horizon Therapeutics. Dr. Zhang reported no potential conflicts of interest. Dr. Motl reported financial relationships with Bristol-Myers Squibb.
A version of this article appeared on Medscape.com.
NASHVILLE, TENNESSEE — a phenomenon that’s driving a shift in priorities including the creation of MS aging centers and a push for more clinical trials aimed at this growing patient population.
Given typical patterns of MS onset and its rate of progression, disease duration has long been thought to be the key variable driving disability, but Jennifer Graves, MD, PhD, director of the neuroimmunology research program at the University of California, San Diego, said she now believes that “patient age is actually more important.”
Speaking at the annual meeting of the Consortium of Multiple Sclerosis Centers (CMSC), Dr. Graves noted that it is well known that key MS symptoms increase over time, particularly during the transition from a relapsing to a progressive phenotype.
However, she maintains that, independent of disease progression, the impact of aging on MS has been underappreciated. She cited research showing that, relative to chronological age, biologic age is more robustly correlated with MS outcomes.
In studies evaluating variables such as telomere length, various markers of senescence, and DNA methylation patterns, Dr. Graves and others have shown that biologic versus chronological aging is more rapid in patients with MS than those without the disease. In addition, within the population with MS, there are also data supporting the premise that disease progression is slower in those with a younger versus older biologic age.
“This raises the question of whether biologic age is a driver of MS and whether we can slow the disease trajectory if we slow [biologic] aging,” Dr. Graves said. While she acknowledged that genetics play an important role in the aging process, she pointed to evidence showing exposure to toxins and other biological stressors, as well as poor lifestyle choices, such as lack of exercise and smoking, are modifiable aging variables.
There are already many avenues of research regarding aging processes and their interaction with MS. Dr. Graves spoke briefly about current research into the relationship between declining ovarian function, declining telomere length, and how this might relate to the transition to progressive MS and advancing disability. To date, her research has revealed a correlation between declining ovarian function and increasing MS disability.
Shifting Priorities
The rapid aging of the population with MS in the United States makes research into slowing biologic aging a priority, said Robert Motl, PhD, professor in the department of physical therapy, University of Alabama at Birmingham Multiple Sclerosis Center. He reported he was able to secure funding from the National MS Society for the Healthy Aging through LifesTyle MS Research Center 10 years ago.
“We are the first and, so far, the only research center devoted to the study of aging in MS,” said Dr. Motl, another participant in the CMSC aging symposium. Dr. Motl said he and a colleague have been evaluating specific strategies to meet the varied needs of aging patients with MS with a key focus on physical therapy and preserving function.
Yinan Zhang, MD, an assistant professor of neurology at the Ohio State University Wexner Medical Center in Columbus, recently started a multidisciplinary clinic for the management of older patients with MS and said he hopes these types of clinics will help shed light on the unmet needs of older adults with MS — particularly the need for better therapies to address common types of neurodegeneration in this population.
“We need to move away from immunomodulatory agents [in older patients],” Dr. Zhang said. Older patients are typically excluded from therapeutic MS trials for a number of reasons, not least because trials have been traditionally targeted at relapsing disease, which is less common in older patients with MS. He believes older patients are particularly appropriate candidates for MS therapy trials aimed at progressive neurodegeneration, which is characteristic of late-stage disease. Therapies with the potential to slow, or even reverse, demyelination are among the novel strategies being pursued in progressive MS.
Multidisciplinary Approach
Dr. Zhang acknowledged that his recently established MS clinic is still in the early phases and is largely focused on comprehensive care designed to meet the diverse needs of older individuals who often have advanced disabilities and comorbidities.
Currently, each patient that attends the clinic consults with six different types of providers, including a psychologist, a pharmacist, and a physical therapist — all in a single appointment.
Dr. Zhang said his decision to open a clinic was motivated by the increased volume of older patients with MS and was inspired by similar clinics for other disease states in older individuals.
“The need is already strong and growing,” said Dr. Zhang, who speculated that these types of clinics will become widespread as the need for this care is more broadly recognized and accepted.
As the clinic evolves and matures, Dr. Zhang anticipates there will be a research component to better characterize cell senescence and aging processes that might eventually be modifiable or even reversible. He also speculated that aging in MS might eventually become a subspecialty.
Dr. Graves reported financial relationships with Horizon Therapeutics. Dr. Zhang reported no potential conflicts of interest. Dr. Motl reported financial relationships with Bristol-Myers Squibb.
A version of this article appeared on Medscape.com.
FROM CMSC 2024
Trial Confirms Treating Gout Based on Uric Acid Level, Not Symptoms
UPDATED July 8, 2024 // Editor's note: This article has been revised to give a more nuanced view from Yael Klionsky, MD, about the need for more accurate and consistent gout management guidelines for busy primary care clinicians who often rely on them in clinical practice.
VIENNA — The first multicenter randomized trial in gout to compare treat-to-target (T2T) and treat for symptom avoidance (T2S) strategies has finally generated data to make the guideline-recommended practice of T2T evidence-based.
The T2T strategy may be guideline-endorsed, but it has never been validated, contended Anusha Moses, MSc, a researcher and PhD candidate at the University of Twente, Enschede, the Netherlands. She argued that this controlled trial fills an evidence gap.
T2T is defined as maintaining a serum uric acid (sUA) level below the physiologic threshold level of 36 mmol/L (< 6 mg/dL). T2S, in contrast, is a strategy of symptom control, typically basing therapy on suppression of symptoms independent of sUA, Dr. Moses explained. 
Both the American College of Rheumatology and European Alliance of Associations for Rheumatology (EULAR) have already endorsed T2T, but other organizations, such as the American College of Physicians (ACP), still accept symptom-based treatment in its gout clinical practice guideline, according to Dr. Moses.
The results of the trial were not surprising based on the pathophysiology of gout. Elevated sUA is considered the driver of both flares and the complications of gout. This well-established association led to endorsement of T2T in guidelines from organizations such as EULAR, but Dr. Moses said a controlled trial allows this to be declared as evidence based.
To provide proof that T2T is superior, 308 gout patients at eight centers were randomized to one of the two strategies in a trial called GO TEST OVERTURE. In the T2T arm, commonly used therapies, such as allopurinol, benzbromarone, and febuxostat were employed to achieve and maintain a target sUA of < 0.36 mmol/L. In the T2S comparator arm, the same drugs were offered to control symptoms and prevent recurrences, but sUA levels were not used to guide treatment.
The 1-year results of a planned 2-year study were presented in an oral abstract session at the annual European Congress of Rheumatology. For this analysis, outcomes were compared in the last 6 months prior to the 1-year data analysis. When assessed at 2 years, the comparison will again be made in the prior 6 months of the study.
For the primary endpoint of flares defined by the validated Gallo criteria, the mean rates were 1.3 for T2T and 1.85 for T2S (P < .001), Dr. Moses reported.
The reduced risk for flares correlated with the greater proportion of patients with sUA < 0.36 mmol/L. These proportions were 72% and 26% (P < .001) for the T2T and T2S groups, respectively. The mean sUA levels were 0.31 mmol/L and 0.42 mmol/L (P < .001), respectively.
At the 1-year mark, none of the secondary endpoints reached statistical significance. These included mean numeric rating pain scale (2.46 vs 2.41), the proportion of patients in remission (8% vs 5.7%), and the mean Health Assessment Questionnaire-Disability Index score (0.65 vs 0.62), according to Dr. Moses, who said all of these endpoints will continue to be followed in the planned second year of the study.
At baseline, there were no differences in any of the variables evaluated, including age (about 62.5 years in both groups), proportion of patients with a body mass index > 30 kg/m2 (about 62%), sUA (about 0.5 mmol/L), or estimated glomerular filtration rate (about 70 mL/min/1.73 m2).
Nonspecialists Should Heed the Results
According to Yael Klionsky, MD, a clinical assistant professor of rheumatology and immunology at Wake Forest University School of Medicine, Winston-Salem, North Carolina, these data are not a surprise.
Even before this trial was completed, the message for clinicians is that they “should be focused on maintaining serum uric acid levels below physiological levels to improve outcomes” in patients with recurrent flares, said Klionsky, citing the validated EULAR and ACR guidelines.
While the ACP does still consider T2S acceptable as a strategy for chronic gout management, Klionsky pointed out that those guidelines have not been updated recently. Specialists in the treatment of gout do not need any more evidence that the T2T approach leads to better outcomes.
However, she agreed with the principle that non-rheumatologists need to be reached with better guidance in regard to gout management. While she expects the ACP to endorse T2T the next time their guidelines are updated, she hopes that primary care physicians recognize that T2T should now be a standard.
“In a 10- to 20-minute visit, managing multiple chronic conditions can be a challenge in primary care,” Klionsky said. “Many clinicians rely on guidelines so it is important to have consistent and accurate information.”
There is currently some distance between specialists and primary care physicians regarding the goals of gout management, according to a study that Klionsky presented at EULAR 2024. In a survey, nonspecialists and specialists did not perceive treatment priorities in the same way.
In this survey, which elicited responses from 151 rheumatologists, 150 nephrologists, and 102 primary care physicians, there was general agreement that preventing flares is a priority, but only 30% of primary care physicians and 35% of nephrologists vs 64% of rheumatologists identified the T2T target of < 0.36 mmol/L as a key step in reaching this goal.
Conversely, 58% of primary care physicians and 42% of nephrologists vs only 34% of rheumatologists considered absence of gout pain to be in the top three criteria.
In addition to the fact that primary care physicians differ from specialists in their goals for gout treatment, these data “highlight the need for the importance of a standardized definition of gout remission that includes serum uric acid control,” Dr. Klionsky said. She further thinks that this type of guidance should be disseminated to nonspecialists.
Dr. Moses reported no potential conflicts of interest. Dr. Klionsky reported financial relationships with Amgen, AstraZeneca, Eli Lilly, and MedIQ.
A version of this article appeared on Medscape.com.
UPDATED July 8, 2024 // Editor's note: This article has been revised to give a more nuanced view from Yael Klionsky, MD, about the need for more accurate and consistent gout management guidelines for busy primary care clinicians who often rely on them in clinical practice.
VIENNA — The first multicenter randomized trial in gout to compare treat-to-target (T2T) and treat for symptom avoidance (T2S) strategies has finally generated data to make the guideline-recommended practice of T2T evidence-based.
The T2T strategy may be guideline-endorsed, but it has never been validated, contended Anusha Moses, MSc, a researcher and PhD candidate at the University of Twente, Enschede, the Netherlands. She argued that this controlled trial fills an evidence gap.
T2T is defined as maintaining a serum uric acid (sUA) level below the physiologic threshold level of 36 mmol/L (< 6 mg/dL). T2S, in contrast, is a strategy of symptom control, typically basing therapy on suppression of symptoms independent of sUA, Dr. Moses explained.
Both the American College of Rheumatology and European Alliance of Associations for Rheumatology (EULAR) have already endorsed T2T, but other organizations, such as the American College of Physicians (ACP), still accept symptom-based treatment in its gout clinical practice guideline, according to Dr. Moses.
The results of the trial were not surprising based on the pathophysiology of gout. Elevated sUA is considered the driver of both flares and the complications of gout. This well-established association led to endorsement of T2T in guidelines from organizations such as EULAR, but Dr. Moses said a controlled trial allows this to be declared as evidence based.
To provide proof that T2T is superior, 308 gout patients at eight centers were randomized to one of the two strategies in a trial called GO TEST OVERTURE. In the T2T arm, commonly used therapies, such as allopurinol, benzbromarone, and febuxostat were employed to achieve and maintain a target sUA of < 0.36 mmol/L. In the T2S comparator arm, the same drugs were offered to control symptoms and prevent recurrences, but sUA levels were not used to guide treatment.
The 1-year results of a planned 2-year study were presented in an oral abstract session at the annual European Congress of Rheumatology. For this analysis, outcomes were compared in the last 6 months prior to the 1-year data analysis. When assessed at 2 years, the comparison will again be made in the prior 6 months of the study.
For the primary endpoint of flares defined by the validated Gallo criteria, the mean rates were 1.3 for T2T and 1.85 for T2S (P < .001), Dr. Moses reported.
The reduced risk for flares correlated with the greater proportion of patients with sUA < 0.36 mmol/L. These proportions were 72% and 26% (P < .001) for the T2T and T2S groups, respectively. The mean sUA levels were 0.31 mmol/L and 0.42 mmol/L (P < .001), respectively.
At the 1-year mark, none of the secondary endpoints reached statistical significance. These included mean numeric rating pain scale (2.46 vs 2.41), the proportion of patients in remission (8% vs 5.7%), and the mean Health Assessment Questionnaire-Disability Index score (0.65 vs 0.62), according to Dr. Moses, who said all of these endpoints will continue to be followed in the planned second year of the study.
At baseline, there were no differences in any of the variables evaluated, including age (about 62.5 years in both groups), proportion of patients with a body mass index > 30 kg/m2 (about 62%), sUA (about 0.5 mmol/L), or estimated glomerular filtration rate (about 70 mL/min/1.73 m2).
Nonspecialists Should Heed the Results
According to Yael Klionsky, MD, a clinical assistant professor of rheumatology and immunology at Wake Forest University School of Medicine, Winston-Salem, North Carolina, these data are not a surprise.
Even before this trial was completed, the message for clinicians is that they “should be focused on maintaining serum uric acid levels below physiological levels to improve outcomes” in patients with recurrent flares, said Klionsky, citing the validated EULAR and ACR guidelines.
While the ACP does still consider T2S acceptable as a strategy for chronic gout management, Klionsky pointed out that those guidelines have not been updated recently. Specialists in the treatment of gout do not need any more evidence that the T2T approach leads to better outcomes.
However, she agreed with the principle that non-rheumatologists need to be reached with better guidance in regard to gout management. While she expects the ACP to endorse T2T the next time their guidelines are updated, she hopes that primary care physicians recognize that T2T should now be a standard.
“In a 10- to 20-minute visit, managing multiple chronic conditions can be a challenge in primary care,” Klionsky said. “Many clinicians rely on guidelines so it is important to have consistent and accurate information.”
There is currently some distance between specialists and primary care physicians regarding the goals of gout management, according to a study that Klionsky presented at EULAR 2024. In a survey, nonspecialists and specialists did not perceive treatment priorities in the same way.
In this survey, which elicited responses from 151 rheumatologists, 150 nephrologists, and 102 primary care physicians, there was general agreement that preventing flares is a priority, but only 30% of primary care physicians and 35% of nephrologists vs 64% of rheumatologists identified the T2T target of < 0.36 mmol/L as a key step in reaching this goal.
Conversely, 58% of primary care physicians and 42% of nephrologists vs only 34% of rheumatologists considered absence of gout pain to be in the top three criteria.
In addition to the fact that primary care physicians differ from specialists in their goals for gout treatment, these data “highlight the need for the importance of a standardized definition of gout remission that includes serum uric acid control,” Dr. Klionsky said. She further thinks that this type of guidance should be disseminated to nonspecialists.
Dr. Moses reported no potential conflicts of interest. Dr. Klionsky reported financial relationships with Amgen, AstraZeneca, Eli Lilly, and MedIQ.
A version of this article appeared on Medscape.com.
UPDATED July 8, 2024 // Editor's note: This article has been revised to give a more nuanced view from Yael Klionsky, MD, about the need for more accurate and consistent gout management guidelines for busy primary care clinicians who often rely on them in clinical practice.
VIENNA — The first multicenter randomized trial in gout to compare treat-to-target (T2T) and treat for symptom avoidance (T2S) strategies has finally generated data to make the guideline-recommended practice of T2T evidence-based.
The T2T strategy may be guideline-endorsed, but it has never been validated, contended Anusha Moses, MSc, a researcher and PhD candidate at the University of Twente, Enschede, the Netherlands. She argued that this controlled trial fills an evidence gap.
T2T is defined as maintaining a serum uric acid (sUA) level below the physiologic threshold level of 36 mmol/L (< 6 mg/dL). T2S, in contrast, is a strategy of symptom control, typically basing therapy on suppression of symptoms independent of sUA, Dr. Moses explained.
Both the American College of Rheumatology and European Alliance of Associations for Rheumatology (EULAR) have already endorsed T2T, but other organizations, such as the American College of Physicians (ACP), still accept symptom-based treatment in its gout clinical practice guideline, according to Dr. Moses.
The results of the trial were not surprising based on the pathophysiology of gout. Elevated sUA is considered the driver of both flares and the complications of gout. This well-established association led to endorsement of T2T in guidelines from organizations such as EULAR, but Dr. Moses said a controlled trial allows this to be declared as evidence based.
To provide proof that T2T is superior, 308 gout patients at eight centers were randomized to one of the two strategies in a trial called GO TEST OVERTURE. In the T2T arm, commonly used therapies, such as allopurinol, benzbromarone, and febuxostat were employed to achieve and maintain a target sUA of < 0.36 mmol/L. In the T2S comparator arm, the same drugs were offered to control symptoms and prevent recurrences, but sUA levels were not used to guide treatment.
The 1-year results of a planned 2-year study were presented in an oral abstract session at the annual European Congress of Rheumatology. For this analysis, outcomes were compared in the last 6 months prior to the 1-year data analysis. When assessed at 2 years, the comparison will again be made in the prior 6 months of the study.
For the primary endpoint of flares defined by the validated Gallo criteria, the mean rates were 1.3 for T2T and 1.85 for T2S (P < .001), Dr. Moses reported.
The reduced risk for flares correlated with the greater proportion of patients with sUA < 0.36 mmol/L. These proportions were 72% and 26% (P < .001) for the T2T and T2S groups, respectively. The mean sUA levels were 0.31 mmol/L and 0.42 mmol/L (P < .001), respectively.
At the 1-year mark, none of the secondary endpoints reached statistical significance. These included mean numeric rating pain scale (2.46 vs 2.41), the proportion of patients in remission (8% vs 5.7%), and the mean Health Assessment Questionnaire-Disability Index score (0.65 vs 0.62), according to Dr. Moses, who said all of these endpoints will continue to be followed in the planned second year of the study.
At baseline, there were no differences in any of the variables evaluated, including age (about 62.5 years in both groups), proportion of patients with a body mass index > 30 kg/m2 (about 62%), sUA (about 0.5 mmol/L), or estimated glomerular filtration rate (about 70 mL/min/1.73 m2).
Nonspecialists Should Heed the Results
According to Yael Klionsky, MD, a clinical assistant professor of rheumatology and immunology at Wake Forest University School of Medicine, Winston-Salem, North Carolina, these data are not a surprise.
Even before this trial was completed, the message for clinicians is that they “should be focused on maintaining serum uric acid levels below physiological levels to improve outcomes” in patients with recurrent flares, said Klionsky, citing the validated EULAR and ACR guidelines.
While the ACP does still consider T2S acceptable as a strategy for chronic gout management, Klionsky pointed out that those guidelines have not been updated recently. Specialists in the treatment of gout do not need any more evidence that the T2T approach leads to better outcomes.
However, she agreed with the principle that non-rheumatologists need to be reached with better guidance in regard to gout management. While she expects the ACP to endorse T2T the next time their guidelines are updated, she hopes that primary care physicians recognize that T2T should now be a standard.
“In a 10- to 20-minute visit, managing multiple chronic conditions can be a challenge in primary care,” Klionsky said. “Many clinicians rely on guidelines so it is important to have consistent and accurate information.”
There is currently some distance between specialists and primary care physicians regarding the goals of gout management, according to a study that Klionsky presented at EULAR 2024. In a survey, nonspecialists and specialists did not perceive treatment priorities in the same way.
In this survey, which elicited responses from 151 rheumatologists, 150 nephrologists, and 102 primary care physicians, there was general agreement that preventing flares is a priority, but only 30% of primary care physicians and 35% of nephrologists vs 64% of rheumatologists identified the T2T target of < 0.36 mmol/L as a key step in reaching this goal.
Conversely, 58% of primary care physicians and 42% of nephrologists vs only 34% of rheumatologists considered absence of gout pain to be in the top three criteria.
In addition to the fact that primary care physicians differ from specialists in their goals for gout treatment, these data “highlight the need for the importance of a standardized definition of gout remission that includes serum uric acid control,” Dr. Klionsky said. She further thinks that this type of guidance should be disseminated to nonspecialists.
Dr. Moses reported no potential conflicts of interest. Dr. Klionsky reported financial relationships with Amgen, AstraZeneca, Eli Lilly, and MedIQ.
A version of this article appeared on Medscape.com.
FROM EULAR 2024
Low Infection Risk, Apart from Herpes Zoster, Seen in Real-World JAK Inhibitor Data for RA
VIENNA — In patients with rheumatoid arthritis (RA), Janus kinase inhibitors (JAKi) are associated with a substantially greater risk for herpes zoster, but the risk for other types of infections is about the same and often numerically lower relative to biologic disease-modifying antirheumatic drugs (bDMARDs), according to new data from the JAK-pot study.
“In the real world, we found no significantly greater risk of serious or nonserious infections, with the exception of herpes zoster,” said Romain Aymon, a statistician in the Department of Rheumatology at the University Hospital of Geneva, Switzerland.
This finding is the latest analysis generated by JAK-pot, a collaboration of 20 national registries to answer real-world questions about the efficacy and safety of JAKi in rheumatic diseases. These data have already been used to address such issues as relative rates of discontinuation for JAKi vs bDMARDs and to compare outcomes of RA patients who are switched to a bDMARD vs those who are cycled to another JAKi.
The main conclusion — that JAKi, relative to bDMARDs for RA, is associated with an increased risk for herpes zoster but not other types of infections — is not a surprise, according to Floris A. van Gaalen, MD, PhD, a clinician and researcher in the Department of Rheumatology, Leiden University in the Netherlands.
“There are a number of risks with JAK inhibitors that have generated concern, but I think most clinicians are aware that they should be warning patients about herpes zoster,” said Dr. van Gaalen, who was not involved in the study. He believes the risk is sufficient to warrant a discussion with patients about taking the herpes zoster vaccine prior to treatment.
“It is nice to have data indicating that risk of other infections is no higher with JAKi than other treatment options, but I am not sure this has been a big concern,” he said. “But I do think more information about other types of risks would be helpful.”
Relative Risk for Infection on JAKi Is Unclear
Although the greater risk for herpes zoster with JAKi vs bDMARDs is well established, the relative risk for other types of infections has been unclear, according to Mr. Aymon. One reason is that some, but not all, of the initial pivotal trials and safety studies associated JAKi with an increased risk for opportunistic infections, Mr. Aymon said.
The JAK-pot data, presented at the annual European Congress of Rheumatology, provide real-world data that shed light on this controversy, Mr. Aymon said.
Of the 20 national registries now providing data to JAK-pot, only 14 were included in this analysis. The study required data on infection rates from the time that JAKi became commercially available, which narrowed the data pool.
For this analysis, JAKi, which included tofacitinib (Xeljanz), baricitinib (Olumiant), upadacitinib (Rinvoq), and filgotinib (Jyseleca), were compared separately and together with two groups of bDMARDs. One consisted of the tumor necrosis factor inhibitors (TNFi), infliximab, etanercept, adalimumab, certolizumab pegol, or golimumab. The other was composed of bDMARDs with other modes of action (OMA). This group included abatacept, rituximab, sarilumab, and tocilizumab.
More Than 50,000 Exposures Included in Analysis
From the pooled registry, data were gathered from 13,374 courses of JAKi, 25,049 courses of TNFi, and 16,482 courses of OMA. There were some differences between these groups, including a significantly lower median age for those in the JAKi pool (57.1 years vs 58.3 and 60.5 years for TNFi and OMA, respectively) and median disease duration (8.3 years vs 11.0 and 11.9 years, respectively).
A greater proportion of patients on TNFi were naive to therapy (44.6%), compared with either JAKi (20.2%) or OMA (16.1%). More patients in the TNFi pool (60.0%) were also on concomitant therapy than those in the JAKi pool (49.5%) or the OMA pool (51.9%).
Other characteristics such as disease activity, body mass index, and percentage of smokers were comparable.
When TNFi was used as the reference, there were no significant differences in the rate of all infections, the rate of all infections excluding herpes zoster, and all serious infections. In all three groups, the incidence rates were numerically but not significantly lower in patients on JAKi vs OMA. With the exception of serious infections, for which the adjusted incidence of JAKi was 0.99 relative to TNFi, both JAKi and OMA had numerically higher incidence rate ratios than TNFi.
Herpes Zoster Risk on JAKi Is > Twofold Higher
Because the CIs overlapped in all cases, none of the differences were significant. The exception was herpes zoster. The 1.07 incidence rate ratio for OMA was not significantly different than the TNFi reference, but the 2.27 rate ratio for JAKi far exceeded either of the other two comparators (95% CI, 1.17-3.02).
In a separate analysis of patients at least 55 years of age with at least one cardiovascular risk factor, the numerical differences between groups were narrower and thus did not reach statistical significance, even for herpes zoster. Although the herpes zoster rate ratio was 1.62 for JAKi vs 1.23 for OMA (TNFi as the reference was 1.0), the CI for JAKi (0.86-3.03) overlapped both.
Based on a Poisson regression analysis, this study took into account a wide variety of variables, including age, disease activity, comorbidities, and tobacco use, Mr. Aymon said. He noted that the analyses were performed on data from each registry as well as with the pooled data, and the data were reasonably consistent.
Initially, the investigators had planned to evaluate differences between therapy groups, if any, for COVID-19 infection, but differences in the availability and use of vaccinations among the countries where the registries were maintained made this analysis too complicated to conduct.
Mr. Aymon reported no potential conflicts of interest, but some coauthors reported financial relationships with manufacturers of both bDMARDs and JAKi. Dr. van Gaalen reported financial relationships with AbbVie, Bristol Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novartis, and UCB.
A version of this article appeared on Medscape.com.
VIENNA — In patients with rheumatoid arthritis (RA), Janus kinase inhibitors (JAKi) are associated with a substantially greater risk for herpes zoster, but the risk for other types of infections is about the same and often numerically lower relative to biologic disease-modifying antirheumatic drugs (bDMARDs), according to new data from the JAK-pot study.
“In the real world, we found no significantly greater risk of serious or nonserious infections, with the exception of herpes zoster,” said Romain Aymon, a statistician in the Department of Rheumatology at the University Hospital of Geneva, Switzerland.
This finding is the latest analysis generated by JAK-pot, a collaboration of 20 national registries to answer real-world questions about the efficacy and safety of JAKi in rheumatic diseases. These data have already been used to address such issues as relative rates of discontinuation for JAKi vs bDMARDs and to compare outcomes of RA patients who are switched to a bDMARD vs those who are cycled to another JAKi.
The main conclusion — that JAKi, relative to bDMARDs for RA, is associated with an increased risk for herpes zoster but not other types of infections — is not a surprise, according to Floris A. van Gaalen, MD, PhD, a clinician and researcher in the Department of Rheumatology, Leiden University in the Netherlands.
“There are a number of risks with JAK inhibitors that have generated concern, but I think most clinicians are aware that they should be warning patients about herpes zoster,” said Dr. van Gaalen, who was not involved in the study. He believes the risk is sufficient to warrant a discussion with patients about taking the herpes zoster vaccine prior to treatment.
“It is nice to have data indicating that risk of other infections is no higher with JAKi than other treatment options, but I am not sure this has been a big concern,” he said. “But I do think more information about other types of risks would be helpful.”
Relative Risk for Infection on JAKi Is Unclear
Although the greater risk for herpes zoster with JAKi vs bDMARDs is well established, the relative risk for other types of infections has been unclear, according to Mr. Aymon. One reason is that some, but not all, of the initial pivotal trials and safety studies associated JAKi with an increased risk for opportunistic infections, Mr. Aymon said.
The JAK-pot data, presented at the annual European Congress of Rheumatology, provide real-world data that shed light on this controversy, Mr. Aymon said.
Of the 20 national registries now providing data to JAK-pot, only 14 were included in this analysis. The study required data on infection rates from the time that JAKi became commercially available, which narrowed the data pool.
For this analysis, JAKi, which included tofacitinib (Xeljanz), baricitinib (Olumiant), upadacitinib (Rinvoq), and filgotinib (Jyseleca), were compared separately and together with two groups of bDMARDs. One consisted of the tumor necrosis factor inhibitors (TNFi), infliximab, etanercept, adalimumab, certolizumab pegol, or golimumab. The other was composed of bDMARDs with other modes of action (OMA). This group included abatacept, rituximab, sarilumab, and tocilizumab.
More Than 50,000 Exposures Included in Analysis
From the pooled registry, data were gathered from 13,374 courses of JAKi, 25,049 courses of TNFi, and 16,482 courses of OMA. There were some differences between these groups, including a significantly lower median age for those in the JAKi pool (57.1 years vs 58.3 and 60.5 years for TNFi and OMA, respectively) and median disease duration (8.3 years vs 11.0 and 11.9 years, respectively).
A greater proportion of patients on TNFi were naive to therapy (44.6%), compared with either JAKi (20.2%) or OMA (16.1%). More patients in the TNFi pool (60.0%) were also on concomitant therapy than those in the JAKi pool (49.5%) or the OMA pool (51.9%).
Other characteristics such as disease activity, body mass index, and percentage of smokers were comparable.
When TNFi was used as the reference, there were no significant differences in the rate of all infections, the rate of all infections excluding herpes zoster, and all serious infections. In all three groups, the incidence rates were numerically but not significantly lower in patients on JAKi vs OMA. With the exception of serious infections, for which the adjusted incidence of JAKi was 0.99 relative to TNFi, both JAKi and OMA had numerically higher incidence rate ratios than TNFi.
Herpes Zoster Risk on JAKi Is > Twofold Higher
Because the CIs overlapped in all cases, none of the differences were significant. The exception was herpes zoster. The 1.07 incidence rate ratio for OMA was not significantly different than the TNFi reference, but the 2.27 rate ratio for JAKi far exceeded either of the other two comparators (95% CI, 1.17-3.02).
In a separate analysis of patients at least 55 years of age with at least one cardiovascular risk factor, the numerical differences between groups were narrower and thus did not reach statistical significance, even for herpes zoster. Although the herpes zoster rate ratio was 1.62 for JAKi vs 1.23 for OMA (TNFi as the reference was 1.0), the CI for JAKi (0.86-3.03) overlapped both.
Based on a Poisson regression analysis, this study took into account a wide variety of variables, including age, disease activity, comorbidities, and tobacco use, Mr. Aymon said. He noted that the analyses were performed on data from each registry as well as with the pooled data, and the data were reasonably consistent.
Initially, the investigators had planned to evaluate differences between therapy groups, if any, for COVID-19 infection, but differences in the availability and use of vaccinations among the countries where the registries were maintained made this analysis too complicated to conduct.
Mr. Aymon reported no potential conflicts of interest, but some coauthors reported financial relationships with manufacturers of both bDMARDs and JAKi. Dr. van Gaalen reported financial relationships with AbbVie, Bristol Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novartis, and UCB.
A version of this article appeared on Medscape.com.
VIENNA — In patients with rheumatoid arthritis (RA), Janus kinase inhibitors (JAKi) are associated with a substantially greater risk for herpes zoster, but the risk for other types of infections is about the same and often numerically lower relative to biologic disease-modifying antirheumatic drugs (bDMARDs), according to new data from the JAK-pot study.
“In the real world, we found no significantly greater risk of serious or nonserious infections, with the exception of herpes zoster,” said Romain Aymon, a statistician in the Department of Rheumatology at the University Hospital of Geneva, Switzerland.
This finding is the latest analysis generated by JAK-pot, a collaboration of 20 national registries to answer real-world questions about the efficacy and safety of JAKi in rheumatic diseases. These data have already been used to address such issues as relative rates of discontinuation for JAKi vs bDMARDs and to compare outcomes of RA patients who are switched to a bDMARD vs those who are cycled to another JAKi.
The main conclusion — that JAKi, relative to bDMARDs for RA, is associated with an increased risk for herpes zoster but not other types of infections — is not a surprise, according to Floris A. van Gaalen, MD, PhD, a clinician and researcher in the Department of Rheumatology, Leiden University in the Netherlands.
“There are a number of risks with JAK inhibitors that have generated concern, but I think most clinicians are aware that they should be warning patients about herpes zoster,” said Dr. van Gaalen, who was not involved in the study. He believes the risk is sufficient to warrant a discussion with patients about taking the herpes zoster vaccine prior to treatment.
“It is nice to have data indicating that risk of other infections is no higher with JAKi than other treatment options, but I am not sure this has been a big concern,” he said. “But I do think more information about other types of risks would be helpful.”
Relative Risk for Infection on JAKi Is Unclear
Although the greater risk for herpes zoster with JAKi vs bDMARDs is well established, the relative risk for other types of infections has been unclear, according to Mr. Aymon. One reason is that some, but not all, of the initial pivotal trials and safety studies associated JAKi with an increased risk for opportunistic infections, Mr. Aymon said.
The JAK-pot data, presented at the annual European Congress of Rheumatology, provide real-world data that shed light on this controversy, Mr. Aymon said.
Of the 20 national registries now providing data to JAK-pot, only 14 were included in this analysis. The study required data on infection rates from the time that JAKi became commercially available, which narrowed the data pool.
For this analysis, JAKi, which included tofacitinib (Xeljanz), baricitinib (Olumiant), upadacitinib (Rinvoq), and filgotinib (Jyseleca), were compared separately and together with two groups of bDMARDs. One consisted of the tumor necrosis factor inhibitors (TNFi), infliximab, etanercept, adalimumab, certolizumab pegol, or golimumab. The other was composed of bDMARDs with other modes of action (OMA). This group included abatacept, rituximab, sarilumab, and tocilizumab.
More Than 50,000 Exposures Included in Analysis
From the pooled registry, data were gathered from 13,374 courses of JAKi, 25,049 courses of TNFi, and 16,482 courses of OMA. There were some differences between these groups, including a significantly lower median age for those in the JAKi pool (57.1 years vs 58.3 and 60.5 years for TNFi and OMA, respectively) and median disease duration (8.3 years vs 11.0 and 11.9 years, respectively).
A greater proportion of patients on TNFi were naive to therapy (44.6%), compared with either JAKi (20.2%) or OMA (16.1%). More patients in the TNFi pool (60.0%) were also on concomitant therapy than those in the JAKi pool (49.5%) or the OMA pool (51.9%).
Other characteristics such as disease activity, body mass index, and percentage of smokers were comparable.
When TNFi was used as the reference, there were no significant differences in the rate of all infections, the rate of all infections excluding herpes zoster, and all serious infections. In all three groups, the incidence rates were numerically but not significantly lower in patients on JAKi vs OMA. With the exception of serious infections, for which the adjusted incidence of JAKi was 0.99 relative to TNFi, both JAKi and OMA had numerically higher incidence rate ratios than TNFi.
Herpes Zoster Risk on JAKi Is > Twofold Higher
Because the CIs overlapped in all cases, none of the differences were significant. The exception was herpes zoster. The 1.07 incidence rate ratio for OMA was not significantly different than the TNFi reference, but the 2.27 rate ratio for JAKi far exceeded either of the other two comparators (95% CI, 1.17-3.02).
In a separate analysis of patients at least 55 years of age with at least one cardiovascular risk factor, the numerical differences between groups were narrower and thus did not reach statistical significance, even for herpes zoster. Although the herpes zoster rate ratio was 1.62 for JAKi vs 1.23 for OMA (TNFi as the reference was 1.0), the CI for JAKi (0.86-3.03) overlapped both.
Based on a Poisson regression analysis, this study took into account a wide variety of variables, including age, disease activity, comorbidities, and tobacco use, Mr. Aymon said. He noted that the analyses were performed on data from each registry as well as with the pooled data, and the data were reasonably consistent.
Initially, the investigators had planned to evaluate differences between therapy groups, if any, for COVID-19 infection, but differences in the availability and use of vaccinations among the countries where the registries were maintained made this analysis too complicated to conduct.
Mr. Aymon reported no potential conflicts of interest, but some coauthors reported financial relationships with manufacturers of both bDMARDs and JAKi. Dr. van Gaalen reported financial relationships with AbbVie, Bristol Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novartis, and UCB.
A version of this article appeared on Medscape.com.
FROM EULAR 2024
Investigational MS Med Nearly Eliminates Disease Activity on MRI
NASHVILLE, TENNESSEE — , new trial data suggested.
Researchers found a near absence of new brain lesions at 48 weeks in patients on the highest dose. At this level of disease suppression, there was no evidence of increased infection risk, which investigators said might relate to its mechanism of action. In addition, there were no thrombotic events, which is what defeated a first-generation drug in this same class.
Among those initially randomly assigned to receive 1200 mg every 4 weeks, 96% were free of new gadolinium-positive (Gd+ T1) lesions at 48 weeks, reported investigator Yang Mao-Draayer, MD, PhD, director of Clinical and Experimental Therapeutics at the Oklahoma Medical Research Foundation’s Multiple Sclerosis Center of Excellence, Oklahoma City. Annual relapse rates were also low.
The findings were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.
No Effect on Lymphocyte Count
As previously reported, 12-week frexalimab results were noteworthy because they provided validation for CD40L as a target in the control of MS. One of the unique features of this therapy relative to many other immunomodulatory therapies is that it has shown little, if any, effect on lymphocyte counts or immunoglobulin levels.
In the double-blind randomized phase 2 trial, 125 patients with MS of all other MS therapy were randomized in a 4:4:4:1 ratio to 1200-mg frexalimab administered intravenously every 4 weeks after a loading dose, to 300-mg frexalimab administered subcutaneously every 2 weeks after a loading dose, or to one of the two matching placebo arms.
For the primary endpoint of new Gd+ T1 lesions at the end of the blinded study, the rates at week 12 were 0.2 and 0.3 in the higher- and lower-dose treatment groups, respectively, and 1.4 in the pooled placebo groups.
At 48 weeks, the results were even better. From 12 weeks, the rate of Gd+ T1 lesions in the high-dose group continued to fall, reaching 0.1 at week 24 and 0.0 at week 48. In the lower-dose group, there was also a stepwise decline over time with a value of 0.2 at week 48. The annual relapse rate at week 48 was 0.4.
Reengineered Agent
In the placebo groups, the same type of suppression of disease activity was observed after they were switched to active therapy at the end of 12 weeks.
By 24 weeks, the number of new Gd+ T1 lesions had fallen to 0.3 in placebo patients switched to the higher dose and 1.0 in those switched to the lower dose.
By week 48, the rates were 0.2 in both of the switch arms.
The proportions of patients free of new Gd+ T1 lesions at 48 weeks were 96% in the group started and maintained on the highest dose of frexalimab, 87% in those started and maintained on the lower dose, 90% in those started on placebo and switched to the highest dose of frexalimab, and 92% of placebo patients switched to the lower dose.
“T2 lesion volume from baseline through week 48 was stable in patients who continued receiving frexalimab and decreased in placebo participants after switching to frexalimab at week 12,” Dr. Mao-Draayer reported.
The CD40-CD40L co-stimulatory pathway that regulates both adaptive and innate immune responses has been pursued as a target for MS therapies for decades, Dr. Mao-Draayer said.
A first-generation monoclonal antibody directed at elevated levels of CD40L, which is implicated in the inflammation that drives MS, showed promise but was abandoned after it was associated with an increased risk for thromboembolic events in a phase 1 trial, she said.
However, the second-generation agent was engineered to avoid an interaction with platelets, which played a role in the risk for thrombosis associated with the failure of the earlier drug.
As with the first-generation agent, frexalimab had little or no impact on lymphocyte count or immunoglobulin G and immunoglobulin M levels. Both remained stable during the 12-week controlled trial and through the ongoing open-label extension, Dr. Mao-Draayer said.
This might be a factor in the low level of adverse events. Most importantly, there have been no thromboembolic events associated with frexalimab so far, but the follow-up data also show rates of infection and other events, such as nasopharyngitis, that were comparable with placebo in the 12-week controlled trial and have not increased over longer-term monitoring.
Such adverse events as headache and COVID-19 infection have also occurred at rates similar to placebo.
Two phase 3 trials are underway. FREXALT is being conducted in relapsing-remitting MS. FREVIV has enrolled patients with nonrelapsing secondary progressive MS.
Impressively Low New Lesion Count
Commenting on the findings, Jeffrey Cohen, MD, director of the Mellen Center for Multiple Sclerosis, Cleveland Clinic, who was not involved in the research, said that over the course of the extended follow-up, MS activity in the central nervous system as measured with new Gd+ T1 lesions was impressively low.
He noted that the phase 2 open-label follow-up continues to support the promise of frexalimab. But Dr. Cohen cautioned that this does not obviate the need for phase 3 data.
In particular, he said that an immunomodulatory agent that does not affect the lymphocyte count has a theoretical advantage, but pointed out that the benefit is still presumably mediated by blocking pathways that mediate autoimmune activity.
Even if lymphocyte count is unaffected, the immunomodulatory pathway by which frexalimab does exert its benefit might pose a different set of risks, he said.
“We will not have sufficient data to judge the promise of this agent until the phase 3 trials are completed,” he said.
Dr. Mao-Draayer reported financial relationships with Acorda, Bayer, Biogen, Bristol Myers Squibb, Celgene, EMD Serono, Genentech, Horizon, Janssen, Novartis, Questor, Teva, and Sanofi, which provided funding for the phase 2 frexalimab trial. Dr. Cohen reported financial relationships with Astoria, Convelo, EMD Serono, FiND, INmune, and Sandoz.
A version of this article appeared on Medscape.com.
NASHVILLE, TENNESSEE — , new trial data suggested.
Researchers found a near absence of new brain lesions at 48 weeks in patients on the highest dose. At this level of disease suppression, there was no evidence of increased infection risk, which investigators said might relate to its mechanism of action. In addition, there were no thrombotic events, which is what defeated a first-generation drug in this same class.
Among those initially randomly assigned to receive 1200 mg every 4 weeks, 96% were free of new gadolinium-positive (Gd+ T1) lesions at 48 weeks, reported investigator Yang Mao-Draayer, MD, PhD, director of Clinical and Experimental Therapeutics at the Oklahoma Medical Research Foundation’s Multiple Sclerosis Center of Excellence, Oklahoma City. Annual relapse rates were also low.
The findings were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.
No Effect on Lymphocyte Count
As previously reported, 12-week frexalimab results were noteworthy because they provided validation for CD40L as a target in the control of MS. One of the unique features of this therapy relative to many other immunomodulatory therapies is that it has shown little, if any, effect on lymphocyte counts or immunoglobulin levels.
In the double-blind randomized phase 2 trial, 125 patients with MS of all other MS therapy were randomized in a 4:4:4:1 ratio to 1200-mg frexalimab administered intravenously every 4 weeks after a loading dose, to 300-mg frexalimab administered subcutaneously every 2 weeks after a loading dose, or to one of the two matching placebo arms.
For the primary endpoint of new Gd+ T1 lesions at the end of the blinded study, the rates at week 12 were 0.2 and 0.3 in the higher- and lower-dose treatment groups, respectively, and 1.4 in the pooled placebo groups.
At 48 weeks, the results were even better. From 12 weeks, the rate of Gd+ T1 lesions in the high-dose group continued to fall, reaching 0.1 at week 24 and 0.0 at week 48. In the lower-dose group, there was also a stepwise decline over time with a value of 0.2 at week 48. The annual relapse rate at week 48 was 0.4.
Reengineered Agent
In the placebo groups, the same type of suppression of disease activity was observed after they were switched to active therapy at the end of 12 weeks.
By 24 weeks, the number of new Gd+ T1 lesions had fallen to 0.3 in placebo patients switched to the higher dose and 1.0 in those switched to the lower dose.
By week 48, the rates were 0.2 in both of the switch arms.
The proportions of patients free of new Gd+ T1 lesions at 48 weeks were 96% in the group started and maintained on the highest dose of frexalimab, 87% in those started and maintained on the lower dose, 90% in those started on placebo and switched to the highest dose of frexalimab, and 92% of placebo patients switched to the lower dose.
“T2 lesion volume from baseline through week 48 was stable in patients who continued receiving frexalimab and decreased in placebo participants after switching to frexalimab at week 12,” Dr. Mao-Draayer reported.
The CD40-CD40L co-stimulatory pathway that regulates both adaptive and innate immune responses has been pursued as a target for MS therapies for decades, Dr. Mao-Draayer said.
A first-generation monoclonal antibody directed at elevated levels of CD40L, which is implicated in the inflammation that drives MS, showed promise but was abandoned after it was associated with an increased risk for thromboembolic events in a phase 1 trial, she said.
However, the second-generation agent was engineered to avoid an interaction with platelets, which played a role in the risk for thrombosis associated with the failure of the earlier drug.
As with the first-generation agent, frexalimab had little or no impact on lymphocyte count or immunoglobulin G and immunoglobulin M levels. Both remained stable during the 12-week controlled trial and through the ongoing open-label extension, Dr. Mao-Draayer said.
This might be a factor in the low level of adverse events. Most importantly, there have been no thromboembolic events associated with frexalimab so far, but the follow-up data also show rates of infection and other events, such as nasopharyngitis, that were comparable with placebo in the 12-week controlled trial and have not increased over longer-term monitoring.
Such adverse events as headache and COVID-19 infection have also occurred at rates similar to placebo.
Two phase 3 trials are underway. FREXALT is being conducted in relapsing-remitting MS. FREVIV has enrolled patients with nonrelapsing secondary progressive MS.
Impressively Low New Lesion Count
Commenting on the findings, Jeffrey Cohen, MD, director of the Mellen Center for Multiple Sclerosis, Cleveland Clinic, who was not involved in the research, said that over the course of the extended follow-up, MS activity in the central nervous system as measured with new Gd+ T1 lesions was impressively low.
He noted that the phase 2 open-label follow-up continues to support the promise of frexalimab. But Dr. Cohen cautioned that this does not obviate the need for phase 3 data.
In particular, he said that an immunomodulatory agent that does not affect the lymphocyte count has a theoretical advantage, but pointed out that the benefit is still presumably mediated by blocking pathways that mediate autoimmune activity.
Even if lymphocyte count is unaffected, the immunomodulatory pathway by which frexalimab does exert its benefit might pose a different set of risks, he said.
“We will not have sufficient data to judge the promise of this agent until the phase 3 trials are completed,” he said.
Dr. Mao-Draayer reported financial relationships with Acorda, Bayer, Biogen, Bristol Myers Squibb, Celgene, EMD Serono, Genentech, Horizon, Janssen, Novartis, Questor, Teva, and Sanofi, which provided funding for the phase 2 frexalimab trial. Dr. Cohen reported financial relationships with Astoria, Convelo, EMD Serono, FiND, INmune, and Sandoz.
A version of this article appeared on Medscape.com.
NASHVILLE, TENNESSEE — , new trial data suggested.
Researchers found a near absence of new brain lesions at 48 weeks in patients on the highest dose. At this level of disease suppression, there was no evidence of increased infection risk, which investigators said might relate to its mechanism of action. In addition, there were no thrombotic events, which is what defeated a first-generation drug in this same class.
Among those initially randomly assigned to receive 1200 mg every 4 weeks, 96% were free of new gadolinium-positive (Gd+ T1) lesions at 48 weeks, reported investigator Yang Mao-Draayer, MD, PhD, director of Clinical and Experimental Therapeutics at the Oklahoma Medical Research Foundation’s Multiple Sclerosis Center of Excellence, Oklahoma City. Annual relapse rates were also low.
The findings were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.
No Effect on Lymphocyte Count
As previously reported, 12-week frexalimab results were noteworthy because they provided validation for CD40L as a target in the control of MS. One of the unique features of this therapy relative to many other immunomodulatory therapies is that it has shown little, if any, effect on lymphocyte counts or immunoglobulin levels.
In the double-blind randomized phase 2 trial, 125 patients with MS of all other MS therapy were randomized in a 4:4:4:1 ratio to 1200-mg frexalimab administered intravenously every 4 weeks after a loading dose, to 300-mg frexalimab administered subcutaneously every 2 weeks after a loading dose, or to one of the two matching placebo arms.
For the primary endpoint of new Gd+ T1 lesions at the end of the blinded study, the rates at week 12 were 0.2 and 0.3 in the higher- and lower-dose treatment groups, respectively, and 1.4 in the pooled placebo groups.
At 48 weeks, the results were even better. From 12 weeks, the rate of Gd+ T1 lesions in the high-dose group continued to fall, reaching 0.1 at week 24 and 0.0 at week 48. In the lower-dose group, there was also a stepwise decline over time with a value of 0.2 at week 48. The annual relapse rate at week 48 was 0.4.
Reengineered Agent
In the placebo groups, the same type of suppression of disease activity was observed after they were switched to active therapy at the end of 12 weeks.
By 24 weeks, the number of new Gd+ T1 lesions had fallen to 0.3 in placebo patients switched to the higher dose and 1.0 in those switched to the lower dose.
By week 48, the rates were 0.2 in both of the switch arms.
The proportions of patients free of new Gd+ T1 lesions at 48 weeks were 96% in the group started and maintained on the highest dose of frexalimab, 87% in those started and maintained on the lower dose, 90% in those started on placebo and switched to the highest dose of frexalimab, and 92% of placebo patients switched to the lower dose.
“T2 lesion volume from baseline through week 48 was stable in patients who continued receiving frexalimab and decreased in placebo participants after switching to frexalimab at week 12,” Dr. Mao-Draayer reported.
The CD40-CD40L co-stimulatory pathway that regulates both adaptive and innate immune responses has been pursued as a target for MS therapies for decades, Dr. Mao-Draayer said.
A first-generation monoclonal antibody directed at elevated levels of CD40L, which is implicated in the inflammation that drives MS, showed promise but was abandoned after it was associated with an increased risk for thromboembolic events in a phase 1 trial, she said.
However, the second-generation agent was engineered to avoid an interaction with platelets, which played a role in the risk for thrombosis associated with the failure of the earlier drug.
As with the first-generation agent, frexalimab had little or no impact on lymphocyte count or immunoglobulin G and immunoglobulin M levels. Both remained stable during the 12-week controlled trial and through the ongoing open-label extension, Dr. Mao-Draayer said.
This might be a factor in the low level of adverse events. Most importantly, there have been no thromboembolic events associated with frexalimab so far, but the follow-up data also show rates of infection and other events, such as nasopharyngitis, that were comparable with placebo in the 12-week controlled trial and have not increased over longer-term monitoring.
Such adverse events as headache and COVID-19 infection have also occurred at rates similar to placebo.
Two phase 3 trials are underway. FREXALT is being conducted in relapsing-remitting MS. FREVIV has enrolled patients with nonrelapsing secondary progressive MS.
Impressively Low New Lesion Count
Commenting on the findings, Jeffrey Cohen, MD, director of the Mellen Center for Multiple Sclerosis, Cleveland Clinic, who was not involved in the research, said that over the course of the extended follow-up, MS activity in the central nervous system as measured with new Gd+ T1 lesions was impressively low.
He noted that the phase 2 open-label follow-up continues to support the promise of frexalimab. But Dr. Cohen cautioned that this does not obviate the need for phase 3 data.
In particular, he said that an immunomodulatory agent that does not affect the lymphocyte count has a theoretical advantage, but pointed out that the benefit is still presumably mediated by blocking pathways that mediate autoimmune activity.
Even if lymphocyte count is unaffected, the immunomodulatory pathway by which frexalimab does exert its benefit might pose a different set of risks, he said.
“We will not have sufficient data to judge the promise of this agent until the phase 3 trials are completed,” he said.
Dr. Mao-Draayer reported financial relationships with Acorda, Bayer, Biogen, Bristol Myers Squibb, Celgene, EMD Serono, Genentech, Horizon, Janssen, Novartis, Questor, Teva, and Sanofi, which provided funding for the phase 2 frexalimab trial. Dr. Cohen reported financial relationships with Astoria, Convelo, EMD Serono, FiND, INmune, and Sandoz.
A version of this article appeared on Medscape.com.
FROM CMSC 2024
New TAVI Platform Adds More Valve Sizes to Choose From
PARIS — Intermediate valve sizes are at least as safe and effective as the standard sizes now available for transcatheter aortic valve implantation (TAVI), according to an international randomized trial.
In a head-to-head comparison, the LANDMARK trial looked at valves from the new balloon-expandable Myval® by Merril Life Sciences and compared them with the balloon-expandable Sapien® from Edwards Lifesciences and the self-expanding Evolut® valve from Medtronic.
The new Myval platform offers multiple valves sized at 1.5 mm intervals, while the other two have valves that are generally sized at intervals of 3.0 mm.
at the Congress of the European Association of Percutaneous Coronary Interventions 2024.
The LANDMARK Trial
The trial enrolled 768 patients at 31 sites in 16 countries. They were randomized in a 1:1 fashion to the new platform or to one of the standards to compare the concept of intermediate valves with contemporary standards.
Seven sizes of Myval valves were used in the study, ranging from 20 mm to 29 mm at 1.5 mm increments. Two more sizes, 30.5 mm and 32.0 mm, were not included in this analysis but are being following in a registry.
The study also used Sapien valves sized 20 mm, 23 mm, 26 mm, and 29 mm and Evolut valves sized 26 mm, 29 mm, and 34 mm. There is also a 23 mm Evolut valve available, but it was not selected by any of the participating investigators.
Of the 336 patients given Myval valves, 48% were an intermediate size not available on one of the other platforms.
For the primary composite efficacy and safety endpoint of all-cause mortality, fatal or nonfatal strokes, VARC 3 or 4 bleeding, acute kidney injury, major vascular injury, moderate or greater valve regurgitation, or conduction disturbances requiring a new permanent pacemaker, the difference in absolute risk was slightly lower in the Myval arm, at 24.7% vs 27.0%, but not statistically significant. With that numerical difference favoring the Myval platform, noninferiority was demonstrated at 30 days with a high level of statistical significance, Dr. Serruys reported.
When each endpoint, with the composite primary endpoint, was evaluated separately in a secondary analysis, all-cause mortality and stroke incidence were identical in the two arms.
Major bleeding and acute kidney injury were nonsignificantly more common in the Myval group, while the incidence of moderate or greater valve regurgitation, placement of a new permanent pacemaker, and major vascular complications were nonsignificantly less common.
Precise Matching
The effective orifice area was consistently higher in the group receiving an intermediate valve relative to a Sapien valve. This was not significant for the 20 mm valve size, but it did reach statistical significance for the rest of the sizes. In contrast, there was no significant difference with the Evolut series.
The data suggest that intermediate sizes “enable precise and appropriate matching of devices to an individual anatomy,” at least relative to Sapien, said Dr. Serruys.
Martin Leon, MD, of Columbia University in New York, called LANDMARK an important step for considering how comparative trials should be conducted in the future.
However, he challenged the idea that this study compared devices for both safety and efficacy. Despite the evidence it provides on device and procedural safety over the short-term, he said few conclusions can be drawn about comparative efficacy after just 30 days. Rather, the true comparative value of the trial will be derived from “rigorous late follow-up,” he said.
Longer Follow-Up to Come
Dr. Serruys acknowledged that the differences seen after 30 days have uncertain relevance to longer-term outcomes. He is planning to conduct a 10-year follow-up that “will unravel whether the documented effective orifice area of the Myval platform will have a beneficial impact on long-term patient prognosis and valve durability,” he said.
Leon agreed that, so far, these data do suggest superior hemodynamic performance with the intermediate sizing relative to valves in the Sapien platform, but the same cannot be said for the Evolut platform, and he pointed out that pooling data from the two platforms for the primary endpoint “makes comparisons difficult.”
And with about half of patients still fitted with the sizes already available, he said a deeper understanding was needed of how “adjustment strategies,” such as oversizing, affect long-term outcomes relative to platforms, such as Myval, with more valve sizes.
A version of this article appeared on Medscape.com.
PARIS — Intermediate valve sizes are at least as safe and effective as the standard sizes now available for transcatheter aortic valve implantation (TAVI), according to an international randomized trial.
In a head-to-head comparison, the LANDMARK trial looked at valves from the new balloon-expandable Myval® by Merril Life Sciences and compared them with the balloon-expandable Sapien® from Edwards Lifesciences and the self-expanding Evolut® valve from Medtronic.
The new Myval platform offers multiple valves sized at 1.5 mm intervals, while the other two have valves that are generally sized at intervals of 3.0 mm.
at the Congress of the European Association of Percutaneous Coronary Interventions 2024.
The LANDMARK Trial
The trial enrolled 768 patients at 31 sites in 16 countries. They were randomized in a 1:1 fashion to the new platform or to one of the standards to compare the concept of intermediate valves with contemporary standards.
Seven sizes of Myval valves were used in the study, ranging from 20 mm to 29 mm at 1.5 mm increments. Two more sizes, 30.5 mm and 32.0 mm, were not included in this analysis but are being following in a registry.
The study also used Sapien valves sized 20 mm, 23 mm, 26 mm, and 29 mm and Evolut valves sized 26 mm, 29 mm, and 34 mm. There is also a 23 mm Evolut valve available, but it was not selected by any of the participating investigators.
Of the 336 patients given Myval valves, 48% were an intermediate size not available on one of the other platforms.
For the primary composite efficacy and safety endpoint of all-cause mortality, fatal or nonfatal strokes, VARC 3 or 4 bleeding, acute kidney injury, major vascular injury, moderate or greater valve regurgitation, or conduction disturbances requiring a new permanent pacemaker, the difference in absolute risk was slightly lower in the Myval arm, at 24.7% vs 27.0%, but not statistically significant. With that numerical difference favoring the Myval platform, noninferiority was demonstrated at 30 days with a high level of statistical significance, Dr. Serruys reported.
When each endpoint, with the composite primary endpoint, was evaluated separately in a secondary analysis, all-cause mortality and stroke incidence were identical in the two arms.
Major bleeding and acute kidney injury were nonsignificantly more common in the Myval group, while the incidence of moderate or greater valve regurgitation, placement of a new permanent pacemaker, and major vascular complications were nonsignificantly less common.
Precise Matching
The effective orifice area was consistently higher in the group receiving an intermediate valve relative to a Sapien valve. This was not significant for the 20 mm valve size, but it did reach statistical significance for the rest of the sizes. In contrast, there was no significant difference with the Evolut series.
The data suggest that intermediate sizes “enable precise and appropriate matching of devices to an individual anatomy,” at least relative to Sapien, said Dr. Serruys.
Martin Leon, MD, of Columbia University in New York, called LANDMARK an important step for considering how comparative trials should be conducted in the future.
However, he challenged the idea that this study compared devices for both safety and efficacy. Despite the evidence it provides on device and procedural safety over the short-term, he said few conclusions can be drawn about comparative efficacy after just 30 days. Rather, the true comparative value of the trial will be derived from “rigorous late follow-up,” he said.
Longer Follow-Up to Come
Dr. Serruys acknowledged that the differences seen after 30 days have uncertain relevance to longer-term outcomes. He is planning to conduct a 10-year follow-up that “will unravel whether the documented effective orifice area of the Myval platform will have a beneficial impact on long-term patient prognosis and valve durability,” he said.
Leon agreed that, so far, these data do suggest superior hemodynamic performance with the intermediate sizing relative to valves in the Sapien platform, but the same cannot be said for the Evolut platform, and he pointed out that pooling data from the two platforms for the primary endpoint “makes comparisons difficult.”
And with about half of patients still fitted with the sizes already available, he said a deeper understanding was needed of how “adjustment strategies,” such as oversizing, affect long-term outcomes relative to platforms, such as Myval, with more valve sizes.
A version of this article appeared on Medscape.com.
PARIS — Intermediate valve sizes are at least as safe and effective as the standard sizes now available for transcatheter aortic valve implantation (TAVI), according to an international randomized trial.
In a head-to-head comparison, the LANDMARK trial looked at valves from the new balloon-expandable Myval® by Merril Life Sciences and compared them with the balloon-expandable Sapien® from Edwards Lifesciences and the self-expanding Evolut® valve from Medtronic.
The new Myval platform offers multiple valves sized at 1.5 mm intervals, while the other two have valves that are generally sized at intervals of 3.0 mm.
at the Congress of the European Association of Percutaneous Coronary Interventions 2024.
The LANDMARK Trial
The trial enrolled 768 patients at 31 sites in 16 countries. They were randomized in a 1:1 fashion to the new platform or to one of the standards to compare the concept of intermediate valves with contemporary standards.
Seven sizes of Myval valves were used in the study, ranging from 20 mm to 29 mm at 1.5 mm increments. Two more sizes, 30.5 mm and 32.0 mm, were not included in this analysis but are being following in a registry.
The study also used Sapien valves sized 20 mm, 23 mm, 26 mm, and 29 mm and Evolut valves sized 26 mm, 29 mm, and 34 mm. There is also a 23 mm Evolut valve available, but it was not selected by any of the participating investigators.
Of the 336 patients given Myval valves, 48% were an intermediate size not available on one of the other platforms.
For the primary composite efficacy and safety endpoint of all-cause mortality, fatal or nonfatal strokes, VARC 3 or 4 bleeding, acute kidney injury, major vascular injury, moderate or greater valve regurgitation, or conduction disturbances requiring a new permanent pacemaker, the difference in absolute risk was slightly lower in the Myval arm, at 24.7% vs 27.0%, but not statistically significant. With that numerical difference favoring the Myval platform, noninferiority was demonstrated at 30 days with a high level of statistical significance, Dr. Serruys reported.
When each endpoint, with the composite primary endpoint, was evaluated separately in a secondary analysis, all-cause mortality and stroke incidence were identical in the two arms.
Major bleeding and acute kidney injury were nonsignificantly more common in the Myval group, while the incidence of moderate or greater valve regurgitation, placement of a new permanent pacemaker, and major vascular complications were nonsignificantly less common.
Precise Matching
The effective orifice area was consistently higher in the group receiving an intermediate valve relative to a Sapien valve. This was not significant for the 20 mm valve size, but it did reach statistical significance for the rest of the sizes. In contrast, there was no significant difference with the Evolut series.
The data suggest that intermediate sizes “enable precise and appropriate matching of devices to an individual anatomy,” at least relative to Sapien, said Dr. Serruys.
Martin Leon, MD, of Columbia University in New York, called LANDMARK an important step for considering how comparative trials should be conducted in the future.
However, he challenged the idea that this study compared devices for both safety and efficacy. Despite the evidence it provides on device and procedural safety over the short-term, he said few conclusions can be drawn about comparative efficacy after just 30 days. Rather, the true comparative value of the trial will be derived from “rigorous late follow-up,” he said.
Longer Follow-Up to Come
Dr. Serruys acknowledged that the differences seen after 30 days have uncertain relevance to longer-term outcomes. He is planning to conduct a 10-year follow-up that “will unravel whether the documented effective orifice area of the Myval platform will have a beneficial impact on long-term patient prognosis and valve durability,” he said.
Leon agreed that, so far, these data do suggest superior hemodynamic performance with the intermediate sizing relative to valves in the Sapien platform, but the same cannot be said for the Evolut platform, and he pointed out that pooling data from the two platforms for the primary endpoint “makes comparisons difficult.”
And with about half of patients still fitted with the sizes already available, he said a deeper understanding was needed of how “adjustment strategies,” such as oversizing, affect long-term outcomes relative to platforms, such as Myval, with more valve sizes.
A version of this article appeared on Medscape.com.
FROM EUROPCR 2024
Pediatricians Face Competing Goals in Well Visits for LGBTQ+ Adolescents
TORONTO — , and there are different preferences for those with a gender identity different from their birth assignment or non-heterosexuals relative to those in neither of these categories.
In a study that surveyed more than 60,000 adolescents, one of the messages was that there is a “balancing act” that involves affirming the child’s self-identity while recognizing the substantial vulnerability at this step in development, reported Scott Jelinek, MD, a third-year pediatrics resident in the Children’s Hospital of Philadelphia, University of Pennsylvania.
Based on his work, there are two aims.
“The first is to determine the comfort level of the adolescent in discussing sensitive health information,” said Dr. Jelinek, referring to the discussion of SOGI irrespective of how the adolescent responds. “To understand this is crucial because this first encounter with healthcare can be formative.”
Yet, for those who identify as lesbian, gay, bisexual, transsexual, queer, or with another sexual or gender orientation (LBGTQ+), the encounter can be more delicate, according to Dr. Jelinek. One reason is that there is greater uncertainty about acceptance of these identities from peers, parents, and others, Dr. Jelinek said.
This was reinforced by results of a cross-sectional study of 62,695 adolescents in 31 pediatric clinics in the Philadelphia area. Of these, 10,381 (16.6%) identified as LGBTQ+. The adolescents aged in range from 13 to 21 years with a mean age of 15.3.
These data were presented at the Pediatric Academic Societies annual meeting. Dr. Jelinek received this year’s Society of Pediatric Research Richard D. Rowe Award for clinical research by a fellow.
Revealing Sensitive Information
With the intention of comparing responses from LBGTQ+ youth to those of cisgender heterosexuals, the first of two primary questions elicited information about comfort level discussing SOGI in the presence of parents or caregivers during a primary care visit. The second asked for a preference regarding electronic or oral capture of the information. “Almost half [49.4%] of the LGBTQ+ adolescents expressed discomfort discussing this information with the caregiver present,” reported Dr. Jelinek. This proportion, which was close to double the 25.5% rate among the cisgender heterosexual respondents, reached significance (P < .01). After adjustment for covariates, there was a 60% greater odds ratio (OR) among LBGTQ+ adolescents for expressing reluctance to share this information in front of a caregiver (adjusted odds ratio [aOR] 0.37; 95% CI: 0.35-0.39).
The greater preference among LBGTQ+ adolescents for electronic capture of SOGI-relevant information also reached statistical significance. Even though the proportional difference was modest (74.2% vs 72.7%; P < .01), it corresponded to about a 10% greater preference for electronic data collection after adjustment (aOR 1.08; 95% CI: 1.03-1.14), Dr. Jelinek reported.
These results were generally consistent across clinics, which were located in urban, suburban, and rural areas. Responses among Black adolescents, which represented 29.7% of the study population, were similar to those provided by White adolescents, which represented 46.1%, and Hispanics, which represented about 10% of the sample.
The results are not entirely surprising in the context of the potential for LBGTQ+ stigma, but Dr. Jelinek emphasized the need for being aware that this discussion is delicate and might have ramifications after the visit for children trying to accept and affirm their self-identification.
“Let us remember that the healthcare system has the potential to be a powerful ally in the lives of LBGTQ+ youth and to meet their unique needs,” he said.
The interaction is also delicate because parents might not yet be aware of their child’s sexual orientation. Indeed, Dr. Jelinek said that completion of the Attitudes Toward Homosexuality Questionnaire (AHQ) might be the first time that these individuals have revealed this aspect of their identity to anyone.
For confirming a non-heterosexual orientation, “pediatricians are on the front line and often the first point of contact for adolescents seeking health support and affirmation,” he said.
For this reason, it is also essential to maintain confidentiality to the degree that the patient specifies. Dr. Jelinek recognizes tension when balancing visibility and affirmation against the need for privacy, but he said both are important. Even if pediatricians should provide a positive experience for adolescents revealing their sexual orientation, there might be personal, family, and social adjustments to navigate over time.
As a result, Dr. Jelinek warned that there are issues for protecting information that an adolescent is not ready to reveal.
In this regard. “there is an urgent need for innovative solutions to balance visibility with privacy in primary care,” he said, reporting that electronic medical records (EMR) do not necessarily guarantee confidentiality, particularly from family members.
When adolescents arrive at the office to complete an AHQ, front desk staff at Dr. Jelinek’s center are instructed to hand the tablet to the child, not the caregiver. However, he recognizes that this does not prevent the caregiver from reviewing the answers or in some cases taking the tablet to complete the answers.
“If I enter the exam room and see the tablet in a parent’s lap, I am going to want to have a conversation with the patient to verify the answers,” he said.
Protecting Patients
The data from this study provoke important questions about how to achieve the goals that Dr. Jelinek described, according to Ashley M. Lekach, MSN, RN, a family nurse practitioner working in pediatric endocrinology at NewYork-Presbyterian’s Methodist Hospital in Brooklyn, New York. Ms. Lekach was not involved with the study.
“My concern is that once we are given this sensitive information, how do we make sure we are going to protect the patient from unwanted disclosure?” Ms. Lekach said. She agreed that there is a risk that EMRs can be accessed by individuals to which the patient would not want SOGI information revealed.
“It is a vote of confidence for the patient to reveal this information to me, and it is clearly our job to make sure the patient feels safe,” she said.
She also expressed concern that adolescents who reveal this information might need resources to cope with issues raised by non-heterosexual identification. She agreed that discussing sexual orientation and gender identity in the clinical setting is often a major step for adolescents, particularly young adolescents, but she believes follow-up and next steps are in the interest of the patient.
Although the need for affirmation and confidentiality are not new ideas, Ms. Lekach said that the talk provided some useful context for thinking about these issues.
Dr. Jelinek and Ms. Lekach report no potential conflicts of interest.
TORONTO — , and there are different preferences for those with a gender identity different from their birth assignment or non-heterosexuals relative to those in neither of these categories.
In a study that surveyed more than 60,000 adolescents, one of the messages was that there is a “balancing act” that involves affirming the child’s self-identity while recognizing the substantial vulnerability at this step in development, reported Scott Jelinek, MD, a third-year pediatrics resident in the Children’s Hospital of Philadelphia, University of Pennsylvania.
Based on his work, there are two aims.
“The first is to determine the comfort level of the adolescent in discussing sensitive health information,” said Dr. Jelinek, referring to the discussion of SOGI irrespective of how the adolescent responds. “To understand this is crucial because this first encounter with healthcare can be formative.”
Yet, for those who identify as lesbian, gay, bisexual, transsexual, queer, or with another sexual or gender orientation (LBGTQ+), the encounter can be more delicate, according to Dr. Jelinek. One reason is that there is greater uncertainty about acceptance of these identities from peers, parents, and others, Dr. Jelinek said.
This was reinforced by results of a cross-sectional study of 62,695 adolescents in 31 pediatric clinics in the Philadelphia area. Of these, 10,381 (16.6%) identified as LGBTQ+. The adolescents aged in range from 13 to 21 years with a mean age of 15.3.
These data were presented at the Pediatric Academic Societies annual meeting. Dr. Jelinek received this year’s Society of Pediatric Research Richard D. Rowe Award for clinical research by a fellow.
Revealing Sensitive Information
With the intention of comparing responses from LBGTQ+ youth to those of cisgender heterosexuals, the first of two primary questions elicited information about comfort level discussing SOGI in the presence of parents or caregivers during a primary care visit. The second asked for a preference regarding electronic or oral capture of the information. “Almost half [49.4%] of the LGBTQ+ adolescents expressed discomfort discussing this information with the caregiver present,” reported Dr. Jelinek. This proportion, which was close to double the 25.5% rate among the cisgender heterosexual respondents, reached significance (P < .01). After adjustment for covariates, there was a 60% greater odds ratio (OR) among LBGTQ+ adolescents for expressing reluctance to share this information in front of a caregiver (adjusted odds ratio [aOR] 0.37; 95% CI: 0.35-0.39).
The greater preference among LBGTQ+ adolescents for electronic capture of SOGI-relevant information also reached statistical significance. Even though the proportional difference was modest (74.2% vs 72.7%; P < .01), it corresponded to about a 10% greater preference for electronic data collection after adjustment (aOR 1.08; 95% CI: 1.03-1.14), Dr. Jelinek reported.
These results were generally consistent across clinics, which were located in urban, suburban, and rural areas. Responses among Black adolescents, which represented 29.7% of the study population, were similar to those provided by White adolescents, which represented 46.1%, and Hispanics, which represented about 10% of the sample.
The results are not entirely surprising in the context of the potential for LBGTQ+ stigma, but Dr. Jelinek emphasized the need for being aware that this discussion is delicate and might have ramifications after the visit for children trying to accept and affirm their self-identification.
“Let us remember that the healthcare system has the potential to be a powerful ally in the lives of LBGTQ+ youth and to meet their unique needs,” he said.
The interaction is also delicate because parents might not yet be aware of their child’s sexual orientation. Indeed, Dr. Jelinek said that completion of the Attitudes Toward Homosexuality Questionnaire (AHQ) might be the first time that these individuals have revealed this aspect of their identity to anyone.
For confirming a non-heterosexual orientation, “pediatricians are on the front line and often the first point of contact for adolescents seeking health support and affirmation,” he said.
For this reason, it is also essential to maintain confidentiality to the degree that the patient specifies. Dr. Jelinek recognizes tension when balancing visibility and affirmation against the need for privacy, but he said both are important. Even if pediatricians should provide a positive experience for adolescents revealing their sexual orientation, there might be personal, family, and social adjustments to navigate over time.
As a result, Dr. Jelinek warned that there are issues for protecting information that an adolescent is not ready to reveal.
In this regard. “there is an urgent need for innovative solutions to balance visibility with privacy in primary care,” he said, reporting that electronic medical records (EMR) do not necessarily guarantee confidentiality, particularly from family members.
When adolescents arrive at the office to complete an AHQ, front desk staff at Dr. Jelinek’s center are instructed to hand the tablet to the child, not the caregiver. However, he recognizes that this does not prevent the caregiver from reviewing the answers or in some cases taking the tablet to complete the answers.
“If I enter the exam room and see the tablet in a parent’s lap, I am going to want to have a conversation with the patient to verify the answers,” he said.
Protecting Patients
The data from this study provoke important questions about how to achieve the goals that Dr. Jelinek described, according to Ashley M. Lekach, MSN, RN, a family nurse practitioner working in pediatric endocrinology at NewYork-Presbyterian’s Methodist Hospital in Brooklyn, New York. Ms. Lekach was not involved with the study.
“My concern is that once we are given this sensitive information, how do we make sure we are going to protect the patient from unwanted disclosure?” Ms. Lekach said. She agreed that there is a risk that EMRs can be accessed by individuals to which the patient would not want SOGI information revealed.
“It is a vote of confidence for the patient to reveal this information to me, and it is clearly our job to make sure the patient feels safe,” she said.
She also expressed concern that adolescents who reveal this information might need resources to cope with issues raised by non-heterosexual identification. She agreed that discussing sexual orientation and gender identity in the clinical setting is often a major step for adolescents, particularly young adolescents, but she believes follow-up and next steps are in the interest of the patient.
Although the need for affirmation and confidentiality are not new ideas, Ms. Lekach said that the talk provided some useful context for thinking about these issues.
Dr. Jelinek and Ms. Lekach report no potential conflicts of interest.
TORONTO — , and there are different preferences for those with a gender identity different from their birth assignment or non-heterosexuals relative to those in neither of these categories.
In a study that surveyed more than 60,000 adolescents, one of the messages was that there is a “balancing act” that involves affirming the child’s self-identity while recognizing the substantial vulnerability at this step in development, reported Scott Jelinek, MD, a third-year pediatrics resident in the Children’s Hospital of Philadelphia, University of Pennsylvania.
Based on his work, there are two aims.
“The first is to determine the comfort level of the adolescent in discussing sensitive health information,” said Dr. Jelinek, referring to the discussion of SOGI irrespective of how the adolescent responds. “To understand this is crucial because this first encounter with healthcare can be formative.”
Yet, for those who identify as lesbian, gay, bisexual, transsexual, queer, or with another sexual or gender orientation (LBGTQ+), the encounter can be more delicate, according to Dr. Jelinek. One reason is that there is greater uncertainty about acceptance of these identities from peers, parents, and others, Dr. Jelinek said.
This was reinforced by results of a cross-sectional study of 62,695 adolescents in 31 pediatric clinics in the Philadelphia area. Of these, 10,381 (16.6%) identified as LGBTQ+. The adolescents aged in range from 13 to 21 years with a mean age of 15.3.
These data were presented at the Pediatric Academic Societies annual meeting. Dr. Jelinek received this year’s Society of Pediatric Research Richard D. Rowe Award for clinical research by a fellow.
Revealing Sensitive Information
With the intention of comparing responses from LBGTQ+ youth to those of cisgender heterosexuals, the first of two primary questions elicited information about comfort level discussing SOGI in the presence of parents or caregivers during a primary care visit. The second asked for a preference regarding electronic or oral capture of the information. “Almost half [49.4%] of the LGBTQ+ adolescents expressed discomfort discussing this information with the caregiver present,” reported Dr. Jelinek. This proportion, which was close to double the 25.5% rate among the cisgender heterosexual respondents, reached significance (P < .01). After adjustment for covariates, there was a 60% greater odds ratio (OR) among LBGTQ+ adolescents for expressing reluctance to share this information in front of a caregiver (adjusted odds ratio [aOR] 0.37; 95% CI: 0.35-0.39).
The greater preference among LBGTQ+ adolescents for electronic capture of SOGI-relevant information also reached statistical significance. Even though the proportional difference was modest (74.2% vs 72.7%; P < .01), it corresponded to about a 10% greater preference for electronic data collection after adjustment (aOR 1.08; 95% CI: 1.03-1.14), Dr. Jelinek reported.
These results were generally consistent across clinics, which were located in urban, suburban, and rural areas. Responses among Black adolescents, which represented 29.7% of the study population, were similar to those provided by White adolescents, which represented 46.1%, and Hispanics, which represented about 10% of the sample.
The results are not entirely surprising in the context of the potential for LBGTQ+ stigma, but Dr. Jelinek emphasized the need for being aware that this discussion is delicate and might have ramifications after the visit for children trying to accept and affirm their self-identification.
“Let us remember that the healthcare system has the potential to be a powerful ally in the lives of LBGTQ+ youth and to meet their unique needs,” he said.
The interaction is also delicate because parents might not yet be aware of their child’s sexual orientation. Indeed, Dr. Jelinek said that completion of the Attitudes Toward Homosexuality Questionnaire (AHQ) might be the first time that these individuals have revealed this aspect of their identity to anyone.
For confirming a non-heterosexual orientation, “pediatricians are on the front line and often the first point of contact for adolescents seeking health support and affirmation,” he said.
For this reason, it is also essential to maintain confidentiality to the degree that the patient specifies. Dr. Jelinek recognizes tension when balancing visibility and affirmation against the need for privacy, but he said both are important. Even if pediatricians should provide a positive experience for adolescents revealing their sexual orientation, there might be personal, family, and social adjustments to navigate over time.
As a result, Dr. Jelinek warned that there are issues for protecting information that an adolescent is not ready to reveal.
In this regard. “there is an urgent need for innovative solutions to balance visibility with privacy in primary care,” he said, reporting that electronic medical records (EMR) do not necessarily guarantee confidentiality, particularly from family members.
When adolescents arrive at the office to complete an AHQ, front desk staff at Dr. Jelinek’s center are instructed to hand the tablet to the child, not the caregiver. However, he recognizes that this does not prevent the caregiver from reviewing the answers or in some cases taking the tablet to complete the answers.
“If I enter the exam room and see the tablet in a parent’s lap, I am going to want to have a conversation with the patient to verify the answers,” he said.
Protecting Patients
The data from this study provoke important questions about how to achieve the goals that Dr. Jelinek described, according to Ashley M. Lekach, MSN, RN, a family nurse practitioner working in pediatric endocrinology at NewYork-Presbyterian’s Methodist Hospital in Brooklyn, New York. Ms. Lekach was not involved with the study.
“My concern is that once we are given this sensitive information, how do we make sure we are going to protect the patient from unwanted disclosure?” Ms. Lekach said. She agreed that there is a risk that EMRs can be accessed by individuals to which the patient would not want SOGI information revealed.
“It is a vote of confidence for the patient to reveal this information to me, and it is clearly our job to make sure the patient feels safe,” she said.
She also expressed concern that adolescents who reveal this information might need resources to cope with issues raised by non-heterosexual identification. She agreed that discussing sexual orientation and gender identity in the clinical setting is often a major step for adolescents, particularly young adolescents, but she believes follow-up and next steps are in the interest of the patient.
Although the need for affirmation and confidentiality are not new ideas, Ms. Lekach said that the talk provided some useful context for thinking about these issues.
Dr. Jelinek and Ms. Lekach report no potential conflicts of interest.
FROM PAS 2024
More Rapid Confirmation of an Autism Diagnosis Is Coming to Primary Care
TORONTO — , according to a series of studies presented at the Pediatric Academic Societies annual meeting.
Accelerated Diagnosis
In one study, 80% of the evaluations were conducted within 6 weeks of patient enrollment, according to Corinna Rea, MD, a clinician in the primary care center at Boston Children’s Hospital as well as an assistant professor at Harvard Medical School, Boston, Massachusetts.
This outcome was drawn from a pilot study with 179 children suspected of autism spectrum disorder (ASD) by clinicians in a pediatric clinic. All were under the age of 3 years. In the first step, families completed the Bayley-4 Social-Emotional and Adaptive Behavior Scale.
The next step was a virtual assessment by a trained clinician using the TELE-ADS-PEDs (TAP) tool developed by Vanderbilt University, Nashville, Tennessee. Patients and families participated from their homes. The diagnosis of ASD was made by a psychologist using the patient’s history and data provided by the two assessment tools.
Through this approach, the median time to diagnosis was 30 days, according to Dr. Rea. Relative to a median time of 168 days to diagnosis among patients considered likely to have ASD at Dr. Rea’s center in the year prior to this pilot study, the time was reduced significantly (P < .001).
All patients in the study were subsequently evaluated by traditional methods. One hundred percent of the ASD diagnoses were confirmed with traditional assessment.
On the basis of these data, the accelerated approach “seems efficient and quite accurate,” Dr. Rea reported. When family members were surveyed at the end of the pilot study, 60% were satisfied and 28% were moderately satisfied. Although 59% reported that they would have preferred an in-person assessment, approximately 90% agreed the child’s development was mostly or completely captured in the accelerated assessment.
Dr. Rea pointed out that the psychologists participating in this study offered the opinion that home-based assessments are in their experience better than in-person evaluations due to the more natural behavior of the child in their own environment. However, she said that the diagnostic approach in the pilot study is still being modified, and one of the goals is to make virtual assessment more acceptable to the families.
A Commercialized Diagnostic Approach
A similar approach has been commercialized by a firm called As You Are, according to Steven D. Hicks, MD, PhD, who is an associate professor of pediatrics at Pennsylvania State University College of Medicine, Hershey, Pennsylvania. Dr. Hicks is a principal in the enterprise, which is also assessing ASD virtually.
Trained pediatricians are evaluating patients with multiple tools in addition to TAP, including the Childhood Autism Rating Scale (CARS) and the Diagnostic and Statistical Manual (DSM-V) checklist for ASD. The company, which began offering this diagnostic service in 2022, now employs more than 30 pediatricians who participated in a 1-month training program.
At the 2024 PAS meeting, quality assurance data were presented on 215 (2.2%) of the 9632 children evaluated between February 2023 and March 2024. The diagnostic assessments of these randomly selected children were reviewed by one of three randomly assigned experts (a developmental pediatrician, a child psychologist, or a pediatrician with 7 years’ diagnostic experience) blinded to the initial scoring.
The diagnostic agreement was 94%, according to the data presented, providing a specificity of 90% and a sensitivity of 90% for ASD. The commercialized diagnostic approach is providing a diagnosis in a mean time of 29 days from initial contact, compared with delays that typically exceed 1 year for many children with suspected ASD, according to Dr. Hicks.
Additional Studies Aim at Streamlining Diagnosis
Two additional studies also evaluated strategies to streamline the diagnosis of ASD. Both were positive. In one, the accuracy and time to diagnosis among pediatricians trained in TAP and CARS were compared with those of ASD specialists in a dedicated autism clinic. Both were located at Nemours Children’s Health Center, Wilmington, Delaware.
In this study, presented by Meghan Harrison, DO, an attending pediatrician at Nemours Children’s Health, time to diagnosis among the 39 patients evaluated by pediatricians relative to the 349 patients evaluated at the dedicated ASD center (2.0 vs 5.1 months; P = .001) was significantly shorter. The age at diagnosis in the pediatrician-assessed population (27.5 vs 36.5 months; P < .001) was also significantly younger.
In another study, led by Ashely L. Early, MSW, a clinical social worker at the Medical University of South Carolina, Charleston, South Carolina, switching to a screening tool called the Rapid Interactive Screening Test for Autism in Toddlers (RITA-1) reduced the wait time to evaluation by approximately 5 months relative to previous practice with a more cumbersome screening method.
An ‘Urgent Need’ to Accelerate Diagnosis
In most places in the United States, children suspected of ASD are referred to specialists for confirmation of the diagnosis, which is needed to quality for ASD services, according to Katherine Zuckerman, MD, a professor of pediatrics the Oregon Health and Science University, Portland, Oregon. Dr. Zuckerman, who was moderator of the session in which all four of these abstracts were presented, explained that there is an urgent need to accelerate the time to diagnosis, which involves long delays for many if not most children with ASD. This is important because treatment and supportive services for ASD are almost always dependent on a diagnosis.
“There are tons of data to show that earlier access to ASD services has important patient benefits, including higher IQs,” she said. Other benefits she listed include a better quality of life for the child and the family.
“It can provide a huge reduction in family stress,” she added, suggesting that early interventions favorably modify the trajectory of the disability over time with accruing benefits.
“The lifetime costs of ASD exceed cancer and most other disease, so there are major implications for the cumulative cost of ASD management,” Dr. Zuckerman said. She suggested that the studies presented at the meeting reflect a likely evolution in who evaluates children for ASD and how quickly the evaluation is performed.
Dr. Rea, Dr. Harrison, Dr. Zuckerman, and Ms. Early reported no potential conflicts of interest. In addition to his executive role in As You Are, Dr. Hicks has financial relationships with Quadrant Biosciences and Spectrum Solutions.
TORONTO — , according to a series of studies presented at the Pediatric Academic Societies annual meeting.
Accelerated Diagnosis
In one study, 80% of the evaluations were conducted within 6 weeks of patient enrollment, according to Corinna Rea, MD, a clinician in the primary care center at Boston Children’s Hospital as well as an assistant professor at Harvard Medical School, Boston, Massachusetts.
This outcome was drawn from a pilot study with 179 children suspected of autism spectrum disorder (ASD) by clinicians in a pediatric clinic. All were under the age of 3 years. In the first step, families completed the Bayley-4 Social-Emotional and Adaptive Behavior Scale.
The next step was a virtual assessment by a trained clinician using the TELE-ADS-PEDs (TAP) tool developed by Vanderbilt University, Nashville, Tennessee. Patients and families participated from their homes. The diagnosis of ASD was made by a psychologist using the patient’s history and data provided by the two assessment tools.
Through this approach, the median time to diagnosis was 30 days, according to Dr. Rea. Relative to a median time of 168 days to diagnosis among patients considered likely to have ASD at Dr. Rea’s center in the year prior to this pilot study, the time was reduced significantly (P < .001).
All patients in the study were subsequently evaluated by traditional methods. One hundred percent of the ASD diagnoses were confirmed with traditional assessment.
On the basis of these data, the accelerated approach “seems efficient and quite accurate,” Dr. Rea reported. When family members were surveyed at the end of the pilot study, 60% were satisfied and 28% were moderately satisfied. Although 59% reported that they would have preferred an in-person assessment, approximately 90% agreed the child’s development was mostly or completely captured in the accelerated assessment.
Dr. Rea pointed out that the psychologists participating in this study offered the opinion that home-based assessments are in their experience better than in-person evaluations due to the more natural behavior of the child in their own environment. However, she said that the diagnostic approach in the pilot study is still being modified, and one of the goals is to make virtual assessment more acceptable to the families.
A Commercialized Diagnostic Approach
A similar approach has been commercialized by a firm called As You Are, according to Steven D. Hicks, MD, PhD, who is an associate professor of pediatrics at Pennsylvania State University College of Medicine, Hershey, Pennsylvania. Dr. Hicks is a principal in the enterprise, which is also assessing ASD virtually.
Trained pediatricians are evaluating patients with multiple tools in addition to TAP, including the Childhood Autism Rating Scale (CARS) and the Diagnostic and Statistical Manual (DSM-V) checklist for ASD. The company, which began offering this diagnostic service in 2022, now employs more than 30 pediatricians who participated in a 1-month training program.
At the 2024 PAS meeting, quality assurance data were presented on 215 (2.2%) of the 9632 children evaluated between February 2023 and March 2024. The diagnostic assessments of these randomly selected children were reviewed by one of three randomly assigned experts (a developmental pediatrician, a child psychologist, or a pediatrician with 7 years’ diagnostic experience) blinded to the initial scoring.
The diagnostic agreement was 94%, according to the data presented, providing a specificity of 90% and a sensitivity of 90% for ASD. The commercialized diagnostic approach is providing a diagnosis in a mean time of 29 days from initial contact, compared with delays that typically exceed 1 year for many children with suspected ASD, according to Dr. Hicks.
Additional Studies Aim at Streamlining Diagnosis
Two additional studies also evaluated strategies to streamline the diagnosis of ASD. Both were positive. In one, the accuracy and time to diagnosis among pediatricians trained in TAP and CARS were compared with those of ASD specialists in a dedicated autism clinic. Both were located at Nemours Children’s Health Center, Wilmington, Delaware.
In this study, presented by Meghan Harrison, DO, an attending pediatrician at Nemours Children’s Health, time to diagnosis among the 39 patients evaluated by pediatricians relative to the 349 patients evaluated at the dedicated ASD center (2.0 vs 5.1 months; P = .001) was significantly shorter. The age at diagnosis in the pediatrician-assessed population (27.5 vs 36.5 months; P < .001) was also significantly younger.
In another study, led by Ashely L. Early, MSW, a clinical social worker at the Medical University of South Carolina, Charleston, South Carolina, switching to a screening tool called the Rapid Interactive Screening Test for Autism in Toddlers (RITA-1) reduced the wait time to evaluation by approximately 5 months relative to previous practice with a more cumbersome screening method.
An ‘Urgent Need’ to Accelerate Diagnosis
In most places in the United States, children suspected of ASD are referred to specialists for confirmation of the diagnosis, which is needed to quality for ASD services, according to Katherine Zuckerman, MD, a professor of pediatrics the Oregon Health and Science University, Portland, Oregon. Dr. Zuckerman, who was moderator of the session in which all four of these abstracts were presented, explained that there is an urgent need to accelerate the time to diagnosis, which involves long delays for many if not most children with ASD. This is important because treatment and supportive services for ASD are almost always dependent on a diagnosis.
“There are tons of data to show that earlier access to ASD services has important patient benefits, including higher IQs,” she said. Other benefits she listed include a better quality of life for the child and the family.
“It can provide a huge reduction in family stress,” she added, suggesting that early interventions favorably modify the trajectory of the disability over time with accruing benefits.
“The lifetime costs of ASD exceed cancer and most other disease, so there are major implications for the cumulative cost of ASD management,” Dr. Zuckerman said. She suggested that the studies presented at the meeting reflect a likely evolution in who evaluates children for ASD and how quickly the evaluation is performed.
Dr. Rea, Dr. Harrison, Dr. Zuckerman, and Ms. Early reported no potential conflicts of interest. In addition to his executive role in As You Are, Dr. Hicks has financial relationships with Quadrant Biosciences and Spectrum Solutions.
TORONTO — , according to a series of studies presented at the Pediatric Academic Societies annual meeting.
Accelerated Diagnosis
In one study, 80% of the evaluations were conducted within 6 weeks of patient enrollment, according to Corinna Rea, MD, a clinician in the primary care center at Boston Children’s Hospital as well as an assistant professor at Harvard Medical School, Boston, Massachusetts.
This outcome was drawn from a pilot study with 179 children suspected of autism spectrum disorder (ASD) by clinicians in a pediatric clinic. All were under the age of 3 years. In the first step, families completed the Bayley-4 Social-Emotional and Adaptive Behavior Scale.
The next step was a virtual assessment by a trained clinician using the TELE-ADS-PEDs (TAP) tool developed by Vanderbilt University, Nashville, Tennessee. Patients and families participated from their homes. The diagnosis of ASD was made by a psychologist using the patient’s history and data provided by the two assessment tools.
Through this approach, the median time to diagnosis was 30 days, according to Dr. Rea. Relative to a median time of 168 days to diagnosis among patients considered likely to have ASD at Dr. Rea’s center in the year prior to this pilot study, the time was reduced significantly (P < .001).
All patients in the study were subsequently evaluated by traditional methods. One hundred percent of the ASD diagnoses were confirmed with traditional assessment.
On the basis of these data, the accelerated approach “seems efficient and quite accurate,” Dr. Rea reported. When family members were surveyed at the end of the pilot study, 60% were satisfied and 28% were moderately satisfied. Although 59% reported that they would have preferred an in-person assessment, approximately 90% agreed the child’s development was mostly or completely captured in the accelerated assessment.
Dr. Rea pointed out that the psychologists participating in this study offered the opinion that home-based assessments are in their experience better than in-person evaluations due to the more natural behavior of the child in their own environment. However, she said that the diagnostic approach in the pilot study is still being modified, and one of the goals is to make virtual assessment more acceptable to the families.
A Commercialized Diagnostic Approach
A similar approach has been commercialized by a firm called As You Are, according to Steven D. Hicks, MD, PhD, who is an associate professor of pediatrics at Pennsylvania State University College of Medicine, Hershey, Pennsylvania. Dr. Hicks is a principal in the enterprise, which is also assessing ASD virtually.
Trained pediatricians are evaluating patients with multiple tools in addition to TAP, including the Childhood Autism Rating Scale (CARS) and the Diagnostic and Statistical Manual (DSM-V) checklist for ASD. The company, which began offering this diagnostic service in 2022, now employs more than 30 pediatricians who participated in a 1-month training program.
At the 2024 PAS meeting, quality assurance data were presented on 215 (2.2%) of the 9632 children evaluated between February 2023 and March 2024. The diagnostic assessments of these randomly selected children were reviewed by one of three randomly assigned experts (a developmental pediatrician, a child psychologist, or a pediatrician with 7 years’ diagnostic experience) blinded to the initial scoring.
The diagnostic agreement was 94%, according to the data presented, providing a specificity of 90% and a sensitivity of 90% for ASD. The commercialized diagnostic approach is providing a diagnosis in a mean time of 29 days from initial contact, compared with delays that typically exceed 1 year for many children with suspected ASD, according to Dr. Hicks.
Additional Studies Aim at Streamlining Diagnosis
Two additional studies also evaluated strategies to streamline the diagnosis of ASD. Both were positive. In one, the accuracy and time to diagnosis among pediatricians trained in TAP and CARS were compared with those of ASD specialists in a dedicated autism clinic. Both were located at Nemours Children’s Health Center, Wilmington, Delaware.
In this study, presented by Meghan Harrison, DO, an attending pediatrician at Nemours Children’s Health, time to diagnosis among the 39 patients evaluated by pediatricians relative to the 349 patients evaluated at the dedicated ASD center (2.0 vs 5.1 months; P = .001) was significantly shorter. The age at diagnosis in the pediatrician-assessed population (27.5 vs 36.5 months; P < .001) was also significantly younger.
In another study, led by Ashely L. Early, MSW, a clinical social worker at the Medical University of South Carolina, Charleston, South Carolina, switching to a screening tool called the Rapid Interactive Screening Test for Autism in Toddlers (RITA-1) reduced the wait time to evaluation by approximately 5 months relative to previous practice with a more cumbersome screening method.
An ‘Urgent Need’ to Accelerate Diagnosis
In most places in the United States, children suspected of ASD are referred to specialists for confirmation of the diagnosis, which is needed to quality for ASD services, according to Katherine Zuckerman, MD, a professor of pediatrics the Oregon Health and Science University, Portland, Oregon. Dr. Zuckerman, who was moderator of the session in which all four of these abstracts were presented, explained that there is an urgent need to accelerate the time to diagnosis, which involves long delays for many if not most children with ASD. This is important because treatment and supportive services for ASD are almost always dependent on a diagnosis.
“There are tons of data to show that earlier access to ASD services has important patient benefits, including higher IQs,” she said. Other benefits she listed include a better quality of life for the child and the family.
“It can provide a huge reduction in family stress,” she added, suggesting that early interventions favorably modify the trajectory of the disability over time with accruing benefits.
“The lifetime costs of ASD exceed cancer and most other disease, so there are major implications for the cumulative cost of ASD management,” Dr. Zuckerman said. She suggested that the studies presented at the meeting reflect a likely evolution in who evaluates children for ASD and how quickly the evaluation is performed.
Dr. Rea, Dr. Harrison, Dr. Zuckerman, and Ms. Early reported no potential conflicts of interest. In addition to his executive role in As You Are, Dr. Hicks has financial relationships with Quadrant Biosciences and Spectrum Solutions.
FROM PAS 2024
Follow-Up for Pediatric Depression Doubles With New Quality Initiative
TORONTO — An ambitious effort at a busy pediatrics clinic to improve follow-up in children and adolescents with a positive depression screen improved this quality metric, and it produced a fundamental change in approach.
“It was a big culture shift,” reported Landon B. Krantz, MD, a clinical fellow in the Division of General and Community Pediatrics at Cincinnati Children’s Hospital in Ohio. From a baseline position of screening, risk identification, and then referral, “we are now taking ownership of the process.”
Based on the substantial risk posed by significant levels of depression, guidelines recommend follow-up for any patient 12 years or older who has a positive screen, according to Dr. Krantz. At his center, they found only 19% had a documented follow-up within 30 days, even though timely intervention is important.
“Nearly half of suicide events in adolescents occur within 30 days after a positive PHQ-9 [9-question Patient Health Questionnaire] is completed,” said Dr. Krantz when presenting his data at the Pediatric Academic Societies annual meeting.
The issue has gained more urgency because of the substantial increase over the past several years in children presenting with depression and suicidal thoughts, according to Dr. Krantz. He said many are characterizing the upsurge as a mental health crisis in the pediatric age group.
Improving Follow-Up
. The goal at the outset was to increase the proportion to 35%.
“We know that a lot of children would receive follow-up at centers outside of our system,” said Dr. Krantz, explaining why the goal was relatively modest. Based on the likelihood that many follow-up visits would not be captured, he expected the final data would represent an underestimate.
Depression at baseline was defined as a score of 10 or higher on the PHQ-9 or any positive answer to item 9 on this screening tool, which asks specifically about thoughts of self-harm.
To be counted, follow-up had to be a documented encounter, whether by phone call, in-person visit, or telehealth visit.
“We needed patients to be checked. We did not count a prescription refill as a true follow-up,” Dr. Krantz specified.
There were numerous strategies implemented to improve follow-up, not least of which was an educational program to reinforce the importance and value of follow-up that was disseminated to clinicians in all of the participating clinics. Medical assistants were instructed to schedule a follow-up appointment for all patients who tested positive before they left the office. A target of 3 weeks was a strategy of overcorrection when so many patients were missing the initial 30-day window by just a few days.
The approach also involved an enhanced collaboration with psychologists to which patients were referred. Asking for expedited appointments when appropriate ensured that those at highest risk were prioritized, although Dr. Krantz said that this step was planned carefully to avoid overwhelming the mental health team.
“We monitored this and made sure it was not increasing the burden for psychologists from a capacity standpoint,” he said.
Other steps, like a depression action plan, which Dr. Krantz compared to an asthma action plan, were also implemented to reduce the risk of losing symptomatic patients before the chance for an effective treatment.
When compared with the 19% 30-day follow-up rate in the preintervention sample of 589 children, the 43.8% 30-day follow-up rate achieved in the 764 patients identified after implementation beat the original goal.
The improvement in follow-up was relatively consistent across all six clinics, which Dr. Krantz believes reflected a broad and shared change in a sense of responsibility for confirming that symptoms of depression were being addressed. Patients were still referred for psychological help, but referral was no longer considered enough.
“Children with mental health issues are still our patients in primary care,” said Dr. Krantz, who considers this an important change in orientation.
While the goal was to schedule patients for a follow-up at the time of a positive depression screen, Dr. Krantz described one important accommodation.
“The screen for depression was being performed in most cases during well visits, so patients and their families were not expecting to be discussing this issue,” he said. The diagnosis might be a particular surprise to parents who were not aware of any symptoms. In this case, Dr. Krantz said patients and families were given time to process the information and were contacted after a week to discuss further workup.
It is also notable that about one third of patients met the criteria for depression by answering positively to the PHQ-9 item on self-harm when they did not meet the 10 or more threshold depression score overall. In other words, these patients would have been missed without this criterion.
In the participating Cincinnati pediatric clinics, about 12%-13% of adolescents met the criteria for depression, which Dr. Krantz said is consistent with reports in the literature. He said the range is about 6%-24%.
Although outcomes were not tracked, there is evidence that early intervention for depression yields better outcomes than delayed intervention, according to Dr. Krantz. Based on approximately 600 positive screens for depression per year at his pediatric clinics, he estimated that his data predict at least 25% more patients will receive timely follow-up.
Seeking Solutions to a Growing Problem
There are several studies documenting the growing problem of adolescent depression and suicide and, for this reason, the topic is attracting a lot of attention, according to Corinna Rea, MD, MPH, a pediatrician working in the primary care center at Boston Children’s Hospital in Massachusetts.
Dr. Rea was not involved with the study, but when asked to comment, she said: “The results of this study were encouraging because we know that getting patients to care quickly is probably important.” She also agreed that referring patients with depression for care might not be enough, noting that a lot of patients do not follow up on recommendations to pursue a consultation or treatment.
“I am now involved in a project with the American Academy of Pediatrics to address this issue,” Dr. Rae said. She thinks that more work in this area is needed and agreed with Dr. Krantz that pediatricians should verify that children with depression are getting help even when other specialists are providing the treatment.
Dr. Krantz and Dr. Rae report no potential conflicts of interest.
TORONTO — An ambitious effort at a busy pediatrics clinic to improve follow-up in children and adolescents with a positive depression screen improved this quality metric, and it produced a fundamental change in approach.
“It was a big culture shift,” reported Landon B. Krantz, MD, a clinical fellow in the Division of General and Community Pediatrics at Cincinnati Children’s Hospital in Ohio. From a baseline position of screening, risk identification, and then referral, “we are now taking ownership of the process.”
Based on the substantial risk posed by significant levels of depression, guidelines recommend follow-up for any patient 12 years or older who has a positive screen, according to Dr. Krantz. At his center, they found only 19% had a documented follow-up within 30 days, even though timely intervention is important.
“Nearly half of suicide events in adolescents occur within 30 days after a positive PHQ-9 [9-question Patient Health Questionnaire] is completed,” said Dr. Krantz when presenting his data at the Pediatric Academic Societies annual meeting.
The issue has gained more urgency because of the substantial increase over the past several years in children presenting with depression and suicidal thoughts, according to Dr. Krantz. He said many are characterizing the upsurge as a mental health crisis in the pediatric age group.
Improving Follow-Up
. The goal at the outset was to increase the proportion to 35%.
“We know that a lot of children would receive follow-up at centers outside of our system,” said Dr. Krantz, explaining why the goal was relatively modest. Based on the likelihood that many follow-up visits would not be captured, he expected the final data would represent an underestimate.
Depression at baseline was defined as a score of 10 or higher on the PHQ-9 or any positive answer to item 9 on this screening tool, which asks specifically about thoughts of self-harm.
To be counted, follow-up had to be a documented encounter, whether by phone call, in-person visit, or telehealth visit.
“We needed patients to be checked. We did not count a prescription refill as a true follow-up,” Dr. Krantz specified.
There were numerous strategies implemented to improve follow-up, not least of which was an educational program to reinforce the importance and value of follow-up that was disseminated to clinicians in all of the participating clinics. Medical assistants were instructed to schedule a follow-up appointment for all patients who tested positive before they left the office. A target of 3 weeks was a strategy of overcorrection when so many patients were missing the initial 30-day window by just a few days.
The approach also involved an enhanced collaboration with psychologists to which patients were referred. Asking for expedited appointments when appropriate ensured that those at highest risk were prioritized, although Dr. Krantz said that this step was planned carefully to avoid overwhelming the mental health team.
“We monitored this and made sure it was not increasing the burden for psychologists from a capacity standpoint,” he said.
Other steps, like a depression action plan, which Dr. Krantz compared to an asthma action plan, were also implemented to reduce the risk of losing symptomatic patients before the chance for an effective treatment.
When compared with the 19% 30-day follow-up rate in the preintervention sample of 589 children, the 43.8% 30-day follow-up rate achieved in the 764 patients identified after implementation beat the original goal.
The improvement in follow-up was relatively consistent across all six clinics, which Dr. Krantz believes reflected a broad and shared change in a sense of responsibility for confirming that symptoms of depression were being addressed. Patients were still referred for psychological help, but referral was no longer considered enough.
“Children with mental health issues are still our patients in primary care,” said Dr. Krantz, who considers this an important change in orientation.
While the goal was to schedule patients for a follow-up at the time of a positive depression screen, Dr. Krantz described one important accommodation.
“The screen for depression was being performed in most cases during well visits, so patients and their families were not expecting to be discussing this issue,” he said. The diagnosis might be a particular surprise to parents who were not aware of any symptoms. In this case, Dr. Krantz said patients and families were given time to process the information and were contacted after a week to discuss further workup.
It is also notable that about one third of patients met the criteria for depression by answering positively to the PHQ-9 item on self-harm when they did not meet the 10 or more threshold depression score overall. In other words, these patients would have been missed without this criterion.
In the participating Cincinnati pediatric clinics, about 12%-13% of adolescents met the criteria for depression, which Dr. Krantz said is consistent with reports in the literature. He said the range is about 6%-24%.
Although outcomes were not tracked, there is evidence that early intervention for depression yields better outcomes than delayed intervention, according to Dr. Krantz. Based on approximately 600 positive screens for depression per year at his pediatric clinics, he estimated that his data predict at least 25% more patients will receive timely follow-up.
Seeking Solutions to a Growing Problem
There are several studies documenting the growing problem of adolescent depression and suicide and, for this reason, the topic is attracting a lot of attention, according to Corinna Rea, MD, MPH, a pediatrician working in the primary care center at Boston Children’s Hospital in Massachusetts.
Dr. Rea was not involved with the study, but when asked to comment, she said: “The results of this study were encouraging because we know that getting patients to care quickly is probably important.” She also agreed that referring patients with depression for care might not be enough, noting that a lot of patients do not follow up on recommendations to pursue a consultation or treatment.
“I am now involved in a project with the American Academy of Pediatrics to address this issue,” Dr. Rae said. She thinks that more work in this area is needed and agreed with Dr. Krantz that pediatricians should verify that children with depression are getting help even when other specialists are providing the treatment.
Dr. Krantz and Dr. Rae report no potential conflicts of interest.
TORONTO — An ambitious effort at a busy pediatrics clinic to improve follow-up in children and adolescents with a positive depression screen improved this quality metric, and it produced a fundamental change in approach.
“It was a big culture shift,” reported Landon B. Krantz, MD, a clinical fellow in the Division of General and Community Pediatrics at Cincinnati Children’s Hospital in Ohio. From a baseline position of screening, risk identification, and then referral, “we are now taking ownership of the process.”
Based on the substantial risk posed by significant levels of depression, guidelines recommend follow-up for any patient 12 years or older who has a positive screen, according to Dr. Krantz. At his center, they found only 19% had a documented follow-up within 30 days, even though timely intervention is important.
“Nearly half of suicide events in adolescents occur within 30 days after a positive PHQ-9 [9-question Patient Health Questionnaire] is completed,” said Dr. Krantz when presenting his data at the Pediatric Academic Societies annual meeting.
The issue has gained more urgency because of the substantial increase over the past several years in children presenting with depression and suicidal thoughts, according to Dr. Krantz. He said many are characterizing the upsurge as a mental health crisis in the pediatric age group.
Improving Follow-Up
. The goal at the outset was to increase the proportion to 35%.
“We know that a lot of children would receive follow-up at centers outside of our system,” said Dr. Krantz, explaining why the goal was relatively modest. Based on the likelihood that many follow-up visits would not be captured, he expected the final data would represent an underestimate.
Depression at baseline was defined as a score of 10 or higher on the PHQ-9 or any positive answer to item 9 on this screening tool, which asks specifically about thoughts of self-harm.
To be counted, follow-up had to be a documented encounter, whether by phone call, in-person visit, or telehealth visit.
“We needed patients to be checked. We did not count a prescription refill as a true follow-up,” Dr. Krantz specified.
There were numerous strategies implemented to improve follow-up, not least of which was an educational program to reinforce the importance and value of follow-up that was disseminated to clinicians in all of the participating clinics. Medical assistants were instructed to schedule a follow-up appointment for all patients who tested positive before they left the office. A target of 3 weeks was a strategy of overcorrection when so many patients were missing the initial 30-day window by just a few days.
The approach also involved an enhanced collaboration with psychologists to which patients were referred. Asking for expedited appointments when appropriate ensured that those at highest risk were prioritized, although Dr. Krantz said that this step was planned carefully to avoid overwhelming the mental health team.
“We monitored this and made sure it was not increasing the burden for psychologists from a capacity standpoint,” he said.
Other steps, like a depression action plan, which Dr. Krantz compared to an asthma action plan, were also implemented to reduce the risk of losing symptomatic patients before the chance for an effective treatment.
When compared with the 19% 30-day follow-up rate in the preintervention sample of 589 children, the 43.8% 30-day follow-up rate achieved in the 764 patients identified after implementation beat the original goal.
The improvement in follow-up was relatively consistent across all six clinics, which Dr. Krantz believes reflected a broad and shared change in a sense of responsibility for confirming that symptoms of depression were being addressed. Patients were still referred for psychological help, but referral was no longer considered enough.
“Children with mental health issues are still our patients in primary care,” said Dr. Krantz, who considers this an important change in orientation.
While the goal was to schedule patients for a follow-up at the time of a positive depression screen, Dr. Krantz described one important accommodation.
“The screen for depression was being performed in most cases during well visits, so patients and their families were not expecting to be discussing this issue,” he said. The diagnosis might be a particular surprise to parents who were not aware of any symptoms. In this case, Dr. Krantz said patients and families were given time to process the information and were contacted after a week to discuss further workup.
It is also notable that about one third of patients met the criteria for depression by answering positively to the PHQ-9 item on self-harm when they did not meet the 10 or more threshold depression score overall. In other words, these patients would have been missed without this criterion.
In the participating Cincinnati pediatric clinics, about 12%-13% of adolescents met the criteria for depression, which Dr. Krantz said is consistent with reports in the literature. He said the range is about 6%-24%.
Although outcomes were not tracked, there is evidence that early intervention for depression yields better outcomes than delayed intervention, according to Dr. Krantz. Based on approximately 600 positive screens for depression per year at his pediatric clinics, he estimated that his data predict at least 25% more patients will receive timely follow-up.
Seeking Solutions to a Growing Problem
There are several studies documenting the growing problem of adolescent depression and suicide and, for this reason, the topic is attracting a lot of attention, according to Corinna Rea, MD, MPH, a pediatrician working in the primary care center at Boston Children’s Hospital in Massachusetts.
Dr. Rea was not involved with the study, but when asked to comment, she said: “The results of this study were encouraging because we know that getting patients to care quickly is probably important.” She also agreed that referring patients with depression for care might not be enough, noting that a lot of patients do not follow up on recommendations to pursue a consultation or treatment.
“I am now involved in a project with the American Academy of Pediatrics to address this issue,” Dr. Rae said. She thinks that more work in this area is needed and agreed with Dr. Krantz that pediatricians should verify that children with depression are getting help even when other specialists are providing the treatment.
Dr. Krantz and Dr. Rae report no potential conflicts of interest.
FROM PAS 2024
Pediatrician Credibility Remains Intact in Midst of Health Misinformation
TORONTO —
Despite acknowledging that health misinformation is on the rise, “nearly all the pediatricians we surveyed agreed or strongly agreed that their patients consider them a trusted information source,” reported Elizabeth A. Gottschlich, MA, a senior research associate with the American Academy of Pediatrics, Itasca, Illinois.
These data were generated by an ongoing cohort analysis called the Pediatricians Life and Career Experience Study (PLACES). Each year, two surveys are conducted with three groups of pediatricians in this cohort. They are defined by years in which they graduated from residency (2002-2004, 2009-2011, or 2016-2018).
While the longer survey of the two captures an array of issues regarding life and practice, the shorter “checkpoint” survey addresses a high-priority topic. In 2023, it was health misinformation. The data from this survey were presented at the Pediatric Academic Societies annual meeting.
About 40% of the 2706 pediatricians who completed this particular survey (just over 65% of the participants in PLACES) were general pediatricians, 50% were pediatric subspecialists, and 10% were hospitalists.
Almost all of the survey questions were answered on a five-point Likert scale.
A Matter of Trust
According to Ms. Gottschlich, approximately 80% of pediatricians agreed or strongly agreed that misinformation is a clinical issue for them. About one third of these strongly agreed, and only 6% disagreed.
There was also strong consensus that the problem has grown worse since the start of the COVID-19 epidemic. To this statement, 70% agreed or strongly agreed and 24% did not agree or disagree. Only 4% disagreed.
However, relatively few respondents appeared to be concerned about the ability of pediatricians to address the problem of misinformation, Ms. Gottschlich reported.
When asked to respond to the statement that the “community recognizes and uses pediatricians as trusted source for health information,” 87% agreed or strongly agreed. Of the remaining, 9% did not agree or disagree, leaving just 4% that disagreed or strongly disagreed.
For a similar but slightly different question, the consensus was even greater. To the statement “patients/families in your practice seek your input as a trusted source for health information,” 94% agreed or strongly agreed.
Encountering Misinformation
The survey went on to ask pediatricians about encounters with misinformation for seven specific issues. On the five-point Likert scale, the choices ranged from a few times per year to every day.
For reproductive health, gender-affirming care, and firearm injury prevention, about 80% of respondents answered at the very low end of the scale, meaning no more than about once per month. Encounters with misinformation was slightly greater with autism; nearly one third responded that they encountered misinformation once a week or more frequently.
For all three questions regarding vaccines, the proportions climbed substantially. Of these, the COVID-19 vaccine was the most common topic of misinformation, with more than half reporting that they addressed incorrect information once a week or more. Seven percent reported this occurs daily.
Nearly 40% of pediatricians responded that they dealt with misinformation about the HPV vaccine once per week or more, while 35% reported that they encountered misinformation this frequently about routine childhood vaccines. There was a small but not necessarily trivial proportion for each of these categories of vaccine who reported that they encountered misinformation on a daily basis.
When stratified by clinical focus, the encounters varied. For the COVID-19 vaccine, general pediatricians (67%) were far more likely to report addressing misinformation on a weekly or more frequent basis than hospitalists (39%) or subspecialists (46%). They were more than twice as likely to encounter misinformation about the HPV vaccine than hospitalists or pediatric subspecialists (46%, 17%, and 19%, respectively).
When stratified by urban, suburban, or rural practice areas, differences were relatively modest. Pediatricians in urban practices were less likely to face misinformation about HPV vaccine (29% vs 44% and 48% for suburban and rural areas, respectively), while pediatricians in rural practice were more likely to face misinformation about routine childhood vaccines (60% vs 33% and 35% for urban and suburban practices, respectively).
Differences were even narrower when misinformation encounters were compared among the West, Midwest, South, and Northeast. For the threshold of once per week or more commonly, misinformation about the COVID-19 vaccine was less common in the South (50% vs 55%-58% in the other areas), while misinformation about routine childhood vaccines was more commonly encountered in the West (41% vs 32%-35% in the other areas).
A Growing Problem
The confidence among pediatricians that their knowledge is valued is reassuring, according to Ms. Gottschlich, who noted that the U.S. Surgeon General declared health misinformation a serious threat to public health in 2021, but the problem of misinformation is growing, according to several sources.
One of these sources, at least in regard to adolescent health, appears to be social media, according to a recently published review article in JAMA Pediatrics. The lead author of that article, Monica L. Wang, DSc, has dual academic appointments at the Boston University School of Public Health and Harvard University’s T.H. Chan School of Public Health, Boston. Asked for a comment on this issue, she suggested that it might not be enough to just respond to misinformation but rather might be better to develop a dialogue that will reveal misconceptions.
“Just as they screen for preventive issues like seat belt use, sunscreen, and safe sex practices, [pediatricians should integrate] questions about health misinformation into visits, which can be a natural and effective way to encourage dialogue, proactively share accurate information, and promote well-being,” she said.
Agreeing with the premise that pediatricians are a credible source of information for parents and children, Dr. Wang very much endorses the principle that “pediatricians can play a critical role in addressing health misinformation.”
Ms. Gottschlich and Dr. Wang report no potential conflicts of interest.
TORONTO —
Despite acknowledging that health misinformation is on the rise, “nearly all the pediatricians we surveyed agreed or strongly agreed that their patients consider them a trusted information source,” reported Elizabeth A. Gottschlich, MA, a senior research associate with the American Academy of Pediatrics, Itasca, Illinois.
These data were generated by an ongoing cohort analysis called the Pediatricians Life and Career Experience Study (PLACES). Each year, two surveys are conducted with three groups of pediatricians in this cohort. They are defined by years in which they graduated from residency (2002-2004, 2009-2011, or 2016-2018).
While the longer survey of the two captures an array of issues regarding life and practice, the shorter “checkpoint” survey addresses a high-priority topic. In 2023, it was health misinformation. The data from this survey were presented at the Pediatric Academic Societies annual meeting.
About 40% of the 2706 pediatricians who completed this particular survey (just over 65% of the participants in PLACES) were general pediatricians, 50% were pediatric subspecialists, and 10% were hospitalists.
Almost all of the survey questions were answered on a five-point Likert scale.
A Matter of Trust
According to Ms. Gottschlich, approximately 80% of pediatricians agreed or strongly agreed that misinformation is a clinical issue for them. About one third of these strongly agreed, and only 6% disagreed.
There was also strong consensus that the problem has grown worse since the start of the COVID-19 epidemic. To this statement, 70% agreed or strongly agreed and 24% did not agree or disagree. Only 4% disagreed.
However, relatively few respondents appeared to be concerned about the ability of pediatricians to address the problem of misinformation, Ms. Gottschlich reported.
When asked to respond to the statement that the “community recognizes and uses pediatricians as trusted source for health information,” 87% agreed or strongly agreed. Of the remaining, 9% did not agree or disagree, leaving just 4% that disagreed or strongly disagreed.
For a similar but slightly different question, the consensus was even greater. To the statement “patients/families in your practice seek your input as a trusted source for health information,” 94% agreed or strongly agreed.
Encountering Misinformation
The survey went on to ask pediatricians about encounters with misinformation for seven specific issues. On the five-point Likert scale, the choices ranged from a few times per year to every day.
For reproductive health, gender-affirming care, and firearm injury prevention, about 80% of respondents answered at the very low end of the scale, meaning no more than about once per month. Encounters with misinformation was slightly greater with autism; nearly one third responded that they encountered misinformation once a week or more frequently.
For all three questions regarding vaccines, the proportions climbed substantially. Of these, the COVID-19 vaccine was the most common topic of misinformation, with more than half reporting that they addressed incorrect information once a week or more. Seven percent reported this occurs daily.
Nearly 40% of pediatricians responded that they dealt with misinformation about the HPV vaccine once per week or more, while 35% reported that they encountered misinformation this frequently about routine childhood vaccines. There was a small but not necessarily trivial proportion for each of these categories of vaccine who reported that they encountered misinformation on a daily basis.
When stratified by clinical focus, the encounters varied. For the COVID-19 vaccine, general pediatricians (67%) were far more likely to report addressing misinformation on a weekly or more frequent basis than hospitalists (39%) or subspecialists (46%). They were more than twice as likely to encounter misinformation about the HPV vaccine than hospitalists or pediatric subspecialists (46%, 17%, and 19%, respectively).
When stratified by urban, suburban, or rural practice areas, differences were relatively modest. Pediatricians in urban practices were less likely to face misinformation about HPV vaccine (29% vs 44% and 48% for suburban and rural areas, respectively), while pediatricians in rural practice were more likely to face misinformation about routine childhood vaccines (60% vs 33% and 35% for urban and suburban practices, respectively).
Differences were even narrower when misinformation encounters were compared among the West, Midwest, South, and Northeast. For the threshold of once per week or more commonly, misinformation about the COVID-19 vaccine was less common in the South (50% vs 55%-58% in the other areas), while misinformation about routine childhood vaccines was more commonly encountered in the West (41% vs 32%-35% in the other areas).
A Growing Problem
The confidence among pediatricians that their knowledge is valued is reassuring, according to Ms. Gottschlich, who noted that the U.S. Surgeon General declared health misinformation a serious threat to public health in 2021, but the problem of misinformation is growing, according to several sources.
One of these sources, at least in regard to adolescent health, appears to be social media, according to a recently published review article in JAMA Pediatrics. The lead author of that article, Monica L. Wang, DSc, has dual academic appointments at the Boston University School of Public Health and Harvard University’s T.H. Chan School of Public Health, Boston. Asked for a comment on this issue, she suggested that it might not be enough to just respond to misinformation but rather might be better to develop a dialogue that will reveal misconceptions.
“Just as they screen for preventive issues like seat belt use, sunscreen, and safe sex practices, [pediatricians should integrate] questions about health misinformation into visits, which can be a natural and effective way to encourage dialogue, proactively share accurate information, and promote well-being,” she said.
Agreeing with the premise that pediatricians are a credible source of information for parents and children, Dr. Wang very much endorses the principle that “pediatricians can play a critical role in addressing health misinformation.”
Ms. Gottschlich and Dr. Wang report no potential conflicts of interest.
TORONTO —
Despite acknowledging that health misinformation is on the rise, “nearly all the pediatricians we surveyed agreed or strongly agreed that their patients consider them a trusted information source,” reported Elizabeth A. Gottschlich, MA, a senior research associate with the American Academy of Pediatrics, Itasca, Illinois.
These data were generated by an ongoing cohort analysis called the Pediatricians Life and Career Experience Study (PLACES). Each year, two surveys are conducted with three groups of pediatricians in this cohort. They are defined by years in which they graduated from residency (2002-2004, 2009-2011, or 2016-2018).
While the longer survey of the two captures an array of issues regarding life and practice, the shorter “checkpoint” survey addresses a high-priority topic. In 2023, it was health misinformation. The data from this survey were presented at the Pediatric Academic Societies annual meeting.
About 40% of the 2706 pediatricians who completed this particular survey (just over 65% of the participants in PLACES) were general pediatricians, 50% were pediatric subspecialists, and 10% were hospitalists.
Almost all of the survey questions were answered on a five-point Likert scale.
A Matter of Trust
According to Ms. Gottschlich, approximately 80% of pediatricians agreed or strongly agreed that misinformation is a clinical issue for them. About one third of these strongly agreed, and only 6% disagreed.
There was also strong consensus that the problem has grown worse since the start of the COVID-19 epidemic. To this statement, 70% agreed or strongly agreed and 24% did not agree or disagree. Only 4% disagreed.
However, relatively few respondents appeared to be concerned about the ability of pediatricians to address the problem of misinformation, Ms. Gottschlich reported.
When asked to respond to the statement that the “community recognizes and uses pediatricians as trusted source for health information,” 87% agreed or strongly agreed. Of the remaining, 9% did not agree or disagree, leaving just 4% that disagreed or strongly disagreed.
For a similar but slightly different question, the consensus was even greater. To the statement “patients/families in your practice seek your input as a trusted source for health information,” 94% agreed or strongly agreed.
Encountering Misinformation
The survey went on to ask pediatricians about encounters with misinformation for seven specific issues. On the five-point Likert scale, the choices ranged from a few times per year to every day.
For reproductive health, gender-affirming care, and firearm injury prevention, about 80% of respondents answered at the very low end of the scale, meaning no more than about once per month. Encounters with misinformation was slightly greater with autism; nearly one third responded that they encountered misinformation once a week or more frequently.
For all three questions regarding vaccines, the proportions climbed substantially. Of these, the COVID-19 vaccine was the most common topic of misinformation, with more than half reporting that they addressed incorrect information once a week or more. Seven percent reported this occurs daily.
Nearly 40% of pediatricians responded that they dealt with misinformation about the HPV vaccine once per week or more, while 35% reported that they encountered misinformation this frequently about routine childhood vaccines. There was a small but not necessarily trivial proportion for each of these categories of vaccine who reported that they encountered misinformation on a daily basis.
When stratified by clinical focus, the encounters varied. For the COVID-19 vaccine, general pediatricians (67%) were far more likely to report addressing misinformation on a weekly or more frequent basis than hospitalists (39%) or subspecialists (46%). They were more than twice as likely to encounter misinformation about the HPV vaccine than hospitalists or pediatric subspecialists (46%, 17%, and 19%, respectively).
When stratified by urban, suburban, or rural practice areas, differences were relatively modest. Pediatricians in urban practices were less likely to face misinformation about HPV vaccine (29% vs 44% and 48% for suburban and rural areas, respectively), while pediatricians in rural practice were more likely to face misinformation about routine childhood vaccines (60% vs 33% and 35% for urban and suburban practices, respectively).
Differences were even narrower when misinformation encounters were compared among the West, Midwest, South, and Northeast. For the threshold of once per week or more commonly, misinformation about the COVID-19 vaccine was less common in the South (50% vs 55%-58% in the other areas), while misinformation about routine childhood vaccines was more commonly encountered in the West (41% vs 32%-35% in the other areas).
A Growing Problem
The confidence among pediatricians that their knowledge is valued is reassuring, according to Ms. Gottschlich, who noted that the U.S. Surgeon General declared health misinformation a serious threat to public health in 2021, but the problem of misinformation is growing, according to several sources.
One of these sources, at least in regard to adolescent health, appears to be social media, according to a recently published review article in JAMA Pediatrics. The lead author of that article, Monica L. Wang, DSc, has dual academic appointments at the Boston University School of Public Health and Harvard University’s T.H. Chan School of Public Health, Boston. Asked for a comment on this issue, she suggested that it might not be enough to just respond to misinformation but rather might be better to develop a dialogue that will reveal misconceptions.
“Just as they screen for preventive issues like seat belt use, sunscreen, and safe sex practices, [pediatricians should integrate] questions about health misinformation into visits, which can be a natural and effective way to encourage dialogue, proactively share accurate information, and promote well-being,” she said.
Agreeing with the premise that pediatricians are a credible source of information for parents and children, Dr. Wang very much endorses the principle that “pediatricians can play a critical role in addressing health misinformation.”
Ms. Gottschlich and Dr. Wang report no potential conflicts of interest.
FROM PAS 2024
The Inconsistency of Preparticipation Sports Evaluations Raises Issues About Their Utility
TORONTO — There is little consistency in the elements and types of information captured in preparticipation physical evaluations (PPE) for sports among school-aged children, which is complicating efforts to determine if they have value, according to a study presented at the Pediatric Academic Societies annual meeting.
The study concept developed when Tammy Ng, MD, a third-year resident in pediatrics at the University of California, Davis, School of Medicine in Sacramento, was surprised to learn that the American Academy of Pediatrics (AAP) had been issuing a standard-of-care PPE for decades.
Dr. Ng had a long-standing interest in pediatric sports medicine and thought that if she was unfamiliar with this form, which was first developed by the AAP in the 1990s in collaboration with other professional organizations, there must be others who were unaware of this resource.
Assuming that this collaborative effort led by the AAP could serve as a standard of care, Dr. Ng evaluated whether PPEs at her own institution were capturing similar information.
In the most recent (5th) edition of the PPE, which was released in 2019 and is available online, medical history is elicited for numerous organ systems relevant to risk. The questions are not directed to any specific sport; the form does not even provide a question about which sports are being considered.
Little Consistency
In evaluating whether PPEs completed at her institution in the previous year elicited similar information, Dr. Ng sought to match 25 elements of patient history from the AAP form to questions posed in the PPEs completed at her institution, some of which had been supplied by school or sports organizations.
Of the 365 PPE forms completed at Dr. Ng’s institution that met study criteria, only 28.6% addressed all 25 elements in the AAP form (range, 0%-78%). Although more than half asked specifically about a history of respiratory symptoms, fewer than half included inquiries about cardiovascular history. There was also little consistency in the capture of information about other relevant medical history.
According to Dr. Ng, these low percentages were observed even when liberally awarding credit. For one example, she said forms that asked any question about syncope with exercise were credited with seeking information about cardiovascular health even though a yes-or-no response might not be helpful.
“We did not distinguish between syncope before or after exercise and this is relevant,” Dr. Ng said. “Syncope during exercise is more likely to be a predictor of sudden cardiac death, whereas syncope after exercise is more likely to be a vasovagal response to exertion.”
Of the 365 PPEs evaluated, about half were completed by pediatricians and half by family medicine clinicians. The average age of the children was about 14 years. Sixty-three percent were male. Only one third of the forms documented the sport for which a pre-participation screen was being submitted.
While almost all states now require PPEs for children considering participation in sports, few specify what information should be elicited, according to Dr. Ng. She further noted that no major study has shown that PPEs have any role in preventing morbidity or mortality related to sports participation.
Does Heterogeneity Negate Worth?
With such diversity across PPEs, evaluating their role is difficult. For example, with such heterogeneity among forms for the information elicited, there is no reasonable approach for testing their sensitivity in predicting medical complications.
Dr. Ng noted that school-created forms were just as likely as forms from other sources to diverge from the AAP-endorsed PPE and ignore organ systems relevant to risk of medical complications. Yet, if the answer is to use the AAP form, Dr. Ng noted that the first sentence on the form reads, “This form should be placed in the athlete’s medical file and should not be shared with schools or sports organizations.”
Although Dr. Ng acknowledged that providing completed PPEs to third parties raises questions about privacy, she questioned how the information should be used by children, parents, and sports organization administrators for discussing risks if not shared.
This concern was seconded in the discussion following Dr. Ng’s presentation.
“You might be signing off on sports participation, but is this for cheerleading or for football?” asked Daniel C. Worthington, MD, a pediatrician in private practice who has a clinical appointment at Case Western Reserve University School of Medicine, Cleveland. “This makes a huge difference when evaluating if participation is safe.”
He has no issue with completing PPEs for the goal of keeping children safe, but he focused on the inconsistency of how information is collected and distributed.
“The major question is: Does it make any difference?” said Dr. Worthington, referring to the completion of PPEs.
Another participant in the discussion that followed Dr. Ng’s presentation pointed out that the urgent care office in a mall near to his office offers a completed PPE form for a price of $20. In their recommendations, the AAP suggests PPEs be completed by the individual’s primary care physician during a well visit, according to Dr. Ng.
Dr. Ng indicated that PPEs and their purpose deserve a closer look. Based on her data, it is reasonable to assume that the priority for some – whether those requiring or those completing the form — is completing the task rather than meaningful screening of risk.
Dr. Ng and Dr. Worthington report no potential conflicts of interest.
TORONTO — There is little consistency in the elements and types of information captured in preparticipation physical evaluations (PPE) for sports among school-aged children, which is complicating efforts to determine if they have value, according to a study presented at the Pediatric Academic Societies annual meeting.
The study concept developed when Tammy Ng, MD, a third-year resident in pediatrics at the University of California, Davis, School of Medicine in Sacramento, was surprised to learn that the American Academy of Pediatrics (AAP) had been issuing a standard-of-care PPE for decades.
Dr. Ng had a long-standing interest in pediatric sports medicine and thought that if she was unfamiliar with this form, which was first developed by the AAP in the 1990s in collaboration with other professional organizations, there must be others who were unaware of this resource.
Assuming that this collaborative effort led by the AAP could serve as a standard of care, Dr. Ng evaluated whether PPEs at her own institution were capturing similar information.
In the most recent (5th) edition of the PPE, which was released in 2019 and is available online, medical history is elicited for numerous organ systems relevant to risk. The questions are not directed to any specific sport; the form does not even provide a question about which sports are being considered.
Little Consistency
In evaluating whether PPEs completed at her institution in the previous year elicited similar information, Dr. Ng sought to match 25 elements of patient history from the AAP form to questions posed in the PPEs completed at her institution, some of which had been supplied by school or sports organizations.
Of the 365 PPE forms completed at Dr. Ng’s institution that met study criteria, only 28.6% addressed all 25 elements in the AAP form (range, 0%-78%). Although more than half asked specifically about a history of respiratory symptoms, fewer than half included inquiries about cardiovascular history. There was also little consistency in the capture of information about other relevant medical history.
According to Dr. Ng, these low percentages were observed even when liberally awarding credit. For one example, she said forms that asked any question about syncope with exercise were credited with seeking information about cardiovascular health even though a yes-or-no response might not be helpful.
“We did not distinguish between syncope before or after exercise and this is relevant,” Dr. Ng said. “Syncope during exercise is more likely to be a predictor of sudden cardiac death, whereas syncope after exercise is more likely to be a vasovagal response to exertion.”
Of the 365 PPEs evaluated, about half were completed by pediatricians and half by family medicine clinicians. The average age of the children was about 14 years. Sixty-three percent were male. Only one third of the forms documented the sport for which a pre-participation screen was being submitted.
While almost all states now require PPEs for children considering participation in sports, few specify what information should be elicited, according to Dr. Ng. She further noted that no major study has shown that PPEs have any role in preventing morbidity or mortality related to sports participation.
Does Heterogeneity Negate Worth?
With such diversity across PPEs, evaluating their role is difficult. For example, with such heterogeneity among forms for the information elicited, there is no reasonable approach for testing their sensitivity in predicting medical complications.
Dr. Ng noted that school-created forms were just as likely as forms from other sources to diverge from the AAP-endorsed PPE and ignore organ systems relevant to risk of medical complications. Yet, if the answer is to use the AAP form, Dr. Ng noted that the first sentence on the form reads, “This form should be placed in the athlete’s medical file and should not be shared with schools or sports organizations.”
Although Dr. Ng acknowledged that providing completed PPEs to third parties raises questions about privacy, she questioned how the information should be used by children, parents, and sports organization administrators for discussing risks if not shared.
This concern was seconded in the discussion following Dr. Ng’s presentation.
“You might be signing off on sports participation, but is this for cheerleading or for football?” asked Daniel C. Worthington, MD, a pediatrician in private practice who has a clinical appointment at Case Western Reserve University School of Medicine, Cleveland. “This makes a huge difference when evaluating if participation is safe.”
He has no issue with completing PPEs for the goal of keeping children safe, but he focused on the inconsistency of how information is collected and distributed.
“The major question is: Does it make any difference?” said Dr. Worthington, referring to the completion of PPEs.
Another participant in the discussion that followed Dr. Ng’s presentation pointed out that the urgent care office in a mall near to his office offers a completed PPE form for a price of $20. In their recommendations, the AAP suggests PPEs be completed by the individual’s primary care physician during a well visit, according to Dr. Ng.
Dr. Ng indicated that PPEs and their purpose deserve a closer look. Based on her data, it is reasonable to assume that the priority for some – whether those requiring or those completing the form — is completing the task rather than meaningful screening of risk.
Dr. Ng and Dr. Worthington report no potential conflicts of interest.
TORONTO — There is little consistency in the elements and types of information captured in preparticipation physical evaluations (PPE) for sports among school-aged children, which is complicating efforts to determine if they have value, according to a study presented at the Pediatric Academic Societies annual meeting.
The study concept developed when Tammy Ng, MD, a third-year resident in pediatrics at the University of California, Davis, School of Medicine in Sacramento, was surprised to learn that the American Academy of Pediatrics (AAP) had been issuing a standard-of-care PPE for decades.
Dr. Ng had a long-standing interest in pediatric sports medicine and thought that if she was unfamiliar with this form, which was first developed by the AAP in the 1990s in collaboration with other professional organizations, there must be others who were unaware of this resource.
Assuming that this collaborative effort led by the AAP could serve as a standard of care, Dr. Ng evaluated whether PPEs at her own institution were capturing similar information.
In the most recent (5th) edition of the PPE, which was released in 2019 and is available online, medical history is elicited for numerous organ systems relevant to risk. The questions are not directed to any specific sport; the form does not even provide a question about which sports are being considered.
Little Consistency
In evaluating whether PPEs completed at her institution in the previous year elicited similar information, Dr. Ng sought to match 25 elements of patient history from the AAP form to questions posed in the PPEs completed at her institution, some of which had been supplied by school or sports organizations.
Of the 365 PPE forms completed at Dr. Ng’s institution that met study criteria, only 28.6% addressed all 25 elements in the AAP form (range, 0%-78%). Although more than half asked specifically about a history of respiratory symptoms, fewer than half included inquiries about cardiovascular history. There was also little consistency in the capture of information about other relevant medical history.
According to Dr. Ng, these low percentages were observed even when liberally awarding credit. For one example, she said forms that asked any question about syncope with exercise were credited with seeking information about cardiovascular health even though a yes-or-no response might not be helpful.
“We did not distinguish between syncope before or after exercise and this is relevant,” Dr. Ng said. “Syncope during exercise is more likely to be a predictor of sudden cardiac death, whereas syncope after exercise is more likely to be a vasovagal response to exertion.”
Of the 365 PPEs evaluated, about half were completed by pediatricians and half by family medicine clinicians. The average age of the children was about 14 years. Sixty-three percent were male. Only one third of the forms documented the sport for which a pre-participation screen was being submitted.
While almost all states now require PPEs for children considering participation in sports, few specify what information should be elicited, according to Dr. Ng. She further noted that no major study has shown that PPEs have any role in preventing morbidity or mortality related to sports participation.
Does Heterogeneity Negate Worth?
With such diversity across PPEs, evaluating their role is difficult. For example, with such heterogeneity among forms for the information elicited, there is no reasonable approach for testing their sensitivity in predicting medical complications.
Dr. Ng noted that school-created forms were just as likely as forms from other sources to diverge from the AAP-endorsed PPE and ignore organ systems relevant to risk of medical complications. Yet, if the answer is to use the AAP form, Dr. Ng noted that the first sentence on the form reads, “This form should be placed in the athlete’s medical file and should not be shared with schools or sports organizations.”
Although Dr. Ng acknowledged that providing completed PPEs to third parties raises questions about privacy, she questioned how the information should be used by children, parents, and sports organization administrators for discussing risks if not shared.
This concern was seconded in the discussion following Dr. Ng’s presentation.
“You might be signing off on sports participation, but is this for cheerleading or for football?” asked Daniel C. Worthington, MD, a pediatrician in private practice who has a clinical appointment at Case Western Reserve University School of Medicine, Cleveland. “This makes a huge difference when evaluating if participation is safe.”
He has no issue with completing PPEs for the goal of keeping children safe, but he focused on the inconsistency of how information is collected and distributed.
“The major question is: Does it make any difference?” said Dr. Worthington, referring to the completion of PPEs.
Another participant in the discussion that followed Dr. Ng’s presentation pointed out that the urgent care office in a mall near to his office offers a completed PPE form for a price of $20. In their recommendations, the AAP suggests PPEs be completed by the individual’s primary care physician during a well visit, according to Dr. Ng.
Dr. Ng indicated that PPEs and their purpose deserve a closer look. Based on her data, it is reasonable to assume that the priority for some – whether those requiring or those completing the form — is completing the task rather than meaningful screening of risk.
Dr. Ng and Dr. Worthington report no potential conflicts of interest.
FROM PAS 2024