Pediatric News

Amplified by the childhood obesity epidemic, primary hypertension is now the leading type of pediatric hypertension, especially in adolescence, yet the condition is “underrecognized,” the American Heart Association said in a new scientific statement.

“Children can have secondary hypertension that is caused by an underlying condition such as chronic kidney disease, endocrine disorders, cardiac anomalies, and some syndromes. However, primary hypertension is now recognized as the most common type of hypertension in childhood,” Bonita Falkner, MD, chair of the writing group and emeritus professor of medicine and pediatrics, Thomas Jefferson University, Philadelphia, said in an interview.

And hypertensive children are “highly likely” to become hypertensive adults and to have measurable target organ injury, particularly left ventricular hypertrophy and vascular stiffening, the writing group noted. 

The AHA statement on primary pediatric hypertension was published online in Hypertension.

Primary or essential hypertension occurs in up to 5% of children and adolescents in the United States and other countries.

The American Academy of Pediatrics (AAP), European Society of Hypertension and Hypertension Canada all define hypertension as repeated BP readings at or above the 95th percentile for children, but the thresholds differ by age.

The AAP adopts 130/80 mm Hg starting at age 13 years; the European Society of Hypertension adopts 140/90 mm Hg starting at age 16 years; and Hypertension Canada adopts 120/80 mm Hg for those aged 6-11 years and 130/85 mm Hg for those aged 12-17 years.

Adolescents entering adulthood with a BP < 120/80 mm Hg is an optimal goal, the writing group advised.

They recommend that health care professionals be trained on evidence-based methods to obtain accurate and reliable BP values with either auscultatory or oscillometric methods.

When the initial BP measurement is abnormal, repeat measurement by auscultation is recommended, within the same visit if possible, and then within weeks if the screening BP is hypertensive, or months if the screening BP is elevated.

Because BP levels are variable, even within a single visit, “best practice” is to obtain up to three BP measurements and to record the average of the latter two measurements unless the first measurement is normal, the writing group said. Further confirmation of diagnosis of hypertension can be obtained with 24-hour ambulatory BP monitoring (ABPM).

“Primary hypertension in youth is difficult to recognize in asymptomatic, otherwise healthy youth. There is now evidence that children and adolescents with primary hypertension may also have cardiac and vascular injury due to the hypertension,” Dr. Falkner told this news organization.

“If not identified and treated, the condition can progress to hypertension in young adulthood with heightened risk of premature cardiovascular events,” Dr. Falkner said.

The writing group said “primordial prevention” is an important public health goal because a population with lower BP will have fewer comorbidities related to hypertension and CVD.

Modifiable risk factors for primary hypertension in childhood include obesity, physical inactivity and poor diet/nutrition, disturbed sleep patterns, and environmental stress.

A healthy lifestyle in childhood – including eating healthy food, encouraging physical activity that leads to improved physical fitness and healthy sleep, and avoiding the development of obesity – may help mitigate the risk of hypertension in childhood, the writing group noted.  

Looking ahead, they said efforts to improve recognition and diagnosis of high BP in children, as well as clinical trials to evaluate medical treatment and recommend public health initiatives, are all vital to combat rising rates of primary hypertension in children.

This scientific statement was prepared by the volunteer writing group on behalf of the American Heart Association’s Council on Hypertension, the Council on Lifelong Congenital Heart Disease and Heart Health in the Young, the Council on Kidney in Cardiovascular Disease, the Council on Lifestyle and Cardiometabolic Health, and the Council on Cardiovascular and Stroke Nursing.
 

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

Amplified by the childhood obesity epidemic, primary hypertension is now the leading type of pediatric hypertension, especially in adolescence, yet the condition is “underrecognized,” the American Heart Association said in a new scientific statement.

“Children can have secondary hypertension that is caused by an underlying condition such as chronic kidney disease, endocrine disorders, cardiac anomalies, and some syndromes. However, primary hypertension is now recognized as the most common type of hypertension in childhood,” Bonita Falkner, MD, chair of the writing group and emeritus professor of medicine and pediatrics, Thomas Jefferson University, Philadelphia, said in an interview.

And hypertensive children are “highly likely” to become hypertensive adults and to have measurable target organ injury, particularly left ventricular hypertrophy and vascular stiffening, the writing group noted. 

The AHA statement on primary pediatric hypertension was published online in Hypertension.

Primary or essential hypertension occurs in up to 5% of children and adolescents in the United States and other countries.

The American Academy of Pediatrics (AAP), European Society of Hypertension and Hypertension Canada all define hypertension as repeated BP readings at or above the 95th percentile for children, but the thresholds differ by age.

The AAP adopts 130/80 mm Hg starting at age 13 years; the European Society of Hypertension adopts 140/90 mm Hg starting at age 16 years; and Hypertension Canada adopts 120/80 mm Hg for those aged 6-11 years and 130/85 mm Hg for those aged 12-17 years.

Adolescents entering adulthood with a BP < 120/80 mm Hg is an optimal goal, the writing group advised.

They recommend that health care professionals be trained on evidence-based methods to obtain accurate and reliable BP values with either auscultatory or oscillometric methods.

When the initial BP measurement is abnormal, repeat measurement by auscultation is recommended, within the same visit if possible, and then within weeks if the screening BP is hypertensive, or months if the screening BP is elevated.

Because BP levels are variable, even within a single visit, “best practice” is to obtain up to three BP measurements and to record the average of the latter two measurements unless the first measurement is normal, the writing group said. Further confirmation of diagnosis of hypertension can be obtained with 24-hour ambulatory BP monitoring (ABPM).

“Primary hypertension in youth is difficult to recognize in asymptomatic, otherwise healthy youth. There is now evidence that children and adolescents with primary hypertension may also have cardiac and vascular injury due to the hypertension,” Dr. Falkner told this news organization.

“If not identified and treated, the condition can progress to hypertension in young adulthood with heightened risk of premature cardiovascular events,” Dr. Falkner said.

The writing group said “primordial prevention” is an important public health goal because a population with lower BP will have fewer comorbidities related to hypertension and CVD.

Modifiable risk factors for primary hypertension in childhood include obesity, physical inactivity and poor diet/nutrition, disturbed sleep patterns, and environmental stress.

A healthy lifestyle in childhood – including eating healthy food, encouraging physical activity that leads to improved physical fitness and healthy sleep, and avoiding the development of obesity – may help mitigate the risk of hypertension in childhood, the writing group noted.  

Looking ahead, they said efforts to improve recognition and diagnosis of high BP in children, as well as clinical trials to evaluate medical treatment and recommend public health initiatives, are all vital to combat rising rates of primary hypertension in children.

This scientific statement was prepared by the volunteer writing group on behalf of the American Heart Association’s Council on Hypertension, the Council on Lifelong Congenital Heart Disease and Heart Health in the Young, the Council on Kidney in Cardiovascular Disease, the Council on Lifestyle and Cardiometabolic Health, and the Council on Cardiovascular and Stroke Nursing.
 

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

Amplified by the childhood obesity epidemic, primary hypertension is now the leading type of pediatric hypertension, especially in adolescence, yet the condition is “underrecognized,” the American Heart Association said in a new scientific statement.

“Children can have secondary hypertension that is caused by an underlying condition such as chronic kidney disease, endocrine disorders, cardiac anomalies, and some syndromes. However, primary hypertension is now recognized as the most common type of hypertension in childhood,” Bonita Falkner, MD, chair of the writing group and emeritus professor of medicine and pediatrics, Thomas Jefferson University, Philadelphia, said in an interview.

And hypertensive children are “highly likely” to become hypertensive adults and to have measurable target organ injury, particularly left ventricular hypertrophy and vascular stiffening, the writing group noted. 

The AHA statement on primary pediatric hypertension was published online in Hypertension.

Primary or essential hypertension occurs in up to 5% of children and adolescents in the United States and other countries.

The American Academy of Pediatrics (AAP), European Society of Hypertension and Hypertension Canada all define hypertension as repeated BP readings at or above the 95th percentile for children, but the thresholds differ by age.

The AAP adopts 130/80 mm Hg starting at age 13 years; the European Society of Hypertension adopts 140/90 mm Hg starting at age 16 years; and Hypertension Canada adopts 120/80 mm Hg for those aged 6-11 years and 130/85 mm Hg for those aged 12-17 years.

Adolescents entering adulthood with a BP < 120/80 mm Hg is an optimal goal, the writing group advised.

They recommend that health care professionals be trained on evidence-based methods to obtain accurate and reliable BP values with either auscultatory or oscillometric methods.

When the initial BP measurement is abnormal, repeat measurement by auscultation is recommended, within the same visit if possible, and then within weeks if the screening BP is hypertensive, or months if the screening BP is elevated.

Because BP levels are variable, even within a single visit, “best practice” is to obtain up to three BP measurements and to record the average of the latter two measurements unless the first measurement is normal, the writing group said. Further confirmation of diagnosis of hypertension can be obtained with 24-hour ambulatory BP monitoring (ABPM).

“Primary hypertension in youth is difficult to recognize in asymptomatic, otherwise healthy youth. There is now evidence that children and adolescents with primary hypertension may also have cardiac and vascular injury due to the hypertension,” Dr. Falkner told this news organization.

“If not identified and treated, the condition can progress to hypertension in young adulthood with heightened risk of premature cardiovascular events,” Dr. Falkner said.

The writing group said “primordial prevention” is an important public health goal because a population with lower BP will have fewer comorbidities related to hypertension and CVD.

Modifiable risk factors for primary hypertension in childhood include obesity, physical inactivity and poor diet/nutrition, disturbed sleep patterns, and environmental stress.

A healthy lifestyle in childhood – including eating healthy food, encouraging physical activity that leads to improved physical fitness and healthy sleep, and avoiding the development of obesity – may help mitigate the risk of hypertension in childhood, the writing group noted.  

Looking ahead, they said efforts to improve recognition and diagnosis of high BP in children, as well as clinical trials to evaluate medical treatment and recommend public health initiatives, are all vital to combat rising rates of primary hypertension in children.

This scientific statement was prepared by the volunteer writing group on behalf of the American Heart Association’s Council on Hypertension, the Council on Lifelong Congenital Heart Disease and Heart Health in the Young, the Council on Kidney in Cardiovascular Disease, the Council on Lifestyle and Cardiometabolic Health, and the Council on Cardiovascular and Stroke Nursing.
 

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

NEW ORLEANS – The sociodemographic characteristics of Black and Hispanic children with systemic lupus erythematosus (SLE) appear to play a strong role in influencing the severity of disease in these patients, according to two studies presented at the Pediatric Rheumatology Symposium.

One study showed an association between multiple determinants of health and disease severity among children seen in a large Texas city, and a separate descriptive cross-sectional cohort study of predominantly Black children at two centers in Mississippi and Alabama reinforced the finding of greater severity of disease and social hardships among this racial group.

The findings from both studies supplement existing evidence that the prevalence of childhood-onset SLE is greater among Black and Hispanic children.

“Several demographic and social determinants of health parameters influenced disease severity at levels that reached statistical significance, including insurance status, race/ethnicity, referral source, PCP [primary care provider] availability, primary language, and transportation needs,” Emily Beil, MD, a pediatric rheumatologist at Texas Children’s Hospital in Houston, told attendees at the conference, which was sponsored by the American College of Rheumatology. Her team’s goal, she said, was to “better understand our patient population and social disparities that contribute to disease severity.”

Dr. Beil and her colleagues conducted a retrospective review of 136 children who had been diagnosed with childhood-onset SLE between January 2018 and May 2022 at Texas Children’s Hospital. Only children who were younger than 18 years at the time of diagnosis at Texas Children’s were included. The analysis considered demographics, clinical characteristics, insurance status, social work consultation, access to a primary care provider, transportation needs, primary language, and other parameters related to social determinants of health.

The average age of the patients was 13 years, and most were girls (82%). Just over half were Hispanic (53%), and just over a quarter were Black (26%). Half had Medicaid or participated in the Children’s Health Insurance Program (CHIP), and 1 in 10 were uninsured (10%). Half the diagnoses were made during an inpatient admission; 36% were made on the floor, and 14% were made in the intensive care unit (ICU).

The average Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score was 12.5, and 48.5% of patients had severe disease, indicated by a score of at least 12. Only two in three children were documented as having a primary care physician (66%), and 32% preferred a language other than English. Most of the children (80%) had a social work consult.

Black and biracial children had higher SLEDAI scores at presentation. Non-Hispanic White children were less likely to have a social work consult, compared with other racial/ethnic groups (P = .01 for both). Central nervous system involvement was most prevalent among Black patients (P = .004). Cyclophosphamide was used most often for Black and biracial patients.

Uninsured patients were most likely to be diagnosed on an inpatient floor. The highest proportion of ICU admissions was among patients insured by Medicaid (P = .034). Average SLEDAI scores were highest among uninsured patients, followed by Medicaid patients. More than half of the patients who did not have insurance lacked access to a regular primary care provider, compared with 12% of Medicaid patients and 7% of privately insured patients (P = .001). All the uninsured patients had transportation needs, which was a significantly higher rate than among those with Medicaid (13%) or private insurance (15%) (P = .001). The highest percentage of social work consults was among patients who were insured by Medicaid or were without insurance (P = .001).
 

Salient demographics and clinical features

In the second presentation, Anita Dhanrajani, MD, assistant professor of pediatrics at the University of Mississippi Medical Center in Jackson, began by noting that Alabama and Mississippi are ranked in the top 10 states for the highest poverty rate: Mississippi is No. 1, and Alabama is No. 7. Further, 40% of children in Mississippi and 29% of children in Alabama are of African American ancestry, she said.

“So, we know that this population that we’re dealing with has several high-risk factors that can lead them to have poor outcomes, and yet, we haven’t really ever characterized their clinical features or their social demographic features,” Dr. Dhanrajani told attendees. “My hope is that with this very miniscule first step, we’re able to move towards solutions to decrease health care disparities in this population.”

She presented findings regarding the first of three aims in the study, which was to describe the baseline clinical, demographic, and socioeconomic profiles of childhood lupus patients at the two centers. The two other aims were to examine genetic factors potentially linked to poor outcomes in the cohort and to assess the mental health status of the population.

The study relied on a retrospective chart review for the 17 patients at the University of Mississippi Medical Center and on Childhood Arthritis and Rheumatology Research Alliance registry data for the 19 patients at the University of Alabama at Birmingham. Most of the patients (86%) were female, Black (78%), and insured by Medicaid (64%). The average age at diagnosis was 13 years. Most (83%) also lived in a ZIP code that met the criteria for a medium-high or high Social Vulnerability Index. The children had to travel an average 75 miles to see a rheumatologist, compared with the national average of 43 miles.

At diagnosis, their average Systemic Lupus International Collaborating Clinics (SLICC) score was 8.8, their average American College of Rheumatology score was 5.2, and their average SLEDAI score was 12.1 – the latter was substantially higher than the average 3.1 score in a multiethnic Canadian cohort (the 1000 Canadian Faces of Lupus Study) with 10% Black children (P < .00001). The SLEDAI score dropped to 6.8 at 6 months and to 4 at 1 year. Nearly half (47%) had a SLICC Damage Index (SDI) greater than 0, and one-third had an SDI of 2 or greater, compared with 16% and 7%, respectively, reported in other recent studies (P < .0001 for both).

“These disparities are very difficult to investigate in terms of causal relationships and [are] likely to be very modifiable,” Coziana Ciurtin, MD, PhD, associate professor of rheumatology at University College London, told this news organization. “I think the socioeconomic status, the level of education, poverty, [type of] medical insurance, and probably genetic variants are all underpinning the presentation, damage, or disease activity being very high, and also organ involvement,” such as the greater CNS involvement seen in non-White patients.

Being mindful of these risk profiles can help doctors in asking about patients’ support at home and their families’ education, beliefs, and cultural practices, Dr. Ciurtin added. “Helping them to engage and be involved in decision-making is probably the most important” aspect of learning this information about families, she said.

Collecting this information should not be the sole responsibility of the physician, added Eve Smith, PhD, MBCHB, an academic clinical lecturer at the University of Liverpool, England, who attended the presentations. Dr. Smith noted a discussion in a work group during the previous day of the conference concerning questionnaires for screening patients regarding the need for social services and for identifying areas in which patients and their families were having difficulties.

“Obviously, if you’re going to do that, you have to have access to someone who can actually help to deal with that. Some hospitals have patient navigators that can help, for example, with a food security issue to highlight resources within the community, so it’s not all on the doctor,” Dr. Smith said. “To really make a difference in this area, it can’t just be down to the doctor. There needs to be social care, there needs to be community-based interventions and things to do about it. Doctors can help identify these patients, or maybe somebody in the [medical] team can help with that, but there needs to be an intervention. Otherwise, you’re left with this problem without a solution that you can’t do anything about.”

The researchers did not note any external funding for either study. Dr. Beil, Dr. Dhanrajani, Dr. Smith, and Dr. Ciurtin reported no relevant financial relationships.

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

NEW ORLEANS – The sociodemographic characteristics of Black and Hispanic children with systemic lupus erythematosus (SLE) appear to play a strong role in influencing the severity of disease in these patients, according to two studies presented at the Pediatric Rheumatology Symposium.

One study showed an association between multiple determinants of health and disease severity among children seen in a large Texas city, and a separate descriptive cross-sectional cohort study of predominantly Black children at two centers in Mississippi and Alabama reinforced the finding of greater severity of disease and social hardships among this racial group.

The findings from both studies supplement existing evidence that the prevalence of childhood-onset SLE is greater among Black and Hispanic children.

“Several demographic and social determinants of health parameters influenced disease severity at levels that reached statistical significance, including insurance status, race/ethnicity, referral source, PCP [primary care provider] availability, primary language, and transportation needs,” Emily Beil, MD, a pediatric rheumatologist at Texas Children’s Hospital in Houston, told attendees at the conference, which was sponsored by the American College of Rheumatology. Her team’s goal, she said, was to “better understand our patient population and social disparities that contribute to disease severity.”

Dr. Beil and her colleagues conducted a retrospective review of 136 children who had been diagnosed with childhood-onset SLE between January 2018 and May 2022 at Texas Children’s Hospital. Only children who were younger than 18 years at the time of diagnosis at Texas Children’s were included. The analysis considered demographics, clinical characteristics, insurance status, social work consultation, access to a primary care provider, transportation needs, primary language, and other parameters related to social determinants of health.

The average age of the patients was 13 years, and most were girls (82%). Just over half were Hispanic (53%), and just over a quarter were Black (26%). Half had Medicaid or participated in the Children’s Health Insurance Program (CHIP), and 1 in 10 were uninsured (10%). Half the diagnoses were made during an inpatient admission; 36% were made on the floor, and 14% were made in the intensive care unit (ICU).

The average Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score was 12.5, and 48.5% of patients had severe disease, indicated by a score of at least 12. Only two in three children were documented as having a primary care physician (66%), and 32% preferred a language other than English. Most of the children (80%) had a social work consult.

Black and biracial children had higher SLEDAI scores at presentation. Non-Hispanic White children were less likely to have a social work consult, compared with other racial/ethnic groups (P = .01 for both). Central nervous system involvement was most prevalent among Black patients (P = .004). Cyclophosphamide was used most often for Black and biracial patients.

Uninsured patients were most likely to be diagnosed on an inpatient floor. The highest proportion of ICU admissions was among patients insured by Medicaid (P = .034). Average SLEDAI scores were highest among uninsured patients, followed by Medicaid patients. More than half of the patients who did not have insurance lacked access to a regular primary care provider, compared with 12% of Medicaid patients and 7% of privately insured patients (P = .001). All the uninsured patients had transportation needs, which was a significantly higher rate than among those with Medicaid (13%) or private insurance (15%) (P = .001). The highest percentage of social work consults was among patients who were insured by Medicaid or were without insurance (P = .001).
 

Salient demographics and clinical features

In the second presentation, Anita Dhanrajani, MD, assistant professor of pediatrics at the University of Mississippi Medical Center in Jackson, began by noting that Alabama and Mississippi are ranked in the top 10 states for the highest poverty rate: Mississippi is No. 1, and Alabama is No. 7. Further, 40% of children in Mississippi and 29% of children in Alabama are of African American ancestry, she said.

“So, we know that this population that we’re dealing with has several high-risk factors that can lead them to have poor outcomes, and yet, we haven’t really ever characterized their clinical features or their social demographic features,” Dr. Dhanrajani told attendees. “My hope is that with this very miniscule first step, we’re able to move towards solutions to decrease health care disparities in this population.”

She presented findings regarding the first of three aims in the study, which was to describe the baseline clinical, demographic, and socioeconomic profiles of childhood lupus patients at the two centers. The two other aims were to examine genetic factors potentially linked to poor outcomes in the cohort and to assess the mental health status of the population.

The study relied on a retrospective chart review for the 17 patients at the University of Mississippi Medical Center and on Childhood Arthritis and Rheumatology Research Alliance registry data for the 19 patients at the University of Alabama at Birmingham. Most of the patients (86%) were female, Black (78%), and insured by Medicaid (64%). The average age at diagnosis was 13 years. Most (83%) also lived in a ZIP code that met the criteria for a medium-high or high Social Vulnerability Index. The children had to travel an average 75 miles to see a rheumatologist, compared with the national average of 43 miles.

At diagnosis, their average Systemic Lupus International Collaborating Clinics (SLICC) score was 8.8, their average American College of Rheumatology score was 5.2, and their average SLEDAI score was 12.1 – the latter was substantially higher than the average 3.1 score in a multiethnic Canadian cohort (the 1000 Canadian Faces of Lupus Study) with 10% Black children (P < .00001). The SLEDAI score dropped to 6.8 at 6 months and to 4 at 1 year. Nearly half (47%) had a SLICC Damage Index (SDI) greater than 0, and one-third had an SDI of 2 or greater, compared with 16% and 7%, respectively, reported in other recent studies (P < .0001 for both).

“These disparities are very difficult to investigate in terms of causal relationships and [are] likely to be very modifiable,” Coziana Ciurtin, MD, PhD, associate professor of rheumatology at University College London, told this news organization. “I think the socioeconomic status, the level of education, poverty, [type of] medical insurance, and probably genetic variants are all underpinning the presentation, damage, or disease activity being very high, and also organ involvement,” such as the greater CNS involvement seen in non-White patients.

Being mindful of these risk profiles can help doctors in asking about patients’ support at home and their families’ education, beliefs, and cultural practices, Dr. Ciurtin added. “Helping them to engage and be involved in decision-making is probably the most important” aspect of learning this information about families, she said.

Collecting this information should not be the sole responsibility of the physician, added Eve Smith, PhD, MBCHB, an academic clinical lecturer at the University of Liverpool, England, who attended the presentations. Dr. Smith noted a discussion in a work group during the previous day of the conference concerning questionnaires for screening patients regarding the need for social services and for identifying areas in which patients and their families were having difficulties.

“Obviously, if you’re going to do that, you have to have access to someone who can actually help to deal with that. Some hospitals have patient navigators that can help, for example, with a food security issue to highlight resources within the community, so it’s not all on the doctor,” Dr. Smith said. “To really make a difference in this area, it can’t just be down to the doctor. There needs to be social care, there needs to be community-based interventions and things to do about it. Doctors can help identify these patients, or maybe somebody in the [medical] team can help with that, but there needs to be an intervention. Otherwise, you’re left with this problem without a solution that you can’t do anything about.”

The researchers did not note any external funding for either study. Dr. Beil, Dr. Dhanrajani, Dr. Smith, and Dr. Ciurtin reported no relevant financial relationships.

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

NEW ORLEANS – The sociodemographic characteristics of Black and Hispanic children with systemic lupus erythematosus (SLE) appear to play a strong role in influencing the severity of disease in these patients, according to two studies presented at the Pediatric Rheumatology Symposium.

One study showed an association between multiple determinants of health and disease severity among children seen in a large Texas city, and a separate descriptive cross-sectional cohort study of predominantly Black children at two centers in Mississippi and Alabama reinforced the finding of greater severity of disease and social hardships among this racial group.

The findings from both studies supplement existing evidence that the prevalence of childhood-onset SLE is greater among Black and Hispanic children.

“Several demographic and social determinants of health parameters influenced disease severity at levels that reached statistical significance, including insurance status, race/ethnicity, referral source, PCP [primary care provider] availability, primary language, and transportation needs,” Emily Beil, MD, a pediatric rheumatologist at Texas Children’s Hospital in Houston, told attendees at the conference, which was sponsored by the American College of Rheumatology. Her team’s goal, she said, was to “better understand our patient population and social disparities that contribute to disease severity.”

Dr. Beil and her colleagues conducted a retrospective review of 136 children who had been diagnosed with childhood-onset SLE between January 2018 and May 2022 at Texas Children’s Hospital. Only children who were younger than 18 years at the time of diagnosis at Texas Children’s were included. The analysis considered demographics, clinical characteristics, insurance status, social work consultation, access to a primary care provider, transportation needs, primary language, and other parameters related to social determinants of health.

The average age of the patients was 13 years, and most were girls (82%). Just over half were Hispanic (53%), and just over a quarter were Black (26%). Half had Medicaid or participated in the Children’s Health Insurance Program (CHIP), and 1 in 10 were uninsured (10%). Half the diagnoses were made during an inpatient admission; 36% were made on the floor, and 14% were made in the intensive care unit (ICU).

The average Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score was 12.5, and 48.5% of patients had severe disease, indicated by a score of at least 12. Only two in three children were documented as having a primary care physician (66%), and 32% preferred a language other than English. Most of the children (80%) had a social work consult.

Black and biracial children had higher SLEDAI scores at presentation. Non-Hispanic White children were less likely to have a social work consult, compared with other racial/ethnic groups (P = .01 for both). Central nervous system involvement was most prevalent among Black patients (P = .004). Cyclophosphamide was used most often for Black and biracial patients.

Uninsured patients were most likely to be diagnosed on an inpatient floor. The highest proportion of ICU admissions was among patients insured by Medicaid (P = .034). Average SLEDAI scores were highest among uninsured patients, followed by Medicaid patients. More than half of the patients who did not have insurance lacked access to a regular primary care provider, compared with 12% of Medicaid patients and 7% of privately insured patients (P = .001). All the uninsured patients had transportation needs, which was a significantly higher rate than among those with Medicaid (13%) or private insurance (15%) (P = .001). The highest percentage of social work consults was among patients who were insured by Medicaid or were without insurance (P = .001).
 

Salient demographics and clinical features

In the second presentation, Anita Dhanrajani, MD, assistant professor of pediatrics at the University of Mississippi Medical Center in Jackson, began by noting that Alabama and Mississippi are ranked in the top 10 states for the highest poverty rate: Mississippi is No. 1, and Alabama is No. 7. Further, 40% of children in Mississippi and 29% of children in Alabama are of African American ancestry, she said.

“So, we know that this population that we’re dealing with has several high-risk factors that can lead them to have poor outcomes, and yet, we haven’t really ever characterized their clinical features or their social demographic features,” Dr. Dhanrajani told attendees. “My hope is that with this very miniscule first step, we’re able to move towards solutions to decrease health care disparities in this population.”

She presented findings regarding the first of three aims in the study, which was to describe the baseline clinical, demographic, and socioeconomic profiles of childhood lupus patients at the two centers. The two other aims were to examine genetic factors potentially linked to poor outcomes in the cohort and to assess the mental health status of the population.

The study relied on a retrospective chart review for the 17 patients at the University of Mississippi Medical Center and on Childhood Arthritis and Rheumatology Research Alliance registry data for the 19 patients at the University of Alabama at Birmingham. Most of the patients (86%) were female, Black (78%), and insured by Medicaid (64%). The average age at diagnosis was 13 years. Most (83%) also lived in a ZIP code that met the criteria for a medium-high or high Social Vulnerability Index. The children had to travel an average 75 miles to see a rheumatologist, compared with the national average of 43 miles.

At diagnosis, their average Systemic Lupus International Collaborating Clinics (SLICC) score was 8.8, their average American College of Rheumatology score was 5.2, and their average SLEDAI score was 12.1 – the latter was substantially higher than the average 3.1 score in a multiethnic Canadian cohort (the 1000 Canadian Faces of Lupus Study) with 10% Black children (P < .00001). The SLEDAI score dropped to 6.8 at 6 months and to 4 at 1 year. Nearly half (47%) had a SLICC Damage Index (SDI) greater than 0, and one-third had an SDI of 2 or greater, compared with 16% and 7%, respectively, reported in other recent studies (P < .0001 for both).

“These disparities are very difficult to investigate in terms of causal relationships and [are] likely to be very modifiable,” Coziana Ciurtin, MD, PhD, associate professor of rheumatology at University College London, told this news organization. “I think the socioeconomic status, the level of education, poverty, [type of] medical insurance, and probably genetic variants are all underpinning the presentation, damage, or disease activity being very high, and also organ involvement,” such as the greater CNS involvement seen in non-White patients.

Being mindful of these risk profiles can help doctors in asking about patients’ support at home and their families’ education, beliefs, and cultural practices, Dr. Ciurtin added. “Helping them to engage and be involved in decision-making is probably the most important” aspect of learning this information about families, she said.

Collecting this information should not be the sole responsibility of the physician, added Eve Smith, PhD, MBCHB, an academic clinical lecturer at the University of Liverpool, England, who attended the presentations. Dr. Smith noted a discussion in a work group during the previous day of the conference concerning questionnaires for screening patients regarding the need for social services and for identifying areas in which patients and their families were having difficulties.

“Obviously, if you’re going to do that, you have to have access to someone who can actually help to deal with that. Some hospitals have patient navigators that can help, for example, with a food security issue to highlight resources within the community, so it’s not all on the doctor,” Dr. Smith said. “To really make a difference in this area, it can’t just be down to the doctor. There needs to be social care, there needs to be community-based interventions and things to do about it. Doctors can help identify these patients, or maybe somebody in the [medical] team can help with that, but there needs to be an intervention. Otherwise, you’re left with this problem without a solution that you can’t do anything about.”

The researchers did not note any external funding for either study. Dr. Beil, Dr. Dhanrajani, Dr. Smith, and Dr. Ciurtin reported no relevant financial relationships.

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

NEW ORLEANS – More than one-third of pediatric residency programs do not have a pediatric rheumatologist on faculty, a situation that has changed little since 2004, according to a poster presented at the Pediatric Rheumatology Symposium 2023 conference.

“This shortage has significant downstream effects,” according to author Miriah Gillispie-Taylor, MD, an assistant professor of pediatric rheumatology at Baylor College of Medicine and Texas Children’s Hospital in Houston. Without adequate education, it’s unreasonable to expect that a pediatrician will recognize the great diversity of presentations among rheumatic diseases, for example. “Without recognition, patients are not referred in a timely manner, and earlier identification and treatment of rheumatic diseases leads to improved outcomes,” Dr. Gillispie-Taylor said.

Currently, eight U.S. states do not have a board-certified pediatric rheumatologist, including Alaska. Dr. Gillispie-Taylor cited a 2006 study that found that one-third of medical schools (33%) and 40% of U.S. pediatric residency programs did not have an on-site pediatric rheumatologist in 2004.

As the long-standing workforce shortage in pediatric rheumatology continues, Dr. Gillispie-Taylor and her colleagues investigated whether increasing awareness of this problem has influenced the number of United States and Puerto Rico residency training programs with pediatric rheumatology faculty from 2004 to present.

The researchers identified 212 pediatric residency programs accredited by the Accreditation Council for Graduate Medical Education for 2022-2023 and reviewed their program website to see which ones had affiliated pediatric rheumatology faculty. After determining the faculty from the website for 85% of the programs, the researchers emailed the other programs to find out whether a pediatric rheumatologist was on faculty, filling out another 6% of the programs. Most of the remaining uncategorized programs (7%) were categorized at a meeting of the Childhood Arthritis and Rheumatology Research Alliance medical education workgroup. Only 2% of programs could not be ultimately categorized.

The region with the greatest proportion of pediatric residency programs that had a pediatric rheumatologist was the Southeast, where 95% (36 of 38 programs) of programs had one on faculty. The Southwest, comprising Texas, Oklahoma, New Mexico, and Arizona, had the lowest proportion: 43% (9 of 21 programs). For the other regions, 69% of the West/Pacific Northwest (18 of 26), 62% of the Midwest (28 of 45), and 61% of the Northeast (39 of 64) programs had a pediatric rheumatologist on faculty. Three of Puerto Rico’s four programs had one as well.

Overall, 63% of programs had a pediatric rheumatologist on faculty, and 36% did not; the state of three programs was unknown.

The large proportion of programs without a pediatric rheumatologist “limits exposure to rheumatologic conditions and learning opportunities during residency and contribute to declining fellow match rates,” the authors concluded. They noted that only 62.8% of pediatric rheumatology fellowship positions were filled in 2022, down slightly from the 69.2% filled in 2021, according to report data from the National Matching Resident Program.

The researchers acknowledged that their results could be skewed if website information was outdated for any programs, and it’s difficult to determine which programs might lack resources on the basis of only publicly available information. Though programs without pediatric rheumatologists might benefit from visiting professorships, it can be difficult to identify which ones, they added.

The authors recommend two next steps: one, establishing areas of essential knowledge in pediatric rheumatology to enable the creation of learning objectives so programs can focus their educational efforts; and two, continuing efforts to understand residents’ motivation to pursue fellowships in pediatric rheumatology for the purpose of improving recruitment.

Two medical students at Dr. Gillispie-Taylor’s institution spoke with this news organization about their thoughts on the findings and how they were approaching their own career goals in medicine in light of these findings.

Kyla Fergason, a second-year medical student at Baylor College of Medicine, said that she thinks she wants to pursue pediatrics or meds-peds. Though she’s not sure whether she specifically wants to pursue pediatric rheumatology, she is very interested in the area and said that she has learned much from the Pediatric Rheumatology Symposium conference. She found the dearth of pediatric rheumatology faculty at residency programs worrisome, particularly in states like Alaska and Hawaii because they aren’t contiguous with the rest of the United States. Only three pediatric rheumatologists are practicing in Hawaii.

“It’s really concerning that sometimes there is not any rheumatologist there to see the patient,” Ms. Fergason told this news organization. “These are diseases that affect people chronically throughout their entire lives, so it’s definitely concerning to think that, at a time when they could be helped and there could be interventions made, none are made because there’s just no one available.”

Kristiana Nasto, a third-year medical student at Baylor College of Medicine, is similarly interested in pediatrics but leaning more toward meds-peds and has an interest in rheumatology as well. She was surprised at how many programs had no pediatric rheumatologist on faculty because Baylor has a robust program.

“I was not aware of the fact that other states or other parts of Texas do not have the luxury of the great rheumatologists that we have at Baylor College of Medicine,” Ms. Nasto said. “That can definitely impact care for many patients because some of these rheumatologic diseases are so unique and challenging to treat that they require specialized care, so it makes me a bit sad that this is the case.”

Dr. Gillispie-Taylor has received an educational grant from Pfizer. Ms. Fergason and Ms. Nasto had no disclosures. No external funding was noted for the study.

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

NEW ORLEANS – More than one-third of pediatric residency programs do not have a pediatric rheumatologist on faculty, a situation that has changed little since 2004, according to a poster presented at the Pediatric Rheumatology Symposium 2023 conference.

“This shortage has significant downstream effects,” according to author Miriah Gillispie-Taylor, MD, an assistant professor of pediatric rheumatology at Baylor College of Medicine and Texas Children’s Hospital in Houston. Without adequate education, it’s unreasonable to expect that a pediatrician will recognize the great diversity of presentations among rheumatic diseases, for example. “Without recognition, patients are not referred in a timely manner, and earlier identification and treatment of rheumatic diseases leads to improved outcomes,” Dr. Gillispie-Taylor said.

Currently, eight U.S. states do not have a board-certified pediatric rheumatologist, including Alaska. Dr. Gillispie-Taylor cited a 2006 study that found that one-third of medical schools (33%) and 40% of U.S. pediatric residency programs did not have an on-site pediatric rheumatologist in 2004.

As the long-standing workforce shortage in pediatric rheumatology continues, Dr. Gillispie-Taylor and her colleagues investigated whether increasing awareness of this problem has influenced the number of United States and Puerto Rico residency training programs with pediatric rheumatology faculty from 2004 to present.

The researchers identified 212 pediatric residency programs accredited by the Accreditation Council for Graduate Medical Education for 2022-2023 and reviewed their program website to see which ones had affiliated pediatric rheumatology faculty. After determining the faculty from the website for 85% of the programs, the researchers emailed the other programs to find out whether a pediatric rheumatologist was on faculty, filling out another 6% of the programs. Most of the remaining uncategorized programs (7%) were categorized at a meeting of the Childhood Arthritis and Rheumatology Research Alliance medical education workgroup. Only 2% of programs could not be ultimately categorized.

The region with the greatest proportion of pediatric residency programs that had a pediatric rheumatologist was the Southeast, where 95% (36 of 38 programs) of programs had one on faculty. The Southwest, comprising Texas, Oklahoma, New Mexico, and Arizona, had the lowest proportion: 43% (9 of 21 programs). For the other regions, 69% of the West/Pacific Northwest (18 of 26), 62% of the Midwest (28 of 45), and 61% of the Northeast (39 of 64) programs had a pediatric rheumatologist on faculty. Three of Puerto Rico’s four programs had one as well.

Overall, 63% of programs had a pediatric rheumatologist on faculty, and 36% did not; the state of three programs was unknown.

The large proportion of programs without a pediatric rheumatologist “limits exposure to rheumatologic conditions and learning opportunities during residency and contribute to declining fellow match rates,” the authors concluded. They noted that only 62.8% of pediatric rheumatology fellowship positions were filled in 2022, down slightly from the 69.2% filled in 2021, according to report data from the National Matching Resident Program.

The researchers acknowledged that their results could be skewed if website information was outdated for any programs, and it’s difficult to determine which programs might lack resources on the basis of only publicly available information. Though programs without pediatric rheumatologists might benefit from visiting professorships, it can be difficult to identify which ones, they added.

The authors recommend two next steps: one, establishing areas of essential knowledge in pediatric rheumatology to enable the creation of learning objectives so programs can focus their educational efforts; and two, continuing efforts to understand residents’ motivation to pursue fellowships in pediatric rheumatology for the purpose of improving recruitment.

Two medical students at Dr. Gillispie-Taylor’s institution spoke with this news organization about their thoughts on the findings and how they were approaching their own career goals in medicine in light of these findings.

Kyla Fergason, a second-year medical student at Baylor College of Medicine, said that she thinks she wants to pursue pediatrics or meds-peds. Though she’s not sure whether she specifically wants to pursue pediatric rheumatology, she is very interested in the area and said that she has learned much from the Pediatric Rheumatology Symposium conference. She found the dearth of pediatric rheumatology faculty at residency programs worrisome, particularly in states like Alaska and Hawaii because they aren’t contiguous with the rest of the United States. Only three pediatric rheumatologists are practicing in Hawaii.

“It’s really concerning that sometimes there is not any rheumatologist there to see the patient,” Ms. Fergason told this news organization. “These are diseases that affect people chronically throughout their entire lives, so it’s definitely concerning to think that, at a time when they could be helped and there could be interventions made, none are made because there’s just no one available.”

Kristiana Nasto, a third-year medical student at Baylor College of Medicine, is similarly interested in pediatrics but leaning more toward meds-peds and has an interest in rheumatology as well. She was surprised at how many programs had no pediatric rheumatologist on faculty because Baylor has a robust program.

“I was not aware of the fact that other states or other parts of Texas do not have the luxury of the great rheumatologists that we have at Baylor College of Medicine,” Ms. Nasto said. “That can definitely impact care for many patients because some of these rheumatologic diseases are so unique and challenging to treat that they require specialized care, so it makes me a bit sad that this is the case.”

Dr. Gillispie-Taylor has received an educational grant from Pfizer. Ms. Fergason and Ms. Nasto had no disclosures. No external funding was noted for the study.

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

NEW ORLEANS – More than one-third of pediatric residency programs do not have a pediatric rheumatologist on faculty, a situation that has changed little since 2004, according to a poster presented at the Pediatric Rheumatology Symposium 2023 conference.

“This shortage has significant downstream effects,” according to author Miriah Gillispie-Taylor, MD, an assistant professor of pediatric rheumatology at Baylor College of Medicine and Texas Children’s Hospital in Houston. Without adequate education, it’s unreasonable to expect that a pediatrician will recognize the great diversity of presentations among rheumatic diseases, for example. “Without recognition, patients are not referred in a timely manner, and earlier identification and treatment of rheumatic diseases leads to improved outcomes,” Dr. Gillispie-Taylor said.

Currently, eight U.S. states do not have a board-certified pediatric rheumatologist, including Alaska. Dr. Gillispie-Taylor cited a 2006 study that found that one-third of medical schools (33%) and 40% of U.S. pediatric residency programs did not have an on-site pediatric rheumatologist in 2004.

As the long-standing workforce shortage in pediatric rheumatology continues, Dr. Gillispie-Taylor and her colleagues investigated whether increasing awareness of this problem has influenced the number of United States and Puerto Rico residency training programs with pediatric rheumatology faculty from 2004 to present.

The researchers identified 212 pediatric residency programs accredited by the Accreditation Council for Graduate Medical Education for 2022-2023 and reviewed their program website to see which ones had affiliated pediatric rheumatology faculty. After determining the faculty from the website for 85% of the programs, the researchers emailed the other programs to find out whether a pediatric rheumatologist was on faculty, filling out another 6% of the programs. Most of the remaining uncategorized programs (7%) were categorized at a meeting of the Childhood Arthritis and Rheumatology Research Alliance medical education workgroup. Only 2% of programs could not be ultimately categorized.

The region with the greatest proportion of pediatric residency programs that had a pediatric rheumatologist was the Southeast, where 95% (36 of 38 programs) of programs had one on faculty. The Southwest, comprising Texas, Oklahoma, New Mexico, and Arizona, had the lowest proportion: 43% (9 of 21 programs). For the other regions, 69% of the West/Pacific Northwest (18 of 26), 62% of the Midwest (28 of 45), and 61% of the Northeast (39 of 64) programs had a pediatric rheumatologist on faculty. Three of Puerto Rico’s four programs had one as well.

Overall, 63% of programs had a pediatric rheumatologist on faculty, and 36% did not; the state of three programs was unknown.

The large proportion of programs without a pediatric rheumatologist “limits exposure to rheumatologic conditions and learning opportunities during residency and contribute to declining fellow match rates,” the authors concluded. They noted that only 62.8% of pediatric rheumatology fellowship positions were filled in 2022, down slightly from the 69.2% filled in 2021, according to report data from the National Matching Resident Program.

The researchers acknowledged that their results could be skewed if website information was outdated for any programs, and it’s difficult to determine which programs might lack resources on the basis of only publicly available information. Though programs without pediatric rheumatologists might benefit from visiting professorships, it can be difficult to identify which ones, they added.

The authors recommend two next steps: one, establishing areas of essential knowledge in pediatric rheumatology to enable the creation of learning objectives so programs can focus their educational efforts; and two, continuing efforts to understand residents’ motivation to pursue fellowships in pediatric rheumatology for the purpose of improving recruitment.

Two medical students at Dr. Gillispie-Taylor’s institution spoke with this news organization about their thoughts on the findings and how they were approaching their own career goals in medicine in light of these findings.

Kyla Fergason, a second-year medical student at Baylor College of Medicine, said that she thinks she wants to pursue pediatrics or meds-peds. Though she’s not sure whether she specifically wants to pursue pediatric rheumatology, she is very interested in the area and said that she has learned much from the Pediatric Rheumatology Symposium conference. She found the dearth of pediatric rheumatology faculty at residency programs worrisome, particularly in states like Alaska and Hawaii because they aren’t contiguous with the rest of the United States. Only three pediatric rheumatologists are practicing in Hawaii.

“It’s really concerning that sometimes there is not any rheumatologist there to see the patient,” Ms. Fergason told this news organization. “These are diseases that affect people chronically throughout their entire lives, so it’s definitely concerning to think that, at a time when they could be helped and there could be interventions made, none are made because there’s just no one available.”

Kristiana Nasto, a third-year medical student at Baylor College of Medicine, is similarly interested in pediatrics but leaning more toward meds-peds and has an interest in rheumatology as well. She was surprised at how many programs had no pediatric rheumatologist on faculty because Baylor has a robust program.

“I was not aware of the fact that other states or other parts of Texas do not have the luxury of the great rheumatologists that we have at Baylor College of Medicine,” Ms. Nasto said. “That can definitely impact care for many patients because some of these rheumatologic diseases are so unique and challenging to treat that they require specialized care, so it makes me a bit sad that this is the case.”

Dr. Gillispie-Taylor has received an educational grant from Pfizer. Ms. Fergason and Ms. Nasto had no disclosures. No external funding was noted for the study.

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

During 2 days of hearings on potential modifications to the isotretinoin iPLEDGE Risk Evaluation and Mitigation Strategy (REMS), there was much agreement among dermatologists, industry representatives, and Food and Drug Administration representatives that provider and patient burdens persist after the chaotic rollout of the new REMS platform at the end of 2021.

On March 29, at the end of the FDA’s joint meeting of two advisory committees that addressed ways to improve the iPLEDGE program, most panelists voted to change the 19-day lockout period for patients who can become pregnant, and the requirement that every month, providers must document counseling of those who cannot get pregnant and are taking the drug for acne.

However, there was no consensus on whether there should be a lockout at all or for how long, and what an appropriate interval for counseling those who cannot get pregnant would be, if not monthly. Those voting on the questions repeatedly cited a lack of data to make well-informed decisions.

The meeting of the two panels, the FDA’s Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee, was held March 28-29, to discuss proposed changes to iPLEDGE requirements, to minimize the program’s burden on patients, prescribers, and pharmacies – while maintaining safe use of the highly teratogenic drug.

Lockout based on outdated reasoning

John S. Barbieri, MD, a dermatologist and epidemiologist, and director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital in Boston, speaking as deputy chair of the American Academy of Dermatology Association (AADA) iPLEDGE work group, described the burden of getting the drug to patients. He was not on the panel, but spoke during the open public hearing.

“Compared to other acne medications, the time it takes to successfully go from prescribed (isotretinoin) to when the patient actually has it in their hands is 5- to 10-fold higher,” he said.

Many don’t have a monthly cycle

But Dr. Barbieri said that reasoning is outdated.

“The current program’s focus on the menstrual cycle is really an antiquated approach,” he said. “Many patients do not have a monthly cycle due to medical conditions like polycystic ovarian syndrome, or due to [certain kinds of] contraception.”

He added, “By removing this 19-day lockout and, really, the archaic timing around the menstrual cycle in general in this program, we can simplify the program, improve it, and better align it with the real-world biology of our patients.” He added that patients are often missing the 7-day window for picking up their prescriptions through no fault of their own. Speakers at the hearing also mentioned insurance hassles and ordering delays.


 

Communication with IPMG

Ilona Frieden, MD, professor of dermatology and pediatrics at the University of California, San Francisco, and outgoing chair of the AADA iPLEDGE work group, cited difficulty in working with IPMG on modifications as another barrier. She also spoke during the open public hearing.

UCSF

“Despite many, many attempts to work with the IPMG, we are not aware of any organizational structure or key leaders to communicate with. Instead we have been given repeatedly a generic email address for trying to establish a working relationship and we believe this may explain the inaction of the IPMG since our proposals 4 years ago in 2019.”

Among those proposals, she said, were allowing telemedicine visits as part of the iPLEDGE REMS program and reducing counseling attestation to every 6 months instead of monthly for those who cannot become pregnant.

She pointed to the chaotic rollout of modifications to the iPLEDGE program on a new website at the end of 2021.

In 2021, she said, “despite 6 months of notification, no prescriber input was solicited before revamping the website. This lack of transparency and accountability has been a major hurdle in improving iPLEDGE.”

Dr. Barbieri called the rollout “a debacle” that could have been mitigated with communication with IPMG. “We warned about every issue that happened and talked about ways to mitigate it and were largely ignored,” he said.

“By including dermatologists and key stakeholders in these discussions, as we move forward with changes to improve this program, we can make sure that it’s patient-centered.”

IPMG did not address the specific complaints about the working relationship with the AADA workgroup at the meeting.
 

Monthly attestation for counseling patients who cannot get pregnant

Dr. Barbieri said the monthly requirement to counsel patients who cannot get pregnant and document that counseling unfairly burdens clinicians and patients. “We’re essentially asking patients to come in monthly just to tell them not to share their drugs [or] donate blood,” he said.

Ken Katz, MD, MSc, a dermatologist at Kaiser Permanente in San Francisco, was among the panel members voting not to continue the 19-day lockout.

“I think this places an unduly high burden physically and psychologically on our patients. It seems arbitrary,” he said. “Likely we will miss some pregnancies; we are missing some already. But the burden is not matched by the benefit.”

IPMG representative Dr. Wedin, said, “while we cannot support eliminating or extending the confirmation interval to a year, the [iPLEDGE] sponsors are agreeable [to] a 120-day confirmation interval.”

He said that while an extension to 120 days would reduce burden on prescribers, it comes with the risk in reducing oversight by a certified iPLEDGE prescriber and potentially increasing the risk for drug sharing.

“A patient may be more likely to share their drug with another person the further along with therapy they get as their condition improves,” Dr. Wedin said.
 

Home pregnancy testing

The advisory groups were also tasked with discussing whether home pregnancy tests, allowed during the COVID-19 public health emergency, should continue to be allowed. Most committee members and those in the public hearing who spoke on the issue agreed that home tests should continue in an effort to increase access and decrease burden.

During the pandemic, iPLEDGE rules have been relaxed from having a pregnancy test done only at a Clinical Laboratory Improvement Amendments–certified laboratory.

Lindsey Crist, PharmD, a risk management analyst at the FDA, who presented the FDA review committee’s analysis, said that the FDA’s review committee recommends ending the allowance of home tests, citing insufficient data on use and the discovery of instances of falsification of pregnancy tests.

“One study at an academic medical center reviewed the medical records of 89 patients who used home pregnancy tests while taking isotretinoin during the public health emergency. It found that 15.7% submitted falsified pregnancy test results,” Dr. Crist said.

Dr. Crist added, however, that the review committee recommends allowing the tests to be done in a provider’s office as an alternative.
 

Workaround to avoid falsification

Advisory committee member Brian P. Green, DO, associate professor of dermatology at Penn State University, Hershey, Pa., spoke in support of home pregnancy tests.

“What we have people do for telemedicine is take the stick, write their name, write the date on it, and send a picture of that the same day as their visit,” he said. “That way we have the pregnancy test the same day. Allowing this to continue to happen at home is important. Bringing people in is burdensome and costly.”

Emmy Graber, MD, a dermatologist who practices in Boston, and a director of the American Acne and Rosacea Society (AARS), relayed an example of the burden for a patient using isotretinoin who lives 1.5 hours away from the dermatology office. She is able to meet the requirements of iPLEDGE only through telehealth.

Suggestions for improvement

At the end of the hearing, advisory committee members were asked to propose improvements to the iPLEDGE REMS program.

Dr. Green advocated for the addition of an iPLEDGE mobile app.

“Most people go to their phones rather than their computers, particularly teenagers and younger people,” he noted.

Advisory committee member Megha M. Tollefson, MD, professor of dermatology and pediatric and adolescent medicine at Mayo Clinic in Rochester, Minn., echoed the need for an iPLEDGE app.

The young patients getting isotretinoin “don’t respond to email, they don’t necessarily go onto web pages. If we’re going to be as effective as possible, it’s going to have to be through an app-based system.”

Dr. Tollefson said she would like to see patient counseling standardized through the app. “I think there’s a lot of variability in what counseling is given when it’s left to the individual prescriber or practice,” she said.
 

Exceptions for long-acting contraceptives?

Advisory committee member Abbey B. Berenson, MD, PhD, professor of obstetrics and gynecology at University of Texas Medical Branch in Galveston, said that patients taking long-acting reversible contraceptives (LARCs) may need to be considered differently when deciding the intervals for attestation or whether to have a lockout period.

“LARC methods’ rate of failure is extremely low,” she said. “While it is true, as it has been pointed out, that all methods can fail, when they’re over 99% effective, I think that we can treat those methods differently than we treat methods such as birth control pills or abstinence that fail far more often. That is one way we could minimize burden on the providers and the patients.”

She also suggested using members of the health care team other than physicians to complete counseling, such as a nurse or pharmacist.
 

Prescriptions for emergency contraception

Advisory committee member Sascha Dublin, MD, PhD, senior scientific investigator for Kaiser Permanente Washington Health Research Institute in Seattle, said most patients taking the drug who can get pregnant should get a prescription for emergency contraception at the time of the first isotretinoin prescription.

“They don’t have to buy it, but to make it available at the very beginning sets the expectation that it would be good to have in your medicine cabinet, particularly if the [contraception] choice is abstinence or birth control pills.”

Dr. Dublin also called for better transparency surrounding the role of IPMG.

She said IPMG should be expected to collect data in a way that allows examination of health disparities, including by race and ethnicity and insurance status. Dr. Dublin added that she was concerned about the poor communication between dermatological societies and IPMG.

“The FDA should really require that IPMG hold periodic, regularly scheduled stakeholder forums,” she said. “There has to be a mechanism in place for IPMG to listen to those concerns in real time and respond.”

The advisory committees’ recommendations to the FDA are nonbinding, but the FDA generally follows the recommendations of advisory panels.

During 2 days of hearings on potential modifications to the isotretinoin iPLEDGE Risk Evaluation and Mitigation Strategy (REMS), there was much agreement among dermatologists, industry representatives, and Food and Drug Administration representatives that provider and patient burdens persist after the chaotic rollout of the new REMS platform at the end of 2021.

On March 29, at the end of the FDA’s joint meeting of two advisory committees that addressed ways to improve the iPLEDGE program, most panelists voted to change the 19-day lockout period for patients who can become pregnant, and the requirement that every month, providers must document counseling of those who cannot get pregnant and are taking the drug for acne.

However, there was no consensus on whether there should be a lockout at all or for how long, and what an appropriate interval for counseling those who cannot get pregnant would be, if not monthly. Those voting on the questions repeatedly cited a lack of data to make well-informed decisions.

The meeting of the two panels, the FDA’s Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee, was held March 28-29, to discuss proposed changes to iPLEDGE requirements, to minimize the program’s burden on patients, prescribers, and pharmacies – while maintaining safe use of the highly teratogenic drug.

Lockout based on outdated reasoning

John S. Barbieri, MD, a dermatologist and epidemiologist, and director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital in Boston, speaking as deputy chair of the American Academy of Dermatology Association (AADA) iPLEDGE work group, described the burden of getting the drug to patients. He was not on the panel, but spoke during the open public hearing.

“Compared to other acne medications, the time it takes to successfully go from prescribed (isotretinoin) to when the patient actually has it in their hands is 5- to 10-fold higher,” he said.

Many don’t have a monthly cycle

But Dr. Barbieri said that reasoning is outdated.

“The current program’s focus on the menstrual cycle is really an antiquated approach,” he said. “Many patients do not have a monthly cycle due to medical conditions like polycystic ovarian syndrome, or due to [certain kinds of] contraception.”

He added, “By removing this 19-day lockout and, really, the archaic timing around the menstrual cycle in general in this program, we can simplify the program, improve it, and better align it with the real-world biology of our patients.” He added that patients are often missing the 7-day window for picking up their prescriptions through no fault of their own. Speakers at the hearing also mentioned insurance hassles and ordering delays.


 

Communication with IPMG

Ilona Frieden, MD, professor of dermatology and pediatrics at the University of California, San Francisco, and outgoing chair of the AADA iPLEDGE work group, cited difficulty in working with IPMG on modifications as another barrier. She also spoke during the open public hearing.

UCSF

“Despite many, many attempts to work with the IPMG, we are not aware of any organizational structure or key leaders to communicate with. Instead we have been given repeatedly a generic email address for trying to establish a working relationship and we believe this may explain the inaction of the IPMG since our proposals 4 years ago in 2019.”

Among those proposals, she said, were allowing telemedicine visits as part of the iPLEDGE REMS program and reducing counseling attestation to every 6 months instead of monthly for those who cannot become pregnant.

She pointed to the chaotic rollout of modifications to the iPLEDGE program on a new website at the end of 2021.

In 2021, she said, “despite 6 months of notification, no prescriber input was solicited before revamping the website. This lack of transparency and accountability has been a major hurdle in improving iPLEDGE.”

Dr. Barbieri called the rollout “a debacle” that could have been mitigated with communication with IPMG. “We warned about every issue that happened and talked about ways to mitigate it and were largely ignored,” he said.

“By including dermatologists and key stakeholders in these discussions, as we move forward with changes to improve this program, we can make sure that it’s patient-centered.”

IPMG did not address the specific complaints about the working relationship with the AADA workgroup at the meeting.
 

Monthly attestation for counseling patients who cannot get pregnant

Dr. Barbieri said the monthly requirement to counsel patients who cannot get pregnant and document that counseling unfairly burdens clinicians and patients. “We’re essentially asking patients to come in monthly just to tell them not to share their drugs [or] donate blood,” he said.

Ken Katz, MD, MSc, a dermatologist at Kaiser Permanente in San Francisco, was among the panel members voting not to continue the 19-day lockout.

“I think this places an unduly high burden physically and psychologically on our patients. It seems arbitrary,” he said. “Likely we will miss some pregnancies; we are missing some already. But the burden is not matched by the benefit.”

IPMG representative Dr. Wedin, said, “while we cannot support eliminating or extending the confirmation interval to a year, the [iPLEDGE] sponsors are agreeable [to] a 120-day confirmation interval.”

He said that while an extension to 120 days would reduce burden on prescribers, it comes with the risk in reducing oversight by a certified iPLEDGE prescriber and potentially increasing the risk for drug sharing.

“A patient may be more likely to share their drug with another person the further along with therapy they get as their condition improves,” Dr. Wedin said.
 

Home pregnancy testing

The advisory groups were also tasked with discussing whether home pregnancy tests, allowed during the COVID-19 public health emergency, should continue to be allowed. Most committee members and those in the public hearing who spoke on the issue agreed that home tests should continue in an effort to increase access and decrease burden.

During the pandemic, iPLEDGE rules have been relaxed from having a pregnancy test done only at a Clinical Laboratory Improvement Amendments–certified laboratory.

Lindsey Crist, PharmD, a risk management analyst at the FDA, who presented the FDA review committee’s analysis, said that the FDA’s review committee recommends ending the allowance of home tests, citing insufficient data on use and the discovery of instances of falsification of pregnancy tests.

“One study at an academic medical center reviewed the medical records of 89 patients who used home pregnancy tests while taking isotretinoin during the public health emergency. It found that 15.7% submitted falsified pregnancy test results,” Dr. Crist said.

Dr. Crist added, however, that the review committee recommends allowing the tests to be done in a provider’s office as an alternative.
 

Workaround to avoid falsification

Advisory committee member Brian P. Green, DO, associate professor of dermatology at Penn State University, Hershey, Pa., spoke in support of home pregnancy tests.

“What we have people do for telemedicine is take the stick, write their name, write the date on it, and send a picture of that the same day as their visit,” he said. “That way we have the pregnancy test the same day. Allowing this to continue to happen at home is important. Bringing people in is burdensome and costly.”

Emmy Graber, MD, a dermatologist who practices in Boston, and a director of the American Acne and Rosacea Society (AARS), relayed an example of the burden for a patient using isotretinoin who lives 1.5 hours away from the dermatology office. She is able to meet the requirements of iPLEDGE only through telehealth.

Suggestions for improvement

At the end of the hearing, advisory committee members were asked to propose improvements to the iPLEDGE REMS program.

Dr. Green advocated for the addition of an iPLEDGE mobile app.

“Most people go to their phones rather than their computers, particularly teenagers and younger people,” he noted.

Advisory committee member Megha M. Tollefson, MD, professor of dermatology and pediatric and adolescent medicine at Mayo Clinic in Rochester, Minn., echoed the need for an iPLEDGE app.

The young patients getting isotretinoin “don’t respond to email, they don’t necessarily go onto web pages. If we’re going to be as effective as possible, it’s going to have to be through an app-based system.”

Dr. Tollefson said she would like to see patient counseling standardized through the app. “I think there’s a lot of variability in what counseling is given when it’s left to the individual prescriber or practice,” she said.
 

Exceptions for long-acting contraceptives?

Advisory committee member Abbey B. Berenson, MD, PhD, professor of obstetrics and gynecology at University of Texas Medical Branch in Galveston, said that patients taking long-acting reversible contraceptives (LARCs) may need to be considered differently when deciding the intervals for attestation or whether to have a lockout period.

“LARC methods’ rate of failure is extremely low,” she said. “While it is true, as it has been pointed out, that all methods can fail, when they’re over 99% effective, I think that we can treat those methods differently than we treat methods such as birth control pills or abstinence that fail far more often. That is one way we could minimize burden on the providers and the patients.”

She also suggested using members of the health care team other than physicians to complete counseling, such as a nurse or pharmacist.
 

Prescriptions for emergency contraception

Advisory committee member Sascha Dublin, MD, PhD, senior scientific investigator for Kaiser Permanente Washington Health Research Institute in Seattle, said most patients taking the drug who can get pregnant should get a prescription for emergency contraception at the time of the first isotretinoin prescription.

“They don’t have to buy it, but to make it available at the very beginning sets the expectation that it would be good to have in your medicine cabinet, particularly if the [contraception] choice is abstinence or birth control pills.”

Dr. Dublin also called for better transparency surrounding the role of IPMG.

She said IPMG should be expected to collect data in a way that allows examination of health disparities, including by race and ethnicity and insurance status. Dr. Dublin added that she was concerned about the poor communication between dermatological societies and IPMG.

“The FDA should really require that IPMG hold periodic, regularly scheduled stakeholder forums,” she said. “There has to be a mechanism in place for IPMG to listen to those concerns in real time and respond.”

The advisory committees’ recommendations to the FDA are nonbinding, but the FDA generally follows the recommendations of advisory panels.

During 2 days of hearings on potential modifications to the isotretinoin iPLEDGE Risk Evaluation and Mitigation Strategy (REMS), there was much agreement among dermatologists, industry representatives, and Food and Drug Administration representatives that provider and patient burdens persist after the chaotic rollout of the new REMS platform at the end of 2021.

On March 29, at the end of the FDA’s joint meeting of two advisory committees that addressed ways to improve the iPLEDGE program, most panelists voted to change the 19-day lockout period for patients who can become pregnant, and the requirement that every month, providers must document counseling of those who cannot get pregnant and are taking the drug for acne.

However, there was no consensus on whether there should be a lockout at all or for how long, and what an appropriate interval for counseling those who cannot get pregnant would be, if not monthly. Those voting on the questions repeatedly cited a lack of data to make well-informed decisions.

The meeting of the two panels, the FDA’s Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee, was held March 28-29, to discuss proposed changes to iPLEDGE requirements, to minimize the program’s burden on patients, prescribers, and pharmacies – while maintaining safe use of the highly teratogenic drug.

Lockout based on outdated reasoning

John S. Barbieri, MD, a dermatologist and epidemiologist, and director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital in Boston, speaking as deputy chair of the American Academy of Dermatology Association (AADA) iPLEDGE work group, described the burden of getting the drug to patients. He was not on the panel, but spoke during the open public hearing.

“Compared to other acne medications, the time it takes to successfully go from prescribed (isotretinoin) to when the patient actually has it in their hands is 5- to 10-fold higher,” he said.

Many don’t have a monthly cycle

But Dr. Barbieri said that reasoning is outdated.

“The current program’s focus on the menstrual cycle is really an antiquated approach,” he said. “Many patients do not have a monthly cycle due to medical conditions like polycystic ovarian syndrome, or due to [certain kinds of] contraception.”

He added, “By removing this 19-day lockout and, really, the archaic timing around the menstrual cycle in general in this program, we can simplify the program, improve it, and better align it with the real-world biology of our patients.” He added that patients are often missing the 7-day window for picking up their prescriptions through no fault of their own. Speakers at the hearing also mentioned insurance hassles and ordering delays.


 

Communication with IPMG

Ilona Frieden, MD, professor of dermatology and pediatrics at the University of California, San Francisco, and outgoing chair of the AADA iPLEDGE work group, cited difficulty in working with IPMG on modifications as another barrier. She also spoke during the open public hearing.

UCSF

“Despite many, many attempts to work with the IPMG, we are not aware of any organizational structure or key leaders to communicate with. Instead we have been given repeatedly a generic email address for trying to establish a working relationship and we believe this may explain the inaction of the IPMG since our proposals 4 years ago in 2019.”

Among those proposals, she said, were allowing telemedicine visits as part of the iPLEDGE REMS program and reducing counseling attestation to every 6 months instead of monthly for those who cannot become pregnant.

She pointed to the chaotic rollout of modifications to the iPLEDGE program on a new website at the end of 2021.

In 2021, she said, “despite 6 months of notification, no prescriber input was solicited before revamping the website. This lack of transparency and accountability has been a major hurdle in improving iPLEDGE.”

Dr. Barbieri called the rollout “a debacle” that could have been mitigated with communication with IPMG. “We warned about every issue that happened and talked about ways to mitigate it and were largely ignored,” he said.

“By including dermatologists and key stakeholders in these discussions, as we move forward with changes to improve this program, we can make sure that it’s patient-centered.”

IPMG did not address the specific complaints about the working relationship with the AADA workgroup at the meeting.
 

Monthly attestation for counseling patients who cannot get pregnant

Dr. Barbieri said the monthly requirement to counsel patients who cannot get pregnant and document that counseling unfairly burdens clinicians and patients. “We’re essentially asking patients to come in monthly just to tell them not to share their drugs [or] donate blood,” he said.

Ken Katz, MD, MSc, a dermatologist at Kaiser Permanente in San Francisco, was among the panel members voting not to continue the 19-day lockout.

“I think this places an unduly high burden physically and psychologically on our patients. It seems arbitrary,” he said. “Likely we will miss some pregnancies; we are missing some already. But the burden is not matched by the benefit.”

IPMG representative Dr. Wedin, said, “while we cannot support eliminating or extending the confirmation interval to a year, the [iPLEDGE] sponsors are agreeable [to] a 120-day confirmation interval.”

He said that while an extension to 120 days would reduce burden on prescribers, it comes with the risk in reducing oversight by a certified iPLEDGE prescriber and potentially increasing the risk for drug sharing.

“A patient may be more likely to share their drug with another person the further along with therapy they get as their condition improves,” Dr. Wedin said.
 

Home pregnancy testing

The advisory groups were also tasked with discussing whether home pregnancy tests, allowed during the COVID-19 public health emergency, should continue to be allowed. Most committee members and those in the public hearing who spoke on the issue agreed that home tests should continue in an effort to increase access and decrease burden.

During the pandemic, iPLEDGE rules have been relaxed from having a pregnancy test done only at a Clinical Laboratory Improvement Amendments–certified laboratory.

Lindsey Crist, PharmD, a risk management analyst at the FDA, who presented the FDA review committee’s analysis, said that the FDA’s review committee recommends ending the allowance of home tests, citing insufficient data on use and the discovery of instances of falsification of pregnancy tests.

“One study at an academic medical center reviewed the medical records of 89 patients who used home pregnancy tests while taking isotretinoin during the public health emergency. It found that 15.7% submitted falsified pregnancy test results,” Dr. Crist said.

Dr. Crist added, however, that the review committee recommends allowing the tests to be done in a provider’s office as an alternative.
 

Workaround to avoid falsification

Advisory committee member Brian P. Green, DO, associate professor of dermatology at Penn State University, Hershey, Pa., spoke in support of home pregnancy tests.

“What we have people do for telemedicine is take the stick, write their name, write the date on it, and send a picture of that the same day as their visit,” he said. “That way we have the pregnancy test the same day. Allowing this to continue to happen at home is important. Bringing people in is burdensome and costly.”

Emmy Graber, MD, a dermatologist who practices in Boston, and a director of the American Acne and Rosacea Society (AARS), relayed an example of the burden for a patient using isotretinoin who lives 1.5 hours away from the dermatology office. She is able to meet the requirements of iPLEDGE only through telehealth.

Suggestions for improvement

At the end of the hearing, advisory committee members were asked to propose improvements to the iPLEDGE REMS program.

Dr. Green advocated for the addition of an iPLEDGE mobile app.

“Most people go to their phones rather than their computers, particularly teenagers and younger people,” he noted.

Advisory committee member Megha M. Tollefson, MD, professor of dermatology and pediatric and adolescent medicine at Mayo Clinic in Rochester, Minn., echoed the need for an iPLEDGE app.

The young patients getting isotretinoin “don’t respond to email, they don’t necessarily go onto web pages. If we’re going to be as effective as possible, it’s going to have to be through an app-based system.”

Dr. Tollefson said she would like to see patient counseling standardized through the app. “I think there’s a lot of variability in what counseling is given when it’s left to the individual prescriber or practice,” she said.
 

Exceptions for long-acting contraceptives?

Advisory committee member Abbey B. Berenson, MD, PhD, professor of obstetrics and gynecology at University of Texas Medical Branch in Galveston, said that patients taking long-acting reversible contraceptives (LARCs) may need to be considered differently when deciding the intervals for attestation or whether to have a lockout period.

“LARC methods’ rate of failure is extremely low,” she said. “While it is true, as it has been pointed out, that all methods can fail, when they’re over 99% effective, I think that we can treat those methods differently than we treat methods such as birth control pills or abstinence that fail far more often. That is one way we could minimize burden on the providers and the patients.”

She also suggested using members of the health care team other than physicians to complete counseling, such as a nurse or pharmacist.
 

Prescriptions for emergency contraception

Advisory committee member Sascha Dublin, MD, PhD, senior scientific investigator for Kaiser Permanente Washington Health Research Institute in Seattle, said most patients taking the drug who can get pregnant should get a prescription for emergency contraception at the time of the first isotretinoin prescription.

“They don’t have to buy it, but to make it available at the very beginning sets the expectation that it would be good to have in your medicine cabinet, particularly if the [contraception] choice is abstinence or birth control pills.”

Dr. Dublin also called for better transparency surrounding the role of IPMG.

She said IPMG should be expected to collect data in a way that allows examination of health disparities, including by race and ethnicity and insurance status. Dr. Dublin added that she was concerned about the poor communication between dermatological societies and IPMG.

“The FDA should really require that IPMG hold periodic, regularly scheduled stakeholder forums,” she said. “There has to be a mechanism in place for IPMG to listen to those concerns in real time and respond.”

The advisory committees’ recommendations to the FDA are nonbinding, but the FDA generally follows the recommendations of advisory panels.

A couple of weeks ago I stumbled across a report of a Pew Research Center’s survey titled “Parenting in America today” (Pew Research Center. Jan. 24, 2023), which found that 40% of parents in the United States with children younger than 18 are “extremely or very worried” that at some point their children might struggle with anxiety or depression. Thirty-six percent replied that they were “somewhat” worried. This total of more than 75% represents a significant change from the 2015 Pew Center survey in which only 54% of parents were “somewhat” worried about their children’s mental health.

Prompted by these findings I began work on a column in which I planned to encourage pediatricians to think more like family physicians when we were working with children who were experiencing serious mental health problems. My primary message was going to be that we should turn more of our attention to the mental health of the anxious parents who must endure the often long and frustrating path toward effective psychiatric care for their children. This might come in the form of some simple suggestions about nonpharmacologic self-help strategies. Or, it could mean encouraging parents to seek psychiatric care or counseling for themselves as they wait for help for their child.

However, as I began that column, my thoughts kept drifting toward a broader consideration of the relationship between parents and pediatric mental health. If mental health of children is causing their parents to be anxious and depressed isn’t it just as likely that this is a bidirectional connection? This was not exactly an “aha” moment for me because it is a relationship I have considered for sometime. However, it is a concept that I have come to realize is receiving far too little attention.

There are exceptions. For example, a recent opinion piece in the New York Times by David French, “What if Kids Are Sad and Stressed Because Their Parents Are?” (March 19, 2023) echoes many of my concerns. Drawing on his experiences traveling around college campuses, Mr. French observes, “Just as parents are upset about their children’s anxiety and depression, children are anxious about their parent’s mental health.”

He notes that an August 2022 NBC News poll found that 58% of registered voters feel this country’s best days are behind it and joins me in imagining that this negative mind set is filtering down to the pediatric population. He acknowledges that there are other likely contributors to teen unhappiness including the ubiquity of smart phones, the secularization of society, and the media’s focus on the political divide. However, Mr. French wonders if the parenting style that results in childhood experiences that are dominated by adult supervision and protection may also be playing a large role.

In his conclusion, Mr. French asks us to consider “How much fear and anxiety should we import to our lives and homes?” as we adults search for an answer.

As I continued to drill down for other possible solutions, I encountered an avenue of psychological research that suggests that instead of, or in addition to, filtering out the anxiety-generating deluge of information, we begin to give some thought to how our beliefs may be coloring our perception of reality.

Jeremy D.W. Clifton, PhD, a psychologist at the University of Pennsylvania Positive Psychology Center has done extensive research on the relationship between our basic beliefs about the world (known as primal beliefs or simply primals in psychologist lingo) and how we interpret reality. For example, one of your primal beliefs may be that the world is a dangerous place. I, on the other hand, may see the world as a stimulating environment offering me endless opportunities to explore. I may see the world as an abundant resource limited only by my creativity. You, however, see it as a barren wasteland.

Dr. Clifton’s research has shown that our primals (at least those of adults) are relatively immutable through one’s lifetime and “do not appear to be the consequence of our experiences.” For example, living in a ZIP code with a high crime rate does not predict that you will see the world as a dangerous place. Nor does being affluent guarantee that an adult sees the world rich with opportunities.

It is unclear exactly when and by what process we develop our primal beliefs, but it is safe to say our parents probably play a large role. Exactly to what degree the tsunami of bad news we are allowing to inundate our children’s lives plays a role is unclear. However, it is reasonable to assume that news about climate change, school shootings, and the pandemic must be a contributor.

According to Dr. Clifton, there is some evidence that certain mind exercises, when applied diligently, can occasionally modify the primal beliefs of an individual who sees the world as dangerous and barren. Until such strategies become more readily accessible, the best we can do is acknowledge that our children are like canaries in a coal mine full of negative perceptions, then do our best to clear the air.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

A couple of weeks ago I stumbled across a report of a Pew Research Center’s survey titled “Parenting in America today” (Pew Research Center. Jan. 24, 2023), which found that 40% of parents in the United States with children younger than 18 are “extremely or very worried” that at some point their children might struggle with anxiety or depression. Thirty-six percent replied that they were “somewhat” worried. This total of more than 75% represents a significant change from the 2015 Pew Center survey in which only 54% of parents were “somewhat” worried about their children’s mental health.

Prompted by these findings I began work on a column in which I planned to encourage pediatricians to think more like family physicians when we were working with children who were experiencing serious mental health problems. My primary message was going to be that we should turn more of our attention to the mental health of the anxious parents who must endure the often long and frustrating path toward effective psychiatric care for their children. This might come in the form of some simple suggestions about nonpharmacologic self-help strategies. Or, it could mean encouraging parents to seek psychiatric care or counseling for themselves as they wait for help for their child.

However, as I began that column, my thoughts kept drifting toward a broader consideration of the relationship between parents and pediatric mental health. If mental health of children is causing their parents to be anxious and depressed isn’t it just as likely that this is a bidirectional connection? This was not exactly an “aha” moment for me because it is a relationship I have considered for sometime. However, it is a concept that I have come to realize is receiving far too little attention.

There are exceptions. For example, a recent opinion piece in the New York Times by David French, “What if Kids Are Sad and Stressed Because Their Parents Are?” (March 19, 2023) echoes many of my concerns. Drawing on his experiences traveling around college campuses, Mr. French observes, “Just as parents are upset about their children’s anxiety and depression, children are anxious about their parent’s mental health.”

He notes that an August 2022 NBC News poll found that 58% of registered voters feel this country’s best days are behind it and joins me in imagining that this negative mind set is filtering down to the pediatric population. He acknowledges that there are other likely contributors to teen unhappiness including the ubiquity of smart phones, the secularization of society, and the media’s focus on the political divide. However, Mr. French wonders if the parenting style that results in childhood experiences that are dominated by adult supervision and protection may also be playing a large role.

In his conclusion, Mr. French asks us to consider “How much fear and anxiety should we import to our lives and homes?” as we adults search for an answer.

As I continued to drill down for other possible solutions, I encountered an avenue of psychological research that suggests that instead of, or in addition to, filtering out the anxiety-generating deluge of information, we begin to give some thought to how our beliefs may be coloring our perception of reality.

Jeremy D.W. Clifton, PhD, a psychologist at the University of Pennsylvania Positive Psychology Center has done extensive research on the relationship between our basic beliefs about the world (known as primal beliefs or simply primals in psychologist lingo) and how we interpret reality. For example, one of your primal beliefs may be that the world is a dangerous place. I, on the other hand, may see the world as a stimulating environment offering me endless opportunities to explore. I may see the world as an abundant resource limited only by my creativity. You, however, see it as a barren wasteland.

Dr. Clifton’s research has shown that our primals (at least those of adults) are relatively immutable through one’s lifetime and “do not appear to be the consequence of our experiences.” For example, living in a ZIP code with a high crime rate does not predict that you will see the world as a dangerous place. Nor does being affluent guarantee that an adult sees the world rich with opportunities.

It is unclear exactly when and by what process we develop our primal beliefs, but it is safe to say our parents probably play a large role. Exactly to what degree the tsunami of bad news we are allowing to inundate our children’s lives plays a role is unclear. However, it is reasonable to assume that news about climate change, school shootings, and the pandemic must be a contributor.

According to Dr. Clifton, there is some evidence that certain mind exercises, when applied diligently, can occasionally modify the primal beliefs of an individual who sees the world as dangerous and barren. Until such strategies become more readily accessible, the best we can do is acknowledge that our children are like canaries in a coal mine full of negative perceptions, then do our best to clear the air.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

A couple of weeks ago I stumbled across a report of a Pew Research Center’s survey titled “Parenting in America today” (Pew Research Center. Jan. 24, 2023), which found that 40% of parents in the United States with children younger than 18 are “extremely or very worried” that at some point their children might struggle with anxiety or depression. Thirty-six percent replied that they were “somewhat” worried. This total of more than 75% represents a significant change from the 2015 Pew Center survey in which only 54% of parents were “somewhat” worried about their children’s mental health.

Prompted by these findings I began work on a column in which I planned to encourage pediatricians to think more like family physicians when we were working with children who were experiencing serious mental health problems. My primary message was going to be that we should turn more of our attention to the mental health of the anxious parents who must endure the often long and frustrating path toward effective psychiatric care for their children. This might come in the form of some simple suggestions about nonpharmacologic self-help strategies. Or, it could mean encouraging parents to seek psychiatric care or counseling for themselves as they wait for help for their child.

However, as I began that column, my thoughts kept drifting toward a broader consideration of the relationship between parents and pediatric mental health. If mental health of children is causing their parents to be anxious and depressed isn’t it just as likely that this is a bidirectional connection? This was not exactly an “aha” moment for me because it is a relationship I have considered for sometime. However, it is a concept that I have come to realize is receiving far too little attention.

There are exceptions. For example, a recent opinion piece in the New York Times by David French, “What if Kids Are Sad and Stressed Because Their Parents Are?” (March 19, 2023) echoes many of my concerns. Drawing on his experiences traveling around college campuses, Mr. French observes, “Just as parents are upset about their children’s anxiety and depression, children are anxious about their parent’s mental health.”

He notes that an August 2022 NBC News poll found that 58% of registered voters feel this country’s best days are behind it and joins me in imagining that this negative mind set is filtering down to the pediatric population. He acknowledges that there are other likely contributors to teen unhappiness including the ubiquity of smart phones, the secularization of society, and the media’s focus on the political divide. However, Mr. French wonders if the parenting style that results in childhood experiences that are dominated by adult supervision and protection may also be playing a large role.

In his conclusion, Mr. French asks us to consider “How much fear and anxiety should we import to our lives and homes?” as we adults search for an answer.

As I continued to drill down for other possible solutions, I encountered an avenue of psychological research that suggests that instead of, or in addition to, filtering out the anxiety-generating deluge of information, we begin to give some thought to how our beliefs may be coloring our perception of reality.

Jeremy D.W. Clifton, PhD, a psychologist at the University of Pennsylvania Positive Psychology Center has done extensive research on the relationship between our basic beliefs about the world (known as primal beliefs or simply primals in psychologist lingo) and how we interpret reality. For example, one of your primal beliefs may be that the world is a dangerous place. I, on the other hand, may see the world as a stimulating environment offering me endless opportunities to explore. I may see the world as an abundant resource limited only by my creativity. You, however, see it as a barren wasteland.

Dr. Clifton’s research has shown that our primals (at least those of adults) are relatively immutable through one’s lifetime and “do not appear to be the consequence of our experiences.” For example, living in a ZIP code with a high crime rate does not predict that you will see the world as a dangerous place. Nor does being affluent guarantee that an adult sees the world rich with opportunities.

It is unclear exactly when and by what process we develop our primal beliefs, but it is safe to say our parents probably play a large role. Exactly to what degree the tsunami of bad news we are allowing to inundate our children’s lives plays a role is unclear. However, it is reasonable to assume that news about climate change, school shootings, and the pandemic must be a contributor.

According to Dr. Clifton, there is some evidence that certain mind exercises, when applied diligently, can occasionally modify the primal beliefs of an individual who sees the world as dangerous and barren. Until such strategies become more readily accessible, the best we can do is acknowledge that our children are like canaries in a coal mine full of negative perceptions, then do our best to clear the air.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

PARIS – Childhood trauma affects women and men equally in terms of its impact on subsequent psychopathology, but trauma type has subsequent differential effects depending on gender, new research shows.

Investigators found childhood emotional and sexual abuse had a greater effect on women than men, whereas men were more adversely affected by emotional and physical neglect.

“Our findings indicate that exposure to childhood maltreatment increases the risk of having psychiatric symptoms in both men and women,” lead researcher Thanavadee Prachason, PhD, department of psychiatry and neuropsychology, Maastricht (the Netherlands) University Medical Center, said in a press release.

“Exposure to emotionally or sexually abusive experiences during childhood increases the risk of a variety of psychiatric symptoms, particularly in women. In contrast, a history of emotional or physical neglect in childhood increases the risk of having psychiatric symptoms more in men,” Dr. Prachason added.

The findings were presented at the European Psychiatric Association 2023 Congress.

A leading mental illness risk factor

Study presenter Laura Fusar-Poli, MD, PhD, from the department of brain and behavioral sciences, University of Pavia (Italy), said that the differential impact of trauma subtypes in men and women indicate that both gender and the type of childhood adversity experienced need to be taken into account in future studies.

Dr. Fusar-Poli began by highlighting that 13%-36% of individuals have experienced some kind of childhood trauma, with 30% exposed to at least two types of trauma.

Trauma has been identified as a risk factor for a range of mental health problems.

“It is estimated that, worldwide, around one third of all psychiatric disorders are related to childhood trauma,” senior researcher Sinan Gülöksüz, MD, PhD, also from Maastricht University Medical Center, said in the release.

Consequently, “childhood trauma is a leading preventable risk factor for mental illness,” he added.

Previous research suggests the subtype of trauma has an impact on subsequent biological changes and clinical outcomes, and that there are gender differences in the effects of childhood trauma.

To investigate, the researchers examined data from TwinssCan, a Belgian cohort of twins and siblings aged 15-35 years without a diagnosis of pervasive mental disorders.

The study included 477 females and 314 males who had completed the Childhood Trauma Questionnaire–Short Form (CTQ) and the Symptom Checklist-90 SR (SCL-90) to determine exposure to childhood adversity and levels of psychopathology, respectively.

Results showed that total CTQ scores were significantly associated with total SCL-90 scores in both men and women, as well as with each of the nine symptom domains of the SCL-90 (P < .001 for all assessments). These included psychoticism, paranoid ideation, anxiety, depression, somatization, obsessive-compulsive, interpersonal sensitivity, hostility, and phobic anxiety.

There were no significant differences in the associations with total CTQ scores between men and women.

However, when the researchers examined trauma subtypes and psychopathology, clear gender differences emerged.

Investigators found a significant association between emotional abuse on the CTQ and total SCL-90 scores in both men (P < .023) and women (P < .001), but that the association was significantly stronger in women (P = .043).

Sexual abuse was significantly associated with total SCL-90 scores in women (P < .001), while emotional neglect and physical neglect were significantly associated with psychopathology scores in men (P = .026 and P < .001, respectively).

“Physical neglect may include experiences of not having enough to eat, wearing dirty clothes, not being taken care of, and not getting taken to the doctor when the person was growing up,” said Dr. Prachason.

“Emotional neglect may include childhood experiences like not feeling loved or important, and not feeling close to the family.”

In women, emotional abuse was significantly associated with all nine symptom domains of the SCL-90, while sexual abuse was associated with seven: psychoticism, paranoid ideation, anxiety, depression, somatization, obsessive-compulsive, and hostility.

Physical neglect, in men, was significantly associated with eight of the symptom domains (all but somatization), but emotional neglect was linked only to depression, Dr. Fusar-Poli reported.

“This study showed a very important consequence of childhood trauma, and not only in people with mental disorders. I would like to underline that this is a general population, composed of adolescents and young adults, which is the age in which the majority of mental disorders starts, Dr. Fusar-Poli said in an interview.

She emphasized that psychotic disorders are only a part of the “broad range” of conditions that may be related to childhood trauma, which “can have an impact on sub-threshold symptoms that can affect functioning and quality of life in the general population.”

Addressing the differential findings in men and women, Dr. Gülöksüz noted women may be more “vulnerable to childhood trauma than men” simply because “they are exposed to more sexual and emotional abuse.”

However, he said, this is “something that we really need understand,” as there is likely an underlying mechanism, “and not only a biological mechanism but probably a societal one.”

Dr. Gülöksüz noted there could also be differences between societies in terms of the impact of childhood trauma. “Our sample was from Belgium, but what would happen if we conducted this study in Italy, or in India,” he said.

Compromised cognitive, emotional function

Commenting on the findings for this news organization, Elaine F. Walker, PhD, professor of psychology and neuroscience at Emory University in Atlanta, said stress exposure in general, including childhood trauma, “has transdiagnostic effects on vulnerability to mental disorders.”

“The effects are primarily mediated by the hypothalamic-pituitary-adrenal axis, which triggers the release of cortisol. When persistently elevated, this can result in neurobiological processes that have adverse effects on brain structure and circuitry which, in turn, compromises cognitive and emotional functioning,” said Dr. Walker, who was not associated with the study.

She noted that, “while it is possible that there are sex differences in biological sensitivity to certain subtypes of childhood trauma, it may also be the case that sex differences in the likelihood of exposure to trauma subtypes is actually the key factor.”

“At the present time, there are not specific treatment protocols aimed at addressing childhood trauma subtypes, but most experienced therapists will incorporate information about the individual’s trauma history in their treatment,” Dr. Walker added.

Also commenting on the research, Philip Gorwood, MD, PhD, head of the Clinique des Maladies Mentales et de l’Encéphale at Centre Hospitalier Sainte Anne in Paris, said the results are “important … as childhood trauma has been clearly recognized as a major risk factor for the vast majority of psychiatric disorders, but with poor knowledge of gender specificities.”

“Understanding which aspects of trauma are more damaging according to gender will facilitate research on the resilience process. Many intervention strategies will indeed benefit from a more personalized approach,” he said in a statement. Dr. Gorwood was not involved with this study.

The study authors, Dr. Gorwood, and Dr. Walker report no relevant financial relationships.

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

PARIS – Childhood trauma affects women and men equally in terms of its impact on subsequent psychopathology, but trauma type has subsequent differential effects depending on gender, new research shows.

Investigators found childhood emotional and sexual abuse had a greater effect on women than men, whereas men were more adversely affected by emotional and physical neglect.

“Our findings indicate that exposure to childhood maltreatment increases the risk of having psychiatric symptoms in both men and women,” lead researcher Thanavadee Prachason, PhD, department of psychiatry and neuropsychology, Maastricht (the Netherlands) University Medical Center, said in a press release.

“Exposure to emotionally or sexually abusive experiences during childhood increases the risk of a variety of psychiatric symptoms, particularly in women. In contrast, a history of emotional or physical neglect in childhood increases the risk of having psychiatric symptoms more in men,” Dr. Prachason added.

The findings were presented at the European Psychiatric Association 2023 Congress.

A leading mental illness risk factor

Study presenter Laura Fusar-Poli, MD, PhD, from the department of brain and behavioral sciences, University of Pavia (Italy), said that the differential impact of trauma subtypes in men and women indicate that both gender and the type of childhood adversity experienced need to be taken into account in future studies.

Dr. Fusar-Poli began by highlighting that 13%-36% of individuals have experienced some kind of childhood trauma, with 30% exposed to at least two types of trauma.

Trauma has been identified as a risk factor for a range of mental health problems.

“It is estimated that, worldwide, around one third of all psychiatric disorders are related to childhood trauma,” senior researcher Sinan Gülöksüz, MD, PhD, also from Maastricht University Medical Center, said in the release.

Consequently, “childhood trauma is a leading preventable risk factor for mental illness,” he added.

Previous research suggests the subtype of trauma has an impact on subsequent biological changes and clinical outcomes, and that there are gender differences in the effects of childhood trauma.

To investigate, the researchers examined data from TwinssCan, a Belgian cohort of twins and siblings aged 15-35 years without a diagnosis of pervasive mental disorders.

The study included 477 females and 314 males who had completed the Childhood Trauma Questionnaire–Short Form (CTQ) and the Symptom Checklist-90 SR (SCL-90) to determine exposure to childhood adversity and levels of psychopathology, respectively.

Results showed that total CTQ scores were significantly associated with total SCL-90 scores in both men and women, as well as with each of the nine symptom domains of the SCL-90 (P < .001 for all assessments). These included psychoticism, paranoid ideation, anxiety, depression, somatization, obsessive-compulsive, interpersonal sensitivity, hostility, and phobic anxiety.

There were no significant differences in the associations with total CTQ scores between men and women.

However, when the researchers examined trauma subtypes and psychopathology, clear gender differences emerged.

Investigators found a significant association between emotional abuse on the CTQ and total SCL-90 scores in both men (P < .023) and women (P < .001), but that the association was significantly stronger in women (P = .043).

Sexual abuse was significantly associated with total SCL-90 scores in women (P < .001), while emotional neglect and physical neglect were significantly associated with psychopathology scores in men (P = .026 and P < .001, respectively).

“Physical neglect may include experiences of not having enough to eat, wearing dirty clothes, not being taken care of, and not getting taken to the doctor when the person was growing up,” said Dr. Prachason.

“Emotional neglect may include childhood experiences like not feeling loved or important, and not feeling close to the family.”

In women, emotional abuse was significantly associated with all nine symptom domains of the SCL-90, while sexual abuse was associated with seven: psychoticism, paranoid ideation, anxiety, depression, somatization, obsessive-compulsive, and hostility.

Physical neglect, in men, was significantly associated with eight of the symptom domains (all but somatization), but emotional neglect was linked only to depression, Dr. Fusar-Poli reported.

“This study showed a very important consequence of childhood trauma, and not only in people with mental disorders. I would like to underline that this is a general population, composed of adolescents and young adults, which is the age in which the majority of mental disorders starts, Dr. Fusar-Poli said in an interview.

She emphasized that psychotic disorders are only a part of the “broad range” of conditions that may be related to childhood trauma, which “can have an impact on sub-threshold symptoms that can affect functioning and quality of life in the general population.”

Addressing the differential findings in men and women, Dr. Gülöksüz noted women may be more “vulnerable to childhood trauma than men” simply because “they are exposed to more sexual and emotional abuse.”

However, he said, this is “something that we really need understand,” as there is likely an underlying mechanism, “and not only a biological mechanism but probably a societal one.”

Dr. Gülöksüz noted there could also be differences between societies in terms of the impact of childhood trauma. “Our sample was from Belgium, but what would happen if we conducted this study in Italy, or in India,” he said.

Compromised cognitive, emotional function

Commenting on the findings for this news organization, Elaine F. Walker, PhD, professor of psychology and neuroscience at Emory University in Atlanta, said stress exposure in general, including childhood trauma, “has transdiagnostic effects on vulnerability to mental disorders.”

“The effects are primarily mediated by the hypothalamic-pituitary-adrenal axis, which triggers the release of cortisol. When persistently elevated, this can result in neurobiological processes that have adverse effects on brain structure and circuitry which, in turn, compromises cognitive and emotional functioning,” said Dr. Walker, who was not associated with the study.

She noted that, “while it is possible that there are sex differences in biological sensitivity to certain subtypes of childhood trauma, it may also be the case that sex differences in the likelihood of exposure to trauma subtypes is actually the key factor.”

“At the present time, there are not specific treatment protocols aimed at addressing childhood trauma subtypes, but most experienced therapists will incorporate information about the individual’s trauma history in their treatment,” Dr. Walker added.

Also commenting on the research, Philip Gorwood, MD, PhD, head of the Clinique des Maladies Mentales et de l’Encéphale at Centre Hospitalier Sainte Anne in Paris, said the results are “important … as childhood trauma has been clearly recognized as a major risk factor for the vast majority of psychiatric disorders, but with poor knowledge of gender specificities.”

“Understanding which aspects of trauma are more damaging according to gender will facilitate research on the resilience process. Many intervention strategies will indeed benefit from a more personalized approach,” he said in a statement. Dr. Gorwood was not involved with this study.

The study authors, Dr. Gorwood, and Dr. Walker report no relevant financial relationships.

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

PARIS – Childhood trauma affects women and men equally in terms of its impact on subsequent psychopathology, but trauma type has subsequent differential effects depending on gender, new research shows.

Investigators found childhood emotional and sexual abuse had a greater effect on women than men, whereas men were more adversely affected by emotional and physical neglect.

“Our findings indicate that exposure to childhood maltreatment increases the risk of having psychiatric symptoms in both men and women,” lead researcher Thanavadee Prachason, PhD, department of psychiatry and neuropsychology, Maastricht (the Netherlands) University Medical Center, said in a press release.

“Exposure to emotionally or sexually abusive experiences during childhood increases the risk of a variety of psychiatric symptoms, particularly in women. In contrast, a history of emotional or physical neglect in childhood increases the risk of having psychiatric symptoms more in men,” Dr. Prachason added.

The findings were presented at the European Psychiatric Association 2023 Congress.

A leading mental illness risk factor

Study presenter Laura Fusar-Poli, MD, PhD, from the department of brain and behavioral sciences, University of Pavia (Italy), said that the differential impact of trauma subtypes in men and women indicate that both gender and the type of childhood adversity experienced need to be taken into account in future studies.

Dr. Fusar-Poli began by highlighting that 13%-36% of individuals have experienced some kind of childhood trauma, with 30% exposed to at least two types of trauma.

Trauma has been identified as a risk factor for a range of mental health problems.

“It is estimated that, worldwide, around one third of all psychiatric disorders are related to childhood trauma,” senior researcher Sinan Gülöksüz, MD, PhD, also from Maastricht University Medical Center, said in the release.

Consequently, “childhood trauma is a leading preventable risk factor for mental illness,” he added.

Previous research suggests the subtype of trauma has an impact on subsequent biological changes and clinical outcomes, and that there are gender differences in the effects of childhood trauma.

To investigate, the researchers examined data from TwinssCan, a Belgian cohort of twins and siblings aged 15-35 years without a diagnosis of pervasive mental disorders.

The study included 477 females and 314 males who had completed the Childhood Trauma Questionnaire–Short Form (CTQ) and the Symptom Checklist-90 SR (SCL-90) to determine exposure to childhood adversity and levels of psychopathology, respectively.

Results showed that total CTQ scores were significantly associated with total SCL-90 scores in both men and women, as well as with each of the nine symptom domains of the SCL-90 (P < .001 for all assessments). These included psychoticism, paranoid ideation, anxiety, depression, somatization, obsessive-compulsive, interpersonal sensitivity, hostility, and phobic anxiety.

There were no significant differences in the associations with total CTQ scores between men and women.

However, when the researchers examined trauma subtypes and psychopathology, clear gender differences emerged.

Investigators found a significant association between emotional abuse on the CTQ and total SCL-90 scores in both men (P < .023) and women (P < .001), but that the association was significantly stronger in women (P = .043).

Sexual abuse was significantly associated with total SCL-90 scores in women (P < .001), while emotional neglect and physical neglect were significantly associated with psychopathology scores in men (P = .026 and P < .001, respectively).

“Physical neglect may include experiences of not having enough to eat, wearing dirty clothes, not being taken care of, and not getting taken to the doctor when the person was growing up,” said Dr. Prachason.

“Emotional neglect may include childhood experiences like not feeling loved or important, and not feeling close to the family.”

In women, emotional abuse was significantly associated with all nine symptom domains of the SCL-90, while sexual abuse was associated with seven: psychoticism, paranoid ideation, anxiety, depression, somatization, obsessive-compulsive, and hostility.

Physical neglect, in men, was significantly associated with eight of the symptom domains (all but somatization), but emotional neglect was linked only to depression, Dr. Fusar-Poli reported.

“This study showed a very important consequence of childhood trauma, and not only in people with mental disorders. I would like to underline that this is a general population, composed of adolescents and young adults, which is the age in which the majority of mental disorders starts, Dr. Fusar-Poli said in an interview.

She emphasized that psychotic disorders are only a part of the “broad range” of conditions that may be related to childhood trauma, which “can have an impact on sub-threshold symptoms that can affect functioning and quality of life in the general population.”

Addressing the differential findings in men and women, Dr. Gülöksüz noted women may be more “vulnerable to childhood trauma than men” simply because “they are exposed to more sexual and emotional abuse.”

However, he said, this is “something that we really need understand,” as there is likely an underlying mechanism, “and not only a biological mechanism but probably a societal one.”

Dr. Gülöksüz noted there could also be differences between societies in terms of the impact of childhood trauma. “Our sample was from Belgium, but what would happen if we conducted this study in Italy, or in India,” he said.

Compromised cognitive, emotional function

Commenting on the findings for this news organization, Elaine F. Walker, PhD, professor of psychology and neuroscience at Emory University in Atlanta, said stress exposure in general, including childhood trauma, “has transdiagnostic effects on vulnerability to mental disorders.”

“The effects are primarily mediated by the hypothalamic-pituitary-adrenal axis, which triggers the release of cortisol. When persistently elevated, this can result in neurobiological processes that have adverse effects on brain structure and circuitry which, in turn, compromises cognitive and emotional functioning,” said Dr. Walker, who was not associated with the study.

She noted that, “while it is possible that there are sex differences in biological sensitivity to certain subtypes of childhood trauma, it may also be the case that sex differences in the likelihood of exposure to trauma subtypes is actually the key factor.”

“At the present time, there are not specific treatment protocols aimed at addressing childhood trauma subtypes, but most experienced therapists will incorporate information about the individual’s trauma history in their treatment,” Dr. Walker added.

Also commenting on the research, Philip Gorwood, MD, PhD, head of the Clinique des Maladies Mentales et de l’Encéphale at Centre Hospitalier Sainte Anne in Paris, said the results are “important … as childhood trauma has been clearly recognized as a major risk factor for the vast majority of psychiatric disorders, but with poor knowledge of gender specificities.”

“Understanding which aspects of trauma are more damaging according to gender will facilitate research on the resilience process. Many intervention strategies will indeed benefit from a more personalized approach,” he said in a statement. Dr. Gorwood was not involved with this study.

The study authors, Dr. Gorwood, and Dr. Walker report no relevant financial relationships.

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

An intervention tailored for Black first-time mothers helped increase their infants’ sleep time, researchers have found, a notable result as many studies have shown Black infants get less sleep on average than White infants.

Less sleep has historically put Black children at higher risk for negative outcomes including obesity and poorer social-emotional functioning and cognitive development. These disparities persist into adulthood, the researchers note, as previous studies have shown.

Justin A. Lavner, PhD, with the department of psychology at the University of Georgia in Athens, led this post hoc secondary analysis of the Sleep SAAF (Strong African American Families) study, a randomized clinical trial of 234 participants comparing a responsive parenting (RP) intervention with a safety control group over the first 16 weeks post partum. The original analysis studied the effects of the intervention on rapid weight gain.

In the original analysis, the authors write that “From birth to 2, the prevalence of high weight for length (above the 95th percentile) is 25% higher among African American children compared to White children. From age 2 to 19, the rate of obesity is more than 50% higher among African American children compared to White children. Similar disparities persist into adulthood: rates of obesity are approximately 25% higher among African American adults compared to White adults.”

The differences in early rapid weight gain may be driving the disparities, the authors write.

Elements of the intervention

The intervention in the current analysis included materials delivered at the 3- and 8-week home visits focused on soothing and crying, feeding, and interactive play in the babies’ first months. Families were recruited from Augusta University Medical Center in Augusta, Ga., and had home visits at 1, 3, 8, and 16 weeks post partum.

Mothers got a packet of handouts and facilitators walked through the information with them. The measures involved hands-on activities, discussion, and videos, all tailored for Black families, the authors state.

Mothers were taught about responding appropriately at night when their baby cries, including giving the baby a couple of minutes to fall back to sleep independently and by using calming messages, such as shushing or white noise, before picking the baby up.
 

Babies learn to fall asleep on their own

They also learned to put infants to bed early (ideally by 8 p.m.) so the babies would be calm but awake and could learn to fall asleep on their own.

The control group’s guidance was matched for intensity and session length but focused on sleep and home safety, such as reducing the risk of sudden infant death syndrome (SIDS), keeping the baby’s sleep area close to, but away from, the mother’s bed, and preventing shaken baby syndrome.

In both groups, the 3-week visit session lasted about 90-120 minutes and the 8-week visit lasted about 45-60 minutes.
 

Longer sleep with the intervention

A total of 212 Black mothers, average age 22.7, were randomized – 108 to the RP group and 104 to the control group. Answers on questionnaires were analyzed and at 16 weeks post partum, infants in the RP group (relative to controls) had:

• Longer reported nighttime sleep (mean difference, 40 minutes [95% confidence interval, 3-77]).
• Longer total sleep duration (mean difference, 73 minutes [95% CI, 14-131]).
• Fewer nighttime wakings (mean difference, −0.4 wakings [95% CI, −0.6 to −0.1]).
• Greater likelihood of meeting guidelines of at least 12 hours of sleep per day (risk ratio, 1.4 [95% CI, 1.1 to 1.8]) than controls.

Findings were published in JAMA Network Open.

Additionally, mothers in the RP group more frequently reported they engaged in practices such as letting babies have a few minutes to fall back to sleep on their own (RR, 1.6 [95% CI, 1.0-2.6]) and being less likely to feed their infant just before the baby’s bedtime (RR, 0.5 [95% CI, 0.3-0.8]).

In an accompanying invited commentary, Sarah M. Honaker, PhD, department of pediatrics, Indiana University, Indianapolis, and Alicia Chung, EdD, Center for Early Childhood Health and Development at New York University, write that though the added average sleep duration is one of the most significant findings, there is a possibility of desirability bias because it was reported by the mothers after specific guidance by the facilitators.

“Nonetheless,” the editorialists write, “even if the true effect were half as small, this additional sleep duration could yield notable benefits in infant development if the effect persisted over time. The difference in night wakings between the intervention and control groups (1.8 vs 1.5 per night) at 16 weeks postpartum was statistically significant, though it is unclear whether this difference is clinically meaningful to families.”

They note that it is unclear from the study how the intervention was culturally adapted and how the adaptation might have affected outcomes.

Sleep intervention trials have focused on White families

The editorialists write that much is known about the benefits of behavioral sleep intervention in controlled trials and general population settings, and no adverse effects on infant attachment or cortisol levels have been linked to the interventions.

However, they add, “Unfortunately, this substantial progress in our understanding of infant BSI [behavioral sleep intervention] comes with a caveat, in that most previous studies have been performed with White families from mid-to-high socioeconomic backgrounds.”

Dr. Honaker and Dr. Chung write, “[I]t is important to note that much work remains to examine the acceptability, feasibility, and efficacy of infant BSI in other groups that have been historically marginalized.”

Dr. Lavner and colleagues point out that before their study, there had been little emphasis on interventions to encourage better sleep in general for Black infants, “as most early sleep interventions for this population have focused on SIDS prevention.”

The study by Dr. Lavner et al. was funded by the National Institutes of Health, a Harrington Faculty Fellowship from the University of Texas, and an award from the Penn State Clinical and Translational Sciences Institute supported by the National Center for Advancing Translational Sciences. Editorialist Dr. Honaker reported receiving grants from Nationwide Children’s Hospital (parent grant, Centers for Disease Control and Prevention) to evaluate the acceptability of infant behavioral sleep intervention in Black families.

An intervention tailored for Black first-time mothers helped increase their infants’ sleep time, researchers have found, a notable result as many studies have shown Black infants get less sleep on average than White infants.

Less sleep has historically put Black children at higher risk for negative outcomes including obesity and poorer social-emotional functioning and cognitive development. These disparities persist into adulthood, the researchers note, as previous studies have shown.

Justin A. Lavner, PhD, with the department of psychology at the University of Georgia in Athens, led this post hoc secondary analysis of the Sleep SAAF (Strong African American Families) study, a randomized clinical trial of 234 participants comparing a responsive parenting (RP) intervention with a safety control group over the first 16 weeks post partum. The original analysis studied the effects of the intervention on rapid weight gain.

In the original analysis, the authors write that “From birth to 2, the prevalence of high weight for length (above the 95th percentile) is 25% higher among African American children compared to White children. From age 2 to 19, the rate of obesity is more than 50% higher among African American children compared to White children. Similar disparities persist into adulthood: rates of obesity are approximately 25% higher among African American adults compared to White adults.”

The differences in early rapid weight gain may be driving the disparities, the authors write.

Elements of the intervention

The intervention in the current analysis included materials delivered at the 3- and 8-week home visits focused on soothing and crying, feeding, and interactive play in the babies’ first months. Families were recruited from Augusta University Medical Center in Augusta, Ga., and had home visits at 1, 3, 8, and 16 weeks post partum.

Mothers got a packet of handouts and facilitators walked through the information with them. The measures involved hands-on activities, discussion, and videos, all tailored for Black families, the authors state.

Mothers were taught about responding appropriately at night when their baby cries, including giving the baby a couple of minutes to fall back to sleep independently and by using calming messages, such as shushing or white noise, before picking the baby up.
 

Babies learn to fall asleep on their own

They also learned to put infants to bed early (ideally by 8 p.m.) so the babies would be calm but awake and could learn to fall asleep on their own.

The control group’s guidance was matched for intensity and session length but focused on sleep and home safety, such as reducing the risk of sudden infant death syndrome (SIDS), keeping the baby’s sleep area close to, but away from, the mother’s bed, and preventing shaken baby syndrome.

In both groups, the 3-week visit session lasted about 90-120 minutes and the 8-week visit lasted about 45-60 minutes.
 

Longer sleep with the intervention

A total of 212 Black mothers, average age 22.7, were randomized – 108 to the RP group and 104 to the control group. Answers on questionnaires were analyzed and at 16 weeks post partum, infants in the RP group (relative to controls) had:

• Longer reported nighttime sleep (mean difference, 40 minutes [95% confidence interval, 3-77]).
• Longer total sleep duration (mean difference, 73 minutes [95% CI, 14-131]).
• Fewer nighttime wakings (mean difference, −0.4 wakings [95% CI, −0.6 to −0.1]).
• Greater likelihood of meeting guidelines of at least 12 hours of sleep per day (risk ratio, 1.4 [95% CI, 1.1 to 1.8]) than controls.

Findings were published in JAMA Network Open.

Additionally, mothers in the RP group more frequently reported they engaged in practices such as letting babies have a few minutes to fall back to sleep on their own (RR, 1.6 [95% CI, 1.0-2.6]) and being less likely to feed their infant just before the baby’s bedtime (RR, 0.5 [95% CI, 0.3-0.8]).

In an accompanying invited commentary, Sarah M. Honaker, PhD, department of pediatrics, Indiana University, Indianapolis, and Alicia Chung, EdD, Center for Early Childhood Health and Development at New York University, write that though the added average sleep duration is one of the most significant findings, there is a possibility of desirability bias because it was reported by the mothers after specific guidance by the facilitators.

“Nonetheless,” the editorialists write, “even if the true effect were half as small, this additional sleep duration could yield notable benefits in infant development if the effect persisted over time. The difference in night wakings between the intervention and control groups (1.8 vs 1.5 per night) at 16 weeks postpartum was statistically significant, though it is unclear whether this difference is clinically meaningful to families.”

They note that it is unclear from the study how the intervention was culturally adapted and how the adaptation might have affected outcomes.

Sleep intervention trials have focused on White families

The editorialists write that much is known about the benefits of behavioral sleep intervention in controlled trials and general population settings, and no adverse effects on infant attachment or cortisol levels have been linked to the interventions.

However, they add, “Unfortunately, this substantial progress in our understanding of infant BSI [behavioral sleep intervention] comes with a caveat, in that most previous studies have been performed with White families from mid-to-high socioeconomic backgrounds.”

Dr. Honaker and Dr. Chung write, “[I]t is important to note that much work remains to examine the acceptability, feasibility, and efficacy of infant BSI in other groups that have been historically marginalized.”

Dr. Lavner and colleagues point out that before their study, there had been little emphasis on interventions to encourage better sleep in general for Black infants, “as most early sleep interventions for this population have focused on SIDS prevention.”

The study by Dr. Lavner et al. was funded by the National Institutes of Health, a Harrington Faculty Fellowship from the University of Texas, and an award from the Penn State Clinical and Translational Sciences Institute supported by the National Center for Advancing Translational Sciences. Editorialist Dr. Honaker reported receiving grants from Nationwide Children’s Hospital (parent grant, Centers for Disease Control and Prevention) to evaluate the acceptability of infant behavioral sleep intervention in Black families.

An intervention tailored for Black first-time mothers helped increase their infants’ sleep time, researchers have found, a notable result as many studies have shown Black infants get less sleep on average than White infants.

Less sleep has historically put Black children at higher risk for negative outcomes including obesity and poorer social-emotional functioning and cognitive development. These disparities persist into adulthood, the researchers note, as previous studies have shown.

Justin A. Lavner, PhD, with the department of psychology at the University of Georgia in Athens, led this post hoc secondary analysis of the Sleep SAAF (Strong African American Families) study, a randomized clinical trial of 234 participants comparing a responsive parenting (RP) intervention with a safety control group over the first 16 weeks post partum. The original analysis studied the effects of the intervention on rapid weight gain.

In the original analysis, the authors write that “From birth to 2, the prevalence of high weight for length (above the 95th percentile) is 25% higher among African American children compared to White children. From age 2 to 19, the rate of obesity is more than 50% higher among African American children compared to White children. Similar disparities persist into adulthood: rates of obesity are approximately 25% higher among African American adults compared to White adults.”

The differences in early rapid weight gain may be driving the disparities, the authors write.

Elements of the intervention

The intervention in the current analysis included materials delivered at the 3- and 8-week home visits focused on soothing and crying, feeding, and interactive play in the babies’ first months. Families were recruited from Augusta University Medical Center in Augusta, Ga., and had home visits at 1, 3, 8, and 16 weeks post partum.

Mothers got a packet of handouts and facilitators walked through the information with them. The measures involved hands-on activities, discussion, and videos, all tailored for Black families, the authors state.

Mothers were taught about responding appropriately at night when their baby cries, including giving the baby a couple of minutes to fall back to sleep independently and by using calming messages, such as shushing or white noise, before picking the baby up.
 

Babies learn to fall asleep on their own

They also learned to put infants to bed early (ideally by 8 p.m.) so the babies would be calm but awake and could learn to fall asleep on their own.

The control group’s guidance was matched for intensity and session length but focused on sleep and home safety, such as reducing the risk of sudden infant death syndrome (SIDS), keeping the baby’s sleep area close to, but away from, the mother’s bed, and preventing shaken baby syndrome.

In both groups, the 3-week visit session lasted about 90-120 minutes and the 8-week visit lasted about 45-60 minutes.
 

Longer sleep with the intervention

A total of 212 Black mothers, average age 22.7, were randomized – 108 to the RP group and 104 to the control group. Answers on questionnaires were analyzed and at 16 weeks post partum, infants in the RP group (relative to controls) had:

• Longer reported nighttime sleep (mean difference, 40 minutes [95% confidence interval, 3-77]).
• Longer total sleep duration (mean difference, 73 minutes [95% CI, 14-131]).
• Fewer nighttime wakings (mean difference, −0.4 wakings [95% CI, −0.6 to −0.1]).
• Greater likelihood of meeting guidelines of at least 12 hours of sleep per day (risk ratio, 1.4 [95% CI, 1.1 to 1.8]) than controls.

Findings were published in JAMA Network Open.

Additionally, mothers in the RP group more frequently reported they engaged in practices such as letting babies have a few minutes to fall back to sleep on their own (RR, 1.6 [95% CI, 1.0-2.6]) and being less likely to feed their infant just before the baby’s bedtime (RR, 0.5 [95% CI, 0.3-0.8]).

In an accompanying invited commentary, Sarah M. Honaker, PhD, department of pediatrics, Indiana University, Indianapolis, and Alicia Chung, EdD, Center for Early Childhood Health and Development at New York University, write that though the added average sleep duration is one of the most significant findings, there is a possibility of desirability bias because it was reported by the mothers after specific guidance by the facilitators.

“Nonetheless,” the editorialists write, “even if the true effect were half as small, this additional sleep duration could yield notable benefits in infant development if the effect persisted over time. The difference in night wakings between the intervention and control groups (1.8 vs 1.5 per night) at 16 weeks postpartum was statistically significant, though it is unclear whether this difference is clinically meaningful to families.”

They note that it is unclear from the study how the intervention was culturally adapted and how the adaptation might have affected outcomes.

Sleep intervention trials have focused on White families

The editorialists write that much is known about the benefits of behavioral sleep intervention in controlled trials and general population settings, and no adverse effects on infant attachment or cortisol levels have been linked to the interventions.

However, they add, “Unfortunately, this substantial progress in our understanding of infant BSI [behavioral sleep intervention] comes with a caveat, in that most previous studies have been performed with White families from mid-to-high socioeconomic backgrounds.”

Dr. Honaker and Dr. Chung write, “[I]t is important to note that much work remains to examine the acceptability, feasibility, and efficacy of infant BSI in other groups that have been historically marginalized.”

Dr. Lavner and colleagues point out that before their study, there had been little emphasis on interventions to encourage better sleep in general for Black infants, “as most early sleep interventions for this population have focused on SIDS prevention.”

The study by Dr. Lavner et al. was funded by the National Institutes of Health, a Harrington Faculty Fellowship from the University of Texas, and an award from the Penn State Clinical and Translational Sciences Institute supported by the National Center for Advancing Translational Sciences. Editorialist Dr. Honaker reported receiving grants from Nationwide Children’s Hospital (parent grant, Centers for Disease Control and Prevention) to evaluate the acceptability of infant behavioral sleep intervention in Black families.

Imaging tests may miss early signs of multiple sclerosis (MS) in children who have no symptoms of the disease, according to a recent study that points to the need for a change in diagnostic criteria for the neuromuscular condition.

The findings suggest that children, unlike adults, may not need to meet the current clinical standard criteria to be considered at risk for MS.

“This is an important study confirming that some children who have no symptoms of demyelinating disease may nonetheless have MRI findings suggestive of demyelination detected on brain imaging,” said Naila Makhani, MD, associate professor of pediatrics and of neurology at Yale University and director of the Yale Pediatric Neuroimmunology Program, New Haven, Conn. Dr. Makhani was not affiliated with the study.

Researchers reviewed the MRI scans of 38 children aged 7-17 years who had radiologically isolated syndrome (RIS), a possible precursor to MS.

Like MS, RIS is characterized by destruction of the myelin. However, RIS is generally asymptomatic.

While RIS has been linked to MS, a diagnosis of RIS does not mean someone will be diagnosed with MS. Previous studies have shown that at least 3% of MS cases begin before age 16.

The children in the study likely received an MRI because of complaints of headaches or after having been diagnosed with a concussion, according to the researchers. The participants also did not show physical symptoms for MS, nor did they meet the McDonald or Barkohf criteria, which are clinical standards used to diagnose the condition in adults and children.

Within an average of 3 years following the imaging and RIS diagnosis, almost 36% of the children experienced a clinical attack, which led to an MS diagnosis. Almost three-fourths of the children developed additional brain and spinal cord lesions in the myelin that were evident on MRI.

MS often is diagnosed after a patient has had a clinical attack, such as vision impairment, loss of balance, inflammation, or severe fatigue. Identifying the potential for the disease earlier may allow clinicians to treat sooner, according to Leslie Benson, MD, assistant director of pediatric neuroimmunology at Massachusetts General Hospital, Boston, and one of the study authors.

“The field is leaning toward [the question of], ‘Should we treat presymptomatic MS?’ ” said Dr. Benson. “If we have the opportunity to prevent disability and improve long-term outcomes with safe medications, then we would like to do so.”

The findings were published in the journal Multiple Sclerosis and Related Disorders.

According to Dr. Benson and her colleagues, adjustments to the McDonald or Barkohf criteria for children may help in the detection of RIS and may allow earlier identification of MS.

“We don’t really know when MS first starts,” Dr. Benson said. “Unless you happen to have an MRI or symptoms, there’s no way to know how long the lesions have been evolving and how long the disease progression that led to those lesions has been there.”

MRI images showing lesions in the brain stem and spinal cord of children appeared to be different from those typically seen in adults, according to Tanuja Chitnis, MD, director of the Mass General Brigham Pediatric MS Center in Boston, who is one of the study’s coauthors.

“The concern of many practitioners is whether we should be treating at the first sign of MS,” Dr. Chitnis said. “We need to understand it better in children, and in teenagers especially, when these probably start biologically.”

Dr. Benson said current criteria for diagnosing MS in children require meeting a high threshold, which may limit diagnoses to those whose condition has progressed.

“This may miss patients at risk for MS,” Dr. Benson said. “That idea of who do you diagnose RIS and what criteria work to accurately diagnose RIS is really important.”

For now, the challenge remains of investigating characteristics of patients with RIS who will later have a clinical attack.

“We need a better understanding of what criteria do need to be met and how we can best risk-stratify our patients,” Dr. Benson said. “If it is recommended to treat presymptomatic cases, that we can best stratify those at risk and not overtreat those not at risk.”

Dr. Makhani receives funding from the National Institutes of Health, the Charles H. Hood Foundation, and the Multiple Sclerosis Society.

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

Imaging tests may miss early signs of multiple sclerosis (MS) in children who have no symptoms of the disease, according to a recent study that points to the need for a change in diagnostic criteria for the neuromuscular condition.

The findings suggest that children, unlike adults, may not need to meet the current clinical standard criteria to be considered at risk for MS.

“This is an important study confirming that some children who have no symptoms of demyelinating disease may nonetheless have MRI findings suggestive of demyelination detected on brain imaging,” said Naila Makhani, MD, associate professor of pediatrics and of neurology at Yale University and director of the Yale Pediatric Neuroimmunology Program, New Haven, Conn. Dr. Makhani was not affiliated with the study.

Researchers reviewed the MRI scans of 38 children aged 7-17 years who had radiologically isolated syndrome (RIS), a possible precursor to MS.

Like MS, RIS is characterized by destruction of the myelin. However, RIS is generally asymptomatic.

While RIS has been linked to MS, a diagnosis of RIS does not mean someone will be diagnosed with MS. Previous studies have shown that at least 3% of MS cases begin before age 16.

The children in the study likely received an MRI because of complaints of headaches or after having been diagnosed with a concussion, according to the researchers. The participants also did not show physical symptoms for MS, nor did they meet the McDonald or Barkohf criteria, which are clinical standards used to diagnose the condition in adults and children.

Within an average of 3 years following the imaging and RIS diagnosis, almost 36% of the children experienced a clinical attack, which led to an MS diagnosis. Almost three-fourths of the children developed additional brain and spinal cord lesions in the myelin that were evident on MRI.

MS often is diagnosed after a patient has had a clinical attack, such as vision impairment, loss of balance, inflammation, or severe fatigue. Identifying the potential for the disease earlier may allow clinicians to treat sooner, according to Leslie Benson, MD, assistant director of pediatric neuroimmunology at Massachusetts General Hospital, Boston, and one of the study authors.

“The field is leaning toward [the question of], ‘Should we treat presymptomatic MS?’ ” said Dr. Benson. “If we have the opportunity to prevent disability and improve long-term outcomes with safe medications, then we would like to do so.”

The findings were published in the journal Multiple Sclerosis and Related Disorders.

According to Dr. Benson and her colleagues, adjustments to the McDonald or Barkohf criteria for children may help in the detection of RIS and may allow earlier identification of MS.

“We don’t really know when MS first starts,” Dr. Benson said. “Unless you happen to have an MRI or symptoms, there’s no way to know how long the lesions have been evolving and how long the disease progression that led to those lesions has been there.”

MRI images showing lesions in the brain stem and spinal cord of children appeared to be different from those typically seen in adults, according to Tanuja Chitnis, MD, director of the Mass General Brigham Pediatric MS Center in Boston, who is one of the study’s coauthors.

“The concern of many practitioners is whether we should be treating at the first sign of MS,” Dr. Chitnis said. “We need to understand it better in children, and in teenagers especially, when these probably start biologically.”

Dr. Benson said current criteria for diagnosing MS in children require meeting a high threshold, which may limit diagnoses to those whose condition has progressed.

“This may miss patients at risk for MS,” Dr. Benson said. “That idea of who do you diagnose RIS and what criteria work to accurately diagnose RIS is really important.”

For now, the challenge remains of investigating characteristics of patients with RIS who will later have a clinical attack.

“We need a better understanding of what criteria do need to be met and how we can best risk-stratify our patients,” Dr. Benson said. “If it is recommended to treat presymptomatic cases, that we can best stratify those at risk and not overtreat those not at risk.”

Dr. Makhani receives funding from the National Institutes of Health, the Charles H. Hood Foundation, and the Multiple Sclerosis Society.

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

Imaging tests may miss early signs of multiple sclerosis (MS) in children who have no symptoms of the disease, according to a recent study that points to the need for a change in diagnostic criteria for the neuromuscular condition.

The findings suggest that children, unlike adults, may not need to meet the current clinical standard criteria to be considered at risk for MS.

“This is an important study confirming that some children who have no symptoms of demyelinating disease may nonetheless have MRI findings suggestive of demyelination detected on brain imaging,” said Naila Makhani, MD, associate professor of pediatrics and of neurology at Yale University and director of the Yale Pediatric Neuroimmunology Program, New Haven, Conn. Dr. Makhani was not affiliated with the study.

Researchers reviewed the MRI scans of 38 children aged 7-17 years who had radiologically isolated syndrome (RIS), a possible precursor to MS.

Like MS, RIS is characterized by destruction of the myelin. However, RIS is generally asymptomatic.

While RIS has been linked to MS, a diagnosis of RIS does not mean someone will be diagnosed with MS. Previous studies have shown that at least 3% of MS cases begin before age 16.

The children in the study likely received an MRI because of complaints of headaches or after having been diagnosed with a concussion, according to the researchers. The participants also did not show physical symptoms for MS, nor did they meet the McDonald or Barkohf criteria, which are clinical standards used to diagnose the condition in adults and children.

Within an average of 3 years following the imaging and RIS diagnosis, almost 36% of the children experienced a clinical attack, which led to an MS diagnosis. Almost three-fourths of the children developed additional brain and spinal cord lesions in the myelin that were evident on MRI.

MS often is diagnosed after a patient has had a clinical attack, such as vision impairment, loss of balance, inflammation, or severe fatigue. Identifying the potential for the disease earlier may allow clinicians to treat sooner, according to Leslie Benson, MD, assistant director of pediatric neuroimmunology at Massachusetts General Hospital, Boston, and one of the study authors.

“The field is leaning toward [the question of], ‘Should we treat presymptomatic MS?’ ” said Dr. Benson. “If we have the opportunity to prevent disability and improve long-term outcomes with safe medications, then we would like to do so.”

The findings were published in the journal Multiple Sclerosis and Related Disorders.

According to Dr. Benson and her colleagues, adjustments to the McDonald or Barkohf criteria for children may help in the detection of RIS and may allow earlier identification of MS.

“We don’t really know when MS first starts,” Dr. Benson said. “Unless you happen to have an MRI or symptoms, there’s no way to know how long the lesions have been evolving and how long the disease progression that led to those lesions has been there.”

MRI images showing lesions in the brain stem and spinal cord of children appeared to be different from those typically seen in adults, according to Tanuja Chitnis, MD, director of the Mass General Brigham Pediatric MS Center in Boston, who is one of the study’s coauthors.

“The concern of many practitioners is whether we should be treating at the first sign of MS,” Dr. Chitnis said. “We need to understand it better in children, and in teenagers especially, when these probably start biologically.”

Dr. Benson said current criteria for diagnosing MS in children require meeting a high threshold, which may limit diagnoses to those whose condition has progressed.

“This may miss patients at risk for MS,” Dr. Benson said. “That idea of who do you diagnose RIS and what criteria work to accurately diagnose RIS is really important.”

For now, the challenge remains of investigating characteristics of patients with RIS who will later have a clinical attack.

“We need a better understanding of what criteria do need to be met and how we can best risk-stratify our patients,” Dr. Benson said. “If it is recommended to treat presymptomatic cases, that we can best stratify those at risk and not overtreat those not at risk.”

Dr. Makhani receives funding from the National Institutes of Health, the Charles H. Hood Foundation, and the Multiple Sclerosis Society.

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

Rheumatologist Marcus Snow, MD, is comfortable with prescribing biosimilars as a first-line, first-time biologic, and discussing them with patients.

“If a biosimilar is on the market, it has gone through rigorous study proving its effectiveness and equivalence to a bio-originator,” said Dr. Snow, a rheumatologist with the University of Nebraska Medical Center, Omaha, and chair of the American College of Rheumatology’s Committee on Rheumatologic Care.

The formulary makes a big difference in the conversation about options, he said. “The formularies dictate what we can prescribe. It may not be appropriate, but it is reality. The cost of biologics for a patient without insurance coverage makes it impossible to afford.”

He will often tell patients that he’ll fight any changes or formulary restrictions he does not agree with. “However, when I see patients in follow-up, even if there is no known change on the horizon, I may bring up biosimilars when we have a moment to chat about them to familiarize them with what may happen in the future.”

The need for patient education on biosimilars presents a barrier to realizing their potential to save money and expand choice, noted Cardinal Health in its 2023 biosimilars report. Of 103 rheumatologists who responded to a Cardinal Health survey, 85% agreed that patient education was important. But those conversations can take an uncomfortable turn if the patient pushes back against taking a biosimilar owing to cost or safety concerns.

It’s not uncommon for a patient to express some anxiety about biosimilars, especially if they’re doing well on a current treatment plan. Most patients do not want any changes that may lead to worsening disease control, Dr. Snow said.

Kaiser Permanente

Patients and physicians alike often don’t understand the mechanics of biosimilars. “There’s a lot of misinformation about this,” said Sameer Awsare, MD, an associate executive director for The Permanente Medical Group in Campbell, Calif. Patients should know that a biosimilar will be as clinically efficacious as the medicine they’ve been on, with the same safety profiles, said Dr. Awsare, who works with Kaiser Permanente’s pharmacy partners on biosimilars.
 

Insurance often drives the conversation

The global anti-inflammatory biologics market is anticipated to reach $150 billion by 2027, according to a recent CVS report. As of March 2023, the Food and Drug Administration had approved 40 biosimilars to 11 different reference products. There are 28 on the U.S. market and 100 more in development. Projected to save more than $180 billion over the next 5 years, they are anticipated to expand choice and drive competition.

Rheumatologists, dermatologists, and gastroenterologists are frequent prescribers, although their choices for immune-mediated inflammatory diseases are limited to tumor necrosis factor inhibitors (infliximab [Remicade] originator and adalimumab [Humira] originator) and anti-CD20 agents, such as rituximab (Rituxan) originator.

Benefit design or formulary usually dictates what medicine a patient receives. “Because of significantly higher out-of-pocket cost or formulary positioning, patients may end up with a generic or a biosimilar instead of a brand-name medicine or branded biologic,” said Robert Popovian, PharmD, MS, chief science policy officer of the Global Healthy Living Foundation.

Insurers rarely offer both Remicade and biosimilar infliximab, allowing the doctor to choose, said Miguel Regueiro, MD, chair of the Cleveland Clinic’s Digestive Disease & Surgery Institute, who prescribes infliximab biosimilars. Most often, the payer will choose the lower-cost biosimilar. “I am fine with the biosimilar, either as a new start or a switch from the reference product.”

However, the patient might feel differently. They can form an attachment to the reference medication if it has prevented severe illness. “They do not want to change, as they feel they are going on a ‘new’ medication that will not work as well,” Dr. Regueiro said.

This is where the education comes in: to reassure patients that a biosimilar will work just as well as the reference product. “For patients who have done well for years on a biologic, more time needs to be spent reassuring them and answering questions,” compared with a patient just starting on a biosimilar, he advised.

But not all physicians are quick to prescribe biosimilars.

Julie Miller Photography

Especially with psoriasis, which has so many strong options for reference drugs, a switch may be hard to justify, said dermatologist Stephanie K. Fabbro, MD, assistant professor at Northeast Ohio Medical University, Rootstown. “If I have a preference, I would rather switch a patient to a drug from a different class without a biosimilar option to reduce the possibility of pushback.”

Dr. Fabbro, part of the core faculty in the Riverside Methodist Hospital Dermatology Residency Program in Columbus, will share data from clinical trials and postmarket surveillance with patients to support her decision.
 

Conversations about cost

Patients may also push back if they don’t save money when switching to a biosimilar. “This dilemma raises the question of who is profiting when a biosimilar is dispensed,” Dr. Popovian said. Insurers and pharmacy benefit managers (PBMs) that take additional concessions from biopharmaceutical manufacturers in the form of rebates and fees will often pocket this money as profit instead of passing savings back to the patient to help reduce their out-of-pocket requirement, he added.

If an originator biologic and a biosimilar are available, “as a pharmacist, I will choose the medicine that will incur the lowest out-of-pocket cost for the patient,” Dr. Popovian said.

Discussing cost – and who dictates which biosimilar is on the formulary – is an important conversation to have with patients, said Vivek Kaul, MD, Segal-Watson Professor of Medicine at the University of Rochester (N.Y.) Medical Center.

Providing equivalent clinical efficacy while saving costs is the economic reality of biosimilars, Dr. Kaul said. Third-party payers regularly evaluate how to provide the same quality of care while saving money. Physicians and patients alike “must be mindful that as time goes on, if the science on biosimilars stays robust, if the adoption is more widespread and the cost-saving proposition turns out to be true, more formularies will be attracted to replacing the reference product with the biosimilar counterpart.”

Providers and patients can weigh the options if a formulary suddenly switches to a biosimilar, Dr. Kaul continued. “You can accept the novel product on the formulary or may have to face out-of-pocket expenses as a patient.” If providers and patients have concerns about the biosimilar, they can always appeal if there’s solid scientific evidence that supports reverting back to the reference product.

“If you think the biosimilar is equally efficacious, comes at a lower cost, and is right for the patient, then the providers should tell the patient that,” he added.

Some studies have questioned whether the biosimilars will save money, compared with the reference drug, Dr. Fabbro noted. Medicare, for example, may pay only for a certain percentage of an approved biosimilar, saddling the patient with a monthly copay costing thousands of dollars. “It is unclear whether biosimilar manufacturers will have the same level of patient support programs as the reference drug companies.”

For that reason, physicians should also inform patients about the robust patient assistance and copay assistance programs many reference drug manufacturers offer, she said.

Biosimilars 101: Familiarizing patients

Safety and ease of use are other common concerns about biosimilars. Patients may ask if the application is different, or why it’s advantageous to switch to a biosimilar, Dr. Awsare said.

Sometimes the syringe or injector for a biosimilar might look different from that of the originator drug, he said.

Anecdotally, Dr. Fabbro has heard stories of patients having injection reactions that they did not experience with the reference drug or having a disease flare-up after starting a biosimilar. 

rubberball/Getty Images

As is the case with reference products, in their conversations with patients, clinicians should address the adverse event profile of biosimilars, offering data points from published studies and clinical guidelines that support the use of these products. “There should be an emphasis on patient education around efficacy and any side effects, and how the profile of the reference product compares with a proposed biosimilar,” Dr. Kaul suggested.

When Dr. Snow discusses biosimilars and generics, “I make sure to share this in an understandable way based on the patient’s scientific background, or lack thereof,” he said. If there is enough time, he also discusses how European- and U.S.-sourced biologics are slightly different.

Pharmacists should tell patients to expect the same clinical outcomes from a biosimilar, Dr. Popovian said. However, if they have any reduction in efficacy or potential safety concerns, they should communicate with their physician or pharmacist immediately.

In Dr. Regueiro’s practice, a pharmacist specializing in inflammatory bowel disease often has a one-on-one meeting with patients to educate and answer questions. “Additionally, we provide them the Crohn’s and Colitis Foundation web link on biosimilars,” said Dr. Regueiro.
 

A village approach to education

When biosimilars first came out, there were no formal education materials, Dr. Awsare said. Kaiser Permanente decided to create its own educational materials, not just for patients but also to help educate its primary care doctors; the rheumatologists, dermatologists, and gastroenterologists using the biosimilars; the nurses infusing patients; and the pharmacists preparing the biosimilars.

The health system also has a different approach to choosing medication. Instead of having an insurance company or PBM decide what’s in the formulary, clinicians work with the pharmacists at Kaiser to look at clinical evidence and decide which biosimilar to use. Most of its plans also provide lower copays to patients when they use the biosimilar. 

This was the approach for Humira biosimilars, Dr. Awsare said. Eight will be on the market in 2023. “Our rheumatologists, dermatologists, and gastroenterologists looked at the data from Europe, looked at some real-world evidence, and then said: ‘We think this one’s going to be the best one for our patients.’ ”

Having clinicians choose the biosimilar instead of a health plan makes it a lot easier to have conversations with patients, he said. “Once we’ve moved that market share to that particular biosimilar, we give our physicians the time to have those discussions.”

Clinical pharmacists also provide educational support, offering guidance on issues such as side effects, as patients transition to the biosimilar. “We like to use the word ‘transition’ because it’s essentially the same biologic. So, you’re not actually switching,” Dr. Awsare said.

No consensus on interchangeability

Whether the conversation on interchangeability will affect patient conversations with physicians depends on who you ask.

If a biosimilar has an interchangeability designation, it means that the pharmacist can substitute it without the intervention of the clinician who prescribed the reference product. It does not relate to the quality, safety, or effectiveness of biosimilars or interchangeable biosimilar products, Dr. Popovian said.

The United States is the only country that has this designation. Even though it’s not identical to the originator drug, a biosimilar has the same clinical efficacy and safety profile. “So clinically, interchangeability is meaningless,” Dr. Awsare said.

In its report on biosimilars in the autoimmune category, CVS acknowledged that interchangeability was important but would not be a significant factor in driving adoption of biosimilars. However, in a Cardinal Health survey of 72 gastroenterologists, 38% cited the interchangeability of biosimilars as a top concern for adalimumab biosimilars, along with transitioning patients from Humira to a biosimilar (44%).

“Patient education regarding biosimilar safety, efficacy, and interchangeability appears paramount to the acceptance of these products, particularly for patients who are switched from a reference product,” Dr. Kaul noted in the Cardinal Health report.

Wherever supported by data, Dr. Kaul recommends incorporating biosimilar use and interchangeability into best practice guidelines going forward. “That will go a long way in disseminating the latest information on this topic and position this paradigm for increased adoption among providers.”

Some physicians like Dr. Snow aren’t that concerned with interchangeability. This hasn’t affected conversations with patients, he said. Multiple studies demonstrating the lack of antibody formation with multiple switches from different biosimilar drugs has eased his concern about multiple switches causing problems.

“Initially, there was a gap in demonstrating the long-term effect of multiple switches on antibody production and drug effectiveness. That gap has started to close as more data from Europe’s experience with biosimilars becomes available,” Dr. Snow said.
 

Resources for physicians, patients

The federal government has taken steps to advance biosimilars education and adoption. In 2021, President Biden signed the Advancing Education on Biosimilars Act into law, which directs the FDA to develop or improve continuing education programs that address prescribing of biosimilars and biological products.

The FDA provides educational materials on its website, including a comprehensive curriculum toolkit. The Accreditation Council for Medical Affairs has also created an online 40-hour curriculum for health care professionals called the Board-Certified Biologics and Biosimilars Specialist Program.

Dr. Fabbro recommended patients use the FDA page Biosimilar Basics for Patients to educate themselves on biosimilars. The Global Healthy Living Foundation’s podcast, Breaking Down Biosimilars, is another free resource for patients.

“While much has changed, the continued need for multistakeholder education, awareness, and dedicated research remains even more important as we expand into newer therapeutic areas and classes,” wrote the authors of the Cardinal Health report.

Help patients understand biologics and biosimilars by using AGA resources for providers and patients available at gastro.org/biosimilars.

Dr. Regueiro is on advisory boards and consults for AbbVie, Janssen, UCB, Takeda, Pfizer, Bristol-Myers Squibb, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, TARGET PharmaSolutions, Trellis, and Boehringer Ingelheim. Dr. Fabbro is a principal investigator for Castle Biosciences, on the speakers bureau for Valchlor, and on the advisory boards of Janssen and Bristol-Myers Squibb. Dr. Popovian, Dr. Snow, Dr. Awsare, and Dr. Kaul had no disclosures.

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

Rheumatologist Marcus Snow, MD, is comfortable with prescribing biosimilars as a first-line, first-time biologic, and discussing them with patients.

“If a biosimilar is on the market, it has gone through rigorous study proving its effectiveness and equivalence to a bio-originator,” said Dr. Snow, a rheumatologist with the University of Nebraska Medical Center, Omaha, and chair of the American College of Rheumatology’s Committee on Rheumatologic Care.

The formulary makes a big difference in the conversation about options, he said. “The formularies dictate what we can prescribe. It may not be appropriate, but it is reality. The cost of biologics for a patient without insurance coverage makes it impossible to afford.”

He will often tell patients that he’ll fight any changes or formulary restrictions he does not agree with. “However, when I see patients in follow-up, even if there is no known change on the horizon, I may bring up biosimilars when we have a moment to chat about them to familiarize them with what may happen in the future.”

The need for patient education on biosimilars presents a barrier to realizing their potential to save money and expand choice, noted Cardinal Health in its 2023 biosimilars report. Of 103 rheumatologists who responded to a Cardinal Health survey, 85% agreed that patient education was important. But those conversations can take an uncomfortable turn if the patient pushes back against taking a biosimilar owing to cost or safety concerns.

It’s not uncommon for a patient to express some anxiety about biosimilars, especially if they’re doing well on a current treatment plan. Most patients do not want any changes that may lead to worsening disease control, Dr. Snow said.

Kaiser Permanente

Patients and physicians alike often don’t understand the mechanics of biosimilars. “There’s a lot of misinformation about this,” said Sameer Awsare, MD, an associate executive director for The Permanente Medical Group in Campbell, Calif. Patients should know that a biosimilar will be as clinically efficacious as the medicine they’ve been on, with the same safety profiles, said Dr. Awsare, who works with Kaiser Permanente’s pharmacy partners on biosimilars.
 

Insurance often drives the conversation

The global anti-inflammatory biologics market is anticipated to reach $150 billion by 2027, according to a recent CVS report. As of March 2023, the Food and Drug Administration had approved 40 biosimilars to 11 different reference products. There are 28 on the U.S. market and 100 more in development. Projected to save more than $180 billion over the next 5 years, they are anticipated to expand choice and drive competition.

Rheumatologists, dermatologists, and gastroenterologists are frequent prescribers, although their choices for immune-mediated inflammatory diseases are limited to tumor necrosis factor inhibitors (infliximab [Remicade] originator and adalimumab [Humira] originator) and anti-CD20 agents, such as rituximab (Rituxan) originator.

Benefit design or formulary usually dictates what medicine a patient receives. “Because of significantly higher out-of-pocket cost or formulary positioning, patients may end up with a generic or a biosimilar instead of a brand-name medicine or branded biologic,” said Robert Popovian, PharmD, MS, chief science policy officer of the Global Healthy Living Foundation.

Insurers rarely offer both Remicade and biosimilar infliximab, allowing the doctor to choose, said Miguel Regueiro, MD, chair of the Cleveland Clinic’s Digestive Disease & Surgery Institute, who prescribes infliximab biosimilars. Most often, the payer will choose the lower-cost biosimilar. “I am fine with the biosimilar, either as a new start or a switch from the reference product.”

However, the patient might feel differently. They can form an attachment to the reference medication if it has prevented severe illness. “They do not want to change, as they feel they are going on a ‘new’ medication that will not work as well,” Dr. Regueiro said.

This is where the education comes in: to reassure patients that a biosimilar will work just as well as the reference product. “For patients who have done well for years on a biologic, more time needs to be spent reassuring them and answering questions,” compared with a patient just starting on a biosimilar, he advised.

But not all physicians are quick to prescribe biosimilars.

Julie Miller Photography

Especially with psoriasis, which has so many strong options for reference drugs, a switch may be hard to justify, said dermatologist Stephanie K. Fabbro, MD, assistant professor at Northeast Ohio Medical University, Rootstown. “If I have a preference, I would rather switch a patient to a drug from a different class without a biosimilar option to reduce the possibility of pushback.”

Dr. Fabbro, part of the core faculty in the Riverside Methodist Hospital Dermatology Residency Program in Columbus, will share data from clinical trials and postmarket surveillance with patients to support her decision.
 

Conversations about cost

Patients may also push back if they don’t save money when switching to a biosimilar. “This dilemma raises the question of who is profiting when a biosimilar is dispensed,” Dr. Popovian said. Insurers and pharmacy benefit managers (PBMs) that take additional concessions from biopharmaceutical manufacturers in the form of rebates and fees will often pocket this money as profit instead of passing savings back to the patient to help reduce their out-of-pocket requirement, he added.

If an originator biologic and a biosimilar are available, “as a pharmacist, I will choose the medicine that will incur the lowest out-of-pocket cost for the patient,” Dr. Popovian said.

Discussing cost – and who dictates which biosimilar is on the formulary – is an important conversation to have with patients, said Vivek Kaul, MD, Segal-Watson Professor of Medicine at the University of Rochester (N.Y.) Medical Center.

Providing equivalent clinical efficacy while saving costs is the economic reality of biosimilars, Dr. Kaul said. Third-party payers regularly evaluate how to provide the same quality of care while saving money. Physicians and patients alike “must be mindful that as time goes on, if the science on biosimilars stays robust, if the adoption is more widespread and the cost-saving proposition turns out to be true, more formularies will be attracted to replacing the reference product with the biosimilar counterpart.”

Providers and patients can weigh the options if a formulary suddenly switches to a biosimilar, Dr. Kaul continued. “You can accept the novel product on the formulary or may have to face out-of-pocket expenses as a patient.” If providers and patients have concerns about the biosimilar, they can always appeal if there’s solid scientific evidence that supports reverting back to the reference product.

“If you think the biosimilar is equally efficacious, comes at a lower cost, and is right for the patient, then the providers should tell the patient that,” he added.

Some studies have questioned whether the biosimilars will save money, compared with the reference drug, Dr. Fabbro noted. Medicare, for example, may pay only for a certain percentage of an approved biosimilar, saddling the patient with a monthly copay costing thousands of dollars. “It is unclear whether biosimilar manufacturers will have the same level of patient support programs as the reference drug companies.”

For that reason, physicians should also inform patients about the robust patient assistance and copay assistance programs many reference drug manufacturers offer, she said.

Biosimilars 101: Familiarizing patients

Safety and ease of use are other common concerns about biosimilars. Patients may ask if the application is different, or why it’s advantageous to switch to a biosimilar, Dr. Awsare said.

Sometimes the syringe or injector for a biosimilar might look different from that of the originator drug, he said.

Anecdotally, Dr. Fabbro has heard stories of patients having injection reactions that they did not experience with the reference drug or having a disease flare-up after starting a biosimilar. 

rubberball/Getty Images

As is the case with reference products, in their conversations with patients, clinicians should address the adverse event profile of biosimilars, offering data points from published studies and clinical guidelines that support the use of these products. “There should be an emphasis on patient education around efficacy and any side effects, and how the profile of the reference product compares with a proposed biosimilar,” Dr. Kaul suggested.

When Dr. Snow discusses biosimilars and generics, “I make sure to share this in an understandable way based on the patient’s scientific background, or lack thereof,” he said. If there is enough time, he also discusses how European- and U.S.-sourced biologics are slightly different.

Pharmacists should tell patients to expect the same clinical outcomes from a biosimilar, Dr. Popovian said. However, if they have any reduction in efficacy or potential safety concerns, they should communicate with their physician or pharmacist immediately.

In Dr. Regueiro’s practice, a pharmacist specializing in inflammatory bowel disease often has a one-on-one meeting with patients to educate and answer questions. “Additionally, we provide them the Crohn’s and Colitis Foundation web link on biosimilars,” said Dr. Regueiro.
 

A village approach to education

When biosimilars first came out, there were no formal education materials, Dr. Awsare said. Kaiser Permanente decided to create its own educational materials, not just for patients but also to help educate its primary care doctors; the rheumatologists, dermatologists, and gastroenterologists using the biosimilars; the nurses infusing patients; and the pharmacists preparing the biosimilars.

The health system also has a different approach to choosing medication. Instead of having an insurance company or PBM decide what’s in the formulary, clinicians work with the pharmacists at Kaiser to look at clinical evidence and decide which biosimilar to use. Most of its plans also provide lower copays to patients when they use the biosimilar. 

This was the approach for Humira biosimilars, Dr. Awsare said. Eight will be on the market in 2023. “Our rheumatologists, dermatologists, and gastroenterologists looked at the data from Europe, looked at some real-world evidence, and then said: ‘We think this one’s going to be the best one for our patients.’ ”

Having clinicians choose the biosimilar instead of a health plan makes it a lot easier to have conversations with patients, he said. “Once we’ve moved that market share to that particular biosimilar, we give our physicians the time to have those discussions.”

Clinical pharmacists also provide educational support, offering guidance on issues such as side effects, as patients transition to the biosimilar. “We like to use the word ‘transition’ because it’s essentially the same biologic. So, you’re not actually switching,” Dr. Awsare said.

No consensus on interchangeability

Whether the conversation on interchangeability will affect patient conversations with physicians depends on who you ask.

If a biosimilar has an interchangeability designation, it means that the pharmacist can substitute it without the intervention of the clinician who prescribed the reference product. It does not relate to the quality, safety, or effectiveness of biosimilars or interchangeable biosimilar products, Dr. Popovian said.

The United States is the only country that has this designation. Even though it’s not identical to the originator drug, a biosimilar has the same clinical efficacy and safety profile. “So clinically, interchangeability is meaningless,” Dr. Awsare said.

In its report on biosimilars in the autoimmune category, CVS acknowledged that interchangeability was important but would not be a significant factor in driving adoption of biosimilars. However, in a Cardinal Health survey of 72 gastroenterologists, 38% cited the interchangeability of biosimilars as a top concern for adalimumab biosimilars, along with transitioning patients from Humira to a biosimilar (44%).

“Patient education regarding biosimilar safety, efficacy, and interchangeability appears paramount to the acceptance of these products, particularly for patients who are switched from a reference product,” Dr. Kaul noted in the Cardinal Health report.

Wherever supported by data, Dr. Kaul recommends incorporating biosimilar use and interchangeability into best practice guidelines going forward. “That will go a long way in disseminating the latest information on this topic and position this paradigm for increased adoption among providers.”

Some physicians like Dr. Snow aren’t that concerned with interchangeability. This hasn’t affected conversations with patients, he said. Multiple studies demonstrating the lack of antibody formation with multiple switches from different biosimilar drugs has eased his concern about multiple switches causing problems.

“Initially, there was a gap in demonstrating the long-term effect of multiple switches on antibody production and drug effectiveness. That gap has started to close as more data from Europe’s experience with biosimilars becomes available,” Dr. Snow said.
 

Resources for physicians, patients

The federal government has taken steps to advance biosimilars education and adoption. In 2021, President Biden signed the Advancing Education on Biosimilars Act into law, which directs the FDA to develop or improve continuing education programs that address prescribing of biosimilars and biological products.

The FDA provides educational materials on its website, including a comprehensive curriculum toolkit. The Accreditation Council for Medical Affairs has also created an online 40-hour curriculum for health care professionals called the Board-Certified Biologics and Biosimilars Specialist Program.

Dr. Fabbro recommended patients use the FDA page Biosimilar Basics for Patients to educate themselves on biosimilars. The Global Healthy Living Foundation’s podcast, Breaking Down Biosimilars, is another free resource for patients.

“While much has changed, the continued need for multistakeholder education, awareness, and dedicated research remains even more important as we expand into newer therapeutic areas and classes,” wrote the authors of the Cardinal Health report.

Help patients understand biologics and biosimilars by using AGA resources for providers and patients available at gastro.org/biosimilars.

Dr. Regueiro is on advisory boards and consults for AbbVie, Janssen, UCB, Takeda, Pfizer, Bristol-Myers Squibb, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, TARGET PharmaSolutions, Trellis, and Boehringer Ingelheim. Dr. Fabbro is a principal investigator for Castle Biosciences, on the speakers bureau for Valchlor, and on the advisory boards of Janssen and Bristol-Myers Squibb. Dr. Popovian, Dr. Snow, Dr. Awsare, and Dr. Kaul had no disclosures.

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

Rheumatologist Marcus Snow, MD, is comfortable with prescribing biosimilars as a first-line, first-time biologic, and discussing them with patients.

“If a biosimilar is on the market, it has gone through rigorous study proving its effectiveness and equivalence to a bio-originator,” said Dr. Snow, a rheumatologist with the University of Nebraska Medical Center, Omaha, and chair of the American College of Rheumatology’s Committee on Rheumatologic Care.

The formulary makes a big difference in the conversation about options, he said. “The formularies dictate what we can prescribe. It may not be appropriate, but it is reality. The cost of biologics for a patient without insurance coverage makes it impossible to afford.”

He will often tell patients that he’ll fight any changes or formulary restrictions he does not agree with. “However, when I see patients in follow-up, even if there is no known change on the horizon, I may bring up biosimilars when we have a moment to chat about them to familiarize them with what may happen in the future.”

The need for patient education on biosimilars presents a barrier to realizing their potential to save money and expand choice, noted Cardinal Health in its 2023 biosimilars report. Of 103 rheumatologists who responded to a Cardinal Health survey, 85% agreed that patient education was important. But those conversations can take an uncomfortable turn if the patient pushes back against taking a biosimilar owing to cost or safety concerns.

It’s not uncommon for a patient to express some anxiety about biosimilars, especially if they’re doing well on a current treatment plan. Most patients do not want any changes that may lead to worsening disease control, Dr. Snow said.

Kaiser Permanente

Patients and physicians alike often don’t understand the mechanics of biosimilars. “There’s a lot of misinformation about this,” said Sameer Awsare, MD, an associate executive director for The Permanente Medical Group in Campbell, Calif. Patients should know that a biosimilar will be as clinically efficacious as the medicine they’ve been on, with the same safety profiles, said Dr. Awsare, who works with Kaiser Permanente’s pharmacy partners on biosimilars.
 

Insurance often drives the conversation

The global anti-inflammatory biologics market is anticipated to reach $150 billion by 2027, according to a recent CVS report. As of March 2023, the Food and Drug Administration had approved 40 biosimilars to 11 different reference products. There are 28 on the U.S. market and 100 more in development. Projected to save more than $180 billion over the next 5 years, they are anticipated to expand choice and drive competition.

Rheumatologists, dermatologists, and gastroenterologists are frequent prescribers, although their choices for immune-mediated inflammatory diseases are limited to tumor necrosis factor inhibitors (infliximab [Remicade] originator and adalimumab [Humira] originator) and anti-CD20 agents, such as rituximab (Rituxan) originator.

Benefit design or formulary usually dictates what medicine a patient receives. “Because of significantly higher out-of-pocket cost or formulary positioning, patients may end up with a generic or a biosimilar instead of a brand-name medicine or branded biologic,” said Robert Popovian, PharmD, MS, chief science policy officer of the Global Healthy Living Foundation.

Insurers rarely offer both Remicade and biosimilar infliximab, allowing the doctor to choose, said Miguel Regueiro, MD, chair of the Cleveland Clinic’s Digestive Disease & Surgery Institute, who prescribes infliximab biosimilars. Most often, the payer will choose the lower-cost biosimilar. “I am fine with the biosimilar, either as a new start or a switch from the reference product.”

However, the patient might feel differently. They can form an attachment to the reference medication if it has prevented severe illness. “They do not want to change, as they feel they are going on a ‘new’ medication that will not work as well,” Dr. Regueiro said.

This is where the education comes in: to reassure patients that a biosimilar will work just as well as the reference product. “For patients who have done well for years on a biologic, more time needs to be spent reassuring them and answering questions,” compared with a patient just starting on a biosimilar, he advised.

But not all physicians are quick to prescribe biosimilars.

Julie Miller Photography

Especially with psoriasis, which has so many strong options for reference drugs, a switch may be hard to justify, said dermatologist Stephanie K. Fabbro, MD, assistant professor at Northeast Ohio Medical University, Rootstown. “If I have a preference, I would rather switch a patient to a drug from a different class without a biosimilar option to reduce the possibility of pushback.”

Dr. Fabbro, part of the core faculty in the Riverside Methodist Hospital Dermatology Residency Program in Columbus, will share data from clinical trials and postmarket surveillance with patients to support her decision.
 

Conversations about cost

Patients may also push back if they don’t save money when switching to a biosimilar. “This dilemma raises the question of who is profiting when a biosimilar is dispensed,” Dr. Popovian said. Insurers and pharmacy benefit managers (PBMs) that take additional concessions from biopharmaceutical manufacturers in the form of rebates and fees will often pocket this money as profit instead of passing savings back to the patient to help reduce their out-of-pocket requirement, he added.

If an originator biologic and a biosimilar are available, “as a pharmacist, I will choose the medicine that will incur the lowest out-of-pocket cost for the patient,” Dr. Popovian said.

Discussing cost – and who dictates which biosimilar is on the formulary – is an important conversation to have with patients, said Vivek Kaul, MD, Segal-Watson Professor of Medicine at the University of Rochester (N.Y.) Medical Center.

Providing equivalent clinical efficacy while saving costs is the economic reality of biosimilars, Dr. Kaul said. Third-party payers regularly evaluate how to provide the same quality of care while saving money. Physicians and patients alike “must be mindful that as time goes on, if the science on biosimilars stays robust, if the adoption is more widespread and the cost-saving proposition turns out to be true, more formularies will be attracted to replacing the reference product with the biosimilar counterpart.”

Providers and patients can weigh the options if a formulary suddenly switches to a biosimilar, Dr. Kaul continued. “You can accept the novel product on the formulary or may have to face out-of-pocket expenses as a patient.” If providers and patients have concerns about the biosimilar, they can always appeal if there’s solid scientific evidence that supports reverting back to the reference product.

“If you think the biosimilar is equally efficacious, comes at a lower cost, and is right for the patient, then the providers should tell the patient that,” he added.

Some studies have questioned whether the biosimilars will save money, compared with the reference drug, Dr. Fabbro noted. Medicare, for example, may pay only for a certain percentage of an approved biosimilar, saddling the patient with a monthly copay costing thousands of dollars. “It is unclear whether biosimilar manufacturers will have the same level of patient support programs as the reference drug companies.”

For that reason, physicians should also inform patients about the robust patient assistance and copay assistance programs many reference drug manufacturers offer, she said.

Biosimilars 101: Familiarizing patients

Safety and ease of use are other common concerns about biosimilars. Patients may ask if the application is different, or why it’s advantageous to switch to a biosimilar, Dr. Awsare said.

Sometimes the syringe or injector for a biosimilar might look different from that of the originator drug, he said.

Anecdotally, Dr. Fabbro has heard stories of patients having injection reactions that they did not experience with the reference drug or having a disease flare-up after starting a biosimilar. 

rubberball/Getty Images

As is the case with reference products, in their conversations with patients, clinicians should address the adverse event profile of biosimilars, offering data points from published studies and clinical guidelines that support the use of these products. “There should be an emphasis on patient education around efficacy and any side effects, and how the profile of the reference product compares with a proposed biosimilar,” Dr. Kaul suggested.

When Dr. Snow discusses biosimilars and generics, “I make sure to share this in an understandable way based on the patient’s scientific background, or lack thereof,” he said. If there is enough time, he also discusses how European- and U.S.-sourced biologics are slightly different.

Pharmacists should tell patients to expect the same clinical outcomes from a biosimilar, Dr. Popovian said. However, if they have any reduction in efficacy or potential safety concerns, they should communicate with their physician or pharmacist immediately.

In Dr. Regueiro’s practice, a pharmacist specializing in inflammatory bowel disease often has a one-on-one meeting with patients to educate and answer questions. “Additionally, we provide them the Crohn’s and Colitis Foundation web link on biosimilars,” said Dr. Regueiro.
 

A village approach to education

When biosimilars first came out, there were no formal education materials, Dr. Awsare said. Kaiser Permanente decided to create its own educational materials, not just for patients but also to help educate its primary care doctors; the rheumatologists, dermatologists, and gastroenterologists using the biosimilars; the nurses infusing patients; and the pharmacists preparing the biosimilars.

The health system also has a different approach to choosing medication. Instead of having an insurance company or PBM decide what’s in the formulary, clinicians work with the pharmacists at Kaiser to look at clinical evidence and decide which biosimilar to use. Most of its plans also provide lower copays to patients when they use the biosimilar. 

This was the approach for Humira biosimilars, Dr. Awsare said. Eight will be on the market in 2023. “Our rheumatologists, dermatologists, and gastroenterologists looked at the data from Europe, looked at some real-world evidence, and then said: ‘We think this one’s going to be the best one for our patients.’ ”

Having clinicians choose the biosimilar instead of a health plan makes it a lot easier to have conversations with patients, he said. “Once we’ve moved that market share to that particular biosimilar, we give our physicians the time to have those discussions.”

Clinical pharmacists also provide educational support, offering guidance on issues such as side effects, as patients transition to the biosimilar. “We like to use the word ‘transition’ because it’s essentially the same biologic. So, you’re not actually switching,” Dr. Awsare said.

No consensus on interchangeability

Whether the conversation on interchangeability will affect patient conversations with physicians depends on who you ask.

If a biosimilar has an interchangeability designation, it means that the pharmacist can substitute it without the intervention of the clinician who prescribed the reference product. It does not relate to the quality, safety, or effectiveness of biosimilars or interchangeable biosimilar products, Dr. Popovian said.

The United States is the only country that has this designation. Even though it’s not identical to the originator drug, a biosimilar has the same clinical efficacy and safety profile. “So clinically, interchangeability is meaningless,” Dr. Awsare said.

In its report on biosimilars in the autoimmune category, CVS acknowledged that interchangeability was important but would not be a significant factor in driving adoption of biosimilars. However, in a Cardinal Health survey of 72 gastroenterologists, 38% cited the interchangeability of biosimilars as a top concern for adalimumab biosimilars, along with transitioning patients from Humira to a biosimilar (44%).

“Patient education regarding biosimilar safety, efficacy, and interchangeability appears paramount to the acceptance of these products, particularly for patients who are switched from a reference product,” Dr. Kaul noted in the Cardinal Health report.

Wherever supported by data, Dr. Kaul recommends incorporating biosimilar use and interchangeability into best practice guidelines going forward. “That will go a long way in disseminating the latest information on this topic and position this paradigm for increased adoption among providers.”

Some physicians like Dr. Snow aren’t that concerned with interchangeability. This hasn’t affected conversations with patients, he said. Multiple studies demonstrating the lack of antibody formation with multiple switches from different biosimilar drugs has eased his concern about multiple switches causing problems.

“Initially, there was a gap in demonstrating the long-term effect of multiple switches on antibody production and drug effectiveness. That gap has started to close as more data from Europe’s experience with biosimilars becomes available,” Dr. Snow said.
 

Resources for physicians, patients

The federal government has taken steps to advance biosimilars education and adoption. In 2021, President Biden signed the Advancing Education on Biosimilars Act into law, which directs the FDA to develop or improve continuing education programs that address prescribing of biosimilars and biological products.

The FDA provides educational materials on its website, including a comprehensive curriculum toolkit. The Accreditation Council for Medical Affairs has also created an online 40-hour curriculum for health care professionals called the Board-Certified Biologics and Biosimilars Specialist Program.

Dr. Fabbro recommended patients use the FDA page Biosimilar Basics for Patients to educate themselves on biosimilars. The Global Healthy Living Foundation’s podcast, Breaking Down Biosimilars, is another free resource for patients.

“While much has changed, the continued need for multistakeholder education, awareness, and dedicated research remains even more important as we expand into newer therapeutic areas and classes,” wrote the authors of the Cardinal Health report.

Help patients understand biologics and biosimilars by using AGA resources for providers and patients available at gastro.org/biosimilars.

Dr. Regueiro is on advisory boards and consults for AbbVie, Janssen, UCB, Takeda, Pfizer, Bristol-Myers Squibb, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, TARGET PharmaSolutions, Trellis, and Boehringer Ingelheim. Dr. Fabbro is a principal investigator for Castle Biosciences, on the speakers bureau for Valchlor, and on the advisory boards of Janssen and Bristol-Myers Squibb. Dr. Popovian, Dr. Snow, Dr. Awsare, and Dr. Kaul had no disclosures.

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

Microbial biomarkers for type 1 diabetes may be present in infants as young as 12 months old, suggesting the potential to mitigate disease onset by nurturing a healthy gut microbiome early, show data from the Swedish general population.

“Our findings indicate that the gut of infants who go on to develop type 1 diabetes is notably different from healthy babies,” said Malin Bélteky, MD, from the Crown Princess Victoria’s Children’s Hospital, Linköping, Sweden, who jointly led the work, which was recently published in Diabetologia, alongside Patricia L. Milletich, PhD candidate, from the University of Florida, Gainesville.

“This discovery could be used to help identity infants at [the] highest risk of developing type 1 diabetes before or during the first stage of disease and could offer the opportunity to bolster a healthy gut microbiome to prevent the disease from becoming established,” added Dr. Bélteky.

Currently, beta-cell autoantibodies are used to predict disease, which are usually only identifiable between 9 and 36 months of age.

Marian Rewers, MD, PhD, professor of pediatrics & medicine, University of Colorado, Denver, and principal investigator of The Environmental Determinants of Diabetes in the Young (TEDDY) study, welcomed the findings, saying it is a well-designed study from a strong group of investigators.

“While the effective number of cases was very small [n = 16], the results were apparently adjusted for multiple comparisons, and significant differences were noted in the microbiome of cases versus controls at 1 year of age. This was 12 years prior to the average age of type 1 diabetes diagnosis in the cases,” he said.

“The differences in diversity and abundances of specific bacteria need to be interpreted with caution; however, the study results are consistent with several previous reports,” he noted.
 

Differences in microbial diversity and function

Data were drawn from children participating in the longitudinal, general population All Babies In Southeast Sweden (ABIS) study. Microbiota from stool samples, taken at age 1 year, were sequenced and analyzed to establish diversity, abundance, and functional status of the component bacteria. Questionnaires were completed at birth and at 1 year of age, allowing for the study of environmental factors that might influence the microbiota or type 1 diabetes risk independently. Parent diaries provided information on pregnancy, nutrition, and lifestyle factors.

Of the cohort of 167 children who developed type 1 diabetes by 2020, stool samples were available for 16 of these participants, which were compared with 268 healthy controls. The microbiomes of the 16 infants who later developed type 1 diabetes were compared with 100 iterations of 32 matched control infants (matched by geographical region, siblings at birth, residence type, duration of breastfeeding, and month of stool collection) who didn’t develop type 1 diabetes by the age of 20.

Specific bacteria found in greater abundance in children who later developed type 1 diabetes, compared with those who didn’t, included Firmicutes (Enterococcus, Gemella, and Hungatella), as well as Bacteroides (Bacteroides and Porphyromonas), known to promote inflammation and be involved in the immune response.

Bacteria with greater abundance in children who didn’t develop type 1 diabetes, compared with those who did, were Firmicutes (Anaerostipes, Flavonifractor, and Ruminococcaceae UBA1819, and Eubacterium). These species help maintain metabolic and immune health and produce butyrate, an important short-chain fatty acid that helps prevent inflammation and fuels the cells of the gut lining.

Alistipes were more abundant in infants who didn’t develop type 1 diabetes, and various abundances of Fusicatenibacter were the strongest factors for differentiating future type 1 diabetes, reported the researchers.

“Gut microbial biomarkers at 12 months would benefit the prediction opportunity well before the onset of multiple autoantibodies,” write the authors.

The youngest age at type 1 diabetes diagnosis was aged 1 year, 4 months, and the oldest was aged 21 years, 4 months. The mean age at diagnosis was 13.3 years.

The microbial differences found between infants who go on to develop type 1 diabetes and those who don’t also shed light on interactions between the developing immune system and short-chain fatty acid production and metabolism in childhood autoimmunity, write the authors.

Prior studies have found fewer short-chain fatty acid–producing microbiota in the gut of children with early-onset autoantibody development. This study confirmed these data, finding a decrease in butyrate-producing bacteria (Anaerostipes, Flavonifractor, Ruminococcaceae UBA1819, and Eubacterium) in infants who went on to develop type 1 diabetes. Likewise, a reduction in pyruvate fermentation was found in those infants with future disease.

According to coauthor Eric Triplett, PhD, from the University of Florida, Gainesville: “The autoimmune processes usually begin long before any clinical signs of disease appear, highlighting how differences in the makeup of the infant gut microbiome could shed important light on the complex interaction between the developing immune system, environmental exposures in childhood, and autoimmunity. Studies with much larger cohorts of prospectively traced individuals will be required to establish which are the strongest biomarkers and how effectively they can predict disease.”

The authors and Dr. Rewers have reported no relevant financial relationships.

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

Microbial biomarkers for type 1 diabetes may be present in infants as young as 12 months old, suggesting the potential to mitigate disease onset by nurturing a healthy gut microbiome early, show data from the Swedish general population.

“Our findings indicate that the gut of infants who go on to develop type 1 diabetes is notably different from healthy babies,” said Malin Bélteky, MD, from the Crown Princess Victoria’s Children’s Hospital, Linköping, Sweden, who jointly led the work, which was recently published in Diabetologia, alongside Patricia L. Milletich, PhD candidate, from the University of Florida, Gainesville.

“This discovery could be used to help identity infants at [the] highest risk of developing type 1 diabetes before or during the first stage of disease and could offer the opportunity to bolster a healthy gut microbiome to prevent the disease from becoming established,” added Dr. Bélteky.

Currently, beta-cell autoantibodies are used to predict disease, which are usually only identifiable between 9 and 36 months of age.

Marian Rewers, MD, PhD, professor of pediatrics & medicine, University of Colorado, Denver, and principal investigator of The Environmental Determinants of Diabetes in the Young (TEDDY) study, welcomed the findings, saying it is a well-designed study from a strong group of investigators.

“While the effective number of cases was very small [n = 16], the results were apparently adjusted for multiple comparisons, and significant differences were noted in the microbiome of cases versus controls at 1 year of age. This was 12 years prior to the average age of type 1 diabetes diagnosis in the cases,” he said.

“The differences in diversity and abundances of specific bacteria need to be interpreted with caution; however, the study results are consistent with several previous reports,” he noted.
 

Differences in microbial diversity and function

Data were drawn from children participating in the longitudinal, general population All Babies In Southeast Sweden (ABIS) study. Microbiota from stool samples, taken at age 1 year, were sequenced and analyzed to establish diversity, abundance, and functional status of the component bacteria. Questionnaires were completed at birth and at 1 year of age, allowing for the study of environmental factors that might influence the microbiota or type 1 diabetes risk independently. Parent diaries provided information on pregnancy, nutrition, and lifestyle factors.

Of the cohort of 167 children who developed type 1 diabetes by 2020, stool samples were available for 16 of these participants, which were compared with 268 healthy controls. The microbiomes of the 16 infants who later developed type 1 diabetes were compared with 100 iterations of 32 matched control infants (matched by geographical region, siblings at birth, residence type, duration of breastfeeding, and month of stool collection) who didn’t develop type 1 diabetes by the age of 20.

Specific bacteria found in greater abundance in children who later developed type 1 diabetes, compared with those who didn’t, included Firmicutes (Enterococcus, Gemella, and Hungatella), as well as Bacteroides (Bacteroides and Porphyromonas), known to promote inflammation and be involved in the immune response.

Bacteria with greater abundance in children who didn’t develop type 1 diabetes, compared with those who did, were Firmicutes (Anaerostipes, Flavonifractor, and Ruminococcaceae UBA1819, and Eubacterium). These species help maintain metabolic and immune health and produce butyrate, an important short-chain fatty acid that helps prevent inflammation and fuels the cells of the gut lining.

Alistipes were more abundant in infants who didn’t develop type 1 diabetes, and various abundances of Fusicatenibacter were the strongest factors for differentiating future type 1 diabetes, reported the researchers.

“Gut microbial biomarkers at 12 months would benefit the prediction opportunity well before the onset of multiple autoantibodies,” write the authors.

The youngest age at type 1 diabetes diagnosis was aged 1 year, 4 months, and the oldest was aged 21 years, 4 months. The mean age at diagnosis was 13.3 years.

The microbial differences found between infants who go on to develop type 1 diabetes and those who don’t also shed light on interactions between the developing immune system and short-chain fatty acid production and metabolism in childhood autoimmunity, write the authors.

Prior studies have found fewer short-chain fatty acid–producing microbiota in the gut of children with early-onset autoantibody development. This study confirmed these data, finding a decrease in butyrate-producing bacteria (Anaerostipes, Flavonifractor, Ruminococcaceae UBA1819, and Eubacterium) in infants who went on to develop type 1 diabetes. Likewise, a reduction in pyruvate fermentation was found in those infants with future disease.

According to coauthor Eric Triplett, PhD, from the University of Florida, Gainesville: “The autoimmune processes usually begin long before any clinical signs of disease appear, highlighting how differences in the makeup of the infant gut microbiome could shed important light on the complex interaction between the developing immune system, environmental exposures in childhood, and autoimmunity. Studies with much larger cohorts of prospectively traced individuals will be required to establish which are the strongest biomarkers and how effectively they can predict disease.”

The authors and Dr. Rewers have reported no relevant financial relationships.

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

Microbial biomarkers for type 1 diabetes may be present in infants as young as 12 months old, suggesting the potential to mitigate disease onset by nurturing a healthy gut microbiome early, show data from the Swedish general population.

“Our findings indicate that the gut of infants who go on to develop type 1 diabetes is notably different from healthy babies,” said Malin Bélteky, MD, from the Crown Princess Victoria’s Children’s Hospital, Linköping, Sweden, who jointly led the work, which was recently published in Diabetologia, alongside Patricia L. Milletich, PhD candidate, from the University of Florida, Gainesville.

“This discovery could be used to help identity infants at [the] highest risk of developing type 1 diabetes before or during the first stage of disease and could offer the opportunity to bolster a healthy gut microbiome to prevent the disease from becoming established,” added Dr. Bélteky.

Currently, beta-cell autoantibodies are used to predict disease, which are usually only identifiable between 9 and 36 months of age.

Marian Rewers, MD, PhD, professor of pediatrics & medicine, University of Colorado, Denver, and principal investigator of The Environmental Determinants of Diabetes in the Young (TEDDY) study, welcomed the findings, saying it is a well-designed study from a strong group of investigators.

“While the effective number of cases was very small [n = 16], the results were apparently adjusted for multiple comparisons, and significant differences were noted in the microbiome of cases versus controls at 1 year of age. This was 12 years prior to the average age of type 1 diabetes diagnosis in the cases,” he said.

“The differences in diversity and abundances of specific bacteria need to be interpreted with caution; however, the study results are consistent with several previous reports,” he noted.
 

Differences in microbial diversity and function

Data were drawn from children participating in the longitudinal, general population All Babies In Southeast Sweden (ABIS) study. Microbiota from stool samples, taken at age 1 year, were sequenced and analyzed to establish diversity, abundance, and functional status of the component bacteria. Questionnaires were completed at birth and at 1 year of age, allowing for the study of environmental factors that might influence the microbiota or type 1 diabetes risk independently. Parent diaries provided information on pregnancy, nutrition, and lifestyle factors.

Of the cohort of 167 children who developed type 1 diabetes by 2020, stool samples were available for 16 of these participants, which were compared with 268 healthy controls. The microbiomes of the 16 infants who later developed type 1 diabetes were compared with 100 iterations of 32 matched control infants (matched by geographical region, siblings at birth, residence type, duration of breastfeeding, and month of stool collection) who didn’t develop type 1 diabetes by the age of 20.

Specific bacteria found in greater abundance in children who later developed type 1 diabetes, compared with those who didn’t, included Firmicutes (Enterococcus, Gemella, and Hungatella), as well as Bacteroides (Bacteroides and Porphyromonas), known to promote inflammation and be involved in the immune response.

Bacteria with greater abundance in children who didn’t develop type 1 diabetes, compared with those who did, were Firmicutes (Anaerostipes, Flavonifractor, and Ruminococcaceae UBA1819, and Eubacterium). These species help maintain metabolic and immune health and produce butyrate, an important short-chain fatty acid that helps prevent inflammation and fuels the cells of the gut lining.

Alistipes were more abundant in infants who didn’t develop type 1 diabetes, and various abundances of Fusicatenibacter were the strongest factors for differentiating future type 1 diabetes, reported the researchers.

“Gut microbial biomarkers at 12 months would benefit the prediction opportunity well before the onset of multiple autoantibodies,” write the authors.

The youngest age at type 1 diabetes diagnosis was aged 1 year, 4 months, and the oldest was aged 21 years, 4 months. The mean age at diagnosis was 13.3 years.

The microbial differences found between infants who go on to develop type 1 diabetes and those who don’t also shed light on interactions between the developing immune system and short-chain fatty acid production and metabolism in childhood autoimmunity, write the authors.

Prior studies have found fewer short-chain fatty acid–producing microbiota in the gut of children with early-onset autoantibody development. This study confirmed these data, finding a decrease in butyrate-producing bacteria (Anaerostipes, Flavonifractor, Ruminococcaceae UBA1819, and Eubacterium) in infants who went on to develop type 1 diabetes. Likewise, a reduction in pyruvate fermentation was found in those infants with future disease.

According to coauthor Eric Triplett, PhD, from the University of Florida, Gainesville: “The autoimmune processes usually begin long before any clinical signs of disease appear, highlighting how differences in the makeup of the infant gut microbiome could shed important light on the complex interaction between the developing immune system, environmental exposures in childhood, and autoimmunity. Studies with much larger cohorts of prospectively traced individuals will be required to establish which are the strongest biomarkers and how effectively they can predict disease.”

The authors and Dr. Rewers have reported no relevant financial relationships.

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