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Preemptive pacifier promotion
I recently encountered an article aimed at parents who were struggling with what to do about their child’s persistent attachment to his pacifier (“How to Ditch the Pacifier,” by Anna Nowogrodski, New York Times, 2019 Sept. 16). For the most part, the author presented a sampling of sound advice from pediatricians and other health experts.
Most children will abandon their pacifiers at a time that is consistent with their developmental stage. Pacifiers seldom do any permanent damage, although they aren’t terribly appealing to look at when hanging out of a toddling toddler’s mouth. Parents were urged to be patient and consistent and were told that allowing the gooey thing to self-destruct often works, as does accelerating the process with a razor blade. Enlisting the aid of the Pacifier Fairy was suggested, but I’m not so sure that would work terribly well.
As I finished perusing the article, I couldn’t help think of how this vexing issue of pacifier removal can be avoided if parents follow a simple rule when they first introduced a pacifier to their child. If experienced parents think back to when they first resorted to using the pacifier, it wasn’t because the plastic and rubber gadget was a family heirloom that had been passed down from generation to generation like an engraved silver spoon. It wasn’t because the dentist told them that children who use pacifiers are less likely to need braces on their teeth. Nor was it a rumor filtered down from speech therapists that pacifiers improve articulation.
Parents reach for a pacifier in hopes that it will help their child will fall asleep. I think most parents of older children agree that at the beginning the pacifier was first and foremost a sleep aid. But here is where the critical oversight occurs: If you give your children pacifiers when you want them to go to sleep, why not simply add the stipulation of where you would like them to go to sleep as well?
Most parents prefer that their children sleep in their own space. We can argue of whether that should be in a side sleeper or their own crib, but most parents don’t want their 3-year-olds sleeping in their bed. Nor do they want their children sleeping on the couch in the living room with them while they watch a movie at 10:30 at night. And as pediatricians, we prefer that children not sleep with their necks flexed in a car seat or baby rocker, particularly if they’re a preemie.
Augmenting the primary association between sleep and the pacifier by adding a place has several important advantages. It gives parents more control of where their children will sleep or, more importantly, where they won’t be sleeping. It helps transitions to nonhome sleeping places like day care and long trips to grandma’s house go more smoothly.
Even more importantly, the crib/pacifier association helps parents who have had trouble reading their children’s cues. If they want a pacifier, it means they are tired and want to go to where the pacifier lives: bed
Finally, maintaining the link between sleeping and the pacifier promotes a more natural weaning process than going cold turkey or hiring the Pacifier Fairy. As naps disappear, the pacifier gradually become a less obvious accessory in the child’s life. However, it may linger in the background as a reminder of when the child needs some restorative sleep.
Of course, helping parents to think clearly enough to create and enforce a simple rule long enough to forge a healthy association when they are sleep deprived themselves is just another one of those challenges we must accept as concerned primary care pediatricians.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “Is My Child Overtired? The Sleep Solution for Raising Happier, Healthier Children.” Email him at [email protected].
I recently encountered an article aimed at parents who were struggling with what to do about their child’s persistent attachment to his pacifier (“How to Ditch the Pacifier,” by Anna Nowogrodski, New York Times, 2019 Sept. 16). For the most part, the author presented a sampling of sound advice from pediatricians and other health experts.
Most children will abandon their pacifiers at a time that is consistent with their developmental stage. Pacifiers seldom do any permanent damage, although they aren’t terribly appealing to look at when hanging out of a toddling toddler’s mouth. Parents were urged to be patient and consistent and were told that allowing the gooey thing to self-destruct often works, as does accelerating the process with a razor blade. Enlisting the aid of the Pacifier Fairy was suggested, but I’m not so sure that would work terribly well.
As I finished perusing the article, I couldn’t help think of how this vexing issue of pacifier removal can be avoided if parents follow a simple rule when they first introduced a pacifier to their child. If experienced parents think back to when they first resorted to using the pacifier, it wasn’t because the plastic and rubber gadget was a family heirloom that had been passed down from generation to generation like an engraved silver spoon. It wasn’t because the dentist told them that children who use pacifiers are less likely to need braces on their teeth. Nor was it a rumor filtered down from speech therapists that pacifiers improve articulation.
Parents reach for a pacifier in hopes that it will help their child will fall asleep. I think most parents of older children agree that at the beginning the pacifier was first and foremost a sleep aid. But here is where the critical oversight occurs: If you give your children pacifiers when you want them to go to sleep, why not simply add the stipulation of where you would like them to go to sleep as well?
Most parents prefer that their children sleep in their own space. We can argue of whether that should be in a side sleeper or their own crib, but most parents don’t want their 3-year-olds sleeping in their bed. Nor do they want their children sleeping on the couch in the living room with them while they watch a movie at 10:30 at night. And as pediatricians, we prefer that children not sleep with their necks flexed in a car seat or baby rocker, particularly if they’re a preemie.
Augmenting the primary association between sleep and the pacifier by adding a place has several important advantages. It gives parents more control of where their children will sleep or, more importantly, where they won’t be sleeping. It helps transitions to nonhome sleeping places like day care and long trips to grandma’s house go more smoothly.
Even more importantly, the crib/pacifier association helps parents who have had trouble reading their children’s cues. If they want a pacifier, it means they are tired and want to go to where the pacifier lives: bed
Finally, maintaining the link between sleeping and the pacifier promotes a more natural weaning process than going cold turkey or hiring the Pacifier Fairy. As naps disappear, the pacifier gradually become a less obvious accessory in the child’s life. However, it may linger in the background as a reminder of when the child needs some restorative sleep.
Of course, helping parents to think clearly enough to create and enforce a simple rule long enough to forge a healthy association when they are sleep deprived themselves is just another one of those challenges we must accept as concerned primary care pediatricians.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “Is My Child Overtired? The Sleep Solution for Raising Happier, Healthier Children.” Email him at [email protected].
I recently encountered an article aimed at parents who were struggling with what to do about their child’s persistent attachment to his pacifier (“How to Ditch the Pacifier,” by Anna Nowogrodski, New York Times, 2019 Sept. 16). For the most part, the author presented a sampling of sound advice from pediatricians and other health experts.
Most children will abandon their pacifiers at a time that is consistent with their developmental stage. Pacifiers seldom do any permanent damage, although they aren’t terribly appealing to look at when hanging out of a toddling toddler’s mouth. Parents were urged to be patient and consistent and were told that allowing the gooey thing to self-destruct often works, as does accelerating the process with a razor blade. Enlisting the aid of the Pacifier Fairy was suggested, but I’m not so sure that would work terribly well.
As I finished perusing the article, I couldn’t help think of how this vexing issue of pacifier removal can be avoided if parents follow a simple rule when they first introduced a pacifier to their child. If experienced parents think back to when they first resorted to using the pacifier, it wasn’t because the plastic and rubber gadget was a family heirloom that had been passed down from generation to generation like an engraved silver spoon. It wasn’t because the dentist told them that children who use pacifiers are less likely to need braces on their teeth. Nor was it a rumor filtered down from speech therapists that pacifiers improve articulation.
Parents reach for a pacifier in hopes that it will help their child will fall asleep. I think most parents of older children agree that at the beginning the pacifier was first and foremost a sleep aid. But here is where the critical oversight occurs: If you give your children pacifiers when you want them to go to sleep, why not simply add the stipulation of where you would like them to go to sleep as well?
Most parents prefer that their children sleep in their own space. We can argue of whether that should be in a side sleeper or their own crib, but most parents don’t want their 3-year-olds sleeping in their bed. Nor do they want their children sleeping on the couch in the living room with them while they watch a movie at 10:30 at night. And as pediatricians, we prefer that children not sleep with their necks flexed in a car seat or baby rocker, particularly if they’re a preemie.
Augmenting the primary association between sleep and the pacifier by adding a place has several important advantages. It gives parents more control of where their children will sleep or, more importantly, where they won’t be sleeping. It helps transitions to nonhome sleeping places like day care and long trips to grandma’s house go more smoothly.
Even more importantly, the crib/pacifier association helps parents who have had trouble reading their children’s cues. If they want a pacifier, it means they are tired and want to go to where the pacifier lives: bed
Finally, maintaining the link between sleeping and the pacifier promotes a more natural weaning process than going cold turkey or hiring the Pacifier Fairy. As naps disappear, the pacifier gradually become a less obvious accessory in the child’s life. However, it may linger in the background as a reminder of when the child needs some restorative sleep.
Of course, helping parents to think clearly enough to create and enforce a simple rule long enough to forge a healthy association when they are sleep deprived themselves is just another one of those challenges we must accept as concerned primary care pediatricians.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “Is My Child Overtired? The Sleep Solution for Raising Happier, Healthier Children.” Email him at [email protected].
FDA approves rituximab to treat children with rare vasculitis
The Food and Drug Administration approved rituximab (Rituxan) by injection to treat granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) in children 2 years of age and older in combination with glucocorticoid treatment, according to an FDA news release.
These rare forms of vasculitis damage small blood vessels through inflammation and can lead to serious organ failure, including lungs and kidneys.
The Genentech drug received priority review and an orphan drug designation based on the results of a pediatric clinical trial of 25 patients aged 6-17 years with active GPA or MPA who were treated with rituximab in an international multicenter, open-label, uncontrolled study. Patients in the trial were also given methylprednisolone prior to starting treatment.
The trial consisted of a 6-month remission induction phase where patients were treated only with rituximab and glucocorticoids. In addition, patients who had not achieved remission could receive additional treatment, including other therapies, at the discretion of the investigator, according to the FDA. By 6 months, 14 of the patients were in remission, and after 18 months, all 25 patients were in remission.
Rituximab contains a boxed warning regarding increased risks of fatal infusion reactions, potentially fatal severe skin and mouth reactions, hepatitis B virus reactivation that may cause serious or lethal liver problems, and progressive multifocal leukoencephalopathy, a rare, potentially lethal brain infection.
The trial was conducted and sponsored by F. Hoffmann-La Roche, which owns Genentech.
The Food and Drug Administration approved rituximab (Rituxan) by injection to treat granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) in children 2 years of age and older in combination with glucocorticoid treatment, according to an FDA news release.
These rare forms of vasculitis damage small blood vessels through inflammation and can lead to serious organ failure, including lungs and kidneys.
The Genentech drug received priority review and an orphan drug designation based on the results of a pediatric clinical trial of 25 patients aged 6-17 years with active GPA or MPA who were treated with rituximab in an international multicenter, open-label, uncontrolled study. Patients in the trial were also given methylprednisolone prior to starting treatment.
The trial consisted of a 6-month remission induction phase where patients were treated only with rituximab and glucocorticoids. In addition, patients who had not achieved remission could receive additional treatment, including other therapies, at the discretion of the investigator, according to the FDA. By 6 months, 14 of the patients were in remission, and after 18 months, all 25 patients were in remission.
Rituximab contains a boxed warning regarding increased risks of fatal infusion reactions, potentially fatal severe skin and mouth reactions, hepatitis B virus reactivation that may cause serious or lethal liver problems, and progressive multifocal leukoencephalopathy, a rare, potentially lethal brain infection.
The trial was conducted and sponsored by F. Hoffmann-La Roche, which owns Genentech.
The Food and Drug Administration approved rituximab (Rituxan) by injection to treat granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) in children 2 years of age and older in combination with glucocorticoid treatment, according to an FDA news release.
These rare forms of vasculitis damage small blood vessels through inflammation and can lead to serious organ failure, including lungs and kidneys.
The Genentech drug received priority review and an orphan drug designation based on the results of a pediatric clinical trial of 25 patients aged 6-17 years with active GPA or MPA who were treated with rituximab in an international multicenter, open-label, uncontrolled study. Patients in the trial were also given methylprednisolone prior to starting treatment.
The trial consisted of a 6-month remission induction phase where patients were treated only with rituximab and glucocorticoids. In addition, patients who had not achieved remission could receive additional treatment, including other therapies, at the discretion of the investigator, according to the FDA. By 6 months, 14 of the patients were in remission, and after 18 months, all 25 patients were in remission.
Rituximab contains a boxed warning regarding increased risks of fatal infusion reactions, potentially fatal severe skin and mouth reactions, hepatitis B virus reactivation that may cause serious or lethal liver problems, and progressive multifocal leukoencephalopathy, a rare, potentially lethal brain infection.
The trial was conducted and sponsored by F. Hoffmann-La Roche, which owns Genentech.
Apple cider vinegar soaks fall short in atopic dermatitis
, in a pilot split-arm study.
The aim of the study was to evaluate the effects of diluted apple cider vinegar application on transepidermal water loss (TEWL) and pH on skin affected by AD and on healthy skin, according to Lydia A. Luu of the department of dermatology at University of Virginia, Charlottesville, and colleagues. “Acetic acid, particularly apple cider vinegar, is prominent among emerging natural remedies used in AD. Therefore, determining the safety of this commonly used product is crucial,” they wrote in the study, published in Pediatric Dermatology.
In total, 11 patients with AD and 11 healthy controls were included; most of those with AD were considered mild (36.4%) or moderate (45.5%). Participants had not used systemic or topical antimicrobial treatments in the month preceding the study, and they were aged 12 years and older (mean ages were 20.6 years in the AD group and 28.8 years among controls). Those with AD had significantly elevated TEWL at baseline, compared with controls.
For 14 days, study participants soaked one forearm in dilute apple cider vinegar (0.5% acetic acid) and the other in tap water for 10 minutes daily. Changes in pH and TEWL before and after application were measured.
The researchers found that TEWL significantly increased immediately post treatment (at 0 and 15 minutes) in both groups, dropping to baseline at 30 minutes among those with AD and at 60 minutes among controls.
Skin pH was similar in both groups at baseline (4.86-4.88). After the cider vinegar soak, there was a transient reduction in skin pH among AD patients that lasted for 15 minutes among those with AD and 60 minutes in controls. This finding “suggests temporary acidification of the skin that has theoretical benefit of correcting disrupted skin pH in AD,” the authors wrote, noting that increased TEWL and alkaline skin pH is common among people with AD because of skin barrier dysfunction.
With respect to safety, 72.7% (16) of the participants experienced skin discomfort, mostly described as mild, limited to the vinegar-treated arm. After discontinuation, the majority of skin irritation resolved quickly, with no additional therapy.
The authors acknowledged two key limitations of the study were the homogeneous patient population and small sample size. “Although epidermal acidification would theoretically be beneficial in treating AD, our study shows that acidification by way of topical bathing in a 0.5% [apple cider vinegar] solution as performed in this study is not useful in AD treatment,” they wrote. “Further studies in a more diverse population will be necessary to fully characterize the risk/benefit profile of topical dilute apple cider vinegar treatments.”
The study was funded by the University of Virginia. The authors did not provide information on financial disclosures.
SOURCE: Luu LA et al. Pediatr Dermatol. 2019 Jul 22. doi: 10.1111/pde.13888.
, in a pilot split-arm study.
The aim of the study was to evaluate the effects of diluted apple cider vinegar application on transepidermal water loss (TEWL) and pH on skin affected by AD and on healthy skin, according to Lydia A. Luu of the department of dermatology at University of Virginia, Charlottesville, and colleagues. “Acetic acid, particularly apple cider vinegar, is prominent among emerging natural remedies used in AD. Therefore, determining the safety of this commonly used product is crucial,” they wrote in the study, published in Pediatric Dermatology.
In total, 11 patients with AD and 11 healthy controls were included; most of those with AD were considered mild (36.4%) or moderate (45.5%). Participants had not used systemic or topical antimicrobial treatments in the month preceding the study, and they were aged 12 years and older (mean ages were 20.6 years in the AD group and 28.8 years among controls). Those with AD had significantly elevated TEWL at baseline, compared with controls.
For 14 days, study participants soaked one forearm in dilute apple cider vinegar (0.5% acetic acid) and the other in tap water for 10 minutes daily. Changes in pH and TEWL before and after application were measured.
The researchers found that TEWL significantly increased immediately post treatment (at 0 and 15 minutes) in both groups, dropping to baseline at 30 minutes among those with AD and at 60 minutes among controls.
Skin pH was similar in both groups at baseline (4.86-4.88). After the cider vinegar soak, there was a transient reduction in skin pH among AD patients that lasted for 15 minutes among those with AD and 60 minutes in controls. This finding “suggests temporary acidification of the skin that has theoretical benefit of correcting disrupted skin pH in AD,” the authors wrote, noting that increased TEWL and alkaline skin pH is common among people with AD because of skin barrier dysfunction.
With respect to safety, 72.7% (16) of the participants experienced skin discomfort, mostly described as mild, limited to the vinegar-treated arm. After discontinuation, the majority of skin irritation resolved quickly, with no additional therapy.
The authors acknowledged two key limitations of the study were the homogeneous patient population and small sample size. “Although epidermal acidification would theoretically be beneficial in treating AD, our study shows that acidification by way of topical bathing in a 0.5% [apple cider vinegar] solution as performed in this study is not useful in AD treatment,” they wrote. “Further studies in a more diverse population will be necessary to fully characterize the risk/benefit profile of topical dilute apple cider vinegar treatments.”
The study was funded by the University of Virginia. The authors did not provide information on financial disclosures.
SOURCE: Luu LA et al. Pediatr Dermatol. 2019 Jul 22. doi: 10.1111/pde.13888.
, in a pilot split-arm study.
The aim of the study was to evaluate the effects of diluted apple cider vinegar application on transepidermal water loss (TEWL) and pH on skin affected by AD and on healthy skin, according to Lydia A. Luu of the department of dermatology at University of Virginia, Charlottesville, and colleagues. “Acetic acid, particularly apple cider vinegar, is prominent among emerging natural remedies used in AD. Therefore, determining the safety of this commonly used product is crucial,” they wrote in the study, published in Pediatric Dermatology.
In total, 11 patients with AD and 11 healthy controls were included; most of those with AD were considered mild (36.4%) or moderate (45.5%). Participants had not used systemic or topical antimicrobial treatments in the month preceding the study, and they were aged 12 years and older (mean ages were 20.6 years in the AD group and 28.8 years among controls). Those with AD had significantly elevated TEWL at baseline, compared with controls.
For 14 days, study participants soaked one forearm in dilute apple cider vinegar (0.5% acetic acid) and the other in tap water for 10 minutes daily. Changes in pH and TEWL before and after application were measured.
The researchers found that TEWL significantly increased immediately post treatment (at 0 and 15 minutes) in both groups, dropping to baseline at 30 minutes among those with AD and at 60 minutes among controls.
Skin pH was similar in both groups at baseline (4.86-4.88). After the cider vinegar soak, there was a transient reduction in skin pH among AD patients that lasted for 15 minutes among those with AD and 60 minutes in controls. This finding “suggests temporary acidification of the skin that has theoretical benefit of correcting disrupted skin pH in AD,” the authors wrote, noting that increased TEWL and alkaline skin pH is common among people with AD because of skin barrier dysfunction.
With respect to safety, 72.7% (16) of the participants experienced skin discomfort, mostly described as mild, limited to the vinegar-treated arm. After discontinuation, the majority of skin irritation resolved quickly, with no additional therapy.
The authors acknowledged two key limitations of the study were the homogeneous patient population and small sample size. “Although epidermal acidification would theoretically be beneficial in treating AD, our study shows that acidification by way of topical bathing in a 0.5% [apple cider vinegar] solution as performed in this study is not useful in AD treatment,” they wrote. “Further studies in a more diverse population will be necessary to fully characterize the risk/benefit profile of topical dilute apple cider vinegar treatments.”
The study was funded by the University of Virginia. The authors did not provide information on financial disclosures.
SOURCE: Luu LA et al. Pediatr Dermatol. 2019 Jul 22. doi: 10.1111/pde.13888.
FROM PEDIATRIC DERMATOLOGY
FDA expands Dysport’s upper-limb spasticity indication to children
The Food and Drug Administration has expanded the indication of abobotulinumtoxinA (Dysport) for upper-limb spasticity to include patients aged 2 years and older, according to a release from Ipsen. This botulinum toxin product received approval for this indication in adults in 2015 and approval for lower-limb spasticity in patients aged 2 years and older in 2016. Notably, Orphan Drug Exclusivity prevents it from being indicated for patients with cerebral palsy because another botulinum toxin product, onabotulinumtoxinA (Botox), already was approved for the indication in June 2019.
Spasticity affects the muscles and joints of extremities, especially in growing children, and is usually caused by nerve damage, such as head trauma or spinal cord injury. The degree of spasticity can vary from mild muscle stiffness to severe, painful, and uncontrollable muscle spasms.
AbobotulinumtoxinA was evaluated for upper-limb spasticity in a phase 3, randomized, double-blind, low-dose controlled, multicenter study; the study enrolled 210 children aged 2-17 years with the condition and a Modified Ashworth Scale grade 2 or greater for elbow and wrist flexors. The children were randomized 1:1:1 to injections of either 8 units/kg, 16 units/kg, or 2 units/kg into the elbow flexors and wrist flexors. At 6 weeks, there were statistically significant improvements in Modified Ashworth Scale grade, the primary endpoint, with least-square mean changes from baseline of –2.0, –2.3, and –1.6, respectively.
AbobotulinumtoxinA and all other botulinum toxin products carry a boxed warning, the most serious warning the FDA issues. This warning refers to risk of botulism-like symptoms caused by the botulinum toxin spreading away from the injection area; these symptoms can included sometimes life-threatening difficulty swallowing or breathing. AbobotulinumtoxinA is contraindicated in patients with known hypersensitivity to any botulinum toxin or any of the components, those with presence of infection at proposed injection site(s), and those with known allergy to cow’s milk protein. It is also important to note that botulinum toxin preparations are not interchangeable; the potency units of one are not the same as those of another. Full prescribing information can be found on the Ipsen website.
The Food and Drug Administration has expanded the indication of abobotulinumtoxinA (Dysport) for upper-limb spasticity to include patients aged 2 years and older, according to a release from Ipsen. This botulinum toxin product received approval for this indication in adults in 2015 and approval for lower-limb spasticity in patients aged 2 years and older in 2016. Notably, Orphan Drug Exclusivity prevents it from being indicated for patients with cerebral palsy because another botulinum toxin product, onabotulinumtoxinA (Botox), already was approved for the indication in June 2019.
Spasticity affects the muscles and joints of extremities, especially in growing children, and is usually caused by nerve damage, such as head trauma or spinal cord injury. The degree of spasticity can vary from mild muscle stiffness to severe, painful, and uncontrollable muscle spasms.
AbobotulinumtoxinA was evaluated for upper-limb spasticity in a phase 3, randomized, double-blind, low-dose controlled, multicenter study; the study enrolled 210 children aged 2-17 years with the condition and a Modified Ashworth Scale grade 2 or greater for elbow and wrist flexors. The children were randomized 1:1:1 to injections of either 8 units/kg, 16 units/kg, or 2 units/kg into the elbow flexors and wrist flexors. At 6 weeks, there were statistically significant improvements in Modified Ashworth Scale grade, the primary endpoint, with least-square mean changes from baseline of –2.0, –2.3, and –1.6, respectively.
AbobotulinumtoxinA and all other botulinum toxin products carry a boxed warning, the most serious warning the FDA issues. This warning refers to risk of botulism-like symptoms caused by the botulinum toxin spreading away from the injection area; these symptoms can included sometimes life-threatening difficulty swallowing or breathing. AbobotulinumtoxinA is contraindicated in patients with known hypersensitivity to any botulinum toxin or any of the components, those with presence of infection at proposed injection site(s), and those with known allergy to cow’s milk protein. It is also important to note that botulinum toxin preparations are not interchangeable; the potency units of one are not the same as those of another. Full prescribing information can be found on the Ipsen website.
The Food and Drug Administration has expanded the indication of abobotulinumtoxinA (Dysport) for upper-limb spasticity to include patients aged 2 years and older, according to a release from Ipsen. This botulinum toxin product received approval for this indication in adults in 2015 and approval for lower-limb spasticity in patients aged 2 years and older in 2016. Notably, Orphan Drug Exclusivity prevents it from being indicated for patients with cerebral palsy because another botulinum toxin product, onabotulinumtoxinA (Botox), already was approved for the indication in June 2019.
Spasticity affects the muscles and joints of extremities, especially in growing children, and is usually caused by nerve damage, such as head trauma or spinal cord injury. The degree of spasticity can vary from mild muscle stiffness to severe, painful, and uncontrollable muscle spasms.
AbobotulinumtoxinA was evaluated for upper-limb spasticity in a phase 3, randomized, double-blind, low-dose controlled, multicenter study; the study enrolled 210 children aged 2-17 years with the condition and a Modified Ashworth Scale grade 2 or greater for elbow and wrist flexors. The children were randomized 1:1:1 to injections of either 8 units/kg, 16 units/kg, or 2 units/kg into the elbow flexors and wrist flexors. At 6 weeks, there were statistically significant improvements in Modified Ashworth Scale grade, the primary endpoint, with least-square mean changes from baseline of –2.0, –2.3, and –1.6, respectively.
AbobotulinumtoxinA and all other botulinum toxin products carry a boxed warning, the most serious warning the FDA issues. This warning refers to risk of botulism-like symptoms caused by the botulinum toxin spreading away from the injection area; these symptoms can included sometimes life-threatening difficulty swallowing or breathing. AbobotulinumtoxinA is contraindicated in patients with known hypersensitivity to any botulinum toxin or any of the components, those with presence of infection at proposed injection site(s), and those with known allergy to cow’s milk protein. It is also important to note that botulinum toxin preparations are not interchangeable; the potency units of one are not the same as those of another. Full prescribing information can be found on the Ipsen website.
Universal ASD screening is feasible, but M-CHAT/F underperforms
, especially in children of color and in those from lower-income households, new research found.
Guidelines for universal autism spectrum disorder (ASD) screening currently conflict, Whitney Guthrie, PhD, of the Children’s Hospital of Philadelphia, and associates wrote in Pediatrics. The American Academy of Pediatrics recommends universal screening in children aged 18 months and 24 months to expedite earlier identification and diagnosis. However, the U.S. Preventive Services Task Force has concluded that “there is insufficient evidence to recommend universal screening, in part because of limited data on outcomes for children who screen negative and from diverse samples.”
Dr. Guthrie and associates conducted a study of 25,999 children aged 16-26 months who had a well-child visit between January 2011 and July 2015 at a Children’s Hospital of Philadelphia site that had implemented universal electronic screening. Of this group, 43% were white, 37% were black, and the remainder were Asian or of other/multiple races; 92% were non-Hispanic. The median parental income was $59,597, 54% had private insurance and 45.3% had public insurance/Medicaid, and 42% came from an urban primary care site while the rest came from suburban primary care.
Screening rates were good over the study period, with 91% of children undergoing at least one screen with the Modified Checklist for Autism in Toddlers with Follow-Up (M-CHAT/F). While 50% were screened more than once, only 48% of children were screened at 18 and 24 months, as per the AAP guideline. Children who were screened multiple times were more likely to be white and non-Hispanic, to be from a suburban site, and to have higher incomes and private insurance.
After the first M-CHAT/F screen, 9.5% of children were positive, a rate comparable with that seen in other large-scale, U.S.-based studies. Of the 2,256 children who tested positive, 41% received a second screen; 782 (95%) of these children tested negative.
After the study period, most children (n = 20,437; 87%) continued receiving care with the Children’s Hospital of Philadelphia system and had diagnostic data available past the age of 4 years. ASD prevalence was 2%, giving the M-CHAT/F a sensitivity of 39%, a specificity of 95%, a positive predictive value of 15%, and a negative predictive value of 99%.
M-CHAT/F sensitivity was higher in older children (49% at 21-26 months vs. 35% at 16-20 months) and with repeated screenings (40% vs. 32%), and positive predictive value was lower in girls (8% vs. 20%). Specificity and positive predictive value were higher in white children (98% and 24%, respectively), compared with black children (92% and 12%, respectively), Asian children (90% and 11%, respectively), and those from other/multiple racial groups (94% and 13%, respectively). Higher-income families also saw increased specificity (97% vs. 92%) and positive predictive value (20% vs. 12%), compared with lower-income families.
While Dr. Guthrie and associates wrote of new methods of screening, such as parental reporting tools supported by picture or video and “direct data-gathering methods that leverage technological advances in computing and machine learning,” Lonnie Zwaigenbaum, MD, MSc, and Jonathon Maguire, MD, MSc, argued in an editorial, also published in Pediatrics, that the M-CHAT/F “remains a strong candidate” for universal ASD screening, despite the notable weaknesses.
“Ultimately, the potential added value of ASD screening must be considered relative to what would occur in its absence,” wrote Dr. Zwaigenbaum of the Women’s and Children’s Health Research Institute at the University of Alberta, Edmonton, and Dr. Maguire of St Michael’s Hospital, Toronto, and the University of Toronto. “Although it is difficult to object to the guidance from the U.S. Preventive Services Task Force to listen carefully to parents’ concerns, we must acknowledge the false dichotomy between screening and surveillance in this context. ... Why not use the best available measurement tools to identify developmental concerns with the highest possible accuracy?”
The study was funded by the Allerton Foundation, Eagles Charitable Foundation, and the National Institute of Mental Health; the study investigators reported that they had no conflicts of interest. Dr. Zwaigenbaum is a member of an independent data monitoring committee for a Roche-funded medication trial and Dr. Maguire reported receiving nonfinancial support from Ddrops for an investigator-initiated study on vitamin D and respiratory tract infections. Dr Zwaigenbaum is supported by the Stollery Children’s Hospital Foundation Chair in Autism Research. Dr Maguire is supported by St. Michael’s Hospital and the Hospital for Sick Children.
SOURCEs: Guthrie W et al. Pediatrics. 2019 Sep 27. doi: 10.1542/peds.2018-3963; Zwaigenbaum L, Maguire J. Pediatrics. 2019 Sep 27. doi: 10.1542/peds.2019-0925.
, especially in children of color and in those from lower-income households, new research found.
Guidelines for universal autism spectrum disorder (ASD) screening currently conflict, Whitney Guthrie, PhD, of the Children’s Hospital of Philadelphia, and associates wrote in Pediatrics. The American Academy of Pediatrics recommends universal screening in children aged 18 months and 24 months to expedite earlier identification and diagnosis. However, the U.S. Preventive Services Task Force has concluded that “there is insufficient evidence to recommend universal screening, in part because of limited data on outcomes for children who screen negative and from diverse samples.”
Dr. Guthrie and associates conducted a study of 25,999 children aged 16-26 months who had a well-child visit between January 2011 and July 2015 at a Children’s Hospital of Philadelphia site that had implemented universal electronic screening. Of this group, 43% were white, 37% were black, and the remainder were Asian or of other/multiple races; 92% were non-Hispanic. The median parental income was $59,597, 54% had private insurance and 45.3% had public insurance/Medicaid, and 42% came from an urban primary care site while the rest came from suburban primary care.
Screening rates were good over the study period, with 91% of children undergoing at least one screen with the Modified Checklist for Autism in Toddlers with Follow-Up (M-CHAT/F). While 50% were screened more than once, only 48% of children were screened at 18 and 24 months, as per the AAP guideline. Children who were screened multiple times were more likely to be white and non-Hispanic, to be from a suburban site, and to have higher incomes and private insurance.
After the first M-CHAT/F screen, 9.5% of children were positive, a rate comparable with that seen in other large-scale, U.S.-based studies. Of the 2,256 children who tested positive, 41% received a second screen; 782 (95%) of these children tested negative.
After the study period, most children (n = 20,437; 87%) continued receiving care with the Children’s Hospital of Philadelphia system and had diagnostic data available past the age of 4 years. ASD prevalence was 2%, giving the M-CHAT/F a sensitivity of 39%, a specificity of 95%, a positive predictive value of 15%, and a negative predictive value of 99%.
M-CHAT/F sensitivity was higher in older children (49% at 21-26 months vs. 35% at 16-20 months) and with repeated screenings (40% vs. 32%), and positive predictive value was lower in girls (8% vs. 20%). Specificity and positive predictive value were higher in white children (98% and 24%, respectively), compared with black children (92% and 12%, respectively), Asian children (90% and 11%, respectively), and those from other/multiple racial groups (94% and 13%, respectively). Higher-income families also saw increased specificity (97% vs. 92%) and positive predictive value (20% vs. 12%), compared with lower-income families.
While Dr. Guthrie and associates wrote of new methods of screening, such as parental reporting tools supported by picture or video and “direct data-gathering methods that leverage technological advances in computing and machine learning,” Lonnie Zwaigenbaum, MD, MSc, and Jonathon Maguire, MD, MSc, argued in an editorial, also published in Pediatrics, that the M-CHAT/F “remains a strong candidate” for universal ASD screening, despite the notable weaknesses.
“Ultimately, the potential added value of ASD screening must be considered relative to what would occur in its absence,” wrote Dr. Zwaigenbaum of the Women’s and Children’s Health Research Institute at the University of Alberta, Edmonton, and Dr. Maguire of St Michael’s Hospital, Toronto, and the University of Toronto. “Although it is difficult to object to the guidance from the U.S. Preventive Services Task Force to listen carefully to parents’ concerns, we must acknowledge the false dichotomy between screening and surveillance in this context. ... Why not use the best available measurement tools to identify developmental concerns with the highest possible accuracy?”
The study was funded by the Allerton Foundation, Eagles Charitable Foundation, and the National Institute of Mental Health; the study investigators reported that they had no conflicts of interest. Dr. Zwaigenbaum is a member of an independent data monitoring committee for a Roche-funded medication trial and Dr. Maguire reported receiving nonfinancial support from Ddrops for an investigator-initiated study on vitamin D and respiratory tract infections. Dr Zwaigenbaum is supported by the Stollery Children’s Hospital Foundation Chair in Autism Research. Dr Maguire is supported by St. Michael’s Hospital and the Hospital for Sick Children.
SOURCEs: Guthrie W et al. Pediatrics. 2019 Sep 27. doi: 10.1542/peds.2018-3963; Zwaigenbaum L, Maguire J. Pediatrics. 2019 Sep 27. doi: 10.1542/peds.2019-0925.
, especially in children of color and in those from lower-income households, new research found.
Guidelines for universal autism spectrum disorder (ASD) screening currently conflict, Whitney Guthrie, PhD, of the Children’s Hospital of Philadelphia, and associates wrote in Pediatrics. The American Academy of Pediatrics recommends universal screening in children aged 18 months and 24 months to expedite earlier identification and diagnosis. However, the U.S. Preventive Services Task Force has concluded that “there is insufficient evidence to recommend universal screening, in part because of limited data on outcomes for children who screen negative and from diverse samples.”
Dr. Guthrie and associates conducted a study of 25,999 children aged 16-26 months who had a well-child visit between January 2011 and July 2015 at a Children’s Hospital of Philadelphia site that had implemented universal electronic screening. Of this group, 43% were white, 37% were black, and the remainder were Asian or of other/multiple races; 92% were non-Hispanic. The median parental income was $59,597, 54% had private insurance and 45.3% had public insurance/Medicaid, and 42% came from an urban primary care site while the rest came from suburban primary care.
Screening rates were good over the study period, with 91% of children undergoing at least one screen with the Modified Checklist for Autism in Toddlers with Follow-Up (M-CHAT/F). While 50% were screened more than once, only 48% of children were screened at 18 and 24 months, as per the AAP guideline. Children who were screened multiple times were more likely to be white and non-Hispanic, to be from a suburban site, and to have higher incomes and private insurance.
After the first M-CHAT/F screen, 9.5% of children were positive, a rate comparable with that seen in other large-scale, U.S.-based studies. Of the 2,256 children who tested positive, 41% received a second screen; 782 (95%) of these children tested negative.
After the study period, most children (n = 20,437; 87%) continued receiving care with the Children’s Hospital of Philadelphia system and had diagnostic data available past the age of 4 years. ASD prevalence was 2%, giving the M-CHAT/F a sensitivity of 39%, a specificity of 95%, a positive predictive value of 15%, and a negative predictive value of 99%.
M-CHAT/F sensitivity was higher in older children (49% at 21-26 months vs. 35% at 16-20 months) and with repeated screenings (40% vs. 32%), and positive predictive value was lower in girls (8% vs. 20%). Specificity and positive predictive value were higher in white children (98% and 24%, respectively), compared with black children (92% and 12%, respectively), Asian children (90% and 11%, respectively), and those from other/multiple racial groups (94% and 13%, respectively). Higher-income families also saw increased specificity (97% vs. 92%) and positive predictive value (20% vs. 12%), compared with lower-income families.
While Dr. Guthrie and associates wrote of new methods of screening, such as parental reporting tools supported by picture or video and “direct data-gathering methods that leverage technological advances in computing and machine learning,” Lonnie Zwaigenbaum, MD, MSc, and Jonathon Maguire, MD, MSc, argued in an editorial, also published in Pediatrics, that the M-CHAT/F “remains a strong candidate” for universal ASD screening, despite the notable weaknesses.
“Ultimately, the potential added value of ASD screening must be considered relative to what would occur in its absence,” wrote Dr. Zwaigenbaum of the Women’s and Children’s Health Research Institute at the University of Alberta, Edmonton, and Dr. Maguire of St Michael’s Hospital, Toronto, and the University of Toronto. “Although it is difficult to object to the guidance from the U.S. Preventive Services Task Force to listen carefully to parents’ concerns, we must acknowledge the false dichotomy between screening and surveillance in this context. ... Why not use the best available measurement tools to identify developmental concerns with the highest possible accuracy?”
The study was funded by the Allerton Foundation, Eagles Charitable Foundation, and the National Institute of Mental Health; the study investigators reported that they had no conflicts of interest. Dr. Zwaigenbaum is a member of an independent data monitoring committee for a Roche-funded medication trial and Dr. Maguire reported receiving nonfinancial support from Ddrops for an investigator-initiated study on vitamin D and respiratory tract infections. Dr Zwaigenbaum is supported by the Stollery Children’s Hospital Foundation Chair in Autism Research. Dr Maguire is supported by St. Michael’s Hospital and the Hospital for Sick Children.
SOURCEs: Guthrie W et al. Pediatrics. 2019 Sep 27. doi: 10.1542/peds.2018-3963; Zwaigenbaum L, Maguire J. Pediatrics. 2019 Sep 27. doi: 10.1542/peds.2019-0925.
FROM PEDIATRICS
Key clinical point: Universal screening for autism in a primary care setting is possible, but accuracy of the Modified Checklist for Autism in Toddlers with Follow-Up (M-CHAT/F) tool was low, especially for children of color and those from lower-income households.
Major finding: Just over 90% of children received screening, with an autism spectrum disorder prevalence of 2%. The M-CHAT/F screen had a sensitivity of 39% and a positive predictive value of 15%
Study details: A total of 25,999 children aged 16-26 months who had a well-child visit between January 2011 and July 2015 at a Children’s Hospital of Philadelphia site that had implemented universal electronic screening.
Disclosures: The study was funded by the Allerton Foundation, Eagles Charitable Foundation, the National Institute of Mental Health, and the National Institutes of Health. The study investigators reported they had no conflicts of interest. Dr. Zwaigenbaum is a member of an independent data monitoring committee for a Roche-funded medication trial and Dr. Maguire reported receiving nonfinancial support from Ddrops for an investigator-initiated study on vitamin D and respiratory tract infections. Dr. Zwaigenbaum and Dr. Maguire receive hospital-supported funding.
Sources: Guthrie W et al. Pediatrics. 2019 Sep 27. doi: 10.1542/peds.2018-3963; Zwaigenbaum L, Maguire J. Pediatrics. 2019 Sep 27. doi: 10.1542/peds.2019-0925.
Early maternal anxiety tied to adolescent hyperactivity
COPENHAGEN – Exposure to maternal somatic anxiety during pregnancy and toddlerhood increases a child’s risk of hyperactivity symptoms in adolescence, Blanca Bolea, MD, said at the annual congress of the European College of Neuropsychopharmacology.
In contrast, the children of mothers who were anxious were not at increased risk for subsequent inattention symptoms in an analysis of 8,725 mothers and their children participating in the Avon Longitudinal Study of Parents and Children, a prospective epidemiologic cohort study ongoing in southwest England since 1991, said Dr. Bolea, a psychiatrist at the University of Toronto.
These findings have practical implications for clinical care: “If we know that women who are anxious in the perinatal period put their children at risk for hyperactivity later on, then we can tackle their anxiety in pregnancy or toddlerhood. And that’s easy to do: You can do group [cognitive-behavioral therapy]; you can give medications, so there are things you can do to reduce that risk. That’s relevant, because we don’t know much about how to reduce levels of ADHD. We know it has a genetic component, but we can’t touch that. You cannot change your genes, so far. But environmental things, we can change. So if we can identify the mothers who are more anxious during pregnancy and toddlerhood and give them resources to reduce their anxiety, then we can potentially reduce hyperactivity later on,” she explained in an interview.
In the Avon study, maternal anxiety was serially assessed from early pregnancy up until a child’s 5th birthday.
“We looked for maternal symptoms similar to panic disorder: shortness of breath, dizziness, sweating, things like that. These are symptoms that any clinician can identify by asking the mothers, so it’s not hard to identify the mothers who could be at risk,” according to the psychiatrist.
Children in the Avon study were assessed for symptoms of inattention at age 8.5 years using the Sky Search, Sky Search Dual Test, and Opposite Worlds subtests of the Tests of Everyday Attention for Children. Hyperactivity symptoms were assessed at age 16 years via the Strengths and Difficulties Questionnaire.
In an analysis adjusted for potentially confounding sociodemographic factors, adolescents whose mothers were rated by investigators as having moderate or high somatic anxiety during pregnancy and the toddlerhood years were at 2.1-fold increased risk of hyperactivity symptoms compared to those whose mothers had low or no anxiety, but increased maternal anxiety wasn’t associated with scores on any of the three tests of inattention.
Dr. Bolea cautioned that, while these Avon study findings document an association between early maternal anxiety and subsequent adolescent hyperactivity, that doesn’t prove causality. The findings are consistent, however, with the fetal origins hypothesis put forth by the late British epidemiologist David J. Barker, MD, PhD, which postulates that stressful fetal circumstances have profound effects later in life.
she said.
The hypothesis has been borne out in animal studies: Stress a pregnant rat, and her offspring will display hyperactivity.
Dr. Bolea reported having no financial conflicts regarding her study. The Avon Longitudinal Study of Parents and Children is funded by the Medical Research Council and the Wellcome Trust.
COPENHAGEN – Exposure to maternal somatic anxiety during pregnancy and toddlerhood increases a child’s risk of hyperactivity symptoms in adolescence, Blanca Bolea, MD, said at the annual congress of the European College of Neuropsychopharmacology.
In contrast, the children of mothers who were anxious were not at increased risk for subsequent inattention symptoms in an analysis of 8,725 mothers and their children participating in the Avon Longitudinal Study of Parents and Children, a prospective epidemiologic cohort study ongoing in southwest England since 1991, said Dr. Bolea, a psychiatrist at the University of Toronto.
These findings have practical implications for clinical care: “If we know that women who are anxious in the perinatal period put their children at risk for hyperactivity later on, then we can tackle their anxiety in pregnancy or toddlerhood. And that’s easy to do: You can do group [cognitive-behavioral therapy]; you can give medications, so there are things you can do to reduce that risk. That’s relevant, because we don’t know much about how to reduce levels of ADHD. We know it has a genetic component, but we can’t touch that. You cannot change your genes, so far. But environmental things, we can change. So if we can identify the mothers who are more anxious during pregnancy and toddlerhood and give them resources to reduce their anxiety, then we can potentially reduce hyperactivity later on,” she explained in an interview.
In the Avon study, maternal anxiety was serially assessed from early pregnancy up until a child’s 5th birthday.
“We looked for maternal symptoms similar to panic disorder: shortness of breath, dizziness, sweating, things like that. These are symptoms that any clinician can identify by asking the mothers, so it’s not hard to identify the mothers who could be at risk,” according to the psychiatrist.
Children in the Avon study were assessed for symptoms of inattention at age 8.5 years using the Sky Search, Sky Search Dual Test, and Opposite Worlds subtests of the Tests of Everyday Attention for Children. Hyperactivity symptoms were assessed at age 16 years via the Strengths and Difficulties Questionnaire.
In an analysis adjusted for potentially confounding sociodemographic factors, adolescents whose mothers were rated by investigators as having moderate or high somatic anxiety during pregnancy and the toddlerhood years were at 2.1-fold increased risk of hyperactivity symptoms compared to those whose mothers had low or no anxiety, but increased maternal anxiety wasn’t associated with scores on any of the three tests of inattention.
Dr. Bolea cautioned that, while these Avon study findings document an association between early maternal anxiety and subsequent adolescent hyperactivity, that doesn’t prove causality. The findings are consistent, however, with the fetal origins hypothesis put forth by the late British epidemiologist David J. Barker, MD, PhD, which postulates that stressful fetal circumstances have profound effects later in life.
she said.
The hypothesis has been borne out in animal studies: Stress a pregnant rat, and her offspring will display hyperactivity.
Dr. Bolea reported having no financial conflicts regarding her study. The Avon Longitudinal Study of Parents and Children is funded by the Medical Research Council and the Wellcome Trust.
COPENHAGEN – Exposure to maternal somatic anxiety during pregnancy and toddlerhood increases a child’s risk of hyperactivity symptoms in adolescence, Blanca Bolea, MD, said at the annual congress of the European College of Neuropsychopharmacology.
In contrast, the children of mothers who were anxious were not at increased risk for subsequent inattention symptoms in an analysis of 8,725 mothers and their children participating in the Avon Longitudinal Study of Parents and Children, a prospective epidemiologic cohort study ongoing in southwest England since 1991, said Dr. Bolea, a psychiatrist at the University of Toronto.
These findings have practical implications for clinical care: “If we know that women who are anxious in the perinatal period put their children at risk for hyperactivity later on, then we can tackle their anxiety in pregnancy or toddlerhood. And that’s easy to do: You can do group [cognitive-behavioral therapy]; you can give medications, so there are things you can do to reduce that risk. That’s relevant, because we don’t know much about how to reduce levels of ADHD. We know it has a genetic component, but we can’t touch that. You cannot change your genes, so far. But environmental things, we can change. So if we can identify the mothers who are more anxious during pregnancy and toddlerhood and give them resources to reduce their anxiety, then we can potentially reduce hyperactivity later on,” she explained in an interview.
In the Avon study, maternal anxiety was serially assessed from early pregnancy up until a child’s 5th birthday.
“We looked for maternal symptoms similar to panic disorder: shortness of breath, dizziness, sweating, things like that. These are symptoms that any clinician can identify by asking the mothers, so it’s not hard to identify the mothers who could be at risk,” according to the psychiatrist.
Children in the Avon study were assessed for symptoms of inattention at age 8.5 years using the Sky Search, Sky Search Dual Test, and Opposite Worlds subtests of the Tests of Everyday Attention for Children. Hyperactivity symptoms were assessed at age 16 years via the Strengths and Difficulties Questionnaire.
In an analysis adjusted for potentially confounding sociodemographic factors, adolescents whose mothers were rated by investigators as having moderate or high somatic anxiety during pregnancy and the toddlerhood years were at 2.1-fold increased risk of hyperactivity symptoms compared to those whose mothers had low or no anxiety, but increased maternal anxiety wasn’t associated with scores on any of the three tests of inattention.
Dr. Bolea cautioned that, while these Avon study findings document an association between early maternal anxiety and subsequent adolescent hyperactivity, that doesn’t prove causality. The findings are consistent, however, with the fetal origins hypothesis put forth by the late British epidemiologist David J. Barker, MD, PhD, which postulates that stressful fetal circumstances have profound effects later in life.
she said.
The hypothesis has been borne out in animal studies: Stress a pregnant rat, and her offspring will display hyperactivity.
Dr. Bolea reported having no financial conflicts regarding her study. The Avon Longitudinal Study of Parents and Children is funded by the Medical Research Council and the Wellcome Trust.
REPORTING FROM ECNP 2019
Review looks at natural course of alopecia areata in young children
, according to a retrospective chart review of 125 children.
Almost 90% of the children presented between aged 2 and 4 years, compared with 11.9% between ages 1 and 2 years, and 1.6% aged under 1 year, “in keeping with the existing literature,” the study authors reported in Pediatric Dermatology. “A high percentage of patients continued to have mild, patchy alopecia at their follow‐up visits,” they added.
Epidemiologic studies of children with alopecia areata are few and have not focused on the youngest patients, said Sneha Rangu, of the section of dermatology at Children’s Hospital of Philadelphia, and coauthors. They performed a retrospective chart review of 125 patients, who initially presented at the hospital with alopecia areata between Jan. 1, 2016, and June 1, 2018, when they were younger than 4 years. Patients who received systemic therapy or topical JAK inhibitors for alopecia were excluded. Severity was measured with the Severity of Alopecia Tool (SALT) score, to monitor progression of hair loss, analyzing scores at the initial presentation, at 3-6 months, at 1 year, and at 2 or more years.
Almost 70% were female, which the authors said was similar to other studies that have found alopecia areata is more prevalent in females; and 86.6% were between ages 2 and 4 years when they first presented. The initial diagnosis was alopecia areata in 72.0%, alopecia totalis in 8.8%, and alopecia universalis in 19.2%. Of the 41 boys, 39% had alopecia totalis or alopecia universalis, as did 22% of the girls, which suggested that boys presenting under aged 4 years were more likely to have more severe disease, or that “guardians of boys are more likely to present for therapy when disease is more severe,” the authors wrote.
About 40% of the children presented with a history of atopic dermatitis, and 4% had an autoimmune disease (vitiligo, celiac disease, or type 1 diabetes). Twenty-eight percent of patients had a family history of alopecia areata, 27.2% had a family history of other autoimmune diseases, and 32% had a family history of hypothyroidism.
At the first visit, 57.6% had patch‐stage alopecia and SALT scores in the mild range (0%‐24% hair loss), which was present in a high proportion of these patients at follow-up: 49.4% at 3-6 months, 39.5% at 1 year, and 42.9% at two or more years.
At the first visit, 28% had high SALT scores (50%-100% hair loss), increasing to 36% at 3-6 months, 41.8% at 1 year, and 46.4% at 2 or more years. They calculated that for those with more than 50% hair loss at the initial presentation, the likelihood of being in a high category of hair loss, as measured by increasing SALT scores, was significantly higher at 1 year (odds ratio, 1.85, P =.033) and at 2 or more years (OR, 2.29, P = .038).
“While there is a likelihood of increasing disease severity, those with higher severity at initial presentation are likely to stay severe after one or 2 years,” the authors noted.
They concluded that their results add to the understanding of the epidemiology of alopecia areata in children “and perhaps can provide clinicians and families with a better sense of prognosis for progression in the youngest patients presenting with alopecia areata.”
They said the retrospective design and small sample size were among the study’s limitations. They had no conflicts of interest to disclose.
SOURCE: Rangu S et al. Pediatr Dermatol. 2019 Aug 29. doi: 10.1111/pde.13990.
, according to a retrospective chart review of 125 children.
Almost 90% of the children presented between aged 2 and 4 years, compared with 11.9% between ages 1 and 2 years, and 1.6% aged under 1 year, “in keeping with the existing literature,” the study authors reported in Pediatric Dermatology. “A high percentage of patients continued to have mild, patchy alopecia at their follow‐up visits,” they added.
Epidemiologic studies of children with alopecia areata are few and have not focused on the youngest patients, said Sneha Rangu, of the section of dermatology at Children’s Hospital of Philadelphia, and coauthors. They performed a retrospective chart review of 125 patients, who initially presented at the hospital with alopecia areata between Jan. 1, 2016, and June 1, 2018, when they were younger than 4 years. Patients who received systemic therapy or topical JAK inhibitors for alopecia were excluded. Severity was measured with the Severity of Alopecia Tool (SALT) score, to monitor progression of hair loss, analyzing scores at the initial presentation, at 3-6 months, at 1 year, and at 2 or more years.
Almost 70% were female, which the authors said was similar to other studies that have found alopecia areata is more prevalent in females; and 86.6% were between ages 2 and 4 years when they first presented. The initial diagnosis was alopecia areata in 72.0%, alopecia totalis in 8.8%, and alopecia universalis in 19.2%. Of the 41 boys, 39% had alopecia totalis or alopecia universalis, as did 22% of the girls, which suggested that boys presenting under aged 4 years were more likely to have more severe disease, or that “guardians of boys are more likely to present for therapy when disease is more severe,” the authors wrote.
About 40% of the children presented with a history of atopic dermatitis, and 4% had an autoimmune disease (vitiligo, celiac disease, or type 1 diabetes). Twenty-eight percent of patients had a family history of alopecia areata, 27.2% had a family history of other autoimmune diseases, and 32% had a family history of hypothyroidism.
At the first visit, 57.6% had patch‐stage alopecia and SALT scores in the mild range (0%‐24% hair loss), which was present in a high proportion of these patients at follow-up: 49.4% at 3-6 months, 39.5% at 1 year, and 42.9% at two or more years.
At the first visit, 28% had high SALT scores (50%-100% hair loss), increasing to 36% at 3-6 months, 41.8% at 1 year, and 46.4% at 2 or more years. They calculated that for those with more than 50% hair loss at the initial presentation, the likelihood of being in a high category of hair loss, as measured by increasing SALT scores, was significantly higher at 1 year (odds ratio, 1.85, P =.033) and at 2 or more years (OR, 2.29, P = .038).
“While there is a likelihood of increasing disease severity, those with higher severity at initial presentation are likely to stay severe after one or 2 years,” the authors noted.
They concluded that their results add to the understanding of the epidemiology of alopecia areata in children “and perhaps can provide clinicians and families with a better sense of prognosis for progression in the youngest patients presenting with alopecia areata.”
They said the retrospective design and small sample size were among the study’s limitations. They had no conflicts of interest to disclose.
SOURCE: Rangu S et al. Pediatr Dermatol. 2019 Aug 29. doi: 10.1111/pde.13990.
, according to a retrospective chart review of 125 children.
Almost 90% of the children presented between aged 2 and 4 years, compared with 11.9% between ages 1 and 2 years, and 1.6% aged under 1 year, “in keeping with the existing literature,” the study authors reported in Pediatric Dermatology. “A high percentage of patients continued to have mild, patchy alopecia at their follow‐up visits,” they added.
Epidemiologic studies of children with alopecia areata are few and have not focused on the youngest patients, said Sneha Rangu, of the section of dermatology at Children’s Hospital of Philadelphia, and coauthors. They performed a retrospective chart review of 125 patients, who initially presented at the hospital with alopecia areata between Jan. 1, 2016, and June 1, 2018, when they were younger than 4 years. Patients who received systemic therapy or topical JAK inhibitors for alopecia were excluded. Severity was measured with the Severity of Alopecia Tool (SALT) score, to monitor progression of hair loss, analyzing scores at the initial presentation, at 3-6 months, at 1 year, and at 2 or more years.
Almost 70% were female, which the authors said was similar to other studies that have found alopecia areata is more prevalent in females; and 86.6% were between ages 2 and 4 years when they first presented. The initial diagnosis was alopecia areata in 72.0%, alopecia totalis in 8.8%, and alopecia universalis in 19.2%. Of the 41 boys, 39% had alopecia totalis or alopecia universalis, as did 22% of the girls, which suggested that boys presenting under aged 4 years were more likely to have more severe disease, or that “guardians of boys are more likely to present for therapy when disease is more severe,” the authors wrote.
About 40% of the children presented with a history of atopic dermatitis, and 4% had an autoimmune disease (vitiligo, celiac disease, or type 1 diabetes). Twenty-eight percent of patients had a family history of alopecia areata, 27.2% had a family history of other autoimmune diseases, and 32% had a family history of hypothyroidism.
At the first visit, 57.6% had patch‐stage alopecia and SALT scores in the mild range (0%‐24% hair loss), which was present in a high proportion of these patients at follow-up: 49.4% at 3-6 months, 39.5% at 1 year, and 42.9% at two or more years.
At the first visit, 28% had high SALT scores (50%-100% hair loss), increasing to 36% at 3-6 months, 41.8% at 1 year, and 46.4% at 2 or more years. They calculated that for those with more than 50% hair loss at the initial presentation, the likelihood of being in a high category of hair loss, as measured by increasing SALT scores, was significantly higher at 1 year (odds ratio, 1.85, P =.033) and at 2 or more years (OR, 2.29, P = .038).
“While there is a likelihood of increasing disease severity, those with higher severity at initial presentation are likely to stay severe after one or 2 years,” the authors noted.
They concluded that their results add to the understanding of the epidemiology of alopecia areata in children “and perhaps can provide clinicians and families with a better sense of prognosis for progression in the youngest patients presenting with alopecia areata.”
They said the retrospective design and small sample size were among the study’s limitations. They had no conflicts of interest to disclose.
SOURCE: Rangu S et al. Pediatr Dermatol. 2019 Aug 29. doi: 10.1111/pde.13990.
FROM PEDIATRIC DERMATOLOGY
Click for Credit: Psoriasis relief; Stress & CV problems; more
Here are 5 articles from the October issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):
1. Bronchiolitis is a feared complication of connective tissue disease
To take the posttest, go to: https://bit.ly/2klWpRb
Expires April 8, 2020
2. Stress incontinence surgery improves sexual dysfunction
To take the posttest, go to: https://bit.ly/2m0wb71
Expires April 10, 2020
3. Survey finds psoriasis patients seek relief with alternative therapies
To take the posttest, go to: https://bit.ly/2lZZDtO
Expires April 10, 2020
4. New data further suggest that stress does a number on the CV system
To take the posttest, go to: https://bit.ly/2lR31ax
Expires April 11, 2020
5. Rate of objects ingested by young children increased over last two decades
To take the posttest, go to: https://bit.ly/2mmYptb
Expires April 12, 2020
Here are 5 articles from the October issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):
1. Bronchiolitis is a feared complication of connective tissue disease
To take the posttest, go to: https://bit.ly/2klWpRb
Expires April 8, 2020
2. Stress incontinence surgery improves sexual dysfunction
To take the posttest, go to: https://bit.ly/2m0wb71
Expires April 10, 2020
3. Survey finds psoriasis patients seek relief with alternative therapies
To take the posttest, go to: https://bit.ly/2lZZDtO
Expires April 10, 2020
4. New data further suggest that stress does a number on the CV system
To take the posttest, go to: https://bit.ly/2lR31ax
Expires April 11, 2020
5. Rate of objects ingested by young children increased over last two decades
To take the posttest, go to: https://bit.ly/2mmYptb
Expires April 12, 2020
Here are 5 articles from the October issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):
1. Bronchiolitis is a feared complication of connective tissue disease
To take the posttest, go to: https://bit.ly/2klWpRb
Expires April 8, 2020
2. Stress incontinence surgery improves sexual dysfunction
To take the posttest, go to: https://bit.ly/2m0wb71
Expires April 10, 2020
3. Survey finds psoriasis patients seek relief with alternative therapies
To take the posttest, go to: https://bit.ly/2lZZDtO
Expires April 10, 2020
4. New data further suggest that stress does a number on the CV system
To take the posttest, go to: https://bit.ly/2lR31ax
Expires April 11, 2020
5. Rate of objects ingested by young children increased over last two decades
To take the posttest, go to: https://bit.ly/2mmYptb
Expires April 12, 2020
Prevalence of developmental disabilities up significantly since 2009
The significant increase in developmental disability prevalence in U.S. children from 2009 to 2017 may have been driven by factors such as better identification and availability of services, according to analysis of National Health Interview Survey (NHIS) data.
The prevalence of any developmental disability rose from 16% in 2009 to 18% in 2017 in children aged 3-17 years, for an increase of 9.5%, Benjamin Zablotsky, PhD, of the National Center for Health Statistics, Hyattsville, Md., and associates reported in Pediatrics.
Changes among the various conditions were not uniform, however, and most of the increase came from ADHD, autism spectrum disorder (ASD), and intellectual disability, which were up by 12.6%, 122.3%, and 25.8%, respectively, they said, based on data for 88,530 children from the NHIS.
Because other studies have shown that the “prevalence of ADHD symptoms and impairment has remained steady over time,” the increase according to NHIS data “could be driven by better identification of children who meet criteria for ADHD, as current estimates of diagnosed prevalence are in line with community-based studies,” Dr. Zablotsky and associates wrote.
Improved identification, “related to increasing parental awareness and changing provider practices” also may account for much of the rise in ASD prevalence, they said.
It also may be related to changes in the survey itself, as “an increase of about 80% was seen in the 2014 NHIS following changes to the wording and ordering of the question capturing ASD.”
The investigators offered a similar explanation for the increase in intellectual disability prevalence, which increased by 72% from 2011 to 2013 when the phrasing of the NHIS question was changed from “mental retardation” to “intellectual disability, also known as mental retardation.”
The other specific conditions – blindness, cerebral palsy, hearing loss, learning disability, seizures, and stuttering/stammering – all saw nonsignificant changes during the study period, with one exception. “Other developmental delay” dropped by a significant 13%. “It is possible that parents have become less likely to select this category because their children have increasingly been diagnosed with another specified condition on the survey,” Dr. Zablotsky and associates said.
“These findings have major implications for pediatric training and workforce needs and more broadly for public health policies and resources to meet the complex medical and educational needs of the rising number of children with disabilities and their families,” Maureen S. Durkin, PhD, DrPH, said in an accompanying editorial.
The trends reported by Dr. Zablotsky and associates, which have been seen in other countries, are the result of improved survival among children, so, “in this sense, a rise in the prevalence of developmental disabilities may be seen as a global indicator of progress in children’s health and pediatric care,” said Dr. Durkin, a epidemiologist in Madison, Wis.
Dr. Zablotsky and coauthors said that there was no external funding for the study and that they had no relevant financial relationships to disclose. Dr. Durkin said that she had no potential conflicts of interest.
SOURCES: Zablotsky B et al. Pediatrics. 2019 Sep 26. 144(4):e20190811. doi: 10.1542/peds.2019-0811; Durkin MS. Pediatrics. 2019 Sep 26. 144[4]:e20192005. doi: 10.1542/peds.2019-2005.
The significant increase in developmental disability prevalence in U.S. children from 2009 to 2017 may have been driven by factors such as better identification and availability of services, according to analysis of National Health Interview Survey (NHIS) data.
The prevalence of any developmental disability rose from 16% in 2009 to 18% in 2017 in children aged 3-17 years, for an increase of 9.5%, Benjamin Zablotsky, PhD, of the National Center for Health Statistics, Hyattsville, Md., and associates reported in Pediatrics.
Changes among the various conditions were not uniform, however, and most of the increase came from ADHD, autism spectrum disorder (ASD), and intellectual disability, which were up by 12.6%, 122.3%, and 25.8%, respectively, they said, based on data for 88,530 children from the NHIS.
Because other studies have shown that the “prevalence of ADHD symptoms and impairment has remained steady over time,” the increase according to NHIS data “could be driven by better identification of children who meet criteria for ADHD, as current estimates of diagnosed prevalence are in line with community-based studies,” Dr. Zablotsky and associates wrote.
Improved identification, “related to increasing parental awareness and changing provider practices” also may account for much of the rise in ASD prevalence, they said.
It also may be related to changes in the survey itself, as “an increase of about 80% was seen in the 2014 NHIS following changes to the wording and ordering of the question capturing ASD.”
The investigators offered a similar explanation for the increase in intellectual disability prevalence, which increased by 72% from 2011 to 2013 when the phrasing of the NHIS question was changed from “mental retardation” to “intellectual disability, also known as mental retardation.”
The other specific conditions – blindness, cerebral palsy, hearing loss, learning disability, seizures, and stuttering/stammering – all saw nonsignificant changes during the study period, with one exception. “Other developmental delay” dropped by a significant 13%. “It is possible that parents have become less likely to select this category because their children have increasingly been diagnosed with another specified condition on the survey,” Dr. Zablotsky and associates said.
“These findings have major implications for pediatric training and workforce needs and more broadly for public health policies and resources to meet the complex medical and educational needs of the rising number of children with disabilities and their families,” Maureen S. Durkin, PhD, DrPH, said in an accompanying editorial.
The trends reported by Dr. Zablotsky and associates, which have been seen in other countries, are the result of improved survival among children, so, “in this sense, a rise in the prevalence of developmental disabilities may be seen as a global indicator of progress in children’s health and pediatric care,” said Dr. Durkin, a epidemiologist in Madison, Wis.
Dr. Zablotsky and coauthors said that there was no external funding for the study and that they had no relevant financial relationships to disclose. Dr. Durkin said that she had no potential conflicts of interest.
SOURCES: Zablotsky B et al. Pediatrics. 2019 Sep 26. 144(4):e20190811. doi: 10.1542/peds.2019-0811; Durkin MS. Pediatrics. 2019 Sep 26. 144[4]:e20192005. doi: 10.1542/peds.2019-2005.
The significant increase in developmental disability prevalence in U.S. children from 2009 to 2017 may have been driven by factors such as better identification and availability of services, according to analysis of National Health Interview Survey (NHIS) data.
The prevalence of any developmental disability rose from 16% in 2009 to 18% in 2017 in children aged 3-17 years, for an increase of 9.5%, Benjamin Zablotsky, PhD, of the National Center for Health Statistics, Hyattsville, Md., and associates reported in Pediatrics.
Changes among the various conditions were not uniform, however, and most of the increase came from ADHD, autism spectrum disorder (ASD), and intellectual disability, which were up by 12.6%, 122.3%, and 25.8%, respectively, they said, based on data for 88,530 children from the NHIS.
Because other studies have shown that the “prevalence of ADHD symptoms and impairment has remained steady over time,” the increase according to NHIS data “could be driven by better identification of children who meet criteria for ADHD, as current estimates of diagnosed prevalence are in line with community-based studies,” Dr. Zablotsky and associates wrote.
Improved identification, “related to increasing parental awareness and changing provider practices” also may account for much of the rise in ASD prevalence, they said.
It also may be related to changes in the survey itself, as “an increase of about 80% was seen in the 2014 NHIS following changes to the wording and ordering of the question capturing ASD.”
The investigators offered a similar explanation for the increase in intellectual disability prevalence, which increased by 72% from 2011 to 2013 when the phrasing of the NHIS question was changed from “mental retardation” to “intellectual disability, also known as mental retardation.”
The other specific conditions – blindness, cerebral palsy, hearing loss, learning disability, seizures, and stuttering/stammering – all saw nonsignificant changes during the study period, with one exception. “Other developmental delay” dropped by a significant 13%. “It is possible that parents have become less likely to select this category because their children have increasingly been diagnosed with another specified condition on the survey,” Dr. Zablotsky and associates said.
“These findings have major implications for pediatric training and workforce needs and more broadly for public health policies and resources to meet the complex medical and educational needs of the rising number of children with disabilities and their families,” Maureen S. Durkin, PhD, DrPH, said in an accompanying editorial.
The trends reported by Dr. Zablotsky and associates, which have been seen in other countries, are the result of improved survival among children, so, “in this sense, a rise in the prevalence of developmental disabilities may be seen as a global indicator of progress in children’s health and pediatric care,” said Dr. Durkin, a epidemiologist in Madison, Wis.
Dr. Zablotsky and coauthors said that there was no external funding for the study and that they had no relevant financial relationships to disclose. Dr. Durkin said that she had no potential conflicts of interest.
SOURCES: Zablotsky B et al. Pediatrics. 2019 Sep 26. 144(4):e20190811. doi: 10.1542/peds.2019-0811; Durkin MS. Pediatrics. 2019 Sep 26. 144[4]:e20192005. doi: 10.1542/peds.2019-2005.
FROM PEDIATRICS
Key clinical point:
Major finding: Among U.S. children aged 3-17 years, prevalence of developmental disabilities increased by 9.5% from 2009 to 2017.
Study details: The sample from the National Health Interview Survey included 88,530 children.
Disclosures: The investigators said that there was no external funding for the study and that they had no relevant financial relationships to disclose.
Source: Zablotsky B et al. Pediatrics. 2019 Sep 26. 144(4):e20190811. doi: 10.1542/peds.2019-0811.
RISE analyses highlight further youth vs. adult T2D differences
BARCELONA – Further differences in how adults and adolescents with type 2 diabetes respond to glucose and glucagon have been demonstrated by new data from the Restoring Insulin SEcretion (RISE) studies presented at the annual meeting of the European Association for the Study of Diabetes.
In a comparison of responses to an oral glucose tolerance test (OGTT), youth (n = 85) were more likely than were adults (n = 353) to have a biphasic type of glucose response curve (18.8% vs. 8.2%, respectively), which is considered a more normal response curve. However, that “did not foretell an advantageous outcome to the RISE interventions in the younger age group,” said study investigator Silva Arslanian, MD, of UPMC Children’s Hospital of Pittsburgh.
Fewer youth than adults had an incessant response (10.6% vs. 14.5%, respectively) or monophasic response to an OGTT (70.6% vs. 77.3%), and that was associated with lower beta-cell responses, compared with individuals with monophasic or biphasic glucose curves.
“Irrespective of curve type, insulin sensitivity was lower in youth than in adults,” Dr. Arslanian said. She added that beta-cell responses were greater in youth than in adults, except in youth with the worst incessant-increase curve type. In youth with the incessant-increase glucose curve, there was no evidence of beta-cell hypersecretion, which suggested youth “have more severe beta-cell dysfunction,” compared with adults.
There were also data presented on whether differences in alpha-cell function between youth and adults might be important. Those data showed that although fasting glucagon concentrations did not increase with fasting glucose in youth, they did in adults. It was found that fasting and stimulated glucagon concentrations were lower in youth than in adults, meaning that “alpha-cell function does not explain the beta-cell hyperresponsiveness seen in youth with impaired glucose tolerance or recently diagnosed type 2 diabetes,” reported study investigator Steven Kahn, MD, ChB, of VA Puget Sound Health Care System, University of Washington, Seattle.
“This is a batch of secondary analyses,” Philip Zeitler, MD, PhD, of Children’s Hospital Colorado, Aurora, said in an interview. Dr. Zeitler, who chaired the session at which the new findings were unveiled, noted that the main data from the RISE Pediatric Medication Study (RISE Peds) were published last year (Diabetes Care. 2018;41[8]:1717-25) and results from the RISE Adult Medication Study (RISE Adult) were just presented this year, and explained that the timing difference was because the adult study took longer to complete its target accrual.
Results of these studies showed that, compared with adults, youth were substantially more insulin resistant and had hyperresponsive beta cells. Furthermore, their beta-cell function deteriorated during and after treatment for type 2 diabetes, whereas it improved during treatment and remained stable after stopping treatment in adults (Diabetes. 2019;68:1670-80).
The idea for the RISE trials came about around 6 years ago, with the overall aim of trying to identify approaches that could preserve or improve beta-cell function in younger patients and adults with dysglycemia, Dr. Zeitler explained. When the trials were being planned it was known that young patients with type 2 diabetes often needed much higher doses of insulin, compared with their adult counterparts. So, it “wasn’t entirely unexpected” that they were found to be insulin resistant, particularly, as puberty is an insulin-resistant state, Dr. Zeitler observed.
“What was new, however, was that [the beta-cells of] youth were hyperresponsive and were really making large amounts of insulin.” Increased insulin production might be expected when there is insulin resistance, he added, but the level seen was “more than you would expect.” Over time, that might be toxic to the beta cells, and evidence from the earlier TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) studies suggested that the rate of beta-cell dysfunction was more rapid in youth than in adults.
Giving his perspective, as a pediatrician, on the new OGTT analyses from the RISE studies, Dr. Zeitler said that these data showed that the characteristic beta-cell hyperresponsiveness seen in youth “actually disappears as glycemia worsens.” In youth with the incessant glucose response pattern, “it shows that they cannot tolerate glucose, and their glucose levels just go up and up and up” until the beta cells fail.
This is a critical observation, Dr. Zeitler said, noting that it “sort of had to be the case, because sooner or later you had to lose beta cells ... this is probably the point where aggressive therapy is needed ... it was always a bit of a paradox, if these kids have such an aggressive course, how come they were starting out being so hyperresponsive?”
With regard to alpha-cell function, “these are really fresh data. We haven’t really had a long time to think about it,” said Dr. Zeitler. “What I find interesting is that there isn’t alpha-cell glucagon hypersecretion in youth like there is in adults.” That may be because youth are making so much insulin that they are suppressing glucagon production, but that’s not an entirely satisfying answer,” he said.
“The TODAY study demonstrated that diabetes in kids is aggressive; these RISE data now start to put some physiology around that, why is it more aggressive? Hyperresponsiveness, loss of beta-cell function over time, lack of response to intervention, compared with the adults.”
As for the clinical implications, Dr. Zeitler said that this is further evidence that the default approach to treating younger patients with greater caution than adults is perhaps not the best way to treat type 2 diabetes.
“These data are really showing that there is a very important toxic period that is occurring in these kids early on [and] that probably argues for more, not less, aggressive therapy,” than with adults. “Clearly, something is happening that is putting them at really big risk for rapid progression, and that’s your chance to treat much more aggressively, much earlier.”
The RISE studies are sponsored by the RISE Study Group in collaboration with the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Zeitler disclosed that he had acted as a consultant to Boehringer-Ingelheim, Eli Lilly, Daiichi-Sankyo and Merck, Sharp & Dohme, and had received research support from Janssen. Dr. Arslanian stated that she has nothing to disclose. Dr. Khan did not provide any disclosure information.
SOURCES: Arslanian S. EASD 2019, Oral presentation S34.1; Kahn S. EASD 2019, Oral presentation S34.3
BARCELONA – Further differences in how adults and adolescents with type 2 diabetes respond to glucose and glucagon have been demonstrated by new data from the Restoring Insulin SEcretion (RISE) studies presented at the annual meeting of the European Association for the Study of Diabetes.
In a comparison of responses to an oral glucose tolerance test (OGTT), youth (n = 85) were more likely than were adults (n = 353) to have a biphasic type of glucose response curve (18.8% vs. 8.2%, respectively), which is considered a more normal response curve. However, that “did not foretell an advantageous outcome to the RISE interventions in the younger age group,” said study investigator Silva Arslanian, MD, of UPMC Children’s Hospital of Pittsburgh.
Fewer youth than adults had an incessant response (10.6% vs. 14.5%, respectively) or monophasic response to an OGTT (70.6% vs. 77.3%), and that was associated with lower beta-cell responses, compared with individuals with monophasic or biphasic glucose curves.
“Irrespective of curve type, insulin sensitivity was lower in youth than in adults,” Dr. Arslanian said. She added that beta-cell responses were greater in youth than in adults, except in youth with the worst incessant-increase curve type. In youth with the incessant-increase glucose curve, there was no evidence of beta-cell hypersecretion, which suggested youth “have more severe beta-cell dysfunction,” compared with adults.
There were also data presented on whether differences in alpha-cell function between youth and adults might be important. Those data showed that although fasting glucagon concentrations did not increase with fasting glucose in youth, they did in adults. It was found that fasting and stimulated glucagon concentrations were lower in youth than in adults, meaning that “alpha-cell function does not explain the beta-cell hyperresponsiveness seen in youth with impaired glucose tolerance or recently diagnosed type 2 diabetes,” reported study investigator Steven Kahn, MD, ChB, of VA Puget Sound Health Care System, University of Washington, Seattle.
“This is a batch of secondary analyses,” Philip Zeitler, MD, PhD, of Children’s Hospital Colorado, Aurora, said in an interview. Dr. Zeitler, who chaired the session at which the new findings were unveiled, noted that the main data from the RISE Pediatric Medication Study (RISE Peds) were published last year (Diabetes Care. 2018;41[8]:1717-25) and results from the RISE Adult Medication Study (RISE Adult) were just presented this year, and explained that the timing difference was because the adult study took longer to complete its target accrual.
Results of these studies showed that, compared with adults, youth were substantially more insulin resistant and had hyperresponsive beta cells. Furthermore, their beta-cell function deteriorated during and after treatment for type 2 diabetes, whereas it improved during treatment and remained stable after stopping treatment in adults (Diabetes. 2019;68:1670-80).
The idea for the RISE trials came about around 6 years ago, with the overall aim of trying to identify approaches that could preserve or improve beta-cell function in younger patients and adults with dysglycemia, Dr. Zeitler explained. When the trials were being planned it was known that young patients with type 2 diabetes often needed much higher doses of insulin, compared with their adult counterparts. So, it “wasn’t entirely unexpected” that they were found to be insulin resistant, particularly, as puberty is an insulin-resistant state, Dr. Zeitler observed.
“What was new, however, was that [the beta-cells of] youth were hyperresponsive and were really making large amounts of insulin.” Increased insulin production might be expected when there is insulin resistance, he added, but the level seen was “more than you would expect.” Over time, that might be toxic to the beta cells, and evidence from the earlier TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) studies suggested that the rate of beta-cell dysfunction was more rapid in youth than in adults.
Giving his perspective, as a pediatrician, on the new OGTT analyses from the RISE studies, Dr. Zeitler said that these data showed that the characteristic beta-cell hyperresponsiveness seen in youth “actually disappears as glycemia worsens.” In youth with the incessant glucose response pattern, “it shows that they cannot tolerate glucose, and their glucose levels just go up and up and up” until the beta cells fail.
This is a critical observation, Dr. Zeitler said, noting that it “sort of had to be the case, because sooner or later you had to lose beta cells ... this is probably the point where aggressive therapy is needed ... it was always a bit of a paradox, if these kids have such an aggressive course, how come they were starting out being so hyperresponsive?”
With regard to alpha-cell function, “these are really fresh data. We haven’t really had a long time to think about it,” said Dr. Zeitler. “What I find interesting is that there isn’t alpha-cell glucagon hypersecretion in youth like there is in adults.” That may be because youth are making so much insulin that they are suppressing glucagon production, but that’s not an entirely satisfying answer,” he said.
“The TODAY study demonstrated that diabetes in kids is aggressive; these RISE data now start to put some physiology around that, why is it more aggressive? Hyperresponsiveness, loss of beta-cell function over time, lack of response to intervention, compared with the adults.”
As for the clinical implications, Dr. Zeitler said that this is further evidence that the default approach to treating younger patients with greater caution than adults is perhaps not the best way to treat type 2 diabetes.
“These data are really showing that there is a very important toxic period that is occurring in these kids early on [and] that probably argues for more, not less, aggressive therapy,” than with adults. “Clearly, something is happening that is putting them at really big risk for rapid progression, and that’s your chance to treat much more aggressively, much earlier.”
The RISE studies are sponsored by the RISE Study Group in collaboration with the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Zeitler disclosed that he had acted as a consultant to Boehringer-Ingelheim, Eli Lilly, Daiichi-Sankyo and Merck, Sharp & Dohme, and had received research support from Janssen. Dr. Arslanian stated that she has nothing to disclose. Dr. Khan did not provide any disclosure information.
SOURCES: Arslanian S. EASD 2019, Oral presentation S34.1; Kahn S. EASD 2019, Oral presentation S34.3
BARCELONA – Further differences in how adults and adolescents with type 2 diabetes respond to glucose and glucagon have been demonstrated by new data from the Restoring Insulin SEcretion (RISE) studies presented at the annual meeting of the European Association for the Study of Diabetes.
In a comparison of responses to an oral glucose tolerance test (OGTT), youth (n = 85) were more likely than were adults (n = 353) to have a biphasic type of glucose response curve (18.8% vs. 8.2%, respectively), which is considered a more normal response curve. However, that “did not foretell an advantageous outcome to the RISE interventions in the younger age group,” said study investigator Silva Arslanian, MD, of UPMC Children’s Hospital of Pittsburgh.
Fewer youth than adults had an incessant response (10.6% vs. 14.5%, respectively) or monophasic response to an OGTT (70.6% vs. 77.3%), and that was associated with lower beta-cell responses, compared with individuals with monophasic or biphasic glucose curves.
“Irrespective of curve type, insulin sensitivity was lower in youth than in adults,” Dr. Arslanian said. She added that beta-cell responses were greater in youth than in adults, except in youth with the worst incessant-increase curve type. In youth with the incessant-increase glucose curve, there was no evidence of beta-cell hypersecretion, which suggested youth “have more severe beta-cell dysfunction,” compared with adults.
There were also data presented on whether differences in alpha-cell function between youth and adults might be important. Those data showed that although fasting glucagon concentrations did not increase with fasting glucose in youth, they did in adults. It was found that fasting and stimulated glucagon concentrations were lower in youth than in adults, meaning that “alpha-cell function does not explain the beta-cell hyperresponsiveness seen in youth with impaired glucose tolerance or recently diagnosed type 2 diabetes,” reported study investigator Steven Kahn, MD, ChB, of VA Puget Sound Health Care System, University of Washington, Seattle.
“This is a batch of secondary analyses,” Philip Zeitler, MD, PhD, of Children’s Hospital Colorado, Aurora, said in an interview. Dr. Zeitler, who chaired the session at which the new findings were unveiled, noted that the main data from the RISE Pediatric Medication Study (RISE Peds) were published last year (Diabetes Care. 2018;41[8]:1717-25) and results from the RISE Adult Medication Study (RISE Adult) were just presented this year, and explained that the timing difference was because the adult study took longer to complete its target accrual.
Results of these studies showed that, compared with adults, youth were substantially more insulin resistant and had hyperresponsive beta cells. Furthermore, their beta-cell function deteriorated during and after treatment for type 2 diabetes, whereas it improved during treatment and remained stable after stopping treatment in adults (Diabetes. 2019;68:1670-80).
The idea for the RISE trials came about around 6 years ago, with the overall aim of trying to identify approaches that could preserve or improve beta-cell function in younger patients and adults with dysglycemia, Dr. Zeitler explained. When the trials were being planned it was known that young patients with type 2 diabetes often needed much higher doses of insulin, compared with their adult counterparts. So, it “wasn’t entirely unexpected” that they were found to be insulin resistant, particularly, as puberty is an insulin-resistant state, Dr. Zeitler observed.
“What was new, however, was that [the beta-cells of] youth were hyperresponsive and were really making large amounts of insulin.” Increased insulin production might be expected when there is insulin resistance, he added, but the level seen was “more than you would expect.” Over time, that might be toxic to the beta cells, and evidence from the earlier TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) studies suggested that the rate of beta-cell dysfunction was more rapid in youth than in adults.
Giving his perspective, as a pediatrician, on the new OGTT analyses from the RISE studies, Dr. Zeitler said that these data showed that the characteristic beta-cell hyperresponsiveness seen in youth “actually disappears as glycemia worsens.” In youth with the incessant glucose response pattern, “it shows that they cannot tolerate glucose, and their glucose levels just go up and up and up” until the beta cells fail.
This is a critical observation, Dr. Zeitler said, noting that it “sort of had to be the case, because sooner or later you had to lose beta cells ... this is probably the point where aggressive therapy is needed ... it was always a bit of a paradox, if these kids have such an aggressive course, how come they were starting out being so hyperresponsive?”
With regard to alpha-cell function, “these are really fresh data. We haven’t really had a long time to think about it,” said Dr. Zeitler. “What I find interesting is that there isn’t alpha-cell glucagon hypersecretion in youth like there is in adults.” That may be because youth are making so much insulin that they are suppressing glucagon production, but that’s not an entirely satisfying answer,” he said.
“The TODAY study demonstrated that diabetes in kids is aggressive; these RISE data now start to put some physiology around that, why is it more aggressive? Hyperresponsiveness, loss of beta-cell function over time, lack of response to intervention, compared with the adults.”
As for the clinical implications, Dr. Zeitler said that this is further evidence that the default approach to treating younger patients with greater caution than adults is perhaps not the best way to treat type 2 diabetes.
“These data are really showing that there is a very important toxic period that is occurring in these kids early on [and] that probably argues for more, not less, aggressive therapy,” than with adults. “Clearly, something is happening that is putting them at really big risk for rapid progression, and that’s your chance to treat much more aggressively, much earlier.”
The RISE studies are sponsored by the RISE Study Group in collaboration with the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Zeitler disclosed that he had acted as a consultant to Boehringer-Ingelheim, Eli Lilly, Daiichi-Sankyo and Merck, Sharp & Dohme, and had received research support from Janssen. Dr. Arslanian stated that she has nothing to disclose. Dr. Khan did not provide any disclosure information.
SOURCES: Arslanian S. EASD 2019, Oral presentation S34.1; Kahn S. EASD 2019, Oral presentation S34.3
REPORTING FROM EASD 2019