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Help parents manage screen time thoughtfully
It has been 2 years since we last wrote about the potential risks to children and adolescents of spending too much time on screens. While there have been studies in the interval that offer us more information about the effects of heavy screen use and the developing brain, there is little certainty about what is optimal for children and adolescents, and less still on how parents might effectively equip their children to make good use of screens without suffering ill effects.
You might recall that back in October of 2016, the American Academy of Pediatrics published screen time guidelines: recommending no screen time for infants and children up to 18 months old, limiting all screen time to 1 hour per day for children up to 5 years old, and 2 hours daily for older children (up to 11 years old), so that it would not interfere with homework, social time, exercise, and sleep. At the time, data suggested that children from 2 to 11 years old were spending an average of 4.5 hours per day on screens (TV, computer, tablets, or smartphones, not counting homework).
The Adolescent Brain Cognitive Development Study began in September 2016 to evaluate the effects of Canadian recommendations for 8- to 11-year-olds (9-11 hours sleep nightly, 1 hour of exercise daily, and 2 hours or less of screen time daily; the study subjects are in the United States). This fall they published their initial results, demonstrating that only 51% get the recommended amount of sleep, only 37% kept their daily screen time to under 2 hours, and only 18% were getting the recommended amount of exercise. Only 5% of children consistently met all three recommendations while 29% of children didn’t meet any of the recommendations.
The researchers assessed the children’s cognitive development and found that after 1 year, those children who met the screen time recommendations, both screen time and sleep, or all three recommendations demonstrated “superior global cognition.” Children were spending an average of 3.7 hours daily on screens, and those children who were spending 2 hours or less on screens performed 4% better on tests of cognitive function than did children spending the average amount of time. Sleep and exercise differences alone did not contribute to significant differences in cognitive function. This study will continue for another 10 years.1
In a much smaller study out of Cincinnati Children’s Hospital, researchers asked parents to describe the amount of time a child spent on reading and in screen-based media activities, then completed MRI scans of the children’s brains.2 They found a strong association between reading time and higher functional connectivity between the parts of the brain responsible for visual word formation and those responsible for language and cognitive control, with a negative correlation between functional connectivity and time spent in screen-based media activities.
While these studies are important pieces of data as we build a deeper understanding about the effects of screen-based media use on children’s cognitive and behavioral development, they do not offer certainty about causality. These studies do not yet clarify whether certain children are especially vulnerable to the untoward effects of heavy screen-based media use. Perhaps the research will someday offer guidelines with certainty, but families need guidance now. Without doubt, digital devices are here to stay, are important to homework, and can facilitate independence, long-distance connections, important technical work-skills, and even senseless fun and relaxation. So we will focus on offering some principles to help you guide young people (or their parents) in approaching screen time thoughtfully.
While recommending no more than 2 hours of daily screen time seems reasonable, it may be more useful to focus on what young people are doing with the rest of their time. Are they getting adequate, restful sleep? Are they able to exercise most days? Do they have enough time for homework? Do they have time for friends (time actually together, not just texting)? What about time for hobbies? When parents focus on the precious resource of time and all of the activities their children both need and want to do, it sets the frame for them to say that their children are allowed to have time to relax with screen-based media as long as it does not take away from these other priorities. Ensuring that the child has at least 8 hours of sleep, after homework and sports, also will set natural limits on screen time.
Parents also can use the frame of development to guide their rules about screen time. If use of an electronic device serves a developmental task, then it is reasonable. If it interferes with a developmental task, then it should be limited. Adolescents (ages 12-20) should be exploring their own identities, establishing independence, deepening social relationships, and learning to manage their impulses. Some interests can be most easily explored with the aid of a computer (such as with programming, art history, or astronomy). Use of cellphones can facilitate teenagers’ being more independent with plans or transportation. Social connections can be supported by texting or FaceTime. Some close friends may be in a different sport or live far away, and it is possible to stay connected only virtually. However, when use of electronic devices keeps the child from engaging with new friends and new interests or from getting into the world to establish real independence (i.e., a job), then there should be limits. In all of these cases, it is critical that adults explain to teenagers what is guiding their thinking about limits on screen time. Open discussions about the great utility and fun that screens can provide, as well as the challenge of keeping those activities in balance with other important activities, helps adolescents set the frame for that rapidly approaching time when they will be making those choices without adult supervision.
Younger children (ages 8-11) should be sampling a wide array of activities and interests and experiencing challenges and eventual mastery across domains. Video games can be very compelling for this age group because they appeal to exactly this drive to master a challenge. Parents want to ensure that their children can have senseless fun, and still have enough time to explore actual activities: social, athletic, creative, and academic. They can be ready to explain the why of rules, but consistent rules, enforced for everyone at home, are most helpful for this age group.
You also can help parents to consider the child’s temperament when thinking about which rules will be appropriate. Anxious children and teenagers may be especially prone to immersive virtual activities that allow them to avoid the stress of real undertakings or interactions. But anxious children may be able to prepare for something anxiety provoking by exploring it virtually first. Youth with ADHD are going to struggle with shifting away from video games or other electronic activities they enjoy that don’t have a natural ending, and will need strict rules and patient support around balanced screen time use. Screen time may play to a child’s strengths, enabling creative children to take in a wide range of art or music and even create their own when other resources are limited.
Finally, all parents should consider what their own screen use is teaching their children. Adolescents are unlikely to listen to their parents’ recommendations if the parents spend hours online after work. Younger children need their parents’ engaged attention: being coaches and cheerleaders for all of their efforts at mastery. You can help parents to imagine rules that the whole family can follow. They can consider how screen time helps them connect with their children, such as watching a favorite program or sport together. They can explore shared interests online together. They can even relax with ridiculous cat videos together! Screen time together is valuable if it supports parents’ connections with their children, while their rules ensure adequate time for sleep, physical activity, and developmental priorities.
Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com.
References
1. Lancet Child Adolesc Health. 2018 Nov 1;2(11):783-91.
2. Acta Paediatra. 2018 Apr;107(4):685-93
It has been 2 years since we last wrote about the potential risks to children and adolescents of spending too much time on screens. While there have been studies in the interval that offer us more information about the effects of heavy screen use and the developing brain, there is little certainty about what is optimal for children and adolescents, and less still on how parents might effectively equip their children to make good use of screens without suffering ill effects.
You might recall that back in October of 2016, the American Academy of Pediatrics published screen time guidelines: recommending no screen time for infants and children up to 18 months old, limiting all screen time to 1 hour per day for children up to 5 years old, and 2 hours daily for older children (up to 11 years old), so that it would not interfere with homework, social time, exercise, and sleep. At the time, data suggested that children from 2 to 11 years old were spending an average of 4.5 hours per day on screens (TV, computer, tablets, or smartphones, not counting homework).
The Adolescent Brain Cognitive Development Study began in September 2016 to evaluate the effects of Canadian recommendations for 8- to 11-year-olds (9-11 hours sleep nightly, 1 hour of exercise daily, and 2 hours or less of screen time daily; the study subjects are in the United States). This fall they published their initial results, demonstrating that only 51% get the recommended amount of sleep, only 37% kept their daily screen time to under 2 hours, and only 18% were getting the recommended amount of exercise. Only 5% of children consistently met all three recommendations while 29% of children didn’t meet any of the recommendations.
The researchers assessed the children’s cognitive development and found that after 1 year, those children who met the screen time recommendations, both screen time and sleep, or all three recommendations demonstrated “superior global cognition.” Children were spending an average of 3.7 hours daily on screens, and those children who were spending 2 hours or less on screens performed 4% better on tests of cognitive function than did children spending the average amount of time. Sleep and exercise differences alone did not contribute to significant differences in cognitive function. This study will continue for another 10 years.1
In a much smaller study out of Cincinnati Children’s Hospital, researchers asked parents to describe the amount of time a child spent on reading and in screen-based media activities, then completed MRI scans of the children’s brains.2 They found a strong association between reading time and higher functional connectivity between the parts of the brain responsible for visual word formation and those responsible for language and cognitive control, with a negative correlation between functional connectivity and time spent in screen-based media activities.
While these studies are important pieces of data as we build a deeper understanding about the effects of screen-based media use on children’s cognitive and behavioral development, they do not offer certainty about causality. These studies do not yet clarify whether certain children are especially vulnerable to the untoward effects of heavy screen-based media use. Perhaps the research will someday offer guidelines with certainty, but families need guidance now. Without doubt, digital devices are here to stay, are important to homework, and can facilitate independence, long-distance connections, important technical work-skills, and even senseless fun and relaxation. So we will focus on offering some principles to help you guide young people (or their parents) in approaching screen time thoughtfully.
While recommending no more than 2 hours of daily screen time seems reasonable, it may be more useful to focus on what young people are doing with the rest of their time. Are they getting adequate, restful sleep? Are they able to exercise most days? Do they have enough time for homework? Do they have time for friends (time actually together, not just texting)? What about time for hobbies? When parents focus on the precious resource of time and all of the activities their children both need and want to do, it sets the frame for them to say that their children are allowed to have time to relax with screen-based media as long as it does not take away from these other priorities. Ensuring that the child has at least 8 hours of sleep, after homework and sports, also will set natural limits on screen time.
Parents also can use the frame of development to guide their rules about screen time. If use of an electronic device serves a developmental task, then it is reasonable. If it interferes with a developmental task, then it should be limited. Adolescents (ages 12-20) should be exploring their own identities, establishing independence, deepening social relationships, and learning to manage their impulses. Some interests can be most easily explored with the aid of a computer (such as with programming, art history, or astronomy). Use of cellphones can facilitate teenagers’ being more independent with plans or transportation. Social connections can be supported by texting or FaceTime. Some close friends may be in a different sport or live far away, and it is possible to stay connected only virtually. However, when use of electronic devices keeps the child from engaging with new friends and new interests or from getting into the world to establish real independence (i.e., a job), then there should be limits. In all of these cases, it is critical that adults explain to teenagers what is guiding their thinking about limits on screen time. Open discussions about the great utility and fun that screens can provide, as well as the challenge of keeping those activities in balance with other important activities, helps adolescents set the frame for that rapidly approaching time when they will be making those choices without adult supervision.
Younger children (ages 8-11) should be sampling a wide array of activities and interests and experiencing challenges and eventual mastery across domains. Video games can be very compelling for this age group because they appeal to exactly this drive to master a challenge. Parents want to ensure that their children can have senseless fun, and still have enough time to explore actual activities: social, athletic, creative, and academic. They can be ready to explain the why of rules, but consistent rules, enforced for everyone at home, are most helpful for this age group.
You also can help parents to consider the child’s temperament when thinking about which rules will be appropriate. Anxious children and teenagers may be especially prone to immersive virtual activities that allow them to avoid the stress of real undertakings or interactions. But anxious children may be able to prepare for something anxiety provoking by exploring it virtually first. Youth with ADHD are going to struggle with shifting away from video games or other electronic activities they enjoy that don’t have a natural ending, and will need strict rules and patient support around balanced screen time use. Screen time may play to a child’s strengths, enabling creative children to take in a wide range of art or music and even create their own when other resources are limited.
Finally, all parents should consider what their own screen use is teaching their children. Adolescents are unlikely to listen to their parents’ recommendations if the parents spend hours online after work. Younger children need their parents’ engaged attention: being coaches and cheerleaders for all of their efforts at mastery. You can help parents to imagine rules that the whole family can follow. They can consider how screen time helps them connect with their children, such as watching a favorite program or sport together. They can explore shared interests online together. They can even relax with ridiculous cat videos together! Screen time together is valuable if it supports parents’ connections with their children, while their rules ensure adequate time for sleep, physical activity, and developmental priorities.
Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com.
References
1. Lancet Child Adolesc Health. 2018 Nov 1;2(11):783-91.
2. Acta Paediatra. 2018 Apr;107(4):685-93
It has been 2 years since we last wrote about the potential risks to children and adolescents of spending too much time on screens. While there have been studies in the interval that offer us more information about the effects of heavy screen use and the developing brain, there is little certainty about what is optimal for children and adolescents, and less still on how parents might effectively equip their children to make good use of screens without suffering ill effects.
You might recall that back in October of 2016, the American Academy of Pediatrics published screen time guidelines: recommending no screen time for infants and children up to 18 months old, limiting all screen time to 1 hour per day for children up to 5 years old, and 2 hours daily for older children (up to 11 years old), so that it would not interfere with homework, social time, exercise, and sleep. At the time, data suggested that children from 2 to 11 years old were spending an average of 4.5 hours per day on screens (TV, computer, tablets, or smartphones, not counting homework).
The Adolescent Brain Cognitive Development Study began in September 2016 to evaluate the effects of Canadian recommendations for 8- to 11-year-olds (9-11 hours sleep nightly, 1 hour of exercise daily, and 2 hours or less of screen time daily; the study subjects are in the United States). This fall they published their initial results, demonstrating that only 51% get the recommended amount of sleep, only 37% kept their daily screen time to under 2 hours, and only 18% were getting the recommended amount of exercise. Only 5% of children consistently met all three recommendations while 29% of children didn’t meet any of the recommendations.
The researchers assessed the children’s cognitive development and found that after 1 year, those children who met the screen time recommendations, both screen time and sleep, or all three recommendations demonstrated “superior global cognition.” Children were spending an average of 3.7 hours daily on screens, and those children who were spending 2 hours or less on screens performed 4% better on tests of cognitive function than did children spending the average amount of time. Sleep and exercise differences alone did not contribute to significant differences in cognitive function. This study will continue for another 10 years.1
In a much smaller study out of Cincinnati Children’s Hospital, researchers asked parents to describe the amount of time a child spent on reading and in screen-based media activities, then completed MRI scans of the children’s brains.2 They found a strong association between reading time and higher functional connectivity between the parts of the brain responsible for visual word formation and those responsible for language and cognitive control, with a negative correlation between functional connectivity and time spent in screen-based media activities.
While these studies are important pieces of data as we build a deeper understanding about the effects of screen-based media use on children’s cognitive and behavioral development, they do not offer certainty about causality. These studies do not yet clarify whether certain children are especially vulnerable to the untoward effects of heavy screen-based media use. Perhaps the research will someday offer guidelines with certainty, but families need guidance now. Without doubt, digital devices are here to stay, are important to homework, and can facilitate independence, long-distance connections, important technical work-skills, and even senseless fun and relaxation. So we will focus on offering some principles to help you guide young people (or their parents) in approaching screen time thoughtfully.
While recommending no more than 2 hours of daily screen time seems reasonable, it may be more useful to focus on what young people are doing with the rest of their time. Are they getting adequate, restful sleep? Are they able to exercise most days? Do they have enough time for homework? Do they have time for friends (time actually together, not just texting)? What about time for hobbies? When parents focus on the precious resource of time and all of the activities their children both need and want to do, it sets the frame for them to say that their children are allowed to have time to relax with screen-based media as long as it does not take away from these other priorities. Ensuring that the child has at least 8 hours of sleep, after homework and sports, also will set natural limits on screen time.
Parents also can use the frame of development to guide their rules about screen time. If use of an electronic device serves a developmental task, then it is reasonable. If it interferes with a developmental task, then it should be limited. Adolescents (ages 12-20) should be exploring their own identities, establishing independence, deepening social relationships, and learning to manage their impulses. Some interests can be most easily explored with the aid of a computer (such as with programming, art history, or astronomy). Use of cellphones can facilitate teenagers’ being more independent with plans or transportation. Social connections can be supported by texting or FaceTime. Some close friends may be in a different sport or live far away, and it is possible to stay connected only virtually. However, when use of electronic devices keeps the child from engaging with new friends and new interests or from getting into the world to establish real independence (i.e., a job), then there should be limits. In all of these cases, it is critical that adults explain to teenagers what is guiding their thinking about limits on screen time. Open discussions about the great utility and fun that screens can provide, as well as the challenge of keeping those activities in balance with other important activities, helps adolescents set the frame for that rapidly approaching time when they will be making those choices without adult supervision.
Younger children (ages 8-11) should be sampling a wide array of activities and interests and experiencing challenges and eventual mastery across domains. Video games can be very compelling for this age group because they appeal to exactly this drive to master a challenge. Parents want to ensure that their children can have senseless fun, and still have enough time to explore actual activities: social, athletic, creative, and academic. They can be ready to explain the why of rules, but consistent rules, enforced for everyone at home, are most helpful for this age group.
You also can help parents to consider the child’s temperament when thinking about which rules will be appropriate. Anxious children and teenagers may be especially prone to immersive virtual activities that allow them to avoid the stress of real undertakings or interactions. But anxious children may be able to prepare for something anxiety provoking by exploring it virtually first. Youth with ADHD are going to struggle with shifting away from video games or other electronic activities they enjoy that don’t have a natural ending, and will need strict rules and patient support around balanced screen time use. Screen time may play to a child’s strengths, enabling creative children to take in a wide range of art or music and even create their own when other resources are limited.
Finally, all parents should consider what their own screen use is teaching their children. Adolescents are unlikely to listen to their parents’ recommendations if the parents spend hours online after work. Younger children need their parents’ engaged attention: being coaches and cheerleaders for all of their efforts at mastery. You can help parents to imagine rules that the whole family can follow. They can consider how screen time helps them connect with their children, such as watching a favorite program or sport together. They can explore shared interests online together. They can even relax with ridiculous cat videos together! Screen time together is valuable if it supports parents’ connections with their children, while their rules ensure adequate time for sleep, physical activity, and developmental priorities.
Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com.
References
1. Lancet Child Adolesc Health. 2018 Nov 1;2(11):783-91.
2. Acta Paediatra. 2018 Apr;107(4):685-93
Review of pediatric data indicates link between vitamin D levels and atopic dermatitis severity
in the majority of studies, but evidence on whether supplementation can improve symptoms of the condition was inconsistent.
The data on the effect of vitamin D supplementation on AD severity “suggested potential benefit but were conflicting,” concluded Christina M. Huang, MD, of Queen’s University, Kingston, Ontario, and her coinvestigators from the department of dermatology, Hospital for Sick Children, Toronto. They reported the results of their systematic review of 21 studies published between 2008 and 2017, which included quantitative data on serum vitamin D levels or vitamin D supplementation and AD severity in patients aged 18 years or younger, in Pediatrics.
In the review, 16 studies explored the relationship between serum vitamin D status and disease severity (one was a randomized controlled trial; the rest were cohort, cross-sectional, or case control studies) in 1,847 children (average age, 5.6 years). Disease severity was measured with the SCORing Atopic Dermatitis (SCORAD) system. In 10 of the 16 studies, there was a significant inverse association between vitamin D levels and AD severity.
The studies that supported this association generally had larger sample sizes, which, the authors pointed out, suggested they were of higher quality and more reliable. However, the randomized controlled study of 89 children did not find a correlation, although in the study, vitamin D level and AD severity was a secondary outcome.
The randomized controlled trial of vitamin D supplementation used lower SCORAD cut-offs for the different severities of AD, which complicated interpretation the results, “as it may indicate that the severities reported in these articles were exaggerated as compared to other studies,” they wrote.
Six studies – four randomized controlled trials (including the study that was among the 16 studies on vitamin D and severity) and two cohort studies – with 354 participants (average age, 6.8 years) looked at the effects of oral vitamin D supplementation on the severity of AD, although dosage and duration of use varied across the studies. In four of the six studies, there were significant improvement in AD in patients given supplements, but the data were “conflicting,” partly because the largest study showing benefit used a different measure of disease severity, the Eczema Area and Severity Index (EASI), not SCORAD. “The inconsistency of tools used to measure outcomes makes it difficult to compare and understand results,” so the effects of vitamin D supplementation “are controversial and should be interpreted with caution, as certain patient populations may benefit more than others,” the authors wrote.
They also drew attention to previous research suggesting that vitamin D supplementation in the first year of life might actually increase the risk of AD in children. “Therefore, although there is a growing body of evidence supporting the beneficial effects of VD [vitamin D] supplementation, the age at which supplementation is given should be considered carefully.” The authors added that the inconclusive findings “may have been due to confounding factors that were not accounted for, such as age, season, latitude, dose, and duration. It is also possible that the lack of a true effect of VD may be contributing to the inconsistent results. Future large‐scale RCTs with consideration of these factors are needed.”
Funding and conflict of interest disclosures were not included in the study.
SOURCE: Huang C et al. Pediatr Dermatol. 2018;35: 754-60. doi: 10.1111/pde.13639.
in the majority of studies, but evidence on whether supplementation can improve symptoms of the condition was inconsistent.
The data on the effect of vitamin D supplementation on AD severity “suggested potential benefit but were conflicting,” concluded Christina M. Huang, MD, of Queen’s University, Kingston, Ontario, and her coinvestigators from the department of dermatology, Hospital for Sick Children, Toronto. They reported the results of their systematic review of 21 studies published between 2008 and 2017, which included quantitative data on serum vitamin D levels or vitamin D supplementation and AD severity in patients aged 18 years or younger, in Pediatrics.
In the review, 16 studies explored the relationship between serum vitamin D status and disease severity (one was a randomized controlled trial; the rest were cohort, cross-sectional, or case control studies) in 1,847 children (average age, 5.6 years). Disease severity was measured with the SCORing Atopic Dermatitis (SCORAD) system. In 10 of the 16 studies, there was a significant inverse association between vitamin D levels and AD severity.
The studies that supported this association generally had larger sample sizes, which, the authors pointed out, suggested they were of higher quality and more reliable. However, the randomized controlled study of 89 children did not find a correlation, although in the study, vitamin D level and AD severity was a secondary outcome.
The randomized controlled trial of vitamin D supplementation used lower SCORAD cut-offs for the different severities of AD, which complicated interpretation the results, “as it may indicate that the severities reported in these articles were exaggerated as compared to other studies,” they wrote.
Six studies – four randomized controlled trials (including the study that was among the 16 studies on vitamin D and severity) and two cohort studies – with 354 participants (average age, 6.8 years) looked at the effects of oral vitamin D supplementation on the severity of AD, although dosage and duration of use varied across the studies. In four of the six studies, there were significant improvement in AD in patients given supplements, but the data were “conflicting,” partly because the largest study showing benefit used a different measure of disease severity, the Eczema Area and Severity Index (EASI), not SCORAD. “The inconsistency of tools used to measure outcomes makes it difficult to compare and understand results,” so the effects of vitamin D supplementation “are controversial and should be interpreted with caution, as certain patient populations may benefit more than others,” the authors wrote.
They also drew attention to previous research suggesting that vitamin D supplementation in the first year of life might actually increase the risk of AD in children. “Therefore, although there is a growing body of evidence supporting the beneficial effects of VD [vitamin D] supplementation, the age at which supplementation is given should be considered carefully.” The authors added that the inconclusive findings “may have been due to confounding factors that were not accounted for, such as age, season, latitude, dose, and duration. It is also possible that the lack of a true effect of VD may be contributing to the inconsistent results. Future large‐scale RCTs with consideration of these factors are needed.”
Funding and conflict of interest disclosures were not included in the study.
SOURCE: Huang C et al. Pediatr Dermatol. 2018;35: 754-60. doi: 10.1111/pde.13639.
in the majority of studies, but evidence on whether supplementation can improve symptoms of the condition was inconsistent.
The data on the effect of vitamin D supplementation on AD severity “suggested potential benefit but were conflicting,” concluded Christina M. Huang, MD, of Queen’s University, Kingston, Ontario, and her coinvestigators from the department of dermatology, Hospital for Sick Children, Toronto. They reported the results of their systematic review of 21 studies published between 2008 and 2017, which included quantitative data on serum vitamin D levels or vitamin D supplementation and AD severity in patients aged 18 years or younger, in Pediatrics.
In the review, 16 studies explored the relationship between serum vitamin D status and disease severity (one was a randomized controlled trial; the rest were cohort, cross-sectional, or case control studies) in 1,847 children (average age, 5.6 years). Disease severity was measured with the SCORing Atopic Dermatitis (SCORAD) system. In 10 of the 16 studies, there was a significant inverse association between vitamin D levels and AD severity.
The studies that supported this association generally had larger sample sizes, which, the authors pointed out, suggested they were of higher quality and more reliable. However, the randomized controlled study of 89 children did not find a correlation, although in the study, vitamin D level and AD severity was a secondary outcome.
The randomized controlled trial of vitamin D supplementation used lower SCORAD cut-offs for the different severities of AD, which complicated interpretation the results, “as it may indicate that the severities reported in these articles were exaggerated as compared to other studies,” they wrote.
Six studies – four randomized controlled trials (including the study that was among the 16 studies on vitamin D and severity) and two cohort studies – with 354 participants (average age, 6.8 years) looked at the effects of oral vitamin D supplementation on the severity of AD, although dosage and duration of use varied across the studies. In four of the six studies, there were significant improvement in AD in patients given supplements, but the data were “conflicting,” partly because the largest study showing benefit used a different measure of disease severity, the Eczema Area and Severity Index (EASI), not SCORAD. “The inconsistency of tools used to measure outcomes makes it difficult to compare and understand results,” so the effects of vitamin D supplementation “are controversial and should be interpreted with caution, as certain patient populations may benefit more than others,” the authors wrote.
They also drew attention to previous research suggesting that vitamin D supplementation in the first year of life might actually increase the risk of AD in children. “Therefore, although there is a growing body of evidence supporting the beneficial effects of VD [vitamin D] supplementation, the age at which supplementation is given should be considered carefully.” The authors added that the inconclusive findings “may have been due to confounding factors that were not accounted for, such as age, season, latitude, dose, and duration. It is also possible that the lack of a true effect of VD may be contributing to the inconsistent results. Future large‐scale RCTs with consideration of these factors are needed.”
Funding and conflict of interest disclosures were not included in the study.
SOURCE: Huang C et al. Pediatr Dermatol. 2018;35: 754-60. doi: 10.1111/pde.13639.
FROM PEDIATRIC DERMATOLOGY
Key clinical point: There is evidence that vitamin D levels in children affect atopic dermatitis severity, but further study is needed.
Major finding: Serum vitamin D levels were significantly inversely correlated with AD severity in children in 10 of 16 studies.
Study details: A systematic review of 21 pediatric studies looking at the association of vitamin D levels or supplementation on AD severity.
Disclosures: No funding or conflicts of declarations interest were available.
Source: Huang C et al. Pediatr Dermatol. 2018;35: 754-60. doi: 10.1111/pde.13639.
Recognize gender expression in youth
It has been known for decades that sex and gender cannot be determined solely by birth anatomy and chromosomes.1 Over the past decade, the medical community has been able to better understand the biologic underpinnings of gender identity, and we are gaining a better appreciation for the diversity of gender identities and gender expressions that exist.
Gender expression can be defined as the manner in which an individual chooses to present their gender to others through physical appearance and behaviors, such as style of hair or dress, voice or movement.2 Gender nonconformity (GNC) is when an individual’s gender expression does not fully conform with societal expectations often based on an individual’s sex assigned at birth. It is important to note that gender expression is independent of gender identity and may or may not align with gender identity. For example, a person whose sex assigned at birth is female may adopt hairstyles and clothing that are considered more masculine and enjoy activities that are typically associated with masculinity (for example, sports) yet identify as female. The majority of research to date focuses most on transgender individuals, broadly defined as those whose gender identity does not fully align with the sex assigned at birth.3,4 As our understanding of gender expression and GNC expands, more research is emerging on the prevalence of gender nonconformity in youth and potential associations with various health outcomes.
Stigma, discrimination, and harassment are known to have documented effects on health. GNC youth have been shown to experience discrimination and harassment at rates higher than their gender conforming peers.5,6 A recent study by Lowry et al. sought to examine the association between GNC and indicators of mental distress and substance use in adolescents.7 The authors analyzed a subset of cross-sectional data from more than 6,000 youth who had participated in the Youth Risk Behavior Surveillance–United States, 2015 (YRBS) in three large urban school districts (two in California and one in Florida). In addition to the standard YRBS questions, students at these three school districts were asked about their gender expression using the following question: “A person’s appearance style, dress, or the way they walk or talk may affect how people describe them. How do you think people at your school would describe you?” Based on responses, youth were categorized on a 7-point GNC scale with 1 being most gender conforming (a very feminine female student or very masculine male student) to 7 being most GNC (a very masculine female student or a very feminine male student). The study sample was ethnically diverse with 16% of students identifying as white non-Hispanic, 19% identifying as black non-Hispanic, and 55% identifying as Hispanic of any race.
In the study population, approximately one in five students reported either moderate (students who described themselves as equally feminine and masculine) or high (female students who described themselves as very/mostly/somewhat masculine or male students who described themselves as very/mostly/somewhat feminine) levels of GNC. Among female students, moderate GNC was significantly associated with feeling sad and hopeless, seriously considering attempting suicide, and making a suicide plan. However, in female students substance use was not associated with GNC. Among male students, suicidal thoughts, plans, and attempts all demonstrated a linear increase with GNC, with the greatest prevalence occurring in male students expressing high levels of GNC. Prevalence of substance use, specifically nonmedical use of prescription drugs, cocaine use, methamphetamine use, heroin use, and intravenous drug also was associated with high GNC in male students. Study authors hypothesize that these differences occur because GNC male youth experience more overt harassment, compared with GNC female youth, but further study is needed.
Our understanding of the diversity of gender expressions present in youth populations continues to evolve. Findings from this study add to a growing body of evidence demonstrating a relatively high prevalence of GNC in youth populations, and potential health disparities these youth may face. This study underscores the need for continued study in this area. Family support and acceptance have been demonstrated to be strong protective factors for transgender-, lesbian-, and gay-identified youth. Studies identifying protective factors for GNC youth are needed.4
As health care providers, we need to continue to ask patients and families about gender identity and be aware of gender expression. When youth present as GNC, we should recognize that they may be at increased risk and, in addition to assessing overall mental health and risk for substance use, also assess for degree of social/familial support and potential stressors.4 We also should continue to advocate for support systems within schools sensitive to the needs of GNC students, as these may be a potential avenue to improve overall mental health for students. It is important to continue to expand our understanding of the diverse gender identities and expressions of the youth we serve. This hopefully will allow us to identify not only potential risk factors and health disparities, but also protective factors that can help better inform the development of effective interventions so all youth can reach their full potential.
Dr. Chelvakumar is an attending physician in the division of adolescent medicine at Nationwide Children’s Hospital and an assistant professor of clinical pediatrics at the Ohio State University, both in Columbus. Email her at pdnews@mdedge.com.
References
1. “WPATH (World Professional Association of Transgender Health) Board Responds to Federal Effort to Redefine Gender,” press release, Oct. 23, 2018.
2. “LGBTQ+ Definitions” at Trans Student Educational Resources.3. J Sex Res. 2013;50(3-4):299-317.
4. JAMA Pediatr. 2018 Nov 1;172(11):1010-1.
5. Psychol Sex Orientat Gend Divers. 2016 Dec;3(4):489-98.
6. J Adolesc Health. 2016; 58(2)(supple):S1-2.
7. JAMA Pediatr. 2018 Nov;172(11):1020-8.
It has been known for decades that sex and gender cannot be determined solely by birth anatomy and chromosomes.1 Over the past decade, the medical community has been able to better understand the biologic underpinnings of gender identity, and we are gaining a better appreciation for the diversity of gender identities and gender expressions that exist.
Gender expression can be defined as the manner in which an individual chooses to present their gender to others through physical appearance and behaviors, such as style of hair or dress, voice or movement.2 Gender nonconformity (GNC) is when an individual’s gender expression does not fully conform with societal expectations often based on an individual’s sex assigned at birth. It is important to note that gender expression is independent of gender identity and may or may not align with gender identity. For example, a person whose sex assigned at birth is female may adopt hairstyles and clothing that are considered more masculine and enjoy activities that are typically associated with masculinity (for example, sports) yet identify as female. The majority of research to date focuses most on transgender individuals, broadly defined as those whose gender identity does not fully align with the sex assigned at birth.3,4 As our understanding of gender expression and GNC expands, more research is emerging on the prevalence of gender nonconformity in youth and potential associations with various health outcomes.
Stigma, discrimination, and harassment are known to have documented effects on health. GNC youth have been shown to experience discrimination and harassment at rates higher than their gender conforming peers.5,6 A recent study by Lowry et al. sought to examine the association between GNC and indicators of mental distress and substance use in adolescents.7 The authors analyzed a subset of cross-sectional data from more than 6,000 youth who had participated in the Youth Risk Behavior Surveillance–United States, 2015 (YRBS) in three large urban school districts (two in California and one in Florida). In addition to the standard YRBS questions, students at these three school districts were asked about their gender expression using the following question: “A person’s appearance style, dress, or the way they walk or talk may affect how people describe them. How do you think people at your school would describe you?” Based on responses, youth were categorized on a 7-point GNC scale with 1 being most gender conforming (a very feminine female student or very masculine male student) to 7 being most GNC (a very masculine female student or a very feminine male student). The study sample was ethnically diverse with 16% of students identifying as white non-Hispanic, 19% identifying as black non-Hispanic, and 55% identifying as Hispanic of any race.
In the study population, approximately one in five students reported either moderate (students who described themselves as equally feminine and masculine) or high (female students who described themselves as very/mostly/somewhat masculine or male students who described themselves as very/mostly/somewhat feminine) levels of GNC. Among female students, moderate GNC was significantly associated with feeling sad and hopeless, seriously considering attempting suicide, and making a suicide plan. However, in female students substance use was not associated with GNC. Among male students, suicidal thoughts, plans, and attempts all demonstrated a linear increase with GNC, with the greatest prevalence occurring in male students expressing high levels of GNC. Prevalence of substance use, specifically nonmedical use of prescription drugs, cocaine use, methamphetamine use, heroin use, and intravenous drug also was associated with high GNC in male students. Study authors hypothesize that these differences occur because GNC male youth experience more overt harassment, compared with GNC female youth, but further study is needed.
Our understanding of the diversity of gender expressions present in youth populations continues to evolve. Findings from this study add to a growing body of evidence demonstrating a relatively high prevalence of GNC in youth populations, and potential health disparities these youth may face. This study underscores the need for continued study in this area. Family support and acceptance have been demonstrated to be strong protective factors for transgender-, lesbian-, and gay-identified youth. Studies identifying protective factors for GNC youth are needed.4
As health care providers, we need to continue to ask patients and families about gender identity and be aware of gender expression. When youth present as GNC, we should recognize that they may be at increased risk and, in addition to assessing overall mental health and risk for substance use, also assess for degree of social/familial support and potential stressors.4 We also should continue to advocate for support systems within schools sensitive to the needs of GNC students, as these may be a potential avenue to improve overall mental health for students. It is important to continue to expand our understanding of the diverse gender identities and expressions of the youth we serve. This hopefully will allow us to identify not only potential risk factors and health disparities, but also protective factors that can help better inform the development of effective interventions so all youth can reach their full potential.
Dr. Chelvakumar is an attending physician in the division of adolescent medicine at Nationwide Children’s Hospital and an assistant professor of clinical pediatrics at the Ohio State University, both in Columbus. Email her at pdnews@mdedge.com.
References
1. “WPATH (World Professional Association of Transgender Health) Board Responds to Federal Effort to Redefine Gender,” press release, Oct. 23, 2018.
2. “LGBTQ+ Definitions” at Trans Student Educational Resources.3. J Sex Res. 2013;50(3-4):299-317.
4. JAMA Pediatr. 2018 Nov 1;172(11):1010-1.
5. Psychol Sex Orientat Gend Divers. 2016 Dec;3(4):489-98.
6. J Adolesc Health. 2016; 58(2)(supple):S1-2.
7. JAMA Pediatr. 2018 Nov;172(11):1020-8.
It has been known for decades that sex and gender cannot be determined solely by birth anatomy and chromosomes.1 Over the past decade, the medical community has been able to better understand the biologic underpinnings of gender identity, and we are gaining a better appreciation for the diversity of gender identities and gender expressions that exist.
Gender expression can be defined as the manner in which an individual chooses to present their gender to others through physical appearance and behaviors, such as style of hair or dress, voice or movement.2 Gender nonconformity (GNC) is when an individual’s gender expression does not fully conform with societal expectations often based on an individual’s sex assigned at birth. It is important to note that gender expression is independent of gender identity and may or may not align with gender identity. For example, a person whose sex assigned at birth is female may adopt hairstyles and clothing that are considered more masculine and enjoy activities that are typically associated with masculinity (for example, sports) yet identify as female. The majority of research to date focuses most on transgender individuals, broadly defined as those whose gender identity does not fully align with the sex assigned at birth.3,4 As our understanding of gender expression and GNC expands, more research is emerging on the prevalence of gender nonconformity in youth and potential associations with various health outcomes.
Stigma, discrimination, and harassment are known to have documented effects on health. GNC youth have been shown to experience discrimination and harassment at rates higher than their gender conforming peers.5,6 A recent study by Lowry et al. sought to examine the association between GNC and indicators of mental distress and substance use in adolescents.7 The authors analyzed a subset of cross-sectional data from more than 6,000 youth who had participated in the Youth Risk Behavior Surveillance–United States, 2015 (YRBS) in three large urban school districts (two in California and one in Florida). In addition to the standard YRBS questions, students at these three school districts were asked about their gender expression using the following question: “A person’s appearance style, dress, or the way they walk or talk may affect how people describe them. How do you think people at your school would describe you?” Based on responses, youth were categorized on a 7-point GNC scale with 1 being most gender conforming (a very feminine female student or very masculine male student) to 7 being most GNC (a very masculine female student or a very feminine male student). The study sample was ethnically diverse with 16% of students identifying as white non-Hispanic, 19% identifying as black non-Hispanic, and 55% identifying as Hispanic of any race.
In the study population, approximately one in five students reported either moderate (students who described themselves as equally feminine and masculine) or high (female students who described themselves as very/mostly/somewhat masculine or male students who described themselves as very/mostly/somewhat feminine) levels of GNC. Among female students, moderate GNC was significantly associated with feeling sad and hopeless, seriously considering attempting suicide, and making a suicide plan. However, in female students substance use was not associated with GNC. Among male students, suicidal thoughts, plans, and attempts all demonstrated a linear increase with GNC, with the greatest prevalence occurring in male students expressing high levels of GNC. Prevalence of substance use, specifically nonmedical use of prescription drugs, cocaine use, methamphetamine use, heroin use, and intravenous drug also was associated with high GNC in male students. Study authors hypothesize that these differences occur because GNC male youth experience more overt harassment, compared with GNC female youth, but further study is needed.
Our understanding of the diversity of gender expressions present in youth populations continues to evolve. Findings from this study add to a growing body of evidence demonstrating a relatively high prevalence of GNC in youth populations, and potential health disparities these youth may face. This study underscores the need for continued study in this area. Family support and acceptance have been demonstrated to be strong protective factors for transgender-, lesbian-, and gay-identified youth. Studies identifying protective factors for GNC youth are needed.4
As health care providers, we need to continue to ask patients and families about gender identity and be aware of gender expression. When youth present as GNC, we should recognize that they may be at increased risk and, in addition to assessing overall mental health and risk for substance use, also assess for degree of social/familial support and potential stressors.4 We also should continue to advocate for support systems within schools sensitive to the needs of GNC students, as these may be a potential avenue to improve overall mental health for students. It is important to continue to expand our understanding of the diverse gender identities and expressions of the youth we serve. This hopefully will allow us to identify not only potential risk factors and health disparities, but also protective factors that can help better inform the development of effective interventions so all youth can reach their full potential.
Dr. Chelvakumar is an attending physician in the division of adolescent medicine at Nationwide Children’s Hospital and an assistant professor of clinical pediatrics at the Ohio State University, both in Columbus. Email her at pdnews@mdedge.com.
References
1. “WPATH (World Professional Association of Transgender Health) Board Responds to Federal Effort to Redefine Gender,” press release, Oct. 23, 2018.
2. “LGBTQ+ Definitions” at Trans Student Educational Resources.3. J Sex Res. 2013;50(3-4):299-317.
4. JAMA Pediatr. 2018 Nov 1;172(11):1010-1.
5. Psychol Sex Orientat Gend Divers. 2016 Dec;3(4):489-98.
6. J Adolesc Health. 2016; 58(2)(supple):S1-2.
7. JAMA Pediatr. 2018 Nov;172(11):1020-8.
The powerful virus inflammatory response
Inflammation is a double-edged sword. Controlled and modest proinflammatory responses can enhance host immunity against viruses and decrease bacterial colonization and infection, whereas excessive uncontrolled proinflammatory responses may increase the susceptibility to bacterial colonization and secondary infection to facilitate disease pathogenesis. The immune system produces both proinflammatory and anti-inflammatory cytokines and chemokines. It is a balanced response that is key to maintaining good health.
Viral upper respiratory tract infections (URIs) are caused by rhinoviruses, coronaviruses, enteroviruses, respiratory syncytial viruses, influenza A and B viruses, parainfluenza viruses, adenoviruses, and human metapneumoviruses. Viruses are powerful. In the nose, they induce hypersecretion of mucus, slow cilia beating, up-regulate nasal epithelial cell receptors to facilitate bacterial attachment, suppress neutrophil function, and cause increased release of proinflammatory cytokines and chemokines. All these actions by respiratory viruses promote bacterial overgrowth in the nasopharynx and thereby facilitate bacterial superinfections. In fact, progression in pathogenesis of the common bacterial respiratory infections – acute otitis media, acute sinusitis, acute conjunctivitis, and pneumonia – almost always is preceded by a viral URI. Viruses activate multiple target cells in the upper respiratory tract to produce an array of proinflammatory cytokines and chemokines. The symptoms of a viral URI resolve coinciding with an anti-inflammatory response and adaptive immunity.
In recent work, we found a higher frequency of viral URIs in children who experienced more frequent acute otitis media (AOM). We sought to understand why this might occur by comparing levels of inflammatory cytokines/chemokines in the nose during viral URI that did not precipitate AOM versus when a viral URI precipitated an AOM episode. When a child had a viral URI but did not go on to experience an AOM, the child had higher proinflammatory responses than when the viral URI precipitated an AOM. When differences of levels of proinflammatory cytokines/chemokines were compared in otitis-prone and non–otitis-prone children, lower nasal responses were associated with higher otitis-prone classification frequency (Clin Infect Dis. 2018. doi: 10.1093/cid/ciy750).
The powerful virus and the inflammatory response it can induce also play a major role in allergy and asthma. Viral URIs enhance allergic sensitization to respiratory viruses, such as influenza and respiratory syncytial virus, cause cytopathic damage to airway epithelium, promote excessive proinflammatory cytokine/chemokine production, and increase the exposure of allergens and irritants to antigen-presenting cells. Viral infections also may induce the release of epithelial mediators and cytokines that may propagate eosinophilia. Viral URIs, particularly with respiratory syncytial virus and rhinovirus, are the most common causes of wheezing in children, and they have important influences on the development of asthma. Studies have shown that viral infections trigger up to 85% of asthma exacerbations in school-aged children.
Because this column is being published during the winter, a brief discussion of influenza as a powerful virus is appropriate. Influenza occurs in winter outbreaks of varying extent every year. The severity of the influenza season reflects the changing nature of the antigenic properties of influenza viruses, and their spread depends on susceptibility of the population. Influenza outbreaks typically peak over a 2-3 week period and last for 2-3 months. Most outbreaks have attack rates of 10%-20% in children. There may be variations in disease severity caused by different influenza virus types. The symptoms are caused by excessive proinflammatory cytokine/chemokine production in the nose and lung.
Influenza and other viruses can precipitate the systemic inflammatory response syndrome (SIRS), a manifestation of extreme immune dysregulation resulting in organ dysfunction that clinically resembles bacterial sepsis. In this syndrome, tissues remote from the original insult display the cardinal signs of inflammation, including vasodilation, increased microvascular permeability, and leukocyte accumulation. SIRS is another example of the double-edged sword of inflammation.
The onset and progression of SIRS occurs because of dysregulation of the normal inflammatory response, usually with an increase in both proinflammatory and anti-inflammatory cytokines and chemokines, initiating a chain of events that leads to organ failure.
Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He reported having no conflicts of interest. Email him at pdnews@mdedge.com.
Inflammation is a double-edged sword. Controlled and modest proinflammatory responses can enhance host immunity against viruses and decrease bacterial colonization and infection, whereas excessive uncontrolled proinflammatory responses may increase the susceptibility to bacterial colonization and secondary infection to facilitate disease pathogenesis. The immune system produces both proinflammatory and anti-inflammatory cytokines and chemokines. It is a balanced response that is key to maintaining good health.
Viral upper respiratory tract infections (URIs) are caused by rhinoviruses, coronaviruses, enteroviruses, respiratory syncytial viruses, influenza A and B viruses, parainfluenza viruses, adenoviruses, and human metapneumoviruses. Viruses are powerful. In the nose, they induce hypersecretion of mucus, slow cilia beating, up-regulate nasal epithelial cell receptors to facilitate bacterial attachment, suppress neutrophil function, and cause increased release of proinflammatory cytokines and chemokines. All these actions by respiratory viruses promote bacterial overgrowth in the nasopharynx and thereby facilitate bacterial superinfections. In fact, progression in pathogenesis of the common bacterial respiratory infections – acute otitis media, acute sinusitis, acute conjunctivitis, and pneumonia – almost always is preceded by a viral URI. Viruses activate multiple target cells in the upper respiratory tract to produce an array of proinflammatory cytokines and chemokines. The symptoms of a viral URI resolve coinciding with an anti-inflammatory response and adaptive immunity.
In recent work, we found a higher frequency of viral URIs in children who experienced more frequent acute otitis media (AOM). We sought to understand why this might occur by comparing levels of inflammatory cytokines/chemokines in the nose during viral URI that did not precipitate AOM versus when a viral URI precipitated an AOM episode. When a child had a viral URI but did not go on to experience an AOM, the child had higher proinflammatory responses than when the viral URI precipitated an AOM. When differences of levels of proinflammatory cytokines/chemokines were compared in otitis-prone and non–otitis-prone children, lower nasal responses were associated with higher otitis-prone classification frequency (Clin Infect Dis. 2018. doi: 10.1093/cid/ciy750).
The powerful virus and the inflammatory response it can induce also play a major role in allergy and asthma. Viral URIs enhance allergic sensitization to respiratory viruses, such as influenza and respiratory syncytial virus, cause cytopathic damage to airway epithelium, promote excessive proinflammatory cytokine/chemokine production, and increase the exposure of allergens and irritants to antigen-presenting cells. Viral infections also may induce the release of epithelial mediators and cytokines that may propagate eosinophilia. Viral URIs, particularly with respiratory syncytial virus and rhinovirus, are the most common causes of wheezing in children, and they have important influences on the development of asthma. Studies have shown that viral infections trigger up to 85% of asthma exacerbations in school-aged children.
Because this column is being published during the winter, a brief discussion of influenza as a powerful virus is appropriate. Influenza occurs in winter outbreaks of varying extent every year. The severity of the influenza season reflects the changing nature of the antigenic properties of influenza viruses, and their spread depends on susceptibility of the population. Influenza outbreaks typically peak over a 2-3 week period and last for 2-3 months. Most outbreaks have attack rates of 10%-20% in children. There may be variations in disease severity caused by different influenza virus types. The symptoms are caused by excessive proinflammatory cytokine/chemokine production in the nose and lung.
Influenza and other viruses can precipitate the systemic inflammatory response syndrome (SIRS), a manifestation of extreme immune dysregulation resulting in organ dysfunction that clinically resembles bacterial sepsis. In this syndrome, tissues remote from the original insult display the cardinal signs of inflammation, including vasodilation, increased microvascular permeability, and leukocyte accumulation. SIRS is another example of the double-edged sword of inflammation.
The onset and progression of SIRS occurs because of dysregulation of the normal inflammatory response, usually with an increase in both proinflammatory and anti-inflammatory cytokines and chemokines, initiating a chain of events that leads to organ failure.
Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He reported having no conflicts of interest. Email him at pdnews@mdedge.com.
Inflammation is a double-edged sword. Controlled and modest proinflammatory responses can enhance host immunity against viruses and decrease bacterial colonization and infection, whereas excessive uncontrolled proinflammatory responses may increase the susceptibility to bacterial colonization and secondary infection to facilitate disease pathogenesis. The immune system produces both proinflammatory and anti-inflammatory cytokines and chemokines. It is a balanced response that is key to maintaining good health.
Viral upper respiratory tract infections (URIs) are caused by rhinoviruses, coronaviruses, enteroviruses, respiratory syncytial viruses, influenza A and B viruses, parainfluenza viruses, adenoviruses, and human metapneumoviruses. Viruses are powerful. In the nose, they induce hypersecretion of mucus, slow cilia beating, up-regulate nasal epithelial cell receptors to facilitate bacterial attachment, suppress neutrophil function, and cause increased release of proinflammatory cytokines and chemokines. All these actions by respiratory viruses promote bacterial overgrowth in the nasopharynx and thereby facilitate bacterial superinfections. In fact, progression in pathogenesis of the common bacterial respiratory infections – acute otitis media, acute sinusitis, acute conjunctivitis, and pneumonia – almost always is preceded by a viral URI. Viruses activate multiple target cells in the upper respiratory tract to produce an array of proinflammatory cytokines and chemokines. The symptoms of a viral URI resolve coinciding with an anti-inflammatory response and adaptive immunity.
In recent work, we found a higher frequency of viral URIs in children who experienced more frequent acute otitis media (AOM). We sought to understand why this might occur by comparing levels of inflammatory cytokines/chemokines in the nose during viral URI that did not precipitate AOM versus when a viral URI precipitated an AOM episode. When a child had a viral URI but did not go on to experience an AOM, the child had higher proinflammatory responses than when the viral URI precipitated an AOM. When differences of levels of proinflammatory cytokines/chemokines were compared in otitis-prone and non–otitis-prone children, lower nasal responses were associated with higher otitis-prone classification frequency (Clin Infect Dis. 2018. doi: 10.1093/cid/ciy750).
The powerful virus and the inflammatory response it can induce also play a major role in allergy and asthma. Viral URIs enhance allergic sensitization to respiratory viruses, such as influenza and respiratory syncytial virus, cause cytopathic damage to airway epithelium, promote excessive proinflammatory cytokine/chemokine production, and increase the exposure of allergens and irritants to antigen-presenting cells. Viral infections also may induce the release of epithelial mediators and cytokines that may propagate eosinophilia. Viral URIs, particularly with respiratory syncytial virus and rhinovirus, are the most common causes of wheezing in children, and they have important influences on the development of asthma. Studies have shown that viral infections trigger up to 85% of asthma exacerbations in school-aged children.
Because this column is being published during the winter, a brief discussion of influenza as a powerful virus is appropriate. Influenza occurs in winter outbreaks of varying extent every year. The severity of the influenza season reflects the changing nature of the antigenic properties of influenza viruses, and their spread depends on susceptibility of the population. Influenza outbreaks typically peak over a 2-3 week period and last for 2-3 months. Most outbreaks have attack rates of 10%-20% in children. There may be variations in disease severity caused by different influenza virus types. The symptoms are caused by excessive proinflammatory cytokine/chemokine production in the nose and lung.
Influenza and other viruses can precipitate the systemic inflammatory response syndrome (SIRS), a manifestation of extreme immune dysregulation resulting in organ dysfunction that clinically resembles bacterial sepsis. In this syndrome, tissues remote from the original insult display the cardinal signs of inflammation, including vasodilation, increased microvascular permeability, and leukocyte accumulation. SIRS is another example of the double-edged sword of inflammation.
The onset and progression of SIRS occurs because of dysregulation of the normal inflammatory response, usually with an increase in both proinflammatory and anti-inflammatory cytokines and chemokines, initiating a chain of events that leads to organ failure.
Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He reported having no conflicts of interest. Email him at pdnews@mdedge.com.
Rapid recovery pathway for pediatric PSF/AIS patients
An important alternative amidst the opioid crisis
Clinical question
In pediatric postoperative spinal fusion/adolescent idiopathic scoliosis patients, do alternatives to traditional opioid-based analgesic pain regimens lead to improved clinical outcomes?
Background
Traditional care for pediatric postoperative spinal fusion (PSF) patients has included late mobilization most often because of significant pain that requires significant opioid administration. This has led to side effects of heavy opioid use, primarily nausea/vomiting and sleepiness.
In the United States, prescribers have become more aware of the pitfalls of opioid use given that more people now die of opioid misuse than breast cancer. An approach of multimodal analgesia with early mobilization has been shown to have decreased length of stay (LOS) and improve patient satisfaction, but data on clinical outcomes have been lacking.
Study design
Single-center quality improvement (QI) project.
Setting
Urban, 527-bed, quaternary care, free-standing children’s hospital.
Synopsis
Based on the recognition that multiple “standards” of care were utilized in the postoperative management of PSF patients, a QI project was undertaken. The primary outcome measured was functional recovery, as measured by average LOS and pain scores at the first 6:00 am after surgery then on postoperative days 1, 2, and 3.
Process measures were: use of multimodal agents (gabapentin and ketorolac) and discontinuation of patient-controlled analgesia (PCA) before postoperative day 3. Balancing measures were 30-day readmissions or ED revisit. Patients were divided into three groups by analyzing outcomes in three consecutive time periods: conventional management (n = 134), transition period (n = 104), and rapid recovery pathway (n = 84). In the conventional management time period, patients received intraoperative methadone and postoperative morphine/hydromorphone PCA. During the transition period, plan-do-study-act (PDSA) cycles with ketorolac and gabapentin pilots were instituted and assessed. Finally, a rapid recovery pathway (RRP) was designed and published as a web-based algorithm. Standardized entry order sets were developed to maintain compliance and consistency among health care professionals, and a transition period was allowed to reach the highest possible percentage of patients adhering to multimodal analgesia regimen.
Adherence to the multimodal regimen led to 90% of patients receiving ketorolac on postoperative day 1, 100% receiving gabapentin on night of surgery, 86% off of IV PCA by postoperative day 3, and 100% order set adherence after full implementation of the RRP. LOS decreased from 5.7 to 4 days after RRP implementation. Pain scores also showed significant improvement on postoperative day 0 (average pain score, 3.8 vs. 4.9) and postoperative day 1 (3.8 vs. 5). Balancing measures of 30-day readmissions or ED visits after discharge was 2.9% and rose to 3.6% after full implementation.
Bottom line
Multimodal analgesia – including preoperative gabapentin and acetaminophen, intraoperative methadone and acetaminophen, and postoperative PCA diazepam, gabapentin, acetaminophen, and ketorolac – results in decreased length of stay and improved self-reported daily pain scores.
Citation
Muhly WT et al. Rapid recovery pathway after spinal fusion for idiopathic scoliosis. Pediatrics. 2016 Apr;137(4):e20151568.
Dr. Giordano is a pediatric neurosurgery hospitalist and assistant professor in pediatrics at Columbia University Irving Medical Center in New York.
An important alternative amidst the opioid crisis
An important alternative amidst the opioid crisis
Clinical question
In pediatric postoperative spinal fusion/adolescent idiopathic scoliosis patients, do alternatives to traditional opioid-based analgesic pain regimens lead to improved clinical outcomes?
Background
Traditional care for pediatric postoperative spinal fusion (PSF) patients has included late mobilization most often because of significant pain that requires significant opioid administration. This has led to side effects of heavy opioid use, primarily nausea/vomiting and sleepiness.
In the United States, prescribers have become more aware of the pitfalls of opioid use given that more people now die of opioid misuse than breast cancer. An approach of multimodal analgesia with early mobilization has been shown to have decreased length of stay (LOS) and improve patient satisfaction, but data on clinical outcomes have been lacking.
Study design
Single-center quality improvement (QI) project.
Setting
Urban, 527-bed, quaternary care, free-standing children’s hospital.
Synopsis
Based on the recognition that multiple “standards” of care were utilized in the postoperative management of PSF patients, a QI project was undertaken. The primary outcome measured was functional recovery, as measured by average LOS and pain scores at the first 6:00 am after surgery then on postoperative days 1, 2, and 3.
Process measures were: use of multimodal agents (gabapentin and ketorolac) and discontinuation of patient-controlled analgesia (PCA) before postoperative day 3. Balancing measures were 30-day readmissions or ED revisit. Patients were divided into three groups by analyzing outcomes in three consecutive time periods: conventional management (n = 134), transition period (n = 104), and rapid recovery pathway (n = 84). In the conventional management time period, patients received intraoperative methadone and postoperative morphine/hydromorphone PCA. During the transition period, plan-do-study-act (PDSA) cycles with ketorolac and gabapentin pilots were instituted and assessed. Finally, a rapid recovery pathway (RRP) was designed and published as a web-based algorithm. Standardized entry order sets were developed to maintain compliance and consistency among health care professionals, and a transition period was allowed to reach the highest possible percentage of patients adhering to multimodal analgesia regimen.
Adherence to the multimodal regimen led to 90% of patients receiving ketorolac on postoperative day 1, 100% receiving gabapentin on night of surgery, 86% off of IV PCA by postoperative day 3, and 100% order set adherence after full implementation of the RRP. LOS decreased from 5.7 to 4 days after RRP implementation. Pain scores also showed significant improvement on postoperative day 0 (average pain score, 3.8 vs. 4.9) and postoperative day 1 (3.8 vs. 5). Balancing measures of 30-day readmissions or ED visits after discharge was 2.9% and rose to 3.6% after full implementation.
Bottom line
Multimodal analgesia – including preoperative gabapentin and acetaminophen, intraoperative methadone and acetaminophen, and postoperative PCA diazepam, gabapentin, acetaminophen, and ketorolac – results in decreased length of stay and improved self-reported daily pain scores.
Citation
Muhly WT et al. Rapid recovery pathway after spinal fusion for idiopathic scoliosis. Pediatrics. 2016 Apr;137(4):e20151568.
Dr. Giordano is a pediatric neurosurgery hospitalist and assistant professor in pediatrics at Columbia University Irving Medical Center in New York.
Clinical question
In pediatric postoperative spinal fusion/adolescent idiopathic scoliosis patients, do alternatives to traditional opioid-based analgesic pain regimens lead to improved clinical outcomes?
Background
Traditional care for pediatric postoperative spinal fusion (PSF) patients has included late mobilization most often because of significant pain that requires significant opioid administration. This has led to side effects of heavy opioid use, primarily nausea/vomiting and sleepiness.
In the United States, prescribers have become more aware of the pitfalls of opioid use given that more people now die of opioid misuse than breast cancer. An approach of multimodal analgesia with early mobilization has been shown to have decreased length of stay (LOS) and improve patient satisfaction, but data on clinical outcomes have been lacking.
Study design
Single-center quality improvement (QI) project.
Setting
Urban, 527-bed, quaternary care, free-standing children’s hospital.
Synopsis
Based on the recognition that multiple “standards” of care were utilized in the postoperative management of PSF patients, a QI project was undertaken. The primary outcome measured was functional recovery, as measured by average LOS and pain scores at the first 6:00 am after surgery then on postoperative days 1, 2, and 3.
Process measures were: use of multimodal agents (gabapentin and ketorolac) and discontinuation of patient-controlled analgesia (PCA) before postoperative day 3. Balancing measures were 30-day readmissions or ED revisit. Patients were divided into three groups by analyzing outcomes in three consecutive time periods: conventional management (n = 134), transition period (n = 104), and rapid recovery pathway (n = 84). In the conventional management time period, patients received intraoperative methadone and postoperative morphine/hydromorphone PCA. During the transition period, plan-do-study-act (PDSA) cycles with ketorolac and gabapentin pilots were instituted and assessed. Finally, a rapid recovery pathway (RRP) was designed and published as a web-based algorithm. Standardized entry order sets were developed to maintain compliance and consistency among health care professionals, and a transition period was allowed to reach the highest possible percentage of patients adhering to multimodal analgesia regimen.
Adherence to the multimodal regimen led to 90% of patients receiving ketorolac on postoperative day 1, 100% receiving gabapentin on night of surgery, 86% off of IV PCA by postoperative day 3, and 100% order set adherence after full implementation of the RRP. LOS decreased from 5.7 to 4 days after RRP implementation. Pain scores also showed significant improvement on postoperative day 0 (average pain score, 3.8 vs. 4.9) and postoperative day 1 (3.8 vs. 5). Balancing measures of 30-day readmissions or ED visits after discharge was 2.9% and rose to 3.6% after full implementation.
Bottom line
Multimodal analgesia – including preoperative gabapentin and acetaminophen, intraoperative methadone and acetaminophen, and postoperative PCA diazepam, gabapentin, acetaminophen, and ketorolac – results in decreased length of stay and improved self-reported daily pain scores.
Citation
Muhly WT et al. Rapid recovery pathway after spinal fusion for idiopathic scoliosis. Pediatrics. 2016 Apr;137(4):e20151568.
Dr. Giordano is a pediatric neurosurgery hospitalist and assistant professor in pediatrics at Columbia University Irving Medical Center in New York.
Fewer hypos with CGM in routine pediatric T1DM care
BERLIN – A significant reduction in severe hypoglycemia was seen within the first year of using continuous glucose monitoring in a registry study of more than 3,000 children with type 1 diabetes mellitus.
Prior to continuous glucose monitoring (CGM) use, 3.9% of 3,171 individuals, aged a median of 12 years, had hypoglycemia events requiring external help. After 6 months of using CGM, however, the rate of severe hypoglycemia had fallen to 1.2% (P = .10), which remained at 1.2% at 12 months (P = .002). The event rate (events per 100 patient-years) was 10.6 at baseline, 7.8 at 6 months, and 6.1 at 12 months.
Fewer hypoglycemia events leading to coma or convulsion were seen with CGM over time, with 1.3%, 0.6%, and 0.7% of patients reporting at least one event at baseline, 6 months (P = .08), and 12 months (P = .15), respectively. Corresponding event rates were 2.5, 1.6, and 1.7 per 100 patient-years.
“The use of continuous glucose monitoring systems has increased considerably in the past years in individuals with type 1 diabetes,” noted Julia Hermann, a PhD student at Ulm University (Germany), at the annual meeting of the European Association for the Study of Diabetes. “In Germany, for example, CGM use rose considerably when reimbursement by health insurance for CGM started in the summer of 2016.”
Ms. Hermann noted that there were studies showing improved metabolic control with CGM but that clinical studies were often limited by the population of patients studied, restricting treatment to selected patients who may have been adhering better to the use of CGM because they were in a trial.
The aim of the present study was to assess metabolic control and acute complications associated with CGM use in children during its first year of use in a real-world population. Anonymized patient records from the prospective German-Austrian-Luxembourg diabetes patient follow-up (DPV) registry were used.
The DPV database is a standardized, computed-based registry of more than 500,000 adult and pediatric patients with all types of diabetes. It was established in 1995 and receives data from 471 diabetes clinics in Germany, Austria, Luxembourg, and Switzerland.
For the current analysis patients had to be aged under 18 years, have had type 1 diabetes mellitus for at least 1 year, have data available for the months prior to starting CGM, and have at least 1 year of follow-up. For inclusion there also had to be documented use of CMG for at least half of the observation time.
The reduction of severe hypoglycemia observed was not accompanied by any deterioration in metabolic control, Ms. Hermann reported. The median baseline glycosylated hemoglobin (HbA1c) was 7.6% (59 mmol/mol) and this did not noticeably change at either the 6- or 12-month follow-up time point. Furthermore, the percentage of patients achieving a target HbA1c of less than 7.5% was 52% at baseline, 55% at 6 months, and 52% at 12 months.
The rate of diabetic ketoacidosis (DKA), defined as a pH of less than 7.3, also did not change significantly from baseline to the two follow-up points, with event rates of 1.5, 1.4, and 1.1, and the percentage of patients with at least one event being 0.8%, 0.5%, and 0.4%.
“We analyzed an overall well-controlled group of pediatric individuals with type 1 diabetes,” Ms. Hermann said. “We observed a significant reduction of severe hypoglycemia. We observed no improvements in HbA1c, but the overall HbA1c remained stable. We observed no statistically significant change in DKA.”
Future research will try to address some of the limitations that the current data may have, such as looking at a longer follow-up period and other endpoints such as hospitalization, Dr. Hermann suggested. Subgroup analyses are also planned.
“Large databases like the DPV registry ... provide a contemporary picture of diabetes treatment and how the use of diabetes technology has changed over the years and also how diabetes outcomes have improved over the years,” Ms. Hermann said. “It has yet to be seen how most recent changes and advances in diabetes technology will affect these long-term trends.”
The work was partially funded by the German Center for Diabetes Research, the German Diabetes Society, Abbott, and Sanofi. Dr. Hermann reported no personal conflicts of interest.
SOURCE: Hermann J et al. EASD 2018, Abstract 149.
BERLIN – A significant reduction in severe hypoglycemia was seen within the first year of using continuous glucose monitoring in a registry study of more than 3,000 children with type 1 diabetes mellitus.
Prior to continuous glucose monitoring (CGM) use, 3.9% of 3,171 individuals, aged a median of 12 years, had hypoglycemia events requiring external help. After 6 months of using CGM, however, the rate of severe hypoglycemia had fallen to 1.2% (P = .10), which remained at 1.2% at 12 months (P = .002). The event rate (events per 100 patient-years) was 10.6 at baseline, 7.8 at 6 months, and 6.1 at 12 months.
Fewer hypoglycemia events leading to coma or convulsion were seen with CGM over time, with 1.3%, 0.6%, and 0.7% of patients reporting at least one event at baseline, 6 months (P = .08), and 12 months (P = .15), respectively. Corresponding event rates were 2.5, 1.6, and 1.7 per 100 patient-years.
“The use of continuous glucose monitoring systems has increased considerably in the past years in individuals with type 1 diabetes,” noted Julia Hermann, a PhD student at Ulm University (Germany), at the annual meeting of the European Association for the Study of Diabetes. “In Germany, for example, CGM use rose considerably when reimbursement by health insurance for CGM started in the summer of 2016.”
Ms. Hermann noted that there were studies showing improved metabolic control with CGM but that clinical studies were often limited by the population of patients studied, restricting treatment to selected patients who may have been adhering better to the use of CGM because they were in a trial.
The aim of the present study was to assess metabolic control and acute complications associated with CGM use in children during its first year of use in a real-world population. Anonymized patient records from the prospective German-Austrian-Luxembourg diabetes patient follow-up (DPV) registry were used.
The DPV database is a standardized, computed-based registry of more than 500,000 adult and pediatric patients with all types of diabetes. It was established in 1995 and receives data from 471 diabetes clinics in Germany, Austria, Luxembourg, and Switzerland.
For the current analysis patients had to be aged under 18 years, have had type 1 diabetes mellitus for at least 1 year, have data available for the months prior to starting CGM, and have at least 1 year of follow-up. For inclusion there also had to be documented use of CMG for at least half of the observation time.
The reduction of severe hypoglycemia observed was not accompanied by any deterioration in metabolic control, Ms. Hermann reported. The median baseline glycosylated hemoglobin (HbA1c) was 7.6% (59 mmol/mol) and this did not noticeably change at either the 6- or 12-month follow-up time point. Furthermore, the percentage of patients achieving a target HbA1c of less than 7.5% was 52% at baseline, 55% at 6 months, and 52% at 12 months.
The rate of diabetic ketoacidosis (DKA), defined as a pH of less than 7.3, also did not change significantly from baseline to the two follow-up points, with event rates of 1.5, 1.4, and 1.1, and the percentage of patients with at least one event being 0.8%, 0.5%, and 0.4%.
“We analyzed an overall well-controlled group of pediatric individuals with type 1 diabetes,” Ms. Hermann said. “We observed a significant reduction of severe hypoglycemia. We observed no improvements in HbA1c, but the overall HbA1c remained stable. We observed no statistically significant change in DKA.”
Future research will try to address some of the limitations that the current data may have, such as looking at a longer follow-up period and other endpoints such as hospitalization, Dr. Hermann suggested. Subgroup analyses are also planned.
“Large databases like the DPV registry ... provide a contemporary picture of diabetes treatment and how the use of diabetes technology has changed over the years and also how diabetes outcomes have improved over the years,” Ms. Hermann said. “It has yet to be seen how most recent changes and advances in diabetes technology will affect these long-term trends.”
The work was partially funded by the German Center for Diabetes Research, the German Diabetes Society, Abbott, and Sanofi. Dr. Hermann reported no personal conflicts of interest.
SOURCE: Hermann J et al. EASD 2018, Abstract 149.
BERLIN – A significant reduction in severe hypoglycemia was seen within the first year of using continuous glucose monitoring in a registry study of more than 3,000 children with type 1 diabetes mellitus.
Prior to continuous glucose monitoring (CGM) use, 3.9% of 3,171 individuals, aged a median of 12 years, had hypoglycemia events requiring external help. After 6 months of using CGM, however, the rate of severe hypoglycemia had fallen to 1.2% (P = .10), which remained at 1.2% at 12 months (P = .002). The event rate (events per 100 patient-years) was 10.6 at baseline, 7.8 at 6 months, and 6.1 at 12 months.
Fewer hypoglycemia events leading to coma or convulsion were seen with CGM over time, with 1.3%, 0.6%, and 0.7% of patients reporting at least one event at baseline, 6 months (P = .08), and 12 months (P = .15), respectively. Corresponding event rates were 2.5, 1.6, and 1.7 per 100 patient-years.
“The use of continuous glucose monitoring systems has increased considerably in the past years in individuals with type 1 diabetes,” noted Julia Hermann, a PhD student at Ulm University (Germany), at the annual meeting of the European Association for the Study of Diabetes. “In Germany, for example, CGM use rose considerably when reimbursement by health insurance for CGM started in the summer of 2016.”
Ms. Hermann noted that there were studies showing improved metabolic control with CGM but that clinical studies were often limited by the population of patients studied, restricting treatment to selected patients who may have been adhering better to the use of CGM because they were in a trial.
The aim of the present study was to assess metabolic control and acute complications associated with CGM use in children during its first year of use in a real-world population. Anonymized patient records from the prospective German-Austrian-Luxembourg diabetes patient follow-up (DPV) registry were used.
The DPV database is a standardized, computed-based registry of more than 500,000 adult and pediatric patients with all types of diabetes. It was established in 1995 and receives data from 471 diabetes clinics in Germany, Austria, Luxembourg, and Switzerland.
For the current analysis patients had to be aged under 18 years, have had type 1 diabetes mellitus for at least 1 year, have data available for the months prior to starting CGM, and have at least 1 year of follow-up. For inclusion there also had to be documented use of CMG for at least half of the observation time.
The reduction of severe hypoglycemia observed was not accompanied by any deterioration in metabolic control, Ms. Hermann reported. The median baseline glycosylated hemoglobin (HbA1c) was 7.6% (59 mmol/mol) and this did not noticeably change at either the 6- or 12-month follow-up time point. Furthermore, the percentage of patients achieving a target HbA1c of less than 7.5% was 52% at baseline, 55% at 6 months, and 52% at 12 months.
The rate of diabetic ketoacidosis (DKA), defined as a pH of less than 7.3, also did not change significantly from baseline to the two follow-up points, with event rates of 1.5, 1.4, and 1.1, and the percentage of patients with at least one event being 0.8%, 0.5%, and 0.4%.
“We analyzed an overall well-controlled group of pediatric individuals with type 1 diabetes,” Ms. Hermann said. “We observed a significant reduction of severe hypoglycemia. We observed no improvements in HbA1c, but the overall HbA1c remained stable. We observed no statistically significant change in DKA.”
Future research will try to address some of the limitations that the current data may have, such as looking at a longer follow-up period and other endpoints such as hospitalization, Dr. Hermann suggested. Subgroup analyses are also planned.
“Large databases like the DPV registry ... provide a contemporary picture of diabetes treatment and how the use of diabetes technology has changed over the years and also how diabetes outcomes have improved over the years,” Ms. Hermann said. “It has yet to be seen how most recent changes and advances in diabetes technology will affect these long-term trends.”
The work was partially funded by the German Center for Diabetes Research, the German Diabetes Society, Abbott, and Sanofi. Dr. Hermann reported no personal conflicts of interest.
SOURCE: Hermann J et al. EASD 2018, Abstract 149.
REPORTING FROM EASD 2018
Key clinical point: Continuous glucose monitoring helped to significantly reduce severe hypoglycemia episodes during the first year.
Major finding: A total of 3.9%, 1.2%, and 1.2% of patients experienced hypoglycemia needing external help at baseline, 6 months, and 12 months, respectively.
Study details: More than 3,000 pediatric patients using continuous glucose monitoring in the German-Austrian-Luxembourg diabetes patient follow-up registry.
Disclosures: The work was partially funded by the German Center for Diabetes Research, the German Diabetes Society, Abbott, and Sanofi. The presenting author reported no personal conflicts of interest.
Source: Hermann J et al. EASD 2018, Abstract 149.
CDC: No medical therapy can yet be recommended for acute flaccid myelitis
The updated guidance on managing acute flaccid myelitis is unlikely to relieve the frustrations of physicians struggling to treat the condition.
After reviewing the extant data on the baffling disorder, the Centers for Disease Control and Prevention found no evidence that corticosteroids, interferon, antivirals, or any other immunologic or biologic therapy is an effective treatment.
All of the treatments mentioned in the guidance have been used anecdotally, and often for cases proven to be associated with enterovirus-related cases. However, there are no well validated studies confirming benefit for any of these approaches, the agency said in its clinical management document.
Acute flaccid myelitis (AFM) has stricken 90 patients in the United States this year and another 252 cases are being investigated, according to new data from the CDC. The number of confirmed cases is triple that seen in 2017. Whether the disease is an infectious or autoimmune process, or something else entirely, remains unknown.
In response to the outbreak – the largest since 2014 – an expert panel of 4 CDC staff physicians reviewed the literature to find what, if any, treatments were effective; another 14 external experts provided input on the recommendations. At this point, nothing can be officially recommended, the agency said.
Corticosteroids
Corticosteroids should not be administered to most patients with AFM. In addition to “a theoretical concern” about the potential adverse effects of these drugs in acute infections, there is some hard evidence that they are associated with worse outcomes in enteroviral neuroinvasive diseases, particularly those caused by EV-71.
This observation, following a 2012 outbreak in Cambodia, led a World Health Organization commission to conclude that corticosteroids were contraindicated in the management of EV-71–associated neuroinvasive disease. This year, there has been an uptick in EV-A71-associated neurologic disease.
The CDC did hedge its advice on corticosteroids a bit in the setting of AFM, however. “There may be theoretical benefit for steroids in the setting of severe cord swelling or long tract signs suggesting white matter involvement, where steroids may salvage tissue that may be harmed due to an ongoing immune/inflammatory response. While AFM is clinically and radiographically defined by the predominance of gray matter damage in the spinal cord, some patients may have some white matter involvement. It is not clear if these different patterns are important relative to therapeutic considerations.”
Nevertheless, the agency does not recommend corticosteroid use for these patients. “The possible benefits of the use of corticosteroids to manage spinal cord edema or white matter involvement in AFM should be balanced with the possible harm due to immunosuppression in the setting of possible viral infection.”
IVIG
While IVIG holds some theoretical benefit for AFM, there are no high-level human data, the guidelines state. The treatment is generally safe and well tolerated, but the few reports of its use in AFM did not show clear benefit. These include two case series. One suggested an acute improvement of neurologic status, but no long-term resolution of deficits. The other indicated neither significant improvement nor deterioration.
However, current practice at Children’s Hospital of Philadelphia is to initiate IVIG therapy at AFM diagnosis in hopes of boosting humoral immunity.
Nevertheless, the CDC said, “For IVIG to modify disease in an active viral infectious process, early administration is likely required, and possibly prior to exposure,” and the treatment cannot be recommended.
Plasma exchange
Plasma exchange in combination with IVIG and corticosteroids was ineffective in a case series of four Argentinian children, although a single case published last year found that the combination was associated with significant improvement. However, there are not enough data to recommend this approach.
Fluoxetine
Fluoxetine’s antiviral potential turned up in a high-throughput screening project to identify novel compounds with antiviral efficacy against enteroviruses. In 2012, researchers from the University of California, Los Angeles, tested more than 1,000 compounds and found that the SSRI is a potent inhibitor of coxsackievirus. A later project at the National Institutes of Health replicated this finding, and determined that fluoxetine inhibited several enteroviruses, including the AFM suspect, EV-D68.
Fluoxetine concentrates more highly in the central nervous system than it does in plasma, but its antiviral properties have nothing to do with neurotransmitter activity. Rather, it appears to inhibit protein 2C, a highly conserved nonstructural protein that’s crucial to the assembly of RNA into virion particles.
In early November, a retrospective study examined fluoxetine’s use in 30 AFM patients, compared with 26 who did not receive it. The primary outcome was change in summative limb strength score. The study did little to clarify any benefit, however. The authors concluded that fluoxetine was preferentially given to patients with EDV-68 infections. They had more severe impairment at nadir, and at the last follow-up of about 1 year, they had worse outcomes.
“There is no clear human evidence for efficacy of fluoxetine in the treatment of AFM based on a single retrospective evaluation conducted in patients with AFM, and data from a mouse model also did not support efficacy,” the CDC said.
Antiviral medications
The CDC is quite clear on its recommendation that these drugs are not indicated in AFM, since it is not yet proven to be an infectious process.
“Any guidance regarding antiviral medications should be interpreted with great caution, given the unknowns about the pathogenesis of this illness at present ... Testing has been conducted at CDC for antiviral activity of compounds pleconaril, pocapavir, and vapendavir and none have significant activity against currently circulating strains of EV-D68 at clinically relevant concentrations.”
Interferon
There is some anecdotal evidence that interferon alpha-2b was beneficial in treating a polio-like syndrome associated with West Nile virus and Saint Louis encephalitis. “Although there are limited in vitro, animal, and anecdotal human data suggesting activity of some interferons against viral infections, sufficient data are lacking in the setting of AFM,” the agency said. “There is no indication that interferon should be used for the treatment of AFM, and there is concern about the potential for harm from the use of interferon given the immunomodulatory effects in the setting of possible ongoing viral replication.”
SOURCE: CDC Acute Flaccid Myelitis: Interim Considerations for Clinical Management
The updated guidance on managing acute flaccid myelitis is unlikely to relieve the frustrations of physicians struggling to treat the condition.
After reviewing the extant data on the baffling disorder, the Centers for Disease Control and Prevention found no evidence that corticosteroids, interferon, antivirals, or any other immunologic or biologic therapy is an effective treatment.
All of the treatments mentioned in the guidance have been used anecdotally, and often for cases proven to be associated with enterovirus-related cases. However, there are no well validated studies confirming benefit for any of these approaches, the agency said in its clinical management document.
Acute flaccid myelitis (AFM) has stricken 90 patients in the United States this year and another 252 cases are being investigated, according to new data from the CDC. The number of confirmed cases is triple that seen in 2017. Whether the disease is an infectious or autoimmune process, or something else entirely, remains unknown.
In response to the outbreak – the largest since 2014 – an expert panel of 4 CDC staff physicians reviewed the literature to find what, if any, treatments were effective; another 14 external experts provided input on the recommendations. At this point, nothing can be officially recommended, the agency said.
Corticosteroids
Corticosteroids should not be administered to most patients with AFM. In addition to “a theoretical concern” about the potential adverse effects of these drugs in acute infections, there is some hard evidence that they are associated with worse outcomes in enteroviral neuroinvasive diseases, particularly those caused by EV-71.
This observation, following a 2012 outbreak in Cambodia, led a World Health Organization commission to conclude that corticosteroids were contraindicated in the management of EV-71–associated neuroinvasive disease. This year, there has been an uptick in EV-A71-associated neurologic disease.
The CDC did hedge its advice on corticosteroids a bit in the setting of AFM, however. “There may be theoretical benefit for steroids in the setting of severe cord swelling or long tract signs suggesting white matter involvement, where steroids may salvage tissue that may be harmed due to an ongoing immune/inflammatory response. While AFM is clinically and radiographically defined by the predominance of gray matter damage in the spinal cord, some patients may have some white matter involvement. It is not clear if these different patterns are important relative to therapeutic considerations.”
Nevertheless, the agency does not recommend corticosteroid use for these patients. “The possible benefits of the use of corticosteroids to manage spinal cord edema or white matter involvement in AFM should be balanced with the possible harm due to immunosuppression in the setting of possible viral infection.”
IVIG
While IVIG holds some theoretical benefit for AFM, there are no high-level human data, the guidelines state. The treatment is generally safe and well tolerated, but the few reports of its use in AFM did not show clear benefit. These include two case series. One suggested an acute improvement of neurologic status, but no long-term resolution of deficits. The other indicated neither significant improvement nor deterioration.
However, current practice at Children’s Hospital of Philadelphia is to initiate IVIG therapy at AFM diagnosis in hopes of boosting humoral immunity.
Nevertheless, the CDC said, “For IVIG to modify disease in an active viral infectious process, early administration is likely required, and possibly prior to exposure,” and the treatment cannot be recommended.
Plasma exchange
Plasma exchange in combination with IVIG and corticosteroids was ineffective in a case series of four Argentinian children, although a single case published last year found that the combination was associated with significant improvement. However, there are not enough data to recommend this approach.
Fluoxetine
Fluoxetine’s antiviral potential turned up in a high-throughput screening project to identify novel compounds with antiviral efficacy against enteroviruses. In 2012, researchers from the University of California, Los Angeles, tested more than 1,000 compounds and found that the SSRI is a potent inhibitor of coxsackievirus. A later project at the National Institutes of Health replicated this finding, and determined that fluoxetine inhibited several enteroviruses, including the AFM suspect, EV-D68.
Fluoxetine concentrates more highly in the central nervous system than it does in plasma, but its antiviral properties have nothing to do with neurotransmitter activity. Rather, it appears to inhibit protein 2C, a highly conserved nonstructural protein that’s crucial to the assembly of RNA into virion particles.
In early November, a retrospective study examined fluoxetine’s use in 30 AFM patients, compared with 26 who did not receive it. The primary outcome was change in summative limb strength score. The study did little to clarify any benefit, however. The authors concluded that fluoxetine was preferentially given to patients with EDV-68 infections. They had more severe impairment at nadir, and at the last follow-up of about 1 year, they had worse outcomes.
“There is no clear human evidence for efficacy of fluoxetine in the treatment of AFM based on a single retrospective evaluation conducted in patients with AFM, and data from a mouse model also did not support efficacy,” the CDC said.
Antiviral medications
The CDC is quite clear on its recommendation that these drugs are not indicated in AFM, since it is not yet proven to be an infectious process.
“Any guidance regarding antiviral medications should be interpreted with great caution, given the unknowns about the pathogenesis of this illness at present ... Testing has been conducted at CDC for antiviral activity of compounds pleconaril, pocapavir, and vapendavir and none have significant activity against currently circulating strains of EV-D68 at clinically relevant concentrations.”
Interferon
There is some anecdotal evidence that interferon alpha-2b was beneficial in treating a polio-like syndrome associated with West Nile virus and Saint Louis encephalitis. “Although there are limited in vitro, animal, and anecdotal human data suggesting activity of some interferons against viral infections, sufficient data are lacking in the setting of AFM,” the agency said. “There is no indication that interferon should be used for the treatment of AFM, and there is concern about the potential for harm from the use of interferon given the immunomodulatory effects in the setting of possible ongoing viral replication.”
SOURCE: CDC Acute Flaccid Myelitis: Interim Considerations for Clinical Management
The updated guidance on managing acute flaccid myelitis is unlikely to relieve the frustrations of physicians struggling to treat the condition.
After reviewing the extant data on the baffling disorder, the Centers for Disease Control and Prevention found no evidence that corticosteroids, interferon, antivirals, or any other immunologic or biologic therapy is an effective treatment.
All of the treatments mentioned in the guidance have been used anecdotally, and often for cases proven to be associated with enterovirus-related cases. However, there are no well validated studies confirming benefit for any of these approaches, the agency said in its clinical management document.
Acute flaccid myelitis (AFM) has stricken 90 patients in the United States this year and another 252 cases are being investigated, according to new data from the CDC. The number of confirmed cases is triple that seen in 2017. Whether the disease is an infectious or autoimmune process, or something else entirely, remains unknown.
In response to the outbreak – the largest since 2014 – an expert panel of 4 CDC staff physicians reviewed the literature to find what, if any, treatments were effective; another 14 external experts provided input on the recommendations. At this point, nothing can be officially recommended, the agency said.
Corticosteroids
Corticosteroids should not be administered to most patients with AFM. In addition to “a theoretical concern” about the potential adverse effects of these drugs in acute infections, there is some hard evidence that they are associated with worse outcomes in enteroviral neuroinvasive diseases, particularly those caused by EV-71.
This observation, following a 2012 outbreak in Cambodia, led a World Health Organization commission to conclude that corticosteroids were contraindicated in the management of EV-71–associated neuroinvasive disease. This year, there has been an uptick in EV-A71-associated neurologic disease.
The CDC did hedge its advice on corticosteroids a bit in the setting of AFM, however. “There may be theoretical benefit for steroids in the setting of severe cord swelling or long tract signs suggesting white matter involvement, where steroids may salvage tissue that may be harmed due to an ongoing immune/inflammatory response. While AFM is clinically and radiographically defined by the predominance of gray matter damage in the spinal cord, some patients may have some white matter involvement. It is not clear if these different patterns are important relative to therapeutic considerations.”
Nevertheless, the agency does not recommend corticosteroid use for these patients. “The possible benefits of the use of corticosteroids to manage spinal cord edema or white matter involvement in AFM should be balanced with the possible harm due to immunosuppression in the setting of possible viral infection.”
IVIG
While IVIG holds some theoretical benefit for AFM, there are no high-level human data, the guidelines state. The treatment is generally safe and well tolerated, but the few reports of its use in AFM did not show clear benefit. These include two case series. One suggested an acute improvement of neurologic status, but no long-term resolution of deficits. The other indicated neither significant improvement nor deterioration.
However, current practice at Children’s Hospital of Philadelphia is to initiate IVIG therapy at AFM diagnosis in hopes of boosting humoral immunity.
Nevertheless, the CDC said, “For IVIG to modify disease in an active viral infectious process, early administration is likely required, and possibly prior to exposure,” and the treatment cannot be recommended.
Plasma exchange
Plasma exchange in combination with IVIG and corticosteroids was ineffective in a case series of four Argentinian children, although a single case published last year found that the combination was associated with significant improvement. However, there are not enough data to recommend this approach.
Fluoxetine
Fluoxetine’s antiviral potential turned up in a high-throughput screening project to identify novel compounds with antiviral efficacy against enteroviruses. In 2012, researchers from the University of California, Los Angeles, tested more than 1,000 compounds and found that the SSRI is a potent inhibitor of coxsackievirus. A later project at the National Institutes of Health replicated this finding, and determined that fluoxetine inhibited several enteroviruses, including the AFM suspect, EV-D68.
Fluoxetine concentrates more highly in the central nervous system than it does in plasma, but its antiviral properties have nothing to do with neurotransmitter activity. Rather, it appears to inhibit protein 2C, a highly conserved nonstructural protein that’s crucial to the assembly of RNA into virion particles.
In early November, a retrospective study examined fluoxetine’s use in 30 AFM patients, compared with 26 who did not receive it. The primary outcome was change in summative limb strength score. The study did little to clarify any benefit, however. The authors concluded that fluoxetine was preferentially given to patients with EDV-68 infections. They had more severe impairment at nadir, and at the last follow-up of about 1 year, they had worse outcomes.
“There is no clear human evidence for efficacy of fluoxetine in the treatment of AFM based on a single retrospective evaluation conducted in patients with AFM, and data from a mouse model also did not support efficacy,” the CDC said.
Antiviral medications
The CDC is quite clear on its recommendation that these drugs are not indicated in AFM, since it is not yet proven to be an infectious process.
“Any guidance regarding antiviral medications should be interpreted with great caution, given the unknowns about the pathogenesis of this illness at present ... Testing has been conducted at CDC for antiviral activity of compounds pleconaril, pocapavir, and vapendavir and none have significant activity against currently circulating strains of EV-D68 at clinically relevant concentrations.”
Interferon
There is some anecdotal evidence that interferon alpha-2b was beneficial in treating a polio-like syndrome associated with West Nile virus and Saint Louis encephalitis. “Although there are limited in vitro, animal, and anecdotal human data suggesting activity of some interferons against viral infections, sufficient data are lacking in the setting of AFM,” the agency said. “There is no indication that interferon should be used for the treatment of AFM, and there is concern about the potential for harm from the use of interferon given the immunomodulatory effects in the setting of possible ongoing viral replication.”
SOURCE: CDC Acute Flaccid Myelitis: Interim Considerations for Clinical Management
Two probiotic products don’t prevent gastroenteritis in children, studies show
Two probiotic products containing strains of Lactobacillus rhamnosus failed to prevent moderate-to-severe gastroenteritis in children, according to the results of large, randomized trials published in the New England Journal of Medicine.
Neither probiotic formulation significantly reduced duration of diarrhea or vomiting, or improved endpoints such as daycare absenteeism in the double-blind, placebo-controlled trials, which together included 1,857 infants or children with acute infectious gastroenteritis treated in the United States or Canada.
In one of the two trials, conducted at 10 U.S. pediatric emergency departments, a 5-day course of L. rhamnosus GG did not improve outcomes, versus placebo, according to investigators, led by David Schnadower, MD, of Cincinnati (Ohio) Children’s Hospital Medical Center.
Results of the trial, which comprised 971 children aged 3 months to 4 years, sharply contrast with results of previous studies and meta-analyses suggesting probiotics do improve outcomes in children with acute gastroenteritis.
However, those studies were hampered by small sample sizes, lack of probiotic quality control, and endpoints “of questionable relevance,” among other limitations, according to Dr. Schnadower and his coauthors.
“The rigor of our research design calls into question recommendations to use L. rhamnosus GG in the treatment of children with acute gastroenteritis,” the authors said in their published report.
Moderate to severe gastroenteritis within 14 days of enrollment, the trial’s primary endpoint, occurred in 11.8% of children who received the probiotic, and in 12.6% of those who received placebo (P = .83).
Diarrhea duration was similar, at 49.7 hours and 50.9 hours in the probiotic and placebo groups, respectively (P = .26). Likewise, there were no significant differences in duration of vomiting, daycare absenteeism, or rate of household transmission between the study arms, investigators reported.
In the Canadian trial, which was similar to the U.S. trial but conducted independently, a probiotic product containing L. rhamnosus R0011 and L. helveticus R0052 also showed no significant benefit over placebo in reducing incidence of moderate to severe gastroenteritis within 14 days of enrollment.
That endpoint occurred in 26.1% of children assigned to probiotics, and 24.7% assigned to placebo (P = .72). The trial comprised 886 children 3-48 months presenting to one of six pediatric emergency departments in Canada.
As in the U.S. trial, investigators said there were no significant differences in diarrhea duration, at 52.5 and 55.5 hours in the probiotic and placebo groups, respectively (P = .31). And there were no significant differences in duration of vomiting, unscheduled health care provider visits, or adverse events.
Both trials used a modified Vesikari scale symptom score of 9 or higher (range, 0-20) to define moderate to severe gastroenteritis.
Rather than focusing on a single symptom such as diarrhea, the modified Vesikari scale score shows a “constellation of symptoms” associated with gastroenteritis, according to the Canadian investigators, led by Stephen B. Freedman, MDCM, of the department of pediatrics at Alberta Children’s Hospital and Research Institute, University of Calgary.
Although the use of composite measures has been questioned, the modified Vesikari scale is externally validated and produced consistent findings for individual symptoms, according to the authors. “Analysis of all individual score elements supported the conclusions based on our primary outcome,” they wrote.
Despite the findings, the conclusions about the particular probiotic product evaluated in the trial cannot be generalized to others in the market, according to Dr. Freedman and his colleagues. Other “large, well conducted trials have aroused similar concerns regarding the effectiveness of probiotics for other conditions,” they added. “Nonetheless, there may be specific indications and populations that will benefit from alternative probiotic agents.”
The U.S. study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, among other sources. Dr. Schnadower reported that he received grants from the NICHD and nonfinancial support from iHealth.
The Canadian study was supported by the Canadian Institutes of Health Research, among other sources. Dr. Freedman reported that he received nonfinancial support from Calgary Laboratory Services, Copan Italia, Lallemand Health Solutions, Luminex, and ProvLab Alberta, along with grants from the Canadian Institutes of Health Research and Alberta Children’s Hospital Foundation.
SOURCES: Schnadower D et al. N Engl J Med. 2018 Nov 22;379(21):2002-14; Freedman SB et al. N Engl J Med. 2018 Nov 22;379(21);2015-26.
These two studies, which are large and well conducted, do not support use of probiotics that contain Lactobacillus rhamnosus for moderate to severe gastroenteritis in children, according to J. Thomas LaMont, MD.
“These negative trial data will be valuable to clinicians and professional bodies in making decisions regarding the use of either of these probiotic formulations in children with diarrhea,” Dr. LaMont said in an editorial.
Recommendations to use probiotics to treat acute gastroenteritis, as published by some professional societies, rely largely on studies that were underpowered or had issues related to study design or choice of endpoint, Dr. LaMont cautioned.
That said, there are many other probiotic formulations beyond the two evaluated in these trials, he added. Other probiotic agents have different mechanisms of action and ability to colonize the bowel, compared with L. rhamnosus, and thus could be effective against infectious diarrhea in children.
A probiotic formula including L. plantarum significantly reduced the sepsis rate in healthy newborns in one recent placebo-controlled trial in India, he added. That probiotic strain can colonize the intestinal tract for extended periods, compared with other probiotics.
“With their low cost and minimal toxic effects, probiotics have potential for the treatment of a variety of gastrointestinal and other diseases, but rigorous trials such as those described in this [study] are required to determine any potential efficacy or effectiveness,” Dr. LaMont concluded.
Dr. LaMont is with the division of gastroenterology, Beth Israel Deaconess Medical Center, Boston. He had no disclosures related to his editorial ( N Engl J Med. 2018 Nov 22;379[21]:2076-7 ).
These two studies, which are large and well conducted, do not support use of probiotics that contain Lactobacillus rhamnosus for moderate to severe gastroenteritis in children, according to J. Thomas LaMont, MD.
“These negative trial data will be valuable to clinicians and professional bodies in making decisions regarding the use of either of these probiotic formulations in children with diarrhea,” Dr. LaMont said in an editorial.
Recommendations to use probiotics to treat acute gastroenteritis, as published by some professional societies, rely largely on studies that were underpowered or had issues related to study design or choice of endpoint, Dr. LaMont cautioned.
That said, there are many other probiotic formulations beyond the two evaluated in these trials, he added. Other probiotic agents have different mechanisms of action and ability to colonize the bowel, compared with L. rhamnosus, and thus could be effective against infectious diarrhea in children.
A probiotic formula including L. plantarum significantly reduced the sepsis rate in healthy newborns in one recent placebo-controlled trial in India, he added. That probiotic strain can colonize the intestinal tract for extended periods, compared with other probiotics.
“With their low cost and minimal toxic effects, probiotics have potential for the treatment of a variety of gastrointestinal and other diseases, but rigorous trials such as those described in this [study] are required to determine any potential efficacy or effectiveness,” Dr. LaMont concluded.
Dr. LaMont is with the division of gastroenterology, Beth Israel Deaconess Medical Center, Boston. He had no disclosures related to his editorial ( N Engl J Med. 2018 Nov 22;379[21]:2076-7 ).
These two studies, which are large and well conducted, do not support use of probiotics that contain Lactobacillus rhamnosus for moderate to severe gastroenteritis in children, according to J. Thomas LaMont, MD.
“These negative trial data will be valuable to clinicians and professional bodies in making decisions regarding the use of either of these probiotic formulations in children with diarrhea,” Dr. LaMont said in an editorial.
Recommendations to use probiotics to treat acute gastroenteritis, as published by some professional societies, rely largely on studies that were underpowered or had issues related to study design or choice of endpoint, Dr. LaMont cautioned.
That said, there are many other probiotic formulations beyond the two evaluated in these trials, he added. Other probiotic agents have different mechanisms of action and ability to colonize the bowel, compared with L. rhamnosus, and thus could be effective against infectious diarrhea in children.
A probiotic formula including L. plantarum significantly reduced the sepsis rate in healthy newborns in one recent placebo-controlled trial in India, he added. That probiotic strain can colonize the intestinal tract for extended periods, compared with other probiotics.
“With their low cost and minimal toxic effects, probiotics have potential for the treatment of a variety of gastrointestinal and other diseases, but rigorous trials such as those described in this [study] are required to determine any potential efficacy or effectiveness,” Dr. LaMont concluded.
Dr. LaMont is with the division of gastroenterology, Beth Israel Deaconess Medical Center, Boston. He had no disclosures related to his editorial ( N Engl J Med. 2018 Nov 22;379[21]:2076-7 ).
Two probiotic products containing strains of Lactobacillus rhamnosus failed to prevent moderate-to-severe gastroenteritis in children, according to the results of large, randomized trials published in the New England Journal of Medicine.
Neither probiotic formulation significantly reduced duration of diarrhea or vomiting, or improved endpoints such as daycare absenteeism in the double-blind, placebo-controlled trials, which together included 1,857 infants or children with acute infectious gastroenteritis treated in the United States or Canada.
In one of the two trials, conducted at 10 U.S. pediatric emergency departments, a 5-day course of L. rhamnosus GG did not improve outcomes, versus placebo, according to investigators, led by David Schnadower, MD, of Cincinnati (Ohio) Children’s Hospital Medical Center.
Results of the trial, which comprised 971 children aged 3 months to 4 years, sharply contrast with results of previous studies and meta-analyses suggesting probiotics do improve outcomes in children with acute gastroenteritis.
However, those studies were hampered by small sample sizes, lack of probiotic quality control, and endpoints “of questionable relevance,” among other limitations, according to Dr. Schnadower and his coauthors.
“The rigor of our research design calls into question recommendations to use L. rhamnosus GG in the treatment of children with acute gastroenteritis,” the authors said in their published report.
Moderate to severe gastroenteritis within 14 days of enrollment, the trial’s primary endpoint, occurred in 11.8% of children who received the probiotic, and in 12.6% of those who received placebo (P = .83).
Diarrhea duration was similar, at 49.7 hours and 50.9 hours in the probiotic and placebo groups, respectively (P = .26). Likewise, there were no significant differences in duration of vomiting, daycare absenteeism, or rate of household transmission between the study arms, investigators reported.
In the Canadian trial, which was similar to the U.S. trial but conducted independently, a probiotic product containing L. rhamnosus R0011 and L. helveticus R0052 also showed no significant benefit over placebo in reducing incidence of moderate to severe gastroenteritis within 14 days of enrollment.
That endpoint occurred in 26.1% of children assigned to probiotics, and 24.7% assigned to placebo (P = .72). The trial comprised 886 children 3-48 months presenting to one of six pediatric emergency departments in Canada.
As in the U.S. trial, investigators said there were no significant differences in diarrhea duration, at 52.5 and 55.5 hours in the probiotic and placebo groups, respectively (P = .31). And there were no significant differences in duration of vomiting, unscheduled health care provider visits, or adverse events.
Both trials used a modified Vesikari scale symptom score of 9 or higher (range, 0-20) to define moderate to severe gastroenteritis.
Rather than focusing on a single symptom such as diarrhea, the modified Vesikari scale score shows a “constellation of symptoms” associated with gastroenteritis, according to the Canadian investigators, led by Stephen B. Freedman, MDCM, of the department of pediatrics at Alberta Children’s Hospital and Research Institute, University of Calgary.
Although the use of composite measures has been questioned, the modified Vesikari scale is externally validated and produced consistent findings for individual symptoms, according to the authors. “Analysis of all individual score elements supported the conclusions based on our primary outcome,” they wrote.
Despite the findings, the conclusions about the particular probiotic product evaluated in the trial cannot be generalized to others in the market, according to Dr. Freedman and his colleagues. Other “large, well conducted trials have aroused similar concerns regarding the effectiveness of probiotics for other conditions,” they added. “Nonetheless, there may be specific indications and populations that will benefit from alternative probiotic agents.”
The U.S. study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, among other sources. Dr. Schnadower reported that he received grants from the NICHD and nonfinancial support from iHealth.
The Canadian study was supported by the Canadian Institutes of Health Research, among other sources. Dr. Freedman reported that he received nonfinancial support from Calgary Laboratory Services, Copan Italia, Lallemand Health Solutions, Luminex, and ProvLab Alberta, along with grants from the Canadian Institutes of Health Research and Alberta Children’s Hospital Foundation.
SOURCES: Schnadower D et al. N Engl J Med. 2018 Nov 22;379(21):2002-14; Freedman SB et al. N Engl J Med. 2018 Nov 22;379(21);2015-26.
Two probiotic products containing strains of Lactobacillus rhamnosus failed to prevent moderate-to-severe gastroenteritis in children, according to the results of large, randomized trials published in the New England Journal of Medicine.
Neither probiotic formulation significantly reduced duration of diarrhea or vomiting, or improved endpoints such as daycare absenteeism in the double-blind, placebo-controlled trials, which together included 1,857 infants or children with acute infectious gastroenteritis treated in the United States or Canada.
In one of the two trials, conducted at 10 U.S. pediatric emergency departments, a 5-day course of L. rhamnosus GG did not improve outcomes, versus placebo, according to investigators, led by David Schnadower, MD, of Cincinnati (Ohio) Children’s Hospital Medical Center.
Results of the trial, which comprised 971 children aged 3 months to 4 years, sharply contrast with results of previous studies and meta-analyses suggesting probiotics do improve outcomes in children with acute gastroenteritis.
However, those studies were hampered by small sample sizes, lack of probiotic quality control, and endpoints “of questionable relevance,” among other limitations, according to Dr. Schnadower and his coauthors.
“The rigor of our research design calls into question recommendations to use L. rhamnosus GG in the treatment of children with acute gastroenteritis,” the authors said in their published report.
Moderate to severe gastroenteritis within 14 days of enrollment, the trial’s primary endpoint, occurred in 11.8% of children who received the probiotic, and in 12.6% of those who received placebo (P = .83).
Diarrhea duration was similar, at 49.7 hours and 50.9 hours in the probiotic and placebo groups, respectively (P = .26). Likewise, there were no significant differences in duration of vomiting, daycare absenteeism, or rate of household transmission between the study arms, investigators reported.
In the Canadian trial, which was similar to the U.S. trial but conducted independently, a probiotic product containing L. rhamnosus R0011 and L. helveticus R0052 also showed no significant benefit over placebo in reducing incidence of moderate to severe gastroenteritis within 14 days of enrollment.
That endpoint occurred in 26.1% of children assigned to probiotics, and 24.7% assigned to placebo (P = .72). The trial comprised 886 children 3-48 months presenting to one of six pediatric emergency departments in Canada.
As in the U.S. trial, investigators said there were no significant differences in diarrhea duration, at 52.5 and 55.5 hours in the probiotic and placebo groups, respectively (P = .31). And there were no significant differences in duration of vomiting, unscheduled health care provider visits, or adverse events.
Both trials used a modified Vesikari scale symptom score of 9 or higher (range, 0-20) to define moderate to severe gastroenteritis.
Rather than focusing on a single symptom such as diarrhea, the modified Vesikari scale score shows a “constellation of symptoms” associated with gastroenteritis, according to the Canadian investigators, led by Stephen B. Freedman, MDCM, of the department of pediatrics at Alberta Children’s Hospital and Research Institute, University of Calgary.
Although the use of composite measures has been questioned, the modified Vesikari scale is externally validated and produced consistent findings for individual symptoms, according to the authors. “Analysis of all individual score elements supported the conclusions based on our primary outcome,” they wrote.
Despite the findings, the conclusions about the particular probiotic product evaluated in the trial cannot be generalized to others in the market, according to Dr. Freedman and his colleagues. Other “large, well conducted trials have aroused similar concerns regarding the effectiveness of probiotics for other conditions,” they added. “Nonetheless, there may be specific indications and populations that will benefit from alternative probiotic agents.”
The U.S. study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, among other sources. Dr. Schnadower reported that he received grants from the NICHD and nonfinancial support from iHealth.
The Canadian study was supported by the Canadian Institutes of Health Research, among other sources. Dr. Freedman reported that he received nonfinancial support from Calgary Laboratory Services, Copan Italia, Lallemand Health Solutions, Luminex, and ProvLab Alberta, along with grants from the Canadian Institutes of Health Research and Alberta Children’s Hospital Foundation.
SOURCES: Schnadower D et al. N Engl J Med. 2018 Nov 22;379(21):2002-14; Freedman SB et al. N Engl J Med. 2018 Nov 22;379(21);2015-26.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Two probiotic products containing strains of Lactobacillus rhamnosus did not prevent moderate to severe gastroenteritis in children.
Major finding: Neither probiotic formulation significantly reduced duration of diarrhea or vomiting, or improved endpoints such as daycare absenteeism.
Study details: Two randomized, controlled trials, comprising 1,857 infants or children with acute infectious gastroenteritis.
Disclosures: The U.S. study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, among other sources. Dr. Schnadower reported that he received grants from the NICHD and nonfinancial support from iHealth. The Canadian study was supported by the Canadian Institutes of Health Research, among other sources. Dr. Freedman reported that he received nonfinancial support from Calgary Laboratory Services, Copan Italia, Lallemand Health Solutions, Luminex, and ProvLab Alberta, along with grants from the Canadian Institutes of Health Research and Alberta Children’s Hospital Foundation.
Sources: Schnadower D et al. N Engl J Med. 2018 Nov 22;379(21):2002-14; Freedman SB et al. N Engl J Med. 2018 Nov 22;379(21);2015-26.
FDA approves emapalumab for primary HLH
The (HLH).
Emapalumab, an interferon gamma-blocking antibody, is approved to treat patients of all ages (newborn and older) with primary HLH who have refractory, recurrent, or progressive disease or who cannot tolerate conventional HLH therapy. Emapalumab is the first treatment to be FDA approved for primary HLH, and it is expected to be available in the United States in the first quarter of 2019. The FDA previously granted emapalumab priority review, breakthrough therapy designation, orphan drug designation, and rare pediatric disease designation. The FDA’s approval of emapalumab is based on results from a phase 2/3 trial (NCT01818492).
The trial included 34 patients, 27 of whom had refractory, recurrent, or progressive disease or could not tolerate conventional HLH therapy. Patients received emapalumab in combination with dexamethasone. At the end of treatment, 63% (17/27) of patients had achieved a response, which was defined as complete response (n = 7), partial response (n=8), or HLH improvement (n = 2). A total of 70% (n=19) of patients went on to hematopoietic stem cell transplant. The most common adverse events were infections (56%), hypertension (41%), infusion-related reactions (27%), and pyrexia (24%).
Results also are scheduled to be presented at the 2018 annual meeting of the American Society of Hematology in the late-breaker abstract session (Abstract LBA-6).
Emapalumab was developed by Novimmune SA. Sobi acquired global rights to the drug in August 2018.
The (HLH).
Emapalumab, an interferon gamma-blocking antibody, is approved to treat patients of all ages (newborn and older) with primary HLH who have refractory, recurrent, or progressive disease or who cannot tolerate conventional HLH therapy. Emapalumab is the first treatment to be FDA approved for primary HLH, and it is expected to be available in the United States in the first quarter of 2019. The FDA previously granted emapalumab priority review, breakthrough therapy designation, orphan drug designation, and rare pediatric disease designation. The FDA’s approval of emapalumab is based on results from a phase 2/3 trial (NCT01818492).
The trial included 34 patients, 27 of whom had refractory, recurrent, or progressive disease or could not tolerate conventional HLH therapy. Patients received emapalumab in combination with dexamethasone. At the end of treatment, 63% (17/27) of patients had achieved a response, which was defined as complete response (n = 7), partial response (n=8), or HLH improvement (n = 2). A total of 70% (n=19) of patients went on to hematopoietic stem cell transplant. The most common adverse events were infections (56%), hypertension (41%), infusion-related reactions (27%), and pyrexia (24%).
Results also are scheduled to be presented at the 2018 annual meeting of the American Society of Hematology in the late-breaker abstract session (Abstract LBA-6).
Emapalumab was developed by Novimmune SA. Sobi acquired global rights to the drug in August 2018.
The (HLH).
Emapalumab, an interferon gamma-blocking antibody, is approved to treat patients of all ages (newborn and older) with primary HLH who have refractory, recurrent, or progressive disease or who cannot tolerate conventional HLH therapy. Emapalumab is the first treatment to be FDA approved for primary HLH, and it is expected to be available in the United States in the first quarter of 2019. The FDA previously granted emapalumab priority review, breakthrough therapy designation, orphan drug designation, and rare pediatric disease designation. The FDA’s approval of emapalumab is based on results from a phase 2/3 trial (NCT01818492).
The trial included 34 patients, 27 of whom had refractory, recurrent, or progressive disease or could not tolerate conventional HLH therapy. Patients received emapalumab in combination with dexamethasone. At the end of treatment, 63% (17/27) of patients had achieved a response, which was defined as complete response (n = 7), partial response (n=8), or HLH improvement (n = 2). A total of 70% (n=19) of patients went on to hematopoietic stem cell transplant. The most common adverse events were infections (56%), hypertension (41%), infusion-related reactions (27%), and pyrexia (24%).
Results also are scheduled to be presented at the 2018 annual meeting of the American Society of Hematology in the late-breaker abstract session (Abstract LBA-6).
Emapalumab was developed by Novimmune SA. Sobi acquired global rights to the drug in August 2018.
FDA approves first treatment for primary HLH
The U.S. Food and Drug Administration (FDA) has approved emapalumab-lzsg (Gamifant®) to treat primary hemophagocytic lymphohistiocytosis (HLH).
Emapalumab, an interferon gamma-blocking antibody, is approved to treat to treat patients of all ages (newborn and older) with primary HLH who have refractory, recurrent, or progressive disease or who cannot tolerate conventional HLH therapy.
Emapalumab is the first treatment to be FDA-approved for primary HLH, and it is expected to be available in the United States in the first quarter of 2019.
The FDA previously granted emapalumab priority review, breakthrough therapy designation, orphan drug designation, and rare pediatric disease designation.
The FDA’s approval of emapalumab is based on results from a phase 2/3 trial (NCT01818492).
The trial included 34 patients, 27 of whom had refractory, recurrent, or progressive disease or could not tolerate conventional HLH therapy.
Patients received emapalumab in combination with dexamethasone.
At the end of treatment, 63% (17/27) of patients had achieved a response, which was defined as complete response (n=7), partial response (n=8), or HLH improvement (n=2).
Seventy percent (n=19) of patients went on to hematopoietic stem cell transplant.
The most common adverse events were infections (56%), hypertension (41%), infusion-related reactions (27%), and pyrexia (24%).
Additional results from this study can be found in the prescribing information for emapalumab, which is available at www.gamifant.com.
Results are also scheduled to be presented at the 2018 ASH Annual Meeting (abstract LBA-6).
Emapalumab was developed by Novimmune SA. Sobi acquired global rights to the drug in August 2018.
The U.S. Food and Drug Administration (FDA) has approved emapalumab-lzsg (Gamifant®) to treat primary hemophagocytic lymphohistiocytosis (HLH).
Emapalumab, an interferon gamma-blocking antibody, is approved to treat to treat patients of all ages (newborn and older) with primary HLH who have refractory, recurrent, or progressive disease or who cannot tolerate conventional HLH therapy.
Emapalumab is the first treatment to be FDA-approved for primary HLH, and it is expected to be available in the United States in the first quarter of 2019.
The FDA previously granted emapalumab priority review, breakthrough therapy designation, orphan drug designation, and rare pediatric disease designation.
The FDA’s approval of emapalumab is based on results from a phase 2/3 trial (NCT01818492).
The trial included 34 patients, 27 of whom had refractory, recurrent, or progressive disease or could not tolerate conventional HLH therapy.
Patients received emapalumab in combination with dexamethasone.
At the end of treatment, 63% (17/27) of patients had achieved a response, which was defined as complete response (n=7), partial response (n=8), or HLH improvement (n=2).
Seventy percent (n=19) of patients went on to hematopoietic stem cell transplant.
The most common adverse events were infections (56%), hypertension (41%), infusion-related reactions (27%), and pyrexia (24%).
Additional results from this study can be found in the prescribing information for emapalumab, which is available at www.gamifant.com.
Results are also scheduled to be presented at the 2018 ASH Annual Meeting (abstract LBA-6).
Emapalumab was developed by Novimmune SA. Sobi acquired global rights to the drug in August 2018.
The U.S. Food and Drug Administration (FDA) has approved emapalumab-lzsg (Gamifant®) to treat primary hemophagocytic lymphohistiocytosis (HLH).
Emapalumab, an interferon gamma-blocking antibody, is approved to treat to treat patients of all ages (newborn and older) with primary HLH who have refractory, recurrent, or progressive disease or who cannot tolerate conventional HLH therapy.
Emapalumab is the first treatment to be FDA-approved for primary HLH, and it is expected to be available in the United States in the first quarter of 2019.
The FDA previously granted emapalumab priority review, breakthrough therapy designation, orphan drug designation, and rare pediatric disease designation.
The FDA’s approval of emapalumab is based on results from a phase 2/3 trial (NCT01818492).
The trial included 34 patients, 27 of whom had refractory, recurrent, or progressive disease or could not tolerate conventional HLH therapy.
Patients received emapalumab in combination with dexamethasone.
At the end of treatment, 63% (17/27) of patients had achieved a response, which was defined as complete response (n=7), partial response (n=8), or HLH improvement (n=2).
Seventy percent (n=19) of patients went on to hematopoietic stem cell transplant.
The most common adverse events were infections (56%), hypertension (41%), infusion-related reactions (27%), and pyrexia (24%).
Additional results from this study can be found in the prescribing information for emapalumab, which is available at www.gamifant.com.
Results are also scheduled to be presented at the 2018 ASH Annual Meeting (abstract LBA-6).
Emapalumab was developed by Novimmune SA. Sobi acquired global rights to the drug in August 2018.