User login
Preschool ASD prevalence estimates lower than grade school estimates
Estimated prevalence of autism spectrum disorder among 4-year-olds falls short of the estimated prevalence among 8-year-olds in a recent study comparing nationally representative age cohorts.
“Because previous reports indicate that many children with ASD are not evaluated until after age 4, ASD prevalence in this 4-year-old age cohort will likely rise when measured at a later age,” Deborah L. Christensen, Ph.D., of the Centers for Disease Control and Prevention, and her associates reported. “Lowering the age at first evaluation may be more relevant than lowering the age at diagnosis given the challenges of diagnosing young children with ASD,” they wrote (J Dev Behav Pediatr. 2016 Jan;37[1]:1-8).
The investigators screened health and education records for all 4-year-old and 8-year-old children participating in 5 of the 11 sites involved in the 2010 Autism and Developmental Disabilities Monitoring Network, an active surveillance system for identifying 4-year-olds with ASD. The authors looked for an ICD billing code and/or special education data that included an ASD diagnosis or a description of “behavior consistent with ASD.”
They then compared autism prevalence, cognitive test scores, demographics, and ages of evaluation and ASD diagnosis among the 58,467 4-year-olds and 56,727 8-year-olds assessed, each cohort representing approximately 1.4% of those age groups in the 2010 U.S. population.
Prevalence of ASD among 4-year-olds was 13/1,000 children overall, approximately 30% lower than prevalence estimates for 8-year-olds and ranging from a low of 9/1,000 in Missouri to a high of 20/1,000 in New Jersey. Other states involved in the analysis included Arizona, Utah, and Wisconsin. Prevalence was significantly higher in states with both education and health records available than in those states with only health records available.
At all five sites, boys significantly proportionally outnumbered girls in ASD diagnosis. Overall, three boys had ASD for every one girl with ASD, but the ratio varied from 2.6 in Arizona, Missouri and Wisconsin to 4.4 in New Jersey. Despite no overall difference in ASD prevalence by race/ethnicity among 4-year-olds, white 8-year-olds had 1.4 times greater prevalence than that among black children and 1.2 greater prevalence than that among Hispanic children the same age.
Among the 70% of children in Arizona, New Jersey, and Utah who had data on cognitive assessments, 46% of 4-year-olds and 28% of 8-year-olds had cognitive impairment, defined as a score of 70 or lower. Prevalence of both ASD and cognitive impairment among 4-year-olds was 6/1,000 children, compared with 5/1,000 children among 8-year-olds. Prevalence of ASD without cognitive impairment was 7/1,000 among 4-year-olds and 12/1,000 among 8-year-olds.
A history of developmental concerns before 3 years old existed for 93% of the 4-year-olds and 87% of the 8-year-olds with ASD. In addition, 71% of the 4-year-olds and 43% of the 8-year-olds had received their first comprehensive evaluation by 36 months.
The research was funded by the Centers for Disease Control and Prevention. Dr. Christensen and her associates reported no disclosures.
In the article by Christensen et al. in the current issue of the Journal of Developmental and Behavioral Pediatrics, it is reasonable to hypothesize that the 30% lower rate found for 4-year-old children, compared with 8-year-old children may be an underestimate of the discrepancy. Recent surveillance reports from the Centers for Disease Control and Prevention show a marked increase in prevalence, compared with the report from 2 years earlier. Therefore, by the time the children who were at age 4 years in 2010 are at age 8 years, the prevalence difference may be even greater.
When considering differences in prevalence at age 4 years and age 8 years in the context of record-review surveillance methodology, two distinct questions must be considered: Is all ASD detectable at early ages, meaning are symptoms at clinically significant levels at the time of assessment? Do records adequately capture all cases that have detectable ASD symptoms?
It is evident from the literature that comorbidities, such as intellectual disability (ID), and co-occurring medical and neurologic conditions, such as seizure disorders or genetic syndromes with dysmorphology, are likely to impact the age at which ASD symptoms are evident. It is likely that not all children with ASD demonstrate clear impairment before age 4 years. Children who do not show ID may be able to compensate for weaknesses in social engagement when the demands are lower, but may show increasing difficulties as the social demands increase with age and maturity.
The second question addresses whether available records are adequate for capturing the total number of children affected by ASD. If children have not yet been identified as needing evaluation or intervention services, these records may not exist by age 4 years. Because evidence indicates that observation by experts is not adequate to detect risk for ASD, these data showing that many children are not captured in record review surveillance at age 4 years should compel us to adopt strategies to maximize early detection.
These comments were excerpted from an editorial by Diana L. Robins, Ph.D., of the AJ Drexel Autism Institute at Drexel University in Philadelphia (J Dev Behav Pediatr. 2016 Jan;37[1]80-2). Dr. Robins reports being co-owner of M-CHAT, which licenses use of M-CHAT for commercial products. She did not receive any royalties connected with this article.
In the article by Christensen et al. in the current issue of the Journal of Developmental and Behavioral Pediatrics, it is reasonable to hypothesize that the 30% lower rate found for 4-year-old children, compared with 8-year-old children may be an underestimate of the discrepancy. Recent surveillance reports from the Centers for Disease Control and Prevention show a marked increase in prevalence, compared with the report from 2 years earlier. Therefore, by the time the children who were at age 4 years in 2010 are at age 8 years, the prevalence difference may be even greater.
When considering differences in prevalence at age 4 years and age 8 years in the context of record-review surveillance methodology, two distinct questions must be considered: Is all ASD detectable at early ages, meaning are symptoms at clinically significant levels at the time of assessment? Do records adequately capture all cases that have detectable ASD symptoms?
It is evident from the literature that comorbidities, such as intellectual disability (ID), and co-occurring medical and neurologic conditions, such as seizure disorders or genetic syndromes with dysmorphology, are likely to impact the age at which ASD symptoms are evident. It is likely that not all children with ASD demonstrate clear impairment before age 4 years. Children who do not show ID may be able to compensate for weaknesses in social engagement when the demands are lower, but may show increasing difficulties as the social demands increase with age and maturity.
The second question addresses whether available records are adequate for capturing the total number of children affected by ASD. If children have not yet been identified as needing evaluation or intervention services, these records may not exist by age 4 years. Because evidence indicates that observation by experts is not adequate to detect risk for ASD, these data showing that many children are not captured in record review surveillance at age 4 years should compel us to adopt strategies to maximize early detection.
These comments were excerpted from an editorial by Diana L. Robins, Ph.D., of the AJ Drexel Autism Institute at Drexel University in Philadelphia (J Dev Behav Pediatr. 2016 Jan;37[1]80-2). Dr. Robins reports being co-owner of M-CHAT, which licenses use of M-CHAT for commercial products. She did not receive any royalties connected with this article.
In the article by Christensen et al. in the current issue of the Journal of Developmental and Behavioral Pediatrics, it is reasonable to hypothesize that the 30% lower rate found for 4-year-old children, compared with 8-year-old children may be an underestimate of the discrepancy. Recent surveillance reports from the Centers for Disease Control and Prevention show a marked increase in prevalence, compared with the report from 2 years earlier. Therefore, by the time the children who were at age 4 years in 2010 are at age 8 years, the prevalence difference may be even greater.
When considering differences in prevalence at age 4 years and age 8 years in the context of record-review surveillance methodology, two distinct questions must be considered: Is all ASD detectable at early ages, meaning are symptoms at clinically significant levels at the time of assessment? Do records adequately capture all cases that have detectable ASD symptoms?
It is evident from the literature that comorbidities, such as intellectual disability (ID), and co-occurring medical and neurologic conditions, such as seizure disorders or genetic syndromes with dysmorphology, are likely to impact the age at which ASD symptoms are evident. It is likely that not all children with ASD demonstrate clear impairment before age 4 years. Children who do not show ID may be able to compensate for weaknesses in social engagement when the demands are lower, but may show increasing difficulties as the social demands increase with age and maturity.
The second question addresses whether available records are adequate for capturing the total number of children affected by ASD. If children have not yet been identified as needing evaluation or intervention services, these records may not exist by age 4 years. Because evidence indicates that observation by experts is not adequate to detect risk for ASD, these data showing that many children are not captured in record review surveillance at age 4 years should compel us to adopt strategies to maximize early detection.
These comments were excerpted from an editorial by Diana L. Robins, Ph.D., of the AJ Drexel Autism Institute at Drexel University in Philadelphia (J Dev Behav Pediatr. 2016 Jan;37[1]80-2). Dr. Robins reports being co-owner of M-CHAT, which licenses use of M-CHAT for commercial products. She did not receive any royalties connected with this article.
Estimated prevalence of autism spectrum disorder among 4-year-olds falls short of the estimated prevalence among 8-year-olds in a recent study comparing nationally representative age cohorts.
“Because previous reports indicate that many children with ASD are not evaluated until after age 4, ASD prevalence in this 4-year-old age cohort will likely rise when measured at a later age,” Deborah L. Christensen, Ph.D., of the Centers for Disease Control and Prevention, and her associates reported. “Lowering the age at first evaluation may be more relevant than lowering the age at diagnosis given the challenges of diagnosing young children with ASD,” they wrote (J Dev Behav Pediatr. 2016 Jan;37[1]:1-8).
The investigators screened health and education records for all 4-year-old and 8-year-old children participating in 5 of the 11 sites involved in the 2010 Autism and Developmental Disabilities Monitoring Network, an active surveillance system for identifying 4-year-olds with ASD. The authors looked for an ICD billing code and/or special education data that included an ASD diagnosis or a description of “behavior consistent with ASD.”
They then compared autism prevalence, cognitive test scores, demographics, and ages of evaluation and ASD diagnosis among the 58,467 4-year-olds and 56,727 8-year-olds assessed, each cohort representing approximately 1.4% of those age groups in the 2010 U.S. population.
Prevalence of ASD among 4-year-olds was 13/1,000 children overall, approximately 30% lower than prevalence estimates for 8-year-olds and ranging from a low of 9/1,000 in Missouri to a high of 20/1,000 in New Jersey. Other states involved in the analysis included Arizona, Utah, and Wisconsin. Prevalence was significantly higher in states with both education and health records available than in those states with only health records available.
At all five sites, boys significantly proportionally outnumbered girls in ASD diagnosis. Overall, three boys had ASD for every one girl with ASD, but the ratio varied from 2.6 in Arizona, Missouri and Wisconsin to 4.4 in New Jersey. Despite no overall difference in ASD prevalence by race/ethnicity among 4-year-olds, white 8-year-olds had 1.4 times greater prevalence than that among black children and 1.2 greater prevalence than that among Hispanic children the same age.
Among the 70% of children in Arizona, New Jersey, and Utah who had data on cognitive assessments, 46% of 4-year-olds and 28% of 8-year-olds had cognitive impairment, defined as a score of 70 or lower. Prevalence of both ASD and cognitive impairment among 4-year-olds was 6/1,000 children, compared with 5/1,000 children among 8-year-olds. Prevalence of ASD without cognitive impairment was 7/1,000 among 4-year-olds and 12/1,000 among 8-year-olds.
A history of developmental concerns before 3 years old existed for 93% of the 4-year-olds and 87% of the 8-year-olds with ASD. In addition, 71% of the 4-year-olds and 43% of the 8-year-olds had received their first comprehensive evaluation by 36 months.
The research was funded by the Centers for Disease Control and Prevention. Dr. Christensen and her associates reported no disclosures.
Estimated prevalence of autism spectrum disorder among 4-year-olds falls short of the estimated prevalence among 8-year-olds in a recent study comparing nationally representative age cohorts.
“Because previous reports indicate that many children with ASD are not evaluated until after age 4, ASD prevalence in this 4-year-old age cohort will likely rise when measured at a later age,” Deborah L. Christensen, Ph.D., of the Centers for Disease Control and Prevention, and her associates reported. “Lowering the age at first evaluation may be more relevant than lowering the age at diagnosis given the challenges of diagnosing young children with ASD,” they wrote (J Dev Behav Pediatr. 2016 Jan;37[1]:1-8).
The investigators screened health and education records for all 4-year-old and 8-year-old children participating in 5 of the 11 sites involved in the 2010 Autism and Developmental Disabilities Monitoring Network, an active surveillance system for identifying 4-year-olds with ASD. The authors looked for an ICD billing code and/or special education data that included an ASD diagnosis or a description of “behavior consistent with ASD.”
They then compared autism prevalence, cognitive test scores, demographics, and ages of evaluation and ASD diagnosis among the 58,467 4-year-olds and 56,727 8-year-olds assessed, each cohort representing approximately 1.4% of those age groups in the 2010 U.S. population.
Prevalence of ASD among 4-year-olds was 13/1,000 children overall, approximately 30% lower than prevalence estimates for 8-year-olds and ranging from a low of 9/1,000 in Missouri to a high of 20/1,000 in New Jersey. Other states involved in the analysis included Arizona, Utah, and Wisconsin. Prevalence was significantly higher in states with both education and health records available than in those states with only health records available.
At all five sites, boys significantly proportionally outnumbered girls in ASD diagnosis. Overall, three boys had ASD for every one girl with ASD, but the ratio varied from 2.6 in Arizona, Missouri and Wisconsin to 4.4 in New Jersey. Despite no overall difference in ASD prevalence by race/ethnicity among 4-year-olds, white 8-year-olds had 1.4 times greater prevalence than that among black children and 1.2 greater prevalence than that among Hispanic children the same age.
Among the 70% of children in Arizona, New Jersey, and Utah who had data on cognitive assessments, 46% of 4-year-olds and 28% of 8-year-olds had cognitive impairment, defined as a score of 70 or lower. Prevalence of both ASD and cognitive impairment among 4-year-olds was 6/1,000 children, compared with 5/1,000 children among 8-year-olds. Prevalence of ASD without cognitive impairment was 7/1,000 among 4-year-olds and 12/1,000 among 8-year-olds.
A history of developmental concerns before 3 years old existed for 93% of the 4-year-olds and 87% of the 8-year-olds with ASD. In addition, 71% of the 4-year-olds and 43% of the 8-year-olds had received their first comprehensive evaluation by 36 months.
The research was funded by the Centers for Disease Control and Prevention. Dr. Christensen and her associates reported no disclosures.
FROM JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS
Key clinical point: The prevalence of autism spectrum disorders among 4-year-olds is about 30% lower than among 8-year-olds.
Major finding: Prevalence of ASD among 4-year-olds was 13/1,000 children across five U.S. states.
Data source: A comparison of health and medical records for nationally representative cohorts involving 58,467 4-year-olds and 56,727 8-year-olds in five U.S. states in 2010.
Disclosures: The Centers for Disease Control and Prevention funded the research. Dr. Christensen and her associates reported no disclosures.
CDC sounds alarm over marketing of e-cigs to teens
Now that data indicate 7 out of 10 American youth are routinely exposed to electronic cigarette imagery, the Centers for Disease Control and Prevention are calling for restrictions on how e-cigarettes are marketed to teens.
“The same advertising tactics the tobacco industry used years ago to get kids addicted to nicotine are now being used to entice a new generation of young people to use e-cigarettes,” CDC director Dr. Thomas R. Frieden said in a media briefing. “I hope all can agree that kids should not use e-cigarettes.”
Data from the 2014 National Youth Tobacco Use Survey of 22,007 students in grades 6-12 indicated that 18.3 million youth take in imagery depicting e-cigarette use as desirable. Over half of all respondents reported retail establishments were responsible for their exposure to e-cigarette marketing. Nearly 40% said they were exposed to e-cigarette ads online, with more than a third saying they saw such advertising on television and in movies. A quarter reported seeing e-cigarette ads in print media (MMWR. 2016 Jan 5; 64[Early Release]:1-6).
E-cigarettes deliver nicotine and other additives to users in aerosol form by way of a battery-powered device. Tobacco use in teens has been implicated in thwarting healthy brain development, and to the development of lifelong addictions.
Marketing the electronic nicotine delivery devices to young Americans as expressions of “independence, rebellion, and sex” is no different from the tobacco industry’s past tactics for addicting youth to regular tobacco products, according to a CDC statement. In 2014, the CDC reported e-cigarettes had surpassed conventional cigarette use by U.S. teens, rising from 1.5% to 13.4% in high schoolers and from 0.6% to 3.9% in middle school-aged students between 2011 and 2014. Concurrently, industry spending on e-cigarette marketing exploded from $6.4 million to $115 million, according to a CDC statement.
Fearing a reversal of the progress made over the years in curbing tobacco use among teens, the CDC is calling for tighter controls on how e-cigarettes are sold. Among its suggested strategies are limiting the sale of nicotine-based products only to facilities where youth are not permitted; creating “tobacco-sales-free” zones around schools; banning online sales of e-cigarettes; and requiring age verification for the purchase and delivery acceptance of e-cigarettes or before customers can enter e-cigarette vendors’ websites.
The CDC also is calling upon health care providers to counsel younger patients about the dangers of tobacco use, including e-cigarettes, to encourage those who use such products to quit, and to offer assistance with quitting.
On Twitter @whitneymcknight
Now that data indicate 7 out of 10 American youth are routinely exposed to electronic cigarette imagery, the Centers for Disease Control and Prevention are calling for restrictions on how e-cigarettes are marketed to teens.
“The same advertising tactics the tobacco industry used years ago to get kids addicted to nicotine are now being used to entice a new generation of young people to use e-cigarettes,” CDC director Dr. Thomas R. Frieden said in a media briefing. “I hope all can agree that kids should not use e-cigarettes.”
Data from the 2014 National Youth Tobacco Use Survey of 22,007 students in grades 6-12 indicated that 18.3 million youth take in imagery depicting e-cigarette use as desirable. Over half of all respondents reported retail establishments were responsible for their exposure to e-cigarette marketing. Nearly 40% said they were exposed to e-cigarette ads online, with more than a third saying they saw such advertising on television and in movies. A quarter reported seeing e-cigarette ads in print media (MMWR. 2016 Jan 5; 64[Early Release]:1-6).
E-cigarettes deliver nicotine and other additives to users in aerosol form by way of a battery-powered device. Tobacco use in teens has been implicated in thwarting healthy brain development, and to the development of lifelong addictions.
Marketing the electronic nicotine delivery devices to young Americans as expressions of “independence, rebellion, and sex” is no different from the tobacco industry’s past tactics for addicting youth to regular tobacco products, according to a CDC statement. In 2014, the CDC reported e-cigarettes had surpassed conventional cigarette use by U.S. teens, rising from 1.5% to 13.4% in high schoolers and from 0.6% to 3.9% in middle school-aged students between 2011 and 2014. Concurrently, industry spending on e-cigarette marketing exploded from $6.4 million to $115 million, according to a CDC statement.
Fearing a reversal of the progress made over the years in curbing tobacco use among teens, the CDC is calling for tighter controls on how e-cigarettes are sold. Among its suggested strategies are limiting the sale of nicotine-based products only to facilities where youth are not permitted; creating “tobacco-sales-free” zones around schools; banning online sales of e-cigarettes; and requiring age verification for the purchase and delivery acceptance of e-cigarettes or before customers can enter e-cigarette vendors’ websites.
The CDC also is calling upon health care providers to counsel younger patients about the dangers of tobacco use, including e-cigarettes, to encourage those who use such products to quit, and to offer assistance with quitting.
On Twitter @whitneymcknight
Now that data indicate 7 out of 10 American youth are routinely exposed to electronic cigarette imagery, the Centers for Disease Control and Prevention are calling for restrictions on how e-cigarettes are marketed to teens.
“The same advertising tactics the tobacco industry used years ago to get kids addicted to nicotine are now being used to entice a new generation of young people to use e-cigarettes,” CDC director Dr. Thomas R. Frieden said in a media briefing. “I hope all can agree that kids should not use e-cigarettes.”
Data from the 2014 National Youth Tobacco Use Survey of 22,007 students in grades 6-12 indicated that 18.3 million youth take in imagery depicting e-cigarette use as desirable. Over half of all respondents reported retail establishments were responsible for their exposure to e-cigarette marketing. Nearly 40% said they were exposed to e-cigarette ads online, with more than a third saying they saw such advertising on television and in movies. A quarter reported seeing e-cigarette ads in print media (MMWR. 2016 Jan 5; 64[Early Release]:1-6).
E-cigarettes deliver nicotine and other additives to users in aerosol form by way of a battery-powered device. Tobacco use in teens has been implicated in thwarting healthy brain development, and to the development of lifelong addictions.
Marketing the electronic nicotine delivery devices to young Americans as expressions of “independence, rebellion, and sex” is no different from the tobacco industry’s past tactics for addicting youth to regular tobacco products, according to a CDC statement. In 2014, the CDC reported e-cigarettes had surpassed conventional cigarette use by U.S. teens, rising from 1.5% to 13.4% in high schoolers and from 0.6% to 3.9% in middle school-aged students between 2011 and 2014. Concurrently, industry spending on e-cigarette marketing exploded from $6.4 million to $115 million, according to a CDC statement.
Fearing a reversal of the progress made over the years in curbing tobacco use among teens, the CDC is calling for tighter controls on how e-cigarettes are sold. Among its suggested strategies are limiting the sale of nicotine-based products only to facilities where youth are not permitted; creating “tobacco-sales-free” zones around schools; banning online sales of e-cigarettes; and requiring age verification for the purchase and delivery acceptance of e-cigarettes or before customers can enter e-cigarette vendors’ websites.
The CDC also is calling upon health care providers to counsel younger patients about the dangers of tobacco use, including e-cigarettes, to encourage those who use such products to quit, and to offer assistance with quitting.
On Twitter @whitneymcknight
FROM A CDC MEDIA BRIEFING
Stimulant use may raise psychosis risk for children of those with mental illness
For children of a parent with a severe mental illness, taking a stimulant for attention-deficit/hyperactivity disorder might be associated with an increased risk of psychotic symptoms, such as delusions and hallucinations.
In a study of 141 children whose parents had bipolar disorder, major depressive disorder, or schizophrenia, 62.5% of the children and young adults who had taken stimulants experienced psychotic symptoms, compared with 27.4% of those who had never taken stimulants (Pediatrics. 2016;137[1]:e20152486).
Lynn E. MacKenzie and her coauthors used a comprehensive testing battery to uncover the association in a cohort of children and young adults enrolled in a study of developmental psychopathology in sons and daughters of parents with severe mental illness. The study built on previous work showing a genetic overlap for adults between stimulant-induced psychosis and risk for schizophrenia, and on other work indicating that for those at familial risk, stimulants can cause schizophrenia. “To our knowledge, psychotic adverse effects of stimulant medication have not been studied in youth at familial risk for mental illness,” wrote Ms. MacKenzie, a PhD candidate in clinical psychology at Dalhousie University, Halifax, N.S., and her coauthors.
The children and young adults in the study group were aged 6-21 (mean, 11.8 years). A total of 24 participants (17%) in the study group had taken stimulants, and 33 (23.4%) had a confirmed diagnosis of attention-deficit/hyperactivity disorder (ADHD). This group did not fully overlap with the group taking stimulants, since 17 of 33 participants with ADHD received stimulants while the remaining 16 did not. Overall, 15 of the 24 participants (62.5%) who had taken stimulants experienced psychotic and related symptoms, compared with 32 of 117 participants (27.4%) who had never taken stimulants.
All of the participants who experienced psychotic symptoms had parents with major depressive disorder or bipolar disorder. Hallucinations were the most frequent psychotic symptoms that children experienced while taking stimulants; methylphenidate was the most common stimulant taken.
The association between stimulant administration and psychotic symptoms persisted even after Ms. MacKenzie and her coauthors adjusted for potential confounding variables, with an odds ratio (OR) of 4.41 (95% confidence interval [CI], 1.8-10.69; P = .001) for psychotic symptoms in those taking stimulants. The study found temporal association between psychotic symptoms and stimulant administration, and also found that hallucinations ceased when children were off stimulants. Those findings provided further support for a causal relationship, the researchers noted.
Though the numbers in the study were small, “the association between current use of stimulant medication and current psychotic symptoms was strong and significant (OR, 7.25; 95% CI: 1.76-29.92; P = .006),” wrote Ms. MacKenzie and her coauthors.
“Our experience suggests that stimulants are a double-edged sword – we see a lot of benefits, but we have also found that the psychotic side effects may be much more common than previously thought – at least in kids who have mental illness in the family,” senior author Dr. Rudolf Uher said in an interview. Doctors “should know about history of depression or other mental illness in the family and should ask the children if they have had unusual experiences when taking stimulants. Children usually do not tell adults unless they ask them,” said Dr. Uher, associate professor of psychiatry and Canada Research Chair in early intervention at Dalhousie University.
The researchers actively sought out the experience of hallucinations or delusions in the study cohort, using several instruments and verifying findings with blinded consensus from child psychiatrists. How can the results of this study inform real-world decisions? For clinicians, Ms. MacKenzie said in an interview, it’s important to ask the right questions of patients and families when stimulants are prescribed. “Stimulant medications can be very beneficial for children, including children with family history of mental illness,” she said. “Our findings indicate that prescribing physicians should inquire about psychotic symptoms in children and adolescents taking stimulant medication.”
Because the prompt for a child to be assessed and treated for ADHD frequently comes from a child’s teachers, Dr. Uher said he thinks it is important for teachers and schools to understand that “prescription of stimulant medication is a complex decision, and that they do not [pressure] parents into having their children treated. Stimulants are effective medications for ADHD, but they may not be suitable for every child with attention problems,” he said.
“We do not want the message to be for or against stimulants,” Dr. Uher added. “It is important that doctors, families, and teachers know and understand the pros and cons, and make the best decisions for a particular child.”
The authors reported no conflicts of interest. The Canadian Institutes of Health Research, the Nova Scotia Health Research Foundation, the Canada Research Chairs Program, and the Department of Psychiatry of Dalhousie University funded the study.
On Twitter @karioakes
For children of a parent with a severe mental illness, taking a stimulant for attention-deficit/hyperactivity disorder might be associated with an increased risk of psychotic symptoms, such as delusions and hallucinations.
In a study of 141 children whose parents had bipolar disorder, major depressive disorder, or schizophrenia, 62.5% of the children and young adults who had taken stimulants experienced psychotic symptoms, compared with 27.4% of those who had never taken stimulants (Pediatrics. 2016;137[1]:e20152486).
Lynn E. MacKenzie and her coauthors used a comprehensive testing battery to uncover the association in a cohort of children and young adults enrolled in a study of developmental psychopathology in sons and daughters of parents with severe mental illness. The study built on previous work showing a genetic overlap for adults between stimulant-induced psychosis and risk for schizophrenia, and on other work indicating that for those at familial risk, stimulants can cause schizophrenia. “To our knowledge, psychotic adverse effects of stimulant medication have not been studied in youth at familial risk for mental illness,” wrote Ms. MacKenzie, a PhD candidate in clinical psychology at Dalhousie University, Halifax, N.S., and her coauthors.
The children and young adults in the study group were aged 6-21 (mean, 11.8 years). A total of 24 participants (17%) in the study group had taken stimulants, and 33 (23.4%) had a confirmed diagnosis of attention-deficit/hyperactivity disorder (ADHD). This group did not fully overlap with the group taking stimulants, since 17 of 33 participants with ADHD received stimulants while the remaining 16 did not. Overall, 15 of the 24 participants (62.5%) who had taken stimulants experienced psychotic and related symptoms, compared with 32 of 117 participants (27.4%) who had never taken stimulants.
All of the participants who experienced psychotic symptoms had parents with major depressive disorder or bipolar disorder. Hallucinations were the most frequent psychotic symptoms that children experienced while taking stimulants; methylphenidate was the most common stimulant taken.
The association between stimulant administration and psychotic symptoms persisted even after Ms. MacKenzie and her coauthors adjusted for potential confounding variables, with an odds ratio (OR) of 4.41 (95% confidence interval [CI], 1.8-10.69; P = .001) for psychotic symptoms in those taking stimulants. The study found temporal association between psychotic symptoms and stimulant administration, and also found that hallucinations ceased when children were off stimulants. Those findings provided further support for a causal relationship, the researchers noted.
Though the numbers in the study were small, “the association between current use of stimulant medication and current psychotic symptoms was strong and significant (OR, 7.25; 95% CI: 1.76-29.92; P = .006),” wrote Ms. MacKenzie and her coauthors.
“Our experience suggests that stimulants are a double-edged sword – we see a lot of benefits, but we have also found that the psychotic side effects may be much more common than previously thought – at least in kids who have mental illness in the family,” senior author Dr. Rudolf Uher said in an interview. Doctors “should know about history of depression or other mental illness in the family and should ask the children if they have had unusual experiences when taking stimulants. Children usually do not tell adults unless they ask them,” said Dr. Uher, associate professor of psychiatry and Canada Research Chair in early intervention at Dalhousie University.
The researchers actively sought out the experience of hallucinations or delusions in the study cohort, using several instruments and verifying findings with blinded consensus from child psychiatrists. How can the results of this study inform real-world decisions? For clinicians, Ms. MacKenzie said in an interview, it’s important to ask the right questions of patients and families when stimulants are prescribed. “Stimulant medications can be very beneficial for children, including children with family history of mental illness,” she said. “Our findings indicate that prescribing physicians should inquire about psychotic symptoms in children and adolescents taking stimulant medication.”
Because the prompt for a child to be assessed and treated for ADHD frequently comes from a child’s teachers, Dr. Uher said he thinks it is important for teachers and schools to understand that “prescription of stimulant medication is a complex decision, and that they do not [pressure] parents into having their children treated. Stimulants are effective medications for ADHD, but they may not be suitable for every child with attention problems,” he said.
“We do not want the message to be for or against stimulants,” Dr. Uher added. “It is important that doctors, families, and teachers know and understand the pros and cons, and make the best decisions for a particular child.”
The authors reported no conflicts of interest. The Canadian Institutes of Health Research, the Nova Scotia Health Research Foundation, the Canada Research Chairs Program, and the Department of Psychiatry of Dalhousie University funded the study.
On Twitter @karioakes
For children of a parent with a severe mental illness, taking a stimulant for attention-deficit/hyperactivity disorder might be associated with an increased risk of psychotic symptoms, such as delusions and hallucinations.
In a study of 141 children whose parents had bipolar disorder, major depressive disorder, or schizophrenia, 62.5% of the children and young adults who had taken stimulants experienced psychotic symptoms, compared with 27.4% of those who had never taken stimulants (Pediatrics. 2016;137[1]:e20152486).
Lynn E. MacKenzie and her coauthors used a comprehensive testing battery to uncover the association in a cohort of children and young adults enrolled in a study of developmental psychopathology in sons and daughters of parents with severe mental illness. The study built on previous work showing a genetic overlap for adults between stimulant-induced psychosis and risk for schizophrenia, and on other work indicating that for those at familial risk, stimulants can cause schizophrenia. “To our knowledge, psychotic adverse effects of stimulant medication have not been studied in youth at familial risk for mental illness,” wrote Ms. MacKenzie, a PhD candidate in clinical psychology at Dalhousie University, Halifax, N.S., and her coauthors.
The children and young adults in the study group were aged 6-21 (mean, 11.8 years). A total of 24 participants (17%) in the study group had taken stimulants, and 33 (23.4%) had a confirmed diagnosis of attention-deficit/hyperactivity disorder (ADHD). This group did not fully overlap with the group taking stimulants, since 17 of 33 participants with ADHD received stimulants while the remaining 16 did not. Overall, 15 of the 24 participants (62.5%) who had taken stimulants experienced psychotic and related symptoms, compared with 32 of 117 participants (27.4%) who had never taken stimulants.
All of the participants who experienced psychotic symptoms had parents with major depressive disorder or bipolar disorder. Hallucinations were the most frequent psychotic symptoms that children experienced while taking stimulants; methylphenidate was the most common stimulant taken.
The association between stimulant administration and psychotic symptoms persisted even after Ms. MacKenzie and her coauthors adjusted for potential confounding variables, with an odds ratio (OR) of 4.41 (95% confidence interval [CI], 1.8-10.69; P = .001) for psychotic symptoms in those taking stimulants. The study found temporal association between psychotic symptoms and stimulant administration, and also found that hallucinations ceased when children were off stimulants. Those findings provided further support for a causal relationship, the researchers noted.
Though the numbers in the study were small, “the association between current use of stimulant medication and current psychotic symptoms was strong and significant (OR, 7.25; 95% CI: 1.76-29.92; P = .006),” wrote Ms. MacKenzie and her coauthors.
“Our experience suggests that stimulants are a double-edged sword – we see a lot of benefits, but we have also found that the psychotic side effects may be much more common than previously thought – at least in kids who have mental illness in the family,” senior author Dr. Rudolf Uher said in an interview. Doctors “should know about history of depression or other mental illness in the family and should ask the children if they have had unusual experiences when taking stimulants. Children usually do not tell adults unless they ask them,” said Dr. Uher, associate professor of psychiatry and Canada Research Chair in early intervention at Dalhousie University.
The researchers actively sought out the experience of hallucinations or delusions in the study cohort, using several instruments and verifying findings with blinded consensus from child psychiatrists. How can the results of this study inform real-world decisions? For clinicians, Ms. MacKenzie said in an interview, it’s important to ask the right questions of patients and families when stimulants are prescribed. “Stimulant medications can be very beneficial for children, including children with family history of mental illness,” she said. “Our findings indicate that prescribing physicians should inquire about psychotic symptoms in children and adolescents taking stimulant medication.”
Because the prompt for a child to be assessed and treated for ADHD frequently comes from a child’s teachers, Dr. Uher said he thinks it is important for teachers and schools to understand that “prescription of stimulant medication is a complex decision, and that they do not [pressure] parents into having their children treated. Stimulants are effective medications for ADHD, but they may not be suitable for every child with attention problems,” he said.
“We do not want the message to be for or against stimulants,” Dr. Uher added. “It is important that doctors, families, and teachers know and understand the pros and cons, and make the best decisions for a particular child.”
The authors reported no conflicts of interest. The Canadian Institutes of Health Research, the Nova Scotia Health Research Foundation, the Canada Research Chairs Program, and the Department of Psychiatry of Dalhousie University funded the study.
On Twitter @karioakes
FROM PEDIATRICS
Key clinical point: Stimulant use was associated with psychotic symptoms in offspring of those with severe mental illness.
Major finding: Of 141 children and young adults whose parents had severe mental illness, 62% of those taking stimulants had psychotic symptoms, compared with 27% of those not taking stimulants.
Data source: Children and young adults enrolled in a study of developmental psychopathology in the sons and daughters of parents with severe mental illness.
Disclosures: The authors reported no conflicts of interest. The Canadian Institutes of Health Research, the Nova Scotia Health Research Foundation, the Canada Research Chairs Program, and the Department of Psychiatry of Dalhousie University funded the study.
Study: PDT with methyl aminolevulinate promising for severe acne
Methyl aminolevulinate plus photodynamic therapy shows promise as a treatment for severe acne vulgaris, according to a U.S. study published in the British Journal of Dermatology.
Dr. David M. Pariser of Eastern Virginia Medical School, Norfolk, and his associates conducted the randomized double-blind, vehicle-controlled trial of photodynamic therapy (PDT) with methyl aminolevulinate (MAL) as a photosensitizer in 153 males and females aged 12-35 years with severe facial acne. Inclusion criteria comprised an Investigator Global Assessment (IGA) rating score of 4, 20-100 noninflammatory lesions, and 25-75 inflammatory lesions with no more than three nodules (Br J Dermatol. 2015 December. doi: 10.1111/bjd.14345).
Participants received topical MAL 80 mg/g (100) or vehicle cream (53) and PDT every 2 weeks for four treatments, and were evaluated at each treatment and at 12 weeks. The MAL or vehicle cream was applied and covered for 1.5 hours, followed by PDT (635 nm of red light for a total dose of 37 J/cm2). Most completed the study (85% in MAL group and 91% in vehicle group).
Those in the MAL PDT group demonstrated a significant reduction in inflammatory lesions based on the percentage change at 12 weeks (a mean reduction of 37.3% vs. 16.2%; P = .003), and absolute change (a mean reduction of 15.6 lesions vs. 7.8; P = .006). However, the reduction in noninflammatory lesions was not significantly different between the two groups (a mean reduction of 11.8 lesions among those on MAL PDT vs. 10.7 with vehicle PDT) .
The rates of treatment success, defined as improvement of 2 or more IGA grades at 12 weeks, were higher among those in the MAL PDT group (44% vs. 26.4%; OR, 3.24; P = .013).
Pain scores were higher during PDT for the MAL group and remained similar with subsequent treatments. The MAL treatment was discontinued in six participants because of pain and PDT was paused briefly in 15 participants. More participants in the MAL group reported moderate erythema after the first PDT session (46% versus 15%) and three reported severe erythema.
The most commonly reported adverse events in the MAL treatment group were a sensation of skin burning and pain, mostly mild to moderate, lasting a median of 3 days. Further, 12% of those in the MAL group withdrew secondary to adverse events.
“This large, controlled randomized clinical study shows the potential of PDT using 80 mg/g MAL cream for treatment of severe acne” in patients aged 12 years and older, with all skin types, the authors concluded, noting that more follow-up data are needed on the duration of treatment response and long-term effect on scarring. “Severe acne has limited therapeutic options with problematic side effects and bacterial resistance and 80 mg/g MAL PDT could be an alternative approach with improved tolerability for these patients,” they added.
The authors noted that for severe cases of acne, treatment is limited, and while oral isotretinoin is often used, it is teratogenic, has side effects, and is associated with reimbursement difficulties.
Dr. Pariser and two colleagues disclosed receiving honoraria from Photocure ASA, which markets MAL as Visonac. The company funded the study.
Methyl aminolevulinate plus photodynamic therapy shows promise as a treatment for severe acne vulgaris, according to a U.S. study published in the British Journal of Dermatology.
Dr. David M. Pariser of Eastern Virginia Medical School, Norfolk, and his associates conducted the randomized double-blind, vehicle-controlled trial of photodynamic therapy (PDT) with methyl aminolevulinate (MAL) as a photosensitizer in 153 males and females aged 12-35 years with severe facial acne. Inclusion criteria comprised an Investigator Global Assessment (IGA) rating score of 4, 20-100 noninflammatory lesions, and 25-75 inflammatory lesions with no more than three nodules (Br J Dermatol. 2015 December. doi: 10.1111/bjd.14345).
Participants received topical MAL 80 mg/g (100) or vehicle cream (53) and PDT every 2 weeks for four treatments, and were evaluated at each treatment and at 12 weeks. The MAL or vehicle cream was applied and covered for 1.5 hours, followed by PDT (635 nm of red light for a total dose of 37 J/cm2). Most completed the study (85% in MAL group and 91% in vehicle group).
Those in the MAL PDT group demonstrated a significant reduction in inflammatory lesions based on the percentage change at 12 weeks (a mean reduction of 37.3% vs. 16.2%; P = .003), and absolute change (a mean reduction of 15.6 lesions vs. 7.8; P = .006). However, the reduction in noninflammatory lesions was not significantly different between the two groups (a mean reduction of 11.8 lesions among those on MAL PDT vs. 10.7 with vehicle PDT) .
The rates of treatment success, defined as improvement of 2 or more IGA grades at 12 weeks, were higher among those in the MAL PDT group (44% vs. 26.4%; OR, 3.24; P = .013).
Pain scores were higher during PDT for the MAL group and remained similar with subsequent treatments. The MAL treatment was discontinued in six participants because of pain and PDT was paused briefly in 15 participants. More participants in the MAL group reported moderate erythema after the first PDT session (46% versus 15%) and three reported severe erythema.
The most commonly reported adverse events in the MAL treatment group were a sensation of skin burning and pain, mostly mild to moderate, lasting a median of 3 days. Further, 12% of those in the MAL group withdrew secondary to adverse events.
“This large, controlled randomized clinical study shows the potential of PDT using 80 mg/g MAL cream for treatment of severe acne” in patients aged 12 years and older, with all skin types, the authors concluded, noting that more follow-up data are needed on the duration of treatment response and long-term effect on scarring. “Severe acne has limited therapeutic options with problematic side effects and bacterial resistance and 80 mg/g MAL PDT could be an alternative approach with improved tolerability for these patients,” they added.
The authors noted that for severe cases of acne, treatment is limited, and while oral isotretinoin is often used, it is teratogenic, has side effects, and is associated with reimbursement difficulties.
Dr. Pariser and two colleagues disclosed receiving honoraria from Photocure ASA, which markets MAL as Visonac. The company funded the study.
Methyl aminolevulinate plus photodynamic therapy shows promise as a treatment for severe acne vulgaris, according to a U.S. study published in the British Journal of Dermatology.
Dr. David M. Pariser of Eastern Virginia Medical School, Norfolk, and his associates conducted the randomized double-blind, vehicle-controlled trial of photodynamic therapy (PDT) with methyl aminolevulinate (MAL) as a photosensitizer in 153 males and females aged 12-35 years with severe facial acne. Inclusion criteria comprised an Investigator Global Assessment (IGA) rating score of 4, 20-100 noninflammatory lesions, and 25-75 inflammatory lesions with no more than three nodules (Br J Dermatol. 2015 December. doi: 10.1111/bjd.14345).
Participants received topical MAL 80 mg/g (100) or vehicle cream (53) and PDT every 2 weeks for four treatments, and were evaluated at each treatment and at 12 weeks. The MAL or vehicle cream was applied and covered for 1.5 hours, followed by PDT (635 nm of red light for a total dose of 37 J/cm2). Most completed the study (85% in MAL group and 91% in vehicle group).
Those in the MAL PDT group demonstrated a significant reduction in inflammatory lesions based on the percentage change at 12 weeks (a mean reduction of 37.3% vs. 16.2%; P = .003), and absolute change (a mean reduction of 15.6 lesions vs. 7.8; P = .006). However, the reduction in noninflammatory lesions was not significantly different between the two groups (a mean reduction of 11.8 lesions among those on MAL PDT vs. 10.7 with vehicle PDT) .
The rates of treatment success, defined as improvement of 2 or more IGA grades at 12 weeks, were higher among those in the MAL PDT group (44% vs. 26.4%; OR, 3.24; P = .013).
Pain scores were higher during PDT for the MAL group and remained similar with subsequent treatments. The MAL treatment was discontinued in six participants because of pain and PDT was paused briefly in 15 participants. More participants in the MAL group reported moderate erythema after the first PDT session (46% versus 15%) and three reported severe erythema.
The most commonly reported adverse events in the MAL treatment group were a sensation of skin burning and pain, mostly mild to moderate, lasting a median of 3 days. Further, 12% of those in the MAL group withdrew secondary to adverse events.
“This large, controlled randomized clinical study shows the potential of PDT using 80 mg/g MAL cream for treatment of severe acne” in patients aged 12 years and older, with all skin types, the authors concluded, noting that more follow-up data are needed on the duration of treatment response and long-term effect on scarring. “Severe acne has limited therapeutic options with problematic side effects and bacterial resistance and 80 mg/g MAL PDT could be an alternative approach with improved tolerability for these patients,” they added.
The authors noted that for severe cases of acne, treatment is limited, and while oral isotretinoin is often used, it is teratogenic, has side effects, and is associated with reimbursement difficulties.
Dr. Pariser and two colleagues disclosed receiving honoraria from Photocure ASA, which markets MAL as Visonac. The company funded the study.
FROM THE BRITISH JOURNAL OF DERMATOLOGY
Key clinical point: Methyl aminolevulinate (MAL) with photodynamic therapy (PDT) shows promise as an alternative treatment for severe acne vulgaris.
Major finding: The MAL/PDT group had a significantly higher rate of treatment success compared with the vehicle/PDT group at 12 weeks (44% vs. 26.4%; P = .013).
Data source: A randomized, double-blind, vehicle-controlled study evaluating the safety and efficacy of PDT with MAL in 153 people aged 12-35 years, with severe facial acne, at 15 outpatient dermatology centers in the United States.
Disclosures: Dr. Pariser and two colleagues disclosed receiving honoraria from MAL manufacturer Photocure ASA, which funded the study.
67% of teens have substantial cardiometabolic risk burden, blood donor survey shows
ORLANDO – Fully two-thirds of nearly 25,000 Dallas-area volunteer blood donors ages 16-19 had elevated or borderline total cholesterol, blood pressure, and/or hemoglobin A1c, Dr. Merlyn H. Sayers reported at the American Heart Association scientific sessions.
“It is startling that such a significant percentage of these young, ostensibly healthy volunteers have abnormal cardiometabolic health metrics,” observed Dr. Sayers, president and chief executive officer of Carter BloodCare of Bedford, Tex., a nonprofit organization that is the largest blood bank in the state.
After all, he noted, longitudinal studies have clearly shown that cardiometabolic risk factors present in adolescence will persist into adulthood and are associated with increased risks of cardiovascular disease and diabetes. Moreover, it’s troubling, albeit not really surprising, that for the most part these adolescents don’t seem to care about their cardiometabolic risk, the hematologist-oncologist added.
“We give all these youngsters an opportunity to go to the Carter BloodCare website and confidentially retrieve their values. But despite all manner of urging on our part that these results are important, at best only about 20% of the individuals actually do so, and that rate varies substantially by race and ethnicity,” according to Dr. Sayers. “Where appropriate, we need to find ways to impose behavior modification on a group that is relatively resistant to guidance and intervention. Even the best kids, as teenagers, really don’t take this sort of advice about their health risk very seriously. They regard themselves as immortal during their teenage years.”
Noting that behavioral change is not a core strength among transfusion medicine specialists, Dr. Sayers appealed to his audience of cardiologists for suggestions as to how to encourage lifestyle modification in this youthful group without browbeating them to the point that they’re driven off from becoming serial blood donors.
It’s not widely appreciated that across the U.S. during the school year, 20% of all unpaid blood donors are high school students. These high school blood drives provide an as-yet untapped opportunity to screen adolescents for cardiometabolic risk at low cost and minimal inconvenience to participants, said Dr. Sayers of the University of Texas, Dallas.
“We need allies to help us to ensure we get the kids’ attention better,” he explained. “I want to leave you with the sense that perhaps you will see these blood drives as an opportunity to find interventions that might address primordial prevention of cardiometabolic risk.”
He presented a study of 24,925 youths aged 16-19 who donated blood to Carter BloodCare during 2011-2012. Since blood is drawn for obligatory infectious diseases screening at each donation, Dr. Sayers and coinvestigators were able to measure nonfasting total cholesterol and HbA1c in every teen donor. Blood pressure is also measured at every donation.
The investigators used widely accepted definitions of elevated blood pressure, cholesterol, and HbA1c: namely, at least 140/80 mm Hg, 200 mg/dL, and 6.5%, respectively.
While the percentage of teen blood donors with borderline or elevated levels of all three cardiometabolic risk factors was in the low single figures, 21% of boys and 15% of girls were positive for two out of the three.
The prevalence of cardiometabolic risk factors varied by ethnicity. Sixteen percent of white adolescents had elevated or borderline levels of two risk factors. So did 24% of African Americans, 22% of Asian Americans, and 18% of Hispanics.
“These are really staggering results,” commented session chair Dr. Seth S. Martin of Johns Hopkins University, Baltimore. “This is a call to action now that you’ve identified all these kids who are on a trajectory that doesn’t look good.”
As to how physicians can help to favorably alter that trajectory, however, audience members admitted to being stumped, especially since many young people stop going to a primary care physician for preventive care during their teenage years.
“The big problem here is how to use this information to initiate lifestyle change,” observed Dr. Lewis H. Kuller, professor and past chair of epidemiology at the University of Pittsburgh.
Dr. Sayers reported having no financial conflicts regarding his study.
ORLANDO – Fully two-thirds of nearly 25,000 Dallas-area volunteer blood donors ages 16-19 had elevated or borderline total cholesterol, blood pressure, and/or hemoglobin A1c, Dr. Merlyn H. Sayers reported at the American Heart Association scientific sessions.
“It is startling that such a significant percentage of these young, ostensibly healthy volunteers have abnormal cardiometabolic health metrics,” observed Dr. Sayers, president and chief executive officer of Carter BloodCare of Bedford, Tex., a nonprofit organization that is the largest blood bank in the state.
After all, he noted, longitudinal studies have clearly shown that cardiometabolic risk factors present in adolescence will persist into adulthood and are associated with increased risks of cardiovascular disease and diabetes. Moreover, it’s troubling, albeit not really surprising, that for the most part these adolescents don’t seem to care about their cardiometabolic risk, the hematologist-oncologist added.
“We give all these youngsters an opportunity to go to the Carter BloodCare website and confidentially retrieve their values. But despite all manner of urging on our part that these results are important, at best only about 20% of the individuals actually do so, and that rate varies substantially by race and ethnicity,” according to Dr. Sayers. “Where appropriate, we need to find ways to impose behavior modification on a group that is relatively resistant to guidance and intervention. Even the best kids, as teenagers, really don’t take this sort of advice about their health risk very seriously. They regard themselves as immortal during their teenage years.”
Noting that behavioral change is not a core strength among transfusion medicine specialists, Dr. Sayers appealed to his audience of cardiologists for suggestions as to how to encourage lifestyle modification in this youthful group without browbeating them to the point that they’re driven off from becoming serial blood donors.
It’s not widely appreciated that across the U.S. during the school year, 20% of all unpaid blood donors are high school students. These high school blood drives provide an as-yet untapped opportunity to screen adolescents for cardiometabolic risk at low cost and minimal inconvenience to participants, said Dr. Sayers of the University of Texas, Dallas.
“We need allies to help us to ensure we get the kids’ attention better,” he explained. “I want to leave you with the sense that perhaps you will see these blood drives as an opportunity to find interventions that might address primordial prevention of cardiometabolic risk.”
He presented a study of 24,925 youths aged 16-19 who donated blood to Carter BloodCare during 2011-2012. Since blood is drawn for obligatory infectious diseases screening at each donation, Dr. Sayers and coinvestigators were able to measure nonfasting total cholesterol and HbA1c in every teen donor. Blood pressure is also measured at every donation.
The investigators used widely accepted definitions of elevated blood pressure, cholesterol, and HbA1c: namely, at least 140/80 mm Hg, 200 mg/dL, and 6.5%, respectively.
While the percentage of teen blood donors with borderline or elevated levels of all three cardiometabolic risk factors was in the low single figures, 21% of boys and 15% of girls were positive for two out of the three.
The prevalence of cardiometabolic risk factors varied by ethnicity. Sixteen percent of white adolescents had elevated or borderline levels of two risk factors. So did 24% of African Americans, 22% of Asian Americans, and 18% of Hispanics.
“These are really staggering results,” commented session chair Dr. Seth S. Martin of Johns Hopkins University, Baltimore. “This is a call to action now that you’ve identified all these kids who are on a trajectory that doesn’t look good.”
As to how physicians can help to favorably alter that trajectory, however, audience members admitted to being stumped, especially since many young people stop going to a primary care physician for preventive care during their teenage years.
“The big problem here is how to use this information to initiate lifestyle change,” observed Dr. Lewis H. Kuller, professor and past chair of epidemiology at the University of Pittsburgh.
Dr. Sayers reported having no financial conflicts regarding his study.
ORLANDO – Fully two-thirds of nearly 25,000 Dallas-area volunteer blood donors ages 16-19 had elevated or borderline total cholesterol, blood pressure, and/or hemoglobin A1c, Dr. Merlyn H. Sayers reported at the American Heart Association scientific sessions.
“It is startling that such a significant percentage of these young, ostensibly healthy volunteers have abnormal cardiometabolic health metrics,” observed Dr. Sayers, president and chief executive officer of Carter BloodCare of Bedford, Tex., a nonprofit organization that is the largest blood bank in the state.
After all, he noted, longitudinal studies have clearly shown that cardiometabolic risk factors present in adolescence will persist into adulthood and are associated with increased risks of cardiovascular disease and diabetes. Moreover, it’s troubling, albeit not really surprising, that for the most part these adolescents don’t seem to care about their cardiometabolic risk, the hematologist-oncologist added.
“We give all these youngsters an opportunity to go to the Carter BloodCare website and confidentially retrieve their values. But despite all manner of urging on our part that these results are important, at best only about 20% of the individuals actually do so, and that rate varies substantially by race and ethnicity,” according to Dr. Sayers. “Where appropriate, we need to find ways to impose behavior modification on a group that is relatively resistant to guidance and intervention. Even the best kids, as teenagers, really don’t take this sort of advice about their health risk very seriously. They regard themselves as immortal during their teenage years.”
Noting that behavioral change is not a core strength among transfusion medicine specialists, Dr. Sayers appealed to his audience of cardiologists for suggestions as to how to encourage lifestyle modification in this youthful group without browbeating them to the point that they’re driven off from becoming serial blood donors.
It’s not widely appreciated that across the U.S. during the school year, 20% of all unpaid blood donors are high school students. These high school blood drives provide an as-yet untapped opportunity to screen adolescents for cardiometabolic risk at low cost and minimal inconvenience to participants, said Dr. Sayers of the University of Texas, Dallas.
“We need allies to help us to ensure we get the kids’ attention better,” he explained. “I want to leave you with the sense that perhaps you will see these blood drives as an opportunity to find interventions that might address primordial prevention of cardiometabolic risk.”
He presented a study of 24,925 youths aged 16-19 who donated blood to Carter BloodCare during 2011-2012. Since blood is drawn for obligatory infectious diseases screening at each donation, Dr. Sayers and coinvestigators were able to measure nonfasting total cholesterol and HbA1c in every teen donor. Blood pressure is also measured at every donation.
The investigators used widely accepted definitions of elevated blood pressure, cholesterol, and HbA1c: namely, at least 140/80 mm Hg, 200 mg/dL, and 6.5%, respectively.
While the percentage of teen blood donors with borderline or elevated levels of all three cardiometabolic risk factors was in the low single figures, 21% of boys and 15% of girls were positive for two out of the three.
The prevalence of cardiometabolic risk factors varied by ethnicity. Sixteen percent of white adolescents had elevated or borderline levels of two risk factors. So did 24% of African Americans, 22% of Asian Americans, and 18% of Hispanics.
“These are really staggering results,” commented session chair Dr. Seth S. Martin of Johns Hopkins University, Baltimore. “This is a call to action now that you’ve identified all these kids who are on a trajectory that doesn’t look good.”
As to how physicians can help to favorably alter that trajectory, however, audience members admitted to being stumped, especially since many young people stop going to a primary care physician for preventive care during their teenage years.
“The big problem here is how to use this information to initiate lifestyle change,” observed Dr. Lewis H. Kuller, professor and past chair of epidemiology at the University of Pittsburgh.
Dr. Sayers reported having no financial conflicts regarding his study.
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point: Two-thirds of 16- to 19-year-olds have borderline or frank hypertension, hypercholesterolemia, and/or high blood glucose.
Major finding: Of a very large group of 16- to 19-year-old blood donors, 67% had borderline or elevated total cholesterol, blood pressure, and/or hemoglobin A1c levels.
Data source: A retrospective analysis of total cholesterol, blood pressure, and HbA1c levels in 24,925 Dallas-area blood donors aged 16-19.
Disclosures: The presenter reported having no financial conflicts of interest regarding this study.
High-risk B-ALL subgroup has ‘outstanding outcomes’
Photo courtesy of ASH
ORLANDO, FL—A subgroup of young patients with high-risk B-cell acute lymphoblastic leukemia (B-ALL) can have “outstanding outcomes” with contemporary therapy, according to researchers.
Results of a large study suggested that patients ages 1 to 30 who have high-risk B-ALL according to National Cancer Institute (NCI) classification can have high rates of event-free survival (EFS) and overall survival (OS) if they have favorable cytogenetic features, have no evidence of CNS disease, and have rapid minimal residual disease (MRD) responses.
The research suggested these patients will not benefit from further chemotherapy intensification.
Elizabeth Raetz, MD, of the University of Utah in Salt Lake City, presented these results at the 2015 ASH Annual Meeting (abstract 807).
She and her colleagues analyzed patients enrolled on the Children’s Oncology Group (COG) AALL03B1 classification study at the time of B-ALL diagnosis. From December 2003 to September 2011, there were 11,144 eligible patients enrolled on this trial.
Eighty-nine percent of these patients were also enrolled on a frontline ALL therapeutic trial, and 96% of these patients were evaluable for post-induction treatment assignment. Sixty-five percent of these patients were treated on a trial for NCI standard-risk B-ALL (COG-AALL0331), and 35% were treated on a trial for high-risk B-ALL (COG-AALL0232).
At the end of induction therapy, patients were classified into low-risk (29%), standard-risk (33%), high-risk (34%), and very-high-risk (4%) groups for further treatment allocation. The variables used for risk classification were age, initial white blood cell count, extramedullary disease status, blast cytogenetics, and early treatment response based on bone marrow morphology and day 29 MRD.
Patients with very-high-risk features (BCR-ABL1, hypodiploidy, induction failure, or poor response at day 43) did not continue on AALL0232/AALL0331 post-induction but did have outcome data captured for analysis.
Response and survival
Rapid early response was defined as M1 (<5% blasts) bone marrow by day 15 plus flow cytometry-based MRD <0.1% on day 29 of induction. Patients with either M2/M3 (≥5% blasts) day 15 marrow or MRD ≥0.1% at day 29 were deemed slow early responders.
Eighty-four percent of patients had a rapid early response to induction, and 16% had a slow early response.
For rapid early responders, the 5-year EFS was 89.3%, and the 5-year OS was 95.2%. For slow early responders, the EFS and OS rates were 67.9% and 84.3%, respectively (P<0.0001 for both EFS and OS comparisons).
Survival according to cytogenetics
Having favorable cytogenetic abnormalities (triple trisomies of chromosomes 4, 10, and 17 or ETV6-RUNX1 fusion) was associated with significantly better EFS and OS than having unfavorable cytogenetics (hypodiploidy [DNA index <0.81 or chromosomes < 44], MLL rearrangements, BCR-ABL1, or iAMP21).
And Dr Raetz pointed out that the 5-year OS exceeded 98% for patients with either standard- or high-risk disease who had favorable cytogenetics.
For patients who were ETV6-RUNX1-positive, the EFS was 93.2% and the OS was 98.3%. For patients who were ETV6-RUNX1 negative, the rates were 83.5% and 92%, respectively (P<0.0001).
For patients with triple trisomy, EFS was 94.7% and OS was 98.7%. For those without triple trisomy, the rates were 83.6% and 92.2%, respectively (P<0.0001).
For patients with MLL rearrangement, the EFS was 73.9% and the OS was 83.1%. For patients without MLL rearrangement, the rates were 85.9% and 93.6%, respectively (P<0.0001).
For patients who were positive for iAMP21, the EFS was 69.5% and the OS was 90.1%. For iAMP21-negative patients, the rates were 86.1% and 93.4%, respectively (P<0.0001 for PFS comparison and P=0.0026 for OS comparison).
Survival according to risk group and MRD
The researchers also assessed EFS and OS among patients with favorable cytogenetics according to NCI risk group and MRD at days 8 and 29.
“One thing to point out is that, regardless of having favorable cytogenetics, those individuals who had end-induction MRD values of greater than 0.01% had inferior outcomes, so that was still a prognostic marker,” Dr Raetz said.
“And one thing that we were pleasantly surprised to see was that, among the NCI high-risk patients, those who had very rapid MRD responses—so less than 1% at day 8 in the blood and less than 0.01% in the marrow on day 29—had a 94.9% 5-year event-free survival and 98.1% overall survival.”
The researchers also divided this group according to age—patients younger than 10 and those 10 years or older. There was no significant difference in EFS or OS between the age groups (P=0.126 and P=0.411).
Standard-risk group
Among patients with <1% MRD on day 8 and <0.01% MRD on day 29, the EFS was 95.7% and the OS was 99.1%.
Among patients with ≥1% MRD on day 8 and <0.01% MRD on day 29, the EFS was 91.7% and the OS was 99.4%.
Among patients with any MRD on day 8 and ≥0.01% MRD on day 29, the EFS was 88.1% and the OS was 96.8%.
High-risk group
Among patients with <1% MRD on day 8 and <0.01% MRD on day 29, the EFS was 94.9% and the OS was 98.1%.
Among patients with ≥1% MRD on day 8 and <0.01% MRD on day 29, the EFS was 93.6% and the OS was 95.5%.
Among patients with any MRD on day 8 and ≥0.01% MRD on day 29, the EFS was 75.4% and the OS was 90.4%.
In closing, Dr Raetz said this study showed that real‐time classification incorporating clinical features, blast cytogenetics, and early response was feasible in a large group of patients enrolled on COG ALL trials and identified patients with varying outcomes for risk‐based treatment allocation.
She noted that early response by marrow morphology was not prognostic when MRD response was used and is therefore no longer used in COG studies.
And although favorable cytogenetic features were not prognostic in NCI high-risk B‐ALL patients in prior COG studies, the current study indicates that these patients can have “excellent outcomes” if they have no evidence of CNS leukemia and are rapid MRD responders. So these patients will not benefit from further chemotherapy intensification. 
Photo courtesy of ASH
ORLANDO, FL—A subgroup of young patients with high-risk B-cell acute lymphoblastic leukemia (B-ALL) can have “outstanding outcomes” with contemporary therapy, according to researchers.
Results of a large study suggested that patients ages 1 to 30 who have high-risk B-ALL according to National Cancer Institute (NCI) classification can have high rates of event-free survival (EFS) and overall survival (OS) if they have favorable cytogenetic features, have no evidence of CNS disease, and have rapid minimal residual disease (MRD) responses.
The research suggested these patients will not benefit from further chemotherapy intensification.
Elizabeth Raetz, MD, of the University of Utah in Salt Lake City, presented these results at the 2015 ASH Annual Meeting (abstract 807).
She and her colleagues analyzed patients enrolled on the Children’s Oncology Group (COG) AALL03B1 classification study at the time of B-ALL diagnosis. From December 2003 to September 2011, there were 11,144 eligible patients enrolled on this trial.
Eighty-nine percent of these patients were also enrolled on a frontline ALL therapeutic trial, and 96% of these patients were evaluable for post-induction treatment assignment. Sixty-five percent of these patients were treated on a trial for NCI standard-risk B-ALL (COG-AALL0331), and 35% were treated on a trial for high-risk B-ALL (COG-AALL0232).
At the end of induction therapy, patients were classified into low-risk (29%), standard-risk (33%), high-risk (34%), and very-high-risk (4%) groups for further treatment allocation. The variables used for risk classification were age, initial white blood cell count, extramedullary disease status, blast cytogenetics, and early treatment response based on bone marrow morphology and day 29 MRD.
Patients with very-high-risk features (BCR-ABL1, hypodiploidy, induction failure, or poor response at day 43) did not continue on AALL0232/AALL0331 post-induction but did have outcome data captured for analysis.
Response and survival
Rapid early response was defined as M1 (<5% blasts) bone marrow by day 15 plus flow cytometry-based MRD <0.1% on day 29 of induction. Patients with either M2/M3 (≥5% blasts) day 15 marrow or MRD ≥0.1% at day 29 were deemed slow early responders.
Eighty-four percent of patients had a rapid early response to induction, and 16% had a slow early response.
For rapid early responders, the 5-year EFS was 89.3%, and the 5-year OS was 95.2%. For slow early responders, the EFS and OS rates were 67.9% and 84.3%, respectively (P<0.0001 for both EFS and OS comparisons).
Survival according to cytogenetics
Having favorable cytogenetic abnormalities (triple trisomies of chromosomes 4, 10, and 17 or ETV6-RUNX1 fusion) was associated with significantly better EFS and OS than having unfavorable cytogenetics (hypodiploidy [DNA index <0.81 or chromosomes < 44], MLL rearrangements, BCR-ABL1, or iAMP21).
And Dr Raetz pointed out that the 5-year OS exceeded 98% for patients with either standard- or high-risk disease who had favorable cytogenetics.
For patients who were ETV6-RUNX1-positive, the EFS was 93.2% and the OS was 98.3%. For patients who were ETV6-RUNX1 negative, the rates were 83.5% and 92%, respectively (P<0.0001).
For patients with triple trisomy, EFS was 94.7% and OS was 98.7%. For those without triple trisomy, the rates were 83.6% and 92.2%, respectively (P<0.0001).
For patients with MLL rearrangement, the EFS was 73.9% and the OS was 83.1%. For patients without MLL rearrangement, the rates were 85.9% and 93.6%, respectively (P<0.0001).
For patients who were positive for iAMP21, the EFS was 69.5% and the OS was 90.1%. For iAMP21-negative patients, the rates were 86.1% and 93.4%, respectively (P<0.0001 for PFS comparison and P=0.0026 for OS comparison).
Survival according to risk group and MRD
The researchers also assessed EFS and OS among patients with favorable cytogenetics according to NCI risk group and MRD at days 8 and 29.
“One thing to point out is that, regardless of having favorable cytogenetics, those individuals who had end-induction MRD values of greater than 0.01% had inferior outcomes, so that was still a prognostic marker,” Dr Raetz said.
“And one thing that we were pleasantly surprised to see was that, among the NCI high-risk patients, those who had very rapid MRD responses—so less than 1% at day 8 in the blood and less than 0.01% in the marrow on day 29—had a 94.9% 5-year event-free survival and 98.1% overall survival.”
The researchers also divided this group according to age—patients younger than 10 and those 10 years or older. There was no significant difference in EFS or OS between the age groups (P=0.126 and P=0.411).
Standard-risk group
Among patients with <1% MRD on day 8 and <0.01% MRD on day 29, the EFS was 95.7% and the OS was 99.1%.
Among patients with ≥1% MRD on day 8 and <0.01% MRD on day 29, the EFS was 91.7% and the OS was 99.4%.
Among patients with any MRD on day 8 and ≥0.01% MRD on day 29, the EFS was 88.1% and the OS was 96.8%.
High-risk group
Among patients with <1% MRD on day 8 and <0.01% MRD on day 29, the EFS was 94.9% and the OS was 98.1%.
Among patients with ≥1% MRD on day 8 and <0.01% MRD on day 29, the EFS was 93.6% and the OS was 95.5%.
Among patients with any MRD on day 8 and ≥0.01% MRD on day 29, the EFS was 75.4% and the OS was 90.4%.
In closing, Dr Raetz said this study showed that real‐time classification incorporating clinical features, blast cytogenetics, and early response was feasible in a large group of patients enrolled on COG ALL trials and identified patients with varying outcomes for risk‐based treatment allocation.
She noted that early response by marrow morphology was not prognostic when MRD response was used and is therefore no longer used in COG studies.
And although favorable cytogenetic features were not prognostic in NCI high-risk B‐ALL patients in prior COG studies, the current study indicates that these patients can have “excellent outcomes” if they have no evidence of CNS leukemia and are rapid MRD responders. So these patients will not benefit from further chemotherapy intensification.
Photo courtesy of ASH
ORLANDO, FL—A subgroup of young patients with high-risk B-cell acute lymphoblastic leukemia (B-ALL) can have “outstanding outcomes” with contemporary therapy, according to researchers.
Results of a large study suggested that patients ages 1 to 30 who have high-risk B-ALL according to National Cancer Institute (NCI) classification can have high rates of event-free survival (EFS) and overall survival (OS) if they have favorable cytogenetic features, have no evidence of CNS disease, and have rapid minimal residual disease (MRD) responses.
The research suggested these patients will not benefit from further chemotherapy intensification.
Elizabeth Raetz, MD, of the University of Utah in Salt Lake City, presented these results at the 2015 ASH Annual Meeting (abstract 807).
She and her colleagues analyzed patients enrolled on the Children’s Oncology Group (COG) AALL03B1 classification study at the time of B-ALL diagnosis. From December 2003 to September 2011, there were 11,144 eligible patients enrolled on this trial.
Eighty-nine percent of these patients were also enrolled on a frontline ALL therapeutic trial, and 96% of these patients were evaluable for post-induction treatment assignment. Sixty-five percent of these patients were treated on a trial for NCI standard-risk B-ALL (COG-AALL0331), and 35% were treated on a trial for high-risk B-ALL (COG-AALL0232).
At the end of induction therapy, patients were classified into low-risk (29%), standard-risk (33%), high-risk (34%), and very-high-risk (4%) groups for further treatment allocation. The variables used for risk classification were age, initial white blood cell count, extramedullary disease status, blast cytogenetics, and early treatment response based on bone marrow morphology and day 29 MRD.
Patients with very-high-risk features (BCR-ABL1, hypodiploidy, induction failure, or poor response at day 43) did not continue on AALL0232/AALL0331 post-induction but did have outcome data captured for analysis.
Response and survival
Rapid early response was defined as M1 (<5% blasts) bone marrow by day 15 plus flow cytometry-based MRD <0.1% on day 29 of induction. Patients with either M2/M3 (≥5% blasts) day 15 marrow or MRD ≥0.1% at day 29 were deemed slow early responders.
Eighty-four percent of patients had a rapid early response to induction, and 16% had a slow early response.
For rapid early responders, the 5-year EFS was 89.3%, and the 5-year OS was 95.2%. For slow early responders, the EFS and OS rates were 67.9% and 84.3%, respectively (P<0.0001 for both EFS and OS comparisons).
Survival according to cytogenetics
Having favorable cytogenetic abnormalities (triple trisomies of chromosomes 4, 10, and 17 or ETV6-RUNX1 fusion) was associated with significantly better EFS and OS than having unfavorable cytogenetics (hypodiploidy [DNA index <0.81 or chromosomes < 44], MLL rearrangements, BCR-ABL1, or iAMP21).
And Dr Raetz pointed out that the 5-year OS exceeded 98% for patients with either standard- or high-risk disease who had favorable cytogenetics.
For patients who were ETV6-RUNX1-positive, the EFS was 93.2% and the OS was 98.3%. For patients who were ETV6-RUNX1 negative, the rates were 83.5% and 92%, respectively (P<0.0001).
For patients with triple trisomy, EFS was 94.7% and OS was 98.7%. For those without triple trisomy, the rates were 83.6% and 92.2%, respectively (P<0.0001).
For patients with MLL rearrangement, the EFS was 73.9% and the OS was 83.1%. For patients without MLL rearrangement, the rates were 85.9% and 93.6%, respectively (P<0.0001).
For patients who were positive for iAMP21, the EFS was 69.5% and the OS was 90.1%. For iAMP21-negative patients, the rates were 86.1% and 93.4%, respectively (P<0.0001 for PFS comparison and P=0.0026 for OS comparison).
Survival according to risk group and MRD
The researchers also assessed EFS and OS among patients with favorable cytogenetics according to NCI risk group and MRD at days 8 and 29.
“One thing to point out is that, regardless of having favorable cytogenetics, those individuals who had end-induction MRD values of greater than 0.01% had inferior outcomes, so that was still a prognostic marker,” Dr Raetz said.
“And one thing that we were pleasantly surprised to see was that, among the NCI high-risk patients, those who had very rapid MRD responses—so less than 1% at day 8 in the blood and less than 0.01% in the marrow on day 29—had a 94.9% 5-year event-free survival and 98.1% overall survival.”
The researchers also divided this group according to age—patients younger than 10 and those 10 years or older. There was no significant difference in EFS or OS between the age groups (P=0.126 and P=0.411).
Standard-risk group
Among patients with <1% MRD on day 8 and <0.01% MRD on day 29, the EFS was 95.7% and the OS was 99.1%.
Among patients with ≥1% MRD on day 8 and <0.01% MRD on day 29, the EFS was 91.7% and the OS was 99.4%.
Among patients with any MRD on day 8 and ≥0.01% MRD on day 29, the EFS was 88.1% and the OS was 96.8%.
High-risk group
Among patients with <1% MRD on day 8 and <0.01% MRD on day 29, the EFS was 94.9% and the OS was 98.1%.
Among patients with ≥1% MRD on day 8 and <0.01% MRD on day 29, the EFS was 93.6% and the OS was 95.5%.
Among patients with any MRD on day 8 and ≥0.01% MRD on day 29, the EFS was 75.4% and the OS was 90.4%.
In closing, Dr Raetz said this study showed that real‐time classification incorporating clinical features, blast cytogenetics, and early response was feasible in a large group of patients enrolled on COG ALL trials and identified patients with varying outcomes for risk‐based treatment allocation.
She noted that early response by marrow morphology was not prognostic when MRD response was used and is therefore no longer used in COG studies.
And although favorable cytogenetic features were not prognostic in NCI high-risk B‐ALL patients in prior COG studies, the current study indicates that these patients can have “excellent outcomes” if they have no evidence of CNS leukemia and are rapid MRD responders. So these patients will not benefit from further chemotherapy intensification.
Study lays groundwork for autologous nerve cell transplantation in Hirschsprung disease
Neural progenitor cells from the proximal colons of patients with Hirschsprung disease divided and formed neurons and glia in their own distal aganglionic colon tissue, according to a study published in the January issue of Cellular and Molecular Gastroenterology and Hepatology.
The approach could lead to “a promising therapeutic strategy” for Hirschsprung disease, because autologous transplantation of nerve progenitor cells would prevent immune rejection, said Dr. Benjamin Rollo of Murdoch Children’s Research Institute in Victoria, Australia, and his associates. But they cautioned against reading too much into their findings, “as there are distributional hurdles to surmount” before cell therapy can be used alone or in combination with surgery.
Hirschsprung disease is a congenital disorder in which embryonic neural crest cells fail to form the distal part of the enteric nervous system. The resulting lack of bowel motility leads to severe constipation and potentially fatal megacolon. Treatment involves surgically resecting the aganglionic distal bowel and anastomosing the normal proximal bowel to the anorectum, but this approach itself can cause constipation as well as fecal soiling, the investigators noted (Cell Molec Gastroenterol Hepatol. 2015 Oct. 22 [doi: 10.1016/j.jcmgh.2015.09.007]).
For the study, they harvested tissue from the proximal (neuronal) and distal (aneuronal) margins of resection of the colons of 31 infants and children with Hirschsprung disease. They cultured cells from the myenteric plexus of the proximal colon, and separated out nerve cells by using flow cytometry for the p75 neural crest marker. To test whether these nerve cells could colonize aganglionic colon, they co-cultured them with aneural avian embryo gut and with patients’ own aneuronal colon muscle. In addition, they co-cultured embryonic mouse enteric nernous system cells with human aneuronal colon muscle. They used quantitative reverse transcriptase PCR and several other standard laboratory techniques to detect cellular markers and mitosis.
Ganglia from the patients’ proximal colons expressed the neural crest markers p75, SOX10, and HNK1, as well as several neuronal, neurite, and glial markers, the researchers reported. The proximal colon specimens also contained ENS progenitor cells, which were SOX10-positive but lacked neuronal or glial markers. The progenitor cells comprised less than 5% of all cells from the proximal colon, but proliferated fourfold more after supplementation with CHIR-99021, a selective inhibitor of glycogen synthase kinase 3. They successfully colonized avian aneural embryonic gut and autologous postnatal aneuronal colon tissue, and the latter also was colonized successfully by mouse enteric neural crest cells.
The study “fulfilled three key requirements” for transplantation – harvesting enteric nervous system cells from the proximal colons of patients with Hirschsprung disease; confirming that postnatal aneuronal colon tissue could support an enteric nervous system; and showing that enteric nervous system–derived cells could colonize both embryonic gut and autologous postnatal colon tissue, said the researchers. More work is needed to sufficiently expand embryonic neural crest stem or progenitor cells and transplant them over a large area of colon, although supplementation with growth factors and use of elastic polymer substrates might help, they added.
The National Health and Medical Research Council, Murdoch Children’s Research Institute, Graham Burke and Yvonne Spencer, the Federation of Chinese Associations, Fonds du Service de chirurgie pédiatrique et de Perfectionnement du CHUV, Fondation SICPA, and Société Académique Vaudoise funded the study. The researchers disclosed no conflicts of interest.
Hirschsprung disease results from a failure of complete neural crest cell migration into the distal colon. Current therapy relies on surgical resection of the aganglionic distal colon. However, for many children, particularly those with large aganglionic segments, surgery often fails to completely normalize function.
One therapeutic approach might be to transplant new enteric neural cells into the aganglionic colon. This has been partially accomplished in rodent and avian models. However, it is not known if human smooth muscle can be colonized or if human postnatal enteric nervous system cells are capable of migration, expansion, and differentiation.
Rollo et al. show that human postnatal enteric nervous system cells isolated from the proximal, i.e., ganglionic, margin of Hirschsprung disease resection specimens can migrate and spread to colonize aganglionic smooth muscle from the distal margin of the same specimen. Remarkably, the transplanted cells differentiated into neurons and glia and formed normal-appearing neural structures.
Many questions remain. If neural cells isolated from the proximal margin can migrate ex vivo, why didn’t they migrate during in utero development? Do the transplanted cells restore normal motility, which requires a complex series of events that must be precisely orchestrated?
Nevertheless, the demonstration that human postnatal neural cells can be isolated from surgical specimens and used to colonize aganglionic smooth muscle suggests that it may be possible to conserve and restore motility and, potentially, to successfully treat Hirschprung disease patients without the need for surgery.
Marion France, Ph.D., is a postdoctoral research fellow at Brigham and Women’s Hospital and Harvard Medical School, Boston. She has no conflicts of interest.
Hirschsprung disease results from a failure of complete neural crest cell migration into the distal colon. Current therapy relies on surgical resection of the aganglionic distal colon. However, for many children, particularly those with large aganglionic segments, surgery often fails to completely normalize function.
One therapeutic approach might be to transplant new enteric neural cells into the aganglionic colon. This has been partially accomplished in rodent and avian models. However, it is not known if human smooth muscle can be colonized or if human postnatal enteric nervous system cells are capable of migration, expansion, and differentiation.
Rollo et al. show that human postnatal enteric nervous system cells isolated from the proximal, i.e., ganglionic, margin of Hirschsprung disease resection specimens can migrate and spread to colonize aganglionic smooth muscle from the distal margin of the same specimen. Remarkably, the transplanted cells differentiated into neurons and glia and formed normal-appearing neural structures.
Many questions remain. If neural cells isolated from the proximal margin can migrate ex vivo, why didn’t they migrate during in utero development? Do the transplanted cells restore normal motility, which requires a complex series of events that must be precisely orchestrated?
Nevertheless, the demonstration that human postnatal neural cells can be isolated from surgical specimens and used to colonize aganglionic smooth muscle suggests that it may be possible to conserve and restore motility and, potentially, to successfully treat Hirschprung disease patients without the need for surgery.
Marion France, Ph.D., is a postdoctoral research fellow at Brigham and Women’s Hospital and Harvard Medical School, Boston. She has no conflicts of interest.
Hirschsprung disease results from a failure of complete neural crest cell migration into the distal colon. Current therapy relies on surgical resection of the aganglionic distal colon. However, for many children, particularly those with large aganglionic segments, surgery often fails to completely normalize function.
One therapeutic approach might be to transplant new enteric neural cells into the aganglionic colon. This has been partially accomplished in rodent and avian models. However, it is not known if human smooth muscle can be colonized or if human postnatal enteric nervous system cells are capable of migration, expansion, and differentiation.
Rollo et al. show that human postnatal enteric nervous system cells isolated from the proximal, i.e., ganglionic, margin of Hirschsprung disease resection specimens can migrate and spread to colonize aganglionic smooth muscle from the distal margin of the same specimen. Remarkably, the transplanted cells differentiated into neurons and glia and formed normal-appearing neural structures.
Many questions remain. If neural cells isolated from the proximal margin can migrate ex vivo, why didn’t they migrate during in utero development? Do the transplanted cells restore normal motility, which requires a complex series of events that must be precisely orchestrated?
Nevertheless, the demonstration that human postnatal neural cells can be isolated from surgical specimens and used to colonize aganglionic smooth muscle suggests that it may be possible to conserve and restore motility and, potentially, to successfully treat Hirschprung disease patients without the need for surgery.
Marion France, Ph.D., is a postdoctoral research fellow at Brigham and Women’s Hospital and Harvard Medical School, Boston. She has no conflicts of interest.
Neural progenitor cells from the proximal colons of patients with Hirschsprung disease divided and formed neurons and glia in their own distal aganglionic colon tissue, according to a study published in the January issue of Cellular and Molecular Gastroenterology and Hepatology.
The approach could lead to “a promising therapeutic strategy” for Hirschsprung disease, because autologous transplantation of nerve progenitor cells would prevent immune rejection, said Dr. Benjamin Rollo of Murdoch Children’s Research Institute in Victoria, Australia, and his associates. But they cautioned against reading too much into their findings, “as there are distributional hurdles to surmount” before cell therapy can be used alone or in combination with surgery.
Hirschsprung disease is a congenital disorder in which embryonic neural crest cells fail to form the distal part of the enteric nervous system. The resulting lack of bowel motility leads to severe constipation and potentially fatal megacolon. Treatment involves surgically resecting the aganglionic distal bowel and anastomosing the normal proximal bowel to the anorectum, but this approach itself can cause constipation as well as fecal soiling, the investigators noted (Cell Molec Gastroenterol Hepatol. 2015 Oct. 22 [doi: 10.1016/j.jcmgh.2015.09.007]).
For the study, they harvested tissue from the proximal (neuronal) and distal (aneuronal) margins of resection of the colons of 31 infants and children with Hirschsprung disease. They cultured cells from the myenteric plexus of the proximal colon, and separated out nerve cells by using flow cytometry for the p75 neural crest marker. To test whether these nerve cells could colonize aganglionic colon, they co-cultured them with aneural avian embryo gut and with patients’ own aneuronal colon muscle. In addition, they co-cultured embryonic mouse enteric nernous system cells with human aneuronal colon muscle. They used quantitative reverse transcriptase PCR and several other standard laboratory techniques to detect cellular markers and mitosis.
Ganglia from the patients’ proximal colons expressed the neural crest markers p75, SOX10, and HNK1, as well as several neuronal, neurite, and glial markers, the researchers reported. The proximal colon specimens also contained ENS progenitor cells, which were SOX10-positive but lacked neuronal or glial markers. The progenitor cells comprised less than 5% of all cells from the proximal colon, but proliferated fourfold more after supplementation with CHIR-99021, a selective inhibitor of glycogen synthase kinase 3. They successfully colonized avian aneural embryonic gut and autologous postnatal aneuronal colon tissue, and the latter also was colonized successfully by mouse enteric neural crest cells.
The study “fulfilled three key requirements” for transplantation – harvesting enteric nervous system cells from the proximal colons of patients with Hirschsprung disease; confirming that postnatal aneuronal colon tissue could support an enteric nervous system; and showing that enteric nervous system–derived cells could colonize both embryonic gut and autologous postnatal colon tissue, said the researchers. More work is needed to sufficiently expand embryonic neural crest stem or progenitor cells and transplant them over a large area of colon, although supplementation with growth factors and use of elastic polymer substrates might help, they added.
The National Health and Medical Research Council, Murdoch Children’s Research Institute, Graham Burke and Yvonne Spencer, the Federation of Chinese Associations, Fonds du Service de chirurgie pédiatrique et de Perfectionnement du CHUV, Fondation SICPA, and Société Académique Vaudoise funded the study. The researchers disclosed no conflicts of interest.
Neural progenitor cells from the proximal colons of patients with Hirschsprung disease divided and formed neurons and glia in their own distal aganglionic colon tissue, according to a study published in the January issue of Cellular and Molecular Gastroenterology and Hepatology.
The approach could lead to “a promising therapeutic strategy” for Hirschsprung disease, because autologous transplantation of nerve progenitor cells would prevent immune rejection, said Dr. Benjamin Rollo of Murdoch Children’s Research Institute in Victoria, Australia, and his associates. But they cautioned against reading too much into their findings, “as there are distributional hurdles to surmount” before cell therapy can be used alone or in combination with surgery.
Hirschsprung disease is a congenital disorder in which embryonic neural crest cells fail to form the distal part of the enteric nervous system. The resulting lack of bowel motility leads to severe constipation and potentially fatal megacolon. Treatment involves surgically resecting the aganglionic distal bowel and anastomosing the normal proximal bowel to the anorectum, but this approach itself can cause constipation as well as fecal soiling, the investigators noted (Cell Molec Gastroenterol Hepatol. 2015 Oct. 22 [doi: 10.1016/j.jcmgh.2015.09.007]).
For the study, they harvested tissue from the proximal (neuronal) and distal (aneuronal) margins of resection of the colons of 31 infants and children with Hirschsprung disease. They cultured cells from the myenteric plexus of the proximal colon, and separated out nerve cells by using flow cytometry for the p75 neural crest marker. To test whether these nerve cells could colonize aganglionic colon, they co-cultured them with aneural avian embryo gut and with patients’ own aneuronal colon muscle. In addition, they co-cultured embryonic mouse enteric nernous system cells with human aneuronal colon muscle. They used quantitative reverse transcriptase PCR and several other standard laboratory techniques to detect cellular markers and mitosis.
Ganglia from the patients’ proximal colons expressed the neural crest markers p75, SOX10, and HNK1, as well as several neuronal, neurite, and glial markers, the researchers reported. The proximal colon specimens also contained ENS progenitor cells, which were SOX10-positive but lacked neuronal or glial markers. The progenitor cells comprised less than 5% of all cells from the proximal colon, but proliferated fourfold more after supplementation with CHIR-99021, a selective inhibitor of glycogen synthase kinase 3. They successfully colonized avian aneural embryonic gut and autologous postnatal aneuronal colon tissue, and the latter also was colonized successfully by mouse enteric neural crest cells.
The study “fulfilled three key requirements” for transplantation – harvesting enteric nervous system cells from the proximal colons of patients with Hirschsprung disease; confirming that postnatal aneuronal colon tissue could support an enteric nervous system; and showing that enteric nervous system–derived cells could colonize both embryonic gut and autologous postnatal colon tissue, said the researchers. More work is needed to sufficiently expand embryonic neural crest stem or progenitor cells and transplant them over a large area of colon, although supplementation with growth factors and use of elastic polymer substrates might help, they added.
The National Health and Medical Research Council, Murdoch Children’s Research Institute, Graham Burke and Yvonne Spencer, the Federation of Chinese Associations, Fonds du Service de chirurgie pédiatrique et de Perfectionnement du CHUV, Fondation SICPA, and Société Académique Vaudoise funded the study. The researchers disclosed no conflicts of interest.
FROM CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: A preclinical study took several key steps toward autologous transplantation of nerve progenitor cells to treat Hirschsprung disease.
Major finding: Neural progenitor cells from the proximal colons of patients with Hirschsprung disease divided and formed neurons and glia in their own distal aganglionic colon tissue.
Data source: Flow cytometry, reverse transcriptase-PCR, immunohistochemistry, and cell culture of proximal (neuronal) and distal (aneuronal) colon tissue from 31 affected patients, and co-culture with avian embryonic gut and mouse enteric nervous system cells.
Disclosures: The National Health and Medical Research Council, Murdoch Children’s Research Institute, Graham Burke and Yvonne Spencer, the Federation of Chinese Associations, Fonds du Service de chirurgie pédiatrique et de Perfectionnement du CHUV, Fondation SICPA, and Société Académique Vaudoise funded the study. The researchers disclosed no conflicts of interest.
PPIs caused remission in about half of esophageal eosinophilia cases
About half of patients with symptomatic esophageal eosinophilia achieved complete clinical and histologic remission on proton pump inhibitors (PPIs), according to a systematic review and meta-analysis of 33 studies.
“Our results support the concept of PPIs as first-line therapy in both children and adults,” Dr. Alfredo Lucendo of the Servicio de Salud de Castillo–La Mancha, Hospital General de Tomelloso, Albacete, Spain, and his associates wrote in the January issue of Clinical Gastroenterology and Hepatology. “Other effective alternatives, such as dietary or topical steroid therapy, likely might be set aside as second-line treatment, owing to long-term safety concerns (topical steroid therapy) and impairment of quality of life and nutritional inadequacy (dietary interventions).”
The study also confirmed that esophageal pH monitoring does not accurately predict therapeutic response to PPI therapy. “The performance of this test before histologic reevaluation on PPI therapy should be discouraged,” according to the researchers (Clin Gastroenterol Hepatol. 2015. [doi:10.1016/j.cgh.2015.07.041]). Eosinophilic esophagitis was first described as a distinct disorder about 20 years ago, but only recently was understood to be the most common cause of chronic esophageal symptoms among children and young adults. Some cases are now known to respond to PPI therapy, but reported remission rates have varied depending on study design and patient population, the investigators said. In addition, no one had systematically reviewed studies of PPI-responsive esophageal eosinophilia for quality or to determine the optimal type of PPI, dose, or treatment duration.
Therefore, the investigators searched MEDLINE, EMBASE, SCOPUS, and abstracts from the annual meetings of the American Gastroenterological Association, the American College of Gastroenterology, and United European Gastroenterology, identifying 33 studies of 619 patients with symptomatic esophageal eosinophilia. Eleven of the studies were prospective, of which only two were randomized controlled trials. The researchers defined a histologic response as less than 15 eosinophils per high-powered frame after PPI therapy. “Missing data regarding PPI therapy were common and prevented us from drawing conclusions on the most effective PPI drug and doses,” they said. In addition, most studies lacked structured or objective survey tools or other measures of clinical improvement, making it impossible to rule out self-adapted coping strategies as a main cause of improvement over time.
With those caveats in mind, about 61% of patients in the pooled analysis had a clinical response to PPI therapy (95% confidence interval, 48%-72%), and half achieved clinical and histologic remission (95% CI, 42%-59%), the investigators reported. Therapy was somewhat more effective when administered twice a day instead of once daily, when clinicians used esophageal pH monitoring, and when studies were prospective instead of retrospective, but the differences were not significant. Nor did therapeutic response significantly differ based on the age of patients, type of report, or quality of the study.
The overall findings “should be interpreted with caution because of poor-quality evidence, heterogeneity, and publication bias,” the researchers said. Prospective studies are needed to examine the best PPI, dose, and dosing interval to use in an initial trial in the clinic; to clarify long-term effects and dosing strategies; to assess the ability of PPIs to reverse fibrotic esophageal remodeling; and to examine the effects of the CYP2C19 genotype on clinical and histologic response, they added. “More quality evidence on pediatric PPI-responsive eosinophilic esophagitis is needed urgently,” they emphasized.
The authors reported no funding sources and had no disclosures.
Proton pump inhibitor–responsive esophageal eosinophilia (PPI-REE) is a condition in which patients have symptoms of esophageal dysfunction (often dysphagia or heartburn), biopsies with at least 15 eosinophils per high-power field (eos/hpf), and symptomatic and histologic resolution after a PPI trial, typically at twice-daily dosing. Currently, PPI-REE and eosinophilic esophagitis (EoE) overlap substantially, but in the most recent guidelines, they are still considered to be distinct entities. PPI-REE was first reported almost 10 years ago, and since then multiple prospective and retrospective studies in both children and adults have further characterized it. The study by Dr. Lucendo and colleagues, a comprehensive and rigorously conducted systematic review and meta-analysis of 33 studies accounting for 619 patients, found that just over 50% of patients with esophageal eosinophilia had histologic remission (less than 15 eos/hpf) and just over 60% had symptomatic improvement after PPI use. Moreover, similar responses were seen whether or not there was pathologic acid exposure on pH testing.
|
| Dr. Evan S. Dellon |
While there was heterogeneity between studies on meta-analysis, there are several important messages from this study. First, PPI-REE is commonly seen in patients with esophageal eosinophilia, and is not always simply due to reflux. Second, PPIs have a potent antieosinophil effect in these patients. Interestingly, novel acid-independent mechanisms for this anti-inflammatory action recently have been described in other studies. Third, a PPI trial remains important prior to confirming the diagnosis of EoE, and PPIs should be considered the first-line treatment when esophageal eosinophilia is identified. However, it bears emphasizing that all esophageal eosinophilia is not due to EoE. If a patient responds to the PPI trial, there is no clear need to move toward topical steroid or dietary elimination therapy specifically for EoE, and starting multiple antieosinophil treatments concomitantly precludes determining which is most effective. In the future, understanding which patients with esophageal eosinophilia will most benefit from a PPI trial will be important, as we are currently unable to predict this from clinical, endoscopic, and histologic factors. Future studies and guidelines will also need to address whether EoE and PPI-REE are distinct diseases or manifestations of the same underlying process.
Dr. Evan S. Dellon, MPH, is associate professor of medicine and epidemiology at the Center for Esophageal Diseases and Swallowing, division of gastroenterology and hepatology, University of North Carolina School of Medicine at Chapel Hill. He has received research funding from Meritage, Miraca, Receptos, and Regeneron and consulted for Aptalis, Banner, Novartis, Receptos, Regeneron, and Roche.
Proton pump inhibitor–responsive esophageal eosinophilia (PPI-REE) is a condition in which patients have symptoms of esophageal dysfunction (often dysphagia or heartburn), biopsies with at least 15 eosinophils per high-power field (eos/hpf), and symptomatic and histologic resolution after a PPI trial, typically at twice-daily dosing. Currently, PPI-REE and eosinophilic esophagitis (EoE) overlap substantially, but in the most recent guidelines, they are still considered to be distinct entities. PPI-REE was first reported almost 10 years ago, and since then multiple prospective and retrospective studies in both children and adults have further characterized it. The study by Dr. Lucendo and colleagues, a comprehensive and rigorously conducted systematic review and meta-analysis of 33 studies accounting for 619 patients, found that just over 50% of patients with esophageal eosinophilia had histologic remission (less than 15 eos/hpf) and just over 60% had symptomatic improvement after PPI use. Moreover, similar responses were seen whether or not there was pathologic acid exposure on pH testing.
|
|
| Dr. Evan S. Dellon |
While there was heterogeneity between studies on meta-analysis, there are several important messages from this study. First, PPI-REE is commonly seen in patients with esophageal eosinophilia, and is not always simply due to reflux. Second, PPIs have a potent antieosinophil effect in these patients. Interestingly, novel acid-independent mechanisms for this anti-inflammatory action recently have been described in other studies. Third, a PPI trial remains important prior to confirming the diagnosis of EoE, and PPIs should be considered the first-line treatment when esophageal eosinophilia is identified. However, it bears emphasizing that all esophageal eosinophilia is not due to EoE. If a patient responds to the PPI trial, there is no clear need to move toward topical steroid or dietary elimination therapy specifically for EoE, and starting multiple antieosinophil treatments concomitantly precludes determining which is most effective. In the future, understanding which patients with esophageal eosinophilia will most benefit from a PPI trial will be important, as we are currently unable to predict this from clinical, endoscopic, and histologic factors. Future studies and guidelines will also need to address whether EoE and PPI-REE are distinct diseases or manifestations of the same underlying process.
Dr. Evan S. Dellon, MPH, is associate professor of medicine and epidemiology at the Center for Esophageal Diseases and Swallowing, division of gastroenterology and hepatology, University of North Carolina School of Medicine at Chapel Hill. He has received research funding from Meritage, Miraca, Receptos, and Regeneron and consulted for Aptalis, Banner, Novartis, Receptos, Regeneron, and Roche.
Proton pump inhibitor–responsive esophageal eosinophilia (PPI-REE) is a condition in which patients have symptoms of esophageal dysfunction (often dysphagia or heartburn), biopsies with at least 15 eosinophils per high-power field (eos/hpf), and symptomatic and histologic resolution after a PPI trial, typically at twice-daily dosing. Currently, PPI-REE and eosinophilic esophagitis (EoE) overlap substantially, but in the most recent guidelines, they are still considered to be distinct entities. PPI-REE was first reported almost 10 years ago, and since then multiple prospective and retrospective studies in both children and adults have further characterized it. The study by Dr. Lucendo and colleagues, a comprehensive and rigorously conducted systematic review and meta-analysis of 33 studies accounting for 619 patients, found that just over 50% of patients with esophageal eosinophilia had histologic remission (less than 15 eos/hpf) and just over 60% had symptomatic improvement after PPI use. Moreover, similar responses were seen whether or not there was pathologic acid exposure on pH testing.
|
|
| Dr. Evan S. Dellon |
While there was heterogeneity between studies on meta-analysis, there are several important messages from this study. First, PPI-REE is commonly seen in patients with esophageal eosinophilia, and is not always simply due to reflux. Second, PPIs have a potent antieosinophil effect in these patients. Interestingly, novel acid-independent mechanisms for this anti-inflammatory action recently have been described in other studies. Third, a PPI trial remains important prior to confirming the diagnosis of EoE, and PPIs should be considered the first-line treatment when esophageal eosinophilia is identified. However, it bears emphasizing that all esophageal eosinophilia is not due to EoE. If a patient responds to the PPI trial, there is no clear need to move toward topical steroid or dietary elimination therapy specifically for EoE, and starting multiple antieosinophil treatments concomitantly precludes determining which is most effective. In the future, understanding which patients with esophageal eosinophilia will most benefit from a PPI trial will be important, as we are currently unable to predict this from clinical, endoscopic, and histologic factors. Future studies and guidelines will also need to address whether EoE and PPI-REE are distinct diseases or manifestations of the same underlying process.
Dr. Evan S. Dellon, MPH, is associate professor of medicine and epidemiology at the Center for Esophageal Diseases and Swallowing, division of gastroenterology and hepatology, University of North Carolina School of Medicine at Chapel Hill. He has received research funding from Meritage, Miraca, Receptos, and Regeneron and consulted for Aptalis, Banner, Novartis, Receptos, Regeneron, and Roche.
About half of patients with symptomatic esophageal eosinophilia achieved complete clinical and histologic remission on proton pump inhibitors (PPIs), according to a systematic review and meta-analysis of 33 studies.
“Our results support the concept of PPIs as first-line therapy in both children and adults,” Dr. Alfredo Lucendo of the Servicio de Salud de Castillo–La Mancha, Hospital General de Tomelloso, Albacete, Spain, and his associates wrote in the January issue of Clinical Gastroenterology and Hepatology. “Other effective alternatives, such as dietary or topical steroid therapy, likely might be set aside as second-line treatment, owing to long-term safety concerns (topical steroid therapy) and impairment of quality of life and nutritional inadequacy (dietary interventions).”
The study also confirmed that esophageal pH monitoring does not accurately predict therapeutic response to PPI therapy. “The performance of this test before histologic reevaluation on PPI therapy should be discouraged,” according to the researchers (Clin Gastroenterol Hepatol. 2015. [doi:10.1016/j.cgh.2015.07.041]). Eosinophilic esophagitis was first described as a distinct disorder about 20 years ago, but only recently was understood to be the most common cause of chronic esophageal symptoms among children and young adults. Some cases are now known to respond to PPI therapy, but reported remission rates have varied depending on study design and patient population, the investigators said. In addition, no one had systematically reviewed studies of PPI-responsive esophageal eosinophilia for quality or to determine the optimal type of PPI, dose, or treatment duration.
Therefore, the investigators searched MEDLINE, EMBASE, SCOPUS, and abstracts from the annual meetings of the American Gastroenterological Association, the American College of Gastroenterology, and United European Gastroenterology, identifying 33 studies of 619 patients with symptomatic esophageal eosinophilia. Eleven of the studies were prospective, of which only two were randomized controlled trials. The researchers defined a histologic response as less than 15 eosinophils per high-powered frame after PPI therapy. “Missing data regarding PPI therapy were common and prevented us from drawing conclusions on the most effective PPI drug and doses,” they said. In addition, most studies lacked structured or objective survey tools or other measures of clinical improvement, making it impossible to rule out self-adapted coping strategies as a main cause of improvement over time.
With those caveats in mind, about 61% of patients in the pooled analysis had a clinical response to PPI therapy (95% confidence interval, 48%-72%), and half achieved clinical and histologic remission (95% CI, 42%-59%), the investigators reported. Therapy was somewhat more effective when administered twice a day instead of once daily, when clinicians used esophageal pH monitoring, and when studies were prospective instead of retrospective, but the differences were not significant. Nor did therapeutic response significantly differ based on the age of patients, type of report, or quality of the study.
The overall findings “should be interpreted with caution because of poor-quality evidence, heterogeneity, and publication bias,” the researchers said. Prospective studies are needed to examine the best PPI, dose, and dosing interval to use in an initial trial in the clinic; to clarify long-term effects and dosing strategies; to assess the ability of PPIs to reverse fibrotic esophageal remodeling; and to examine the effects of the CYP2C19 genotype on clinical and histologic response, they added. “More quality evidence on pediatric PPI-responsive eosinophilic esophagitis is needed urgently,” they emphasized.
The authors reported no funding sources and had no disclosures.
About half of patients with symptomatic esophageal eosinophilia achieved complete clinical and histologic remission on proton pump inhibitors (PPIs), according to a systematic review and meta-analysis of 33 studies.
“Our results support the concept of PPIs as first-line therapy in both children and adults,” Dr. Alfredo Lucendo of the Servicio de Salud de Castillo–La Mancha, Hospital General de Tomelloso, Albacete, Spain, and his associates wrote in the January issue of Clinical Gastroenterology and Hepatology. “Other effective alternatives, such as dietary or topical steroid therapy, likely might be set aside as second-line treatment, owing to long-term safety concerns (topical steroid therapy) and impairment of quality of life and nutritional inadequacy (dietary interventions).”
The study also confirmed that esophageal pH monitoring does not accurately predict therapeutic response to PPI therapy. “The performance of this test before histologic reevaluation on PPI therapy should be discouraged,” according to the researchers (Clin Gastroenterol Hepatol. 2015. [doi:10.1016/j.cgh.2015.07.041]). Eosinophilic esophagitis was first described as a distinct disorder about 20 years ago, but only recently was understood to be the most common cause of chronic esophageal symptoms among children and young adults. Some cases are now known to respond to PPI therapy, but reported remission rates have varied depending on study design and patient population, the investigators said. In addition, no one had systematically reviewed studies of PPI-responsive esophageal eosinophilia for quality or to determine the optimal type of PPI, dose, or treatment duration.
Therefore, the investigators searched MEDLINE, EMBASE, SCOPUS, and abstracts from the annual meetings of the American Gastroenterological Association, the American College of Gastroenterology, and United European Gastroenterology, identifying 33 studies of 619 patients with symptomatic esophageal eosinophilia. Eleven of the studies were prospective, of which only two were randomized controlled trials. The researchers defined a histologic response as less than 15 eosinophils per high-powered frame after PPI therapy. “Missing data regarding PPI therapy were common and prevented us from drawing conclusions on the most effective PPI drug and doses,” they said. In addition, most studies lacked structured or objective survey tools or other measures of clinical improvement, making it impossible to rule out self-adapted coping strategies as a main cause of improvement over time.
With those caveats in mind, about 61% of patients in the pooled analysis had a clinical response to PPI therapy (95% confidence interval, 48%-72%), and half achieved clinical and histologic remission (95% CI, 42%-59%), the investigators reported. Therapy was somewhat more effective when administered twice a day instead of once daily, when clinicians used esophageal pH monitoring, and when studies were prospective instead of retrospective, but the differences were not significant. Nor did therapeutic response significantly differ based on the age of patients, type of report, or quality of the study.
The overall findings “should be interpreted with caution because of poor-quality evidence, heterogeneity, and publication bias,” the researchers said. Prospective studies are needed to examine the best PPI, dose, and dosing interval to use in an initial trial in the clinic; to clarify long-term effects and dosing strategies; to assess the ability of PPIs to reverse fibrotic esophageal remodeling; and to examine the effects of the CYP2C19 genotype on clinical and histologic response, they added. “More quality evidence on pediatric PPI-responsive eosinophilic esophagitis is needed urgently,” they emphasized.
The authors reported no funding sources and had no disclosures.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Proton pump inhibitors should be considered in the first-line treatment of esophageal eosinophilia.
Major finding: Half of patients achieved clinical and histologic remission after a trial of PPIs.
Data source: Meta-analysis of 33 studies of 619 patients with symptomatic esophageal eosinophilia indicative of eosinophilic esophagitis.
Disclosures: The authors reported no funding sources and had no disclosures.
Case Report: Perianal Streptococcal Infection
Case
The mother of a 3-year-old boy presented her son to the ED for evaluation after she noticed peeling of the skin in his perianal region. She stated that the peeling had started 1 day prior to presentation. Two days earlier, the mother had brought the same patient to the ED for evaluation of a fever, sore throat, and a slight rash over his face. The boy’s vital signs at the initial presentation were: temperature, 101.8°F; heart rate, 102 beats/minute; and respiratory rate, 28 breaths/minute. Oxygen saturation was 98% on room air.
During this first visit, the mother denied the child having had any fever, chills, headache, sore throat, facial rash, joint pain, or pain on defecation. He had no significant medical history and no known drug allergies. After examination, a throat culture was taken, and the patient was given acetaminophen and discharged home with a diagnosis of viral syndrome.
At the second presentation, physical examination revealed a well-developed child in no distress. The examination was negative except for a 4 x 2 cm area of desquamation present over the perianal region (Figure).
The area of desquamation was dry, mildly erythematous without discharge, and nontender. The patient’s vital signs at this presentation were stable, and he was afebrile. The remaining physical examination findings were normal. The throat culture taken during the first ED presentation was reported as negative. A perianal swab was sent for culture and sensitivity. This was later reported to be positive for group A β-hemolytic streptococci (GABHS), which is sensitive to penicillin. The patient was discharged home in the care of his mother with a prescription of penicillin. A 10-day follow-up showed complete resolution of the skin rash.
Discussion
The rash in this case was most likely the result of scarlet fever with an unusual presentation of PSD; the signs and symptoms of which include perianal erythema, itching, rectal pain, sometimes blood-streaked stools, rectal bleeding, irritation or pruritus, tissue loss and exudation, secondary constipation, and cellulitis. Perianal streptococcal dermatitis has also been described in the adult literature.2 As with pediatric cases, PSD in adults is usually caused by GABHS.
Evaluation and Diagnosis
A rapid streptococcal test of suspicious areas can confirm the diagnosis. Fever, sore throat, and arthralgia are rare; however, culture from the perianal region grows GABHS. Titers are usually not elevated in laboratory evaluation. A routine skin culture is an alternative diagnostic aid.
Brilliant2 described the bright red color of PSD as a sharply demarcated rash that is caused by GABHS. As previously stated, symptoms include perianal rash, itching, and rectal pain; blood-streaked stools may also be seen in one-third of patients. It primarily occurs in children between 6 months and 10 years of age and is often misdiagnosed and treated inappropriately.3
Prompt diagnosis of GABHS is important. If untreated, it can cause serious systemic infections, especially in elderly and in newborn patients. Treatment with antibiotics resolves the condition in the majority of patients.2 In the acute stage, a white pseudomembrane may be present. As the rash becomes more chronic, the perianal eruption may consist of painful fissures, a dry mucoid discharge, or psoriasiform plaques. Perianal dermatitis can also be caused by Staphylococcus aureus or Candida. Confirmation of the diagnosis is accomplished by culturing a moderate-to-heavy growth of GABHS on 5% sheep-blood agar.
Treatment
A 10-day course of oral penicillin produces resolution of the dermatitis and other symptoms in most patients, but a relapse rate as high as 39% has been reported. Other treatment plans include amoxicillin, 40 mg/kg per day, divided into three doses, and/or topical applications of mupirocin 2% three times per day for 10 days. Penicillin, clindamycin phosphate, and erythromycin have also been used.
Although penicillin is generally recommended for treatment of GABHS infection, amoxicillin is often better tolerated in the pediatric population due to its superior palatability. Early antibiotic treatment causes a dramatic and rapid improvement of symptoms. However, according to Olson et al,4 PSD initially treated with amoxicillin or penicillin is consistently associated with a high risk of clinical recurrence. Whether treatment with a β-lactamase–resistant agent reduces this risk is uncertain.
Conclusion
This case represents an unusual presentation of scarlet fever manifesting as perianal dermatitis caused by GABHS. Although more common in the pediatric population, adult cases have been documented in the literature. As this case illustrates, early recognition and treatment with penicillin (or amoxicillin) produces rapid improvement and resolution of symptoms.
Dr Nibhanipudi is a professor of clinical emergency medicine at New York Medical College - Metropolitan Hospital Center, New York.
- Case Report: Perianal Streptococcal Infection
- Landolt M, Heininger U. Prevalence of perianal streptococcal dermatitis in children and adolescents [in German]. Praxis (Bern 1994). 2005;94(38):1467-1471.
- Kahlke V, Jongen J, Peleikis HG, Herbst RA. Perianal streptococcal dermatitis in adults: its association with pruritic anorectal diseases is mainly caused by group B Streptococci. Colorectal Dis. 2013;15(5):602-607.
- Brilliant LC. Perianal streptococcal dermatitis. Am Fam Physician. 2000;61(2):391-393.
- Olson D, Edmonson MB. Outcomes in children treated for perineal group A beta-hemolytic streptococcal dermatitis. Pediatr Infect Dis J. 2011;30(11):933-936.
Case
The mother of a 3-year-old boy presented her son to the ED for evaluation after she noticed peeling of the skin in his perianal region. She stated that the peeling had started 1 day prior to presentation. Two days earlier, the mother had brought the same patient to the ED for evaluation of a fever, sore throat, and a slight rash over his face. The boy’s vital signs at the initial presentation were: temperature, 101.8°F; heart rate, 102 beats/minute; and respiratory rate, 28 breaths/minute. Oxygen saturation was 98% on room air.
During this first visit, the mother denied the child having had any fever, chills, headache, sore throat, facial rash, joint pain, or pain on defecation. He had no significant medical history and no known drug allergies. After examination, a throat culture was taken, and the patient was given acetaminophen and discharged home with a diagnosis of viral syndrome.
At the second presentation, physical examination revealed a well-developed child in no distress. The examination was negative except for a 4 x 2 cm area of desquamation present over the perianal region (Figure).
The area of desquamation was dry, mildly erythematous without discharge, and nontender. The patient’s vital signs at this presentation were stable, and he was afebrile. The remaining physical examination findings were normal. The throat culture taken during the first ED presentation was reported as negative. A perianal swab was sent for culture and sensitivity. This was later reported to be positive for group A β-hemolytic streptococci (GABHS), which is sensitive to penicillin. The patient was discharged home in the care of his mother with a prescription of penicillin. A 10-day follow-up showed complete resolution of the skin rash.
Discussion
The rash in this case was most likely the result of scarlet fever with an unusual presentation of PSD; the signs and symptoms of which include perianal erythema, itching, rectal pain, sometimes blood-streaked stools, rectal bleeding, irritation or pruritus, tissue loss and exudation, secondary constipation, and cellulitis. Perianal streptococcal dermatitis has also been described in the adult literature.2 As with pediatric cases, PSD in adults is usually caused by GABHS.
Evaluation and Diagnosis
A rapid streptococcal test of suspicious areas can confirm the diagnosis. Fever, sore throat, and arthralgia are rare; however, culture from the perianal region grows GABHS. Titers are usually not elevated in laboratory evaluation. A routine skin culture is an alternative diagnostic aid.
Brilliant2 described the bright red color of PSD as a sharply demarcated rash that is caused by GABHS. As previously stated, symptoms include perianal rash, itching, and rectal pain; blood-streaked stools may also be seen in one-third of patients. It primarily occurs in children between 6 months and 10 years of age and is often misdiagnosed and treated inappropriately.3
Prompt diagnosis of GABHS is important. If untreated, it can cause serious systemic infections, especially in elderly and in newborn patients. Treatment with antibiotics resolves the condition in the majority of patients.2 In the acute stage, a white pseudomembrane may be present. As the rash becomes more chronic, the perianal eruption may consist of painful fissures, a dry mucoid discharge, or psoriasiform plaques. Perianal dermatitis can also be caused by Staphylococcus aureus or Candida. Confirmation of the diagnosis is accomplished by culturing a moderate-to-heavy growth of GABHS on 5% sheep-blood agar.
Treatment
A 10-day course of oral penicillin produces resolution of the dermatitis and other symptoms in most patients, but a relapse rate as high as 39% has been reported. Other treatment plans include amoxicillin, 40 mg/kg per day, divided into three doses, and/or topical applications of mupirocin 2% three times per day for 10 days. Penicillin, clindamycin phosphate, and erythromycin have also been used.
Although penicillin is generally recommended for treatment of GABHS infection, amoxicillin is often better tolerated in the pediatric population due to its superior palatability. Early antibiotic treatment causes a dramatic and rapid improvement of symptoms. However, according to Olson et al,4 PSD initially treated with amoxicillin or penicillin is consistently associated with a high risk of clinical recurrence. Whether treatment with a β-lactamase–resistant agent reduces this risk is uncertain.
Conclusion
This case represents an unusual presentation of scarlet fever manifesting as perianal dermatitis caused by GABHS. Although more common in the pediatric population, adult cases have been documented in the literature. As this case illustrates, early recognition and treatment with penicillin (or amoxicillin) produces rapid improvement and resolution of symptoms.
Dr Nibhanipudi is a professor of clinical emergency medicine at New York Medical College - Metropolitan Hospital Center, New York.
Case
The mother of a 3-year-old boy presented her son to the ED for evaluation after she noticed peeling of the skin in his perianal region. She stated that the peeling had started 1 day prior to presentation. Two days earlier, the mother had brought the same patient to the ED for evaluation of a fever, sore throat, and a slight rash over his face. The boy’s vital signs at the initial presentation were: temperature, 101.8°F; heart rate, 102 beats/minute; and respiratory rate, 28 breaths/minute. Oxygen saturation was 98% on room air.
During this first visit, the mother denied the child having had any fever, chills, headache, sore throat, facial rash, joint pain, or pain on defecation. He had no significant medical history and no known drug allergies. After examination, a throat culture was taken, and the patient was given acetaminophen and discharged home with a diagnosis of viral syndrome.
At the second presentation, physical examination revealed a well-developed child in no distress. The examination was negative except for a 4 x 2 cm area of desquamation present over the perianal region (Figure).
The area of desquamation was dry, mildly erythematous without discharge, and nontender. The patient’s vital signs at this presentation were stable, and he was afebrile. The remaining physical examination findings were normal. The throat culture taken during the first ED presentation was reported as negative. A perianal swab was sent for culture and sensitivity. This was later reported to be positive for group A β-hemolytic streptococci (GABHS), which is sensitive to penicillin. The patient was discharged home in the care of his mother with a prescription of penicillin. A 10-day follow-up showed complete resolution of the skin rash.
Discussion
The rash in this case was most likely the result of scarlet fever with an unusual presentation of PSD; the signs and symptoms of which include perianal erythema, itching, rectal pain, sometimes blood-streaked stools, rectal bleeding, irritation or pruritus, tissue loss and exudation, secondary constipation, and cellulitis. Perianal streptococcal dermatitis has also been described in the adult literature.2 As with pediatric cases, PSD in adults is usually caused by GABHS.
Evaluation and Diagnosis
A rapid streptococcal test of suspicious areas can confirm the diagnosis. Fever, sore throat, and arthralgia are rare; however, culture from the perianal region grows GABHS. Titers are usually not elevated in laboratory evaluation. A routine skin culture is an alternative diagnostic aid.
Brilliant2 described the bright red color of PSD as a sharply demarcated rash that is caused by GABHS. As previously stated, symptoms include perianal rash, itching, and rectal pain; blood-streaked stools may also be seen in one-third of patients. It primarily occurs in children between 6 months and 10 years of age and is often misdiagnosed and treated inappropriately.3
Prompt diagnosis of GABHS is important. If untreated, it can cause serious systemic infections, especially in elderly and in newborn patients. Treatment with antibiotics resolves the condition in the majority of patients.2 In the acute stage, a white pseudomembrane may be present. As the rash becomes more chronic, the perianal eruption may consist of painful fissures, a dry mucoid discharge, or psoriasiform plaques. Perianal dermatitis can also be caused by Staphylococcus aureus or Candida. Confirmation of the diagnosis is accomplished by culturing a moderate-to-heavy growth of GABHS on 5% sheep-blood agar.
Treatment
A 10-day course of oral penicillin produces resolution of the dermatitis and other symptoms in most patients, but a relapse rate as high as 39% has been reported. Other treatment plans include amoxicillin, 40 mg/kg per day, divided into three doses, and/or topical applications of mupirocin 2% three times per day for 10 days. Penicillin, clindamycin phosphate, and erythromycin have also been used.
Although penicillin is generally recommended for treatment of GABHS infection, amoxicillin is often better tolerated in the pediatric population due to its superior palatability. Early antibiotic treatment causes a dramatic and rapid improvement of symptoms. However, according to Olson et al,4 PSD initially treated with amoxicillin or penicillin is consistently associated with a high risk of clinical recurrence. Whether treatment with a β-lactamase–resistant agent reduces this risk is uncertain.
Conclusion
This case represents an unusual presentation of scarlet fever manifesting as perianal dermatitis caused by GABHS. Although more common in the pediatric population, adult cases have been documented in the literature. As this case illustrates, early recognition and treatment with penicillin (or amoxicillin) produces rapid improvement and resolution of symptoms.
Dr Nibhanipudi is a professor of clinical emergency medicine at New York Medical College - Metropolitan Hospital Center, New York.
- Case Report: Perianal Streptococcal Infection
- Landolt M, Heininger U. Prevalence of perianal streptococcal dermatitis in children and adolescents [in German]. Praxis (Bern 1994). 2005;94(38):1467-1471.
- Kahlke V, Jongen J, Peleikis HG, Herbst RA. Perianal streptococcal dermatitis in adults: its association with pruritic anorectal diseases is mainly caused by group B Streptococci. Colorectal Dis. 2013;15(5):602-607.
- Brilliant LC. Perianal streptococcal dermatitis. Am Fam Physician. 2000;61(2):391-393.
- Olson D, Edmonson MB. Outcomes in children treated for perineal group A beta-hemolytic streptococcal dermatitis. Pediatr Infect Dis J. 2011;30(11):933-936.
- Case Report: Perianal Streptococcal Infection
- Landolt M, Heininger U. Prevalence of perianal streptococcal dermatitis in children and adolescents [in German]. Praxis (Bern 1994). 2005;94(38):1467-1471.
- Kahlke V, Jongen J, Peleikis HG, Herbst RA. Perianal streptococcal dermatitis in adults: its association with pruritic anorectal diseases is mainly caused by group B Streptococci. Colorectal Dis. 2013;15(5):602-607.
- Brilliant LC. Perianal streptococcal dermatitis. Am Fam Physician. 2000;61(2):391-393.
- Olson D, Edmonson MB. Outcomes in children treated for perineal group A beta-hemolytic streptococcal dermatitis. Pediatr Infect Dis J. 2011;30(11):933-936.
Tool may provide new insight into pediatric cancers
and Xin Zhou, PhD
Photo by Peter Barta/St. Jude
Children’s Research Hospital
Researchers say they have developed a tool that may advance our understanding of the mutations that drive pediatric cancers.
The tool, called ProteinPaint, is a web application that allows the user to visualize genetic lesions and RNA expression in pediatric cancers.
ProteinPaint’s infographics let users see all mutations in individual genes and their corresponding proteins, including detailed information about mutation type, frequency in cancer subtype, and location in the protein domain.
That information provides clues about how a change might contribute to cancer’s start, progression, or relapse.
Jinghui Zhang, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and her colleagues described ProteinPaint in a letter to Nature Genetics.
ProteinPaint currently integrates information from 5 studies, but Dr Zhang and her colleagues said the data will be updated as new studies are published.
ProteinPaint now includes information on almost 27,500 mutations discovered in more than 1000 pediatric patients with 21 cancer subtypes. The application also includes RNA-sequencing data from 928 pediatric tumors belonging to 36 different subtypes.
Xin Zhou, PhD, also of St. Jude, developed ProteinPaint’s infographics to display the genomic information in an interactive format. A click of the mouse gives users additional details about the mutations listed, including the pediatric cancer subtype where the change has been validated and a link to the publication.
“ProteinPaint’s focus on pediatric cancer and presentation of mutations at the gene level complements existing cancer genome data portals,” Dr Zhang said. “For St. Jude, the application is the foundation for developing a global reference database for information about pediatric cancer.”
Dr Zhou added that the ProteinPaint software has the potential to help researchers studying other disorders, including sickle cell disease, that involve a mutation that affects protein function.
ProteinPaint is available at no cost to academic researchers who are free to use the tool to analyze their own data. The application also lets researchers compare information about pediatric and adult cancer genomes by providing a parallel view of data from COSMIC, the world’s largest database of somatic mutations, primarily from adult cancer.
ProteinPaint has already been used to study the role played by germline mutations in pediatric cancers. That research was published in NEJM in November.
More information about ProteinPaint is available on the St. Jude PeCan Data Portal.
and Xin Zhou, PhD
Photo by Peter Barta/St. Jude
Children’s Research Hospital
Researchers say they have developed a tool that may advance our understanding of the mutations that drive pediatric cancers.
The tool, called ProteinPaint, is a web application that allows the user to visualize genetic lesions and RNA expression in pediatric cancers.
ProteinPaint’s infographics let users see all mutations in individual genes and their corresponding proteins, including detailed information about mutation type, frequency in cancer subtype, and location in the protein domain.
That information provides clues about how a change might contribute to cancer’s start, progression, or relapse.
Jinghui Zhang, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and her colleagues described ProteinPaint in a letter to Nature Genetics.
ProteinPaint currently integrates information from 5 studies, but Dr Zhang and her colleagues said the data will be updated as new studies are published.
ProteinPaint now includes information on almost 27,500 mutations discovered in more than 1000 pediatric patients with 21 cancer subtypes. The application also includes RNA-sequencing data from 928 pediatric tumors belonging to 36 different subtypes.
Xin Zhou, PhD, also of St. Jude, developed ProteinPaint’s infographics to display the genomic information in an interactive format. A click of the mouse gives users additional details about the mutations listed, including the pediatric cancer subtype where the change has been validated and a link to the publication.
“ProteinPaint’s focus on pediatric cancer and presentation of mutations at the gene level complements existing cancer genome data portals,” Dr Zhang said. “For St. Jude, the application is the foundation for developing a global reference database for information about pediatric cancer.”
Dr Zhou added that the ProteinPaint software has the potential to help researchers studying other disorders, including sickle cell disease, that involve a mutation that affects protein function.
ProteinPaint is available at no cost to academic researchers who are free to use the tool to analyze their own data. The application also lets researchers compare information about pediatric and adult cancer genomes by providing a parallel view of data from COSMIC, the world’s largest database of somatic mutations, primarily from adult cancer.
ProteinPaint has already been used to study the role played by germline mutations in pediatric cancers. That research was published in NEJM in November.
More information about ProteinPaint is available on the St. Jude PeCan Data Portal.
and Xin Zhou, PhD
Photo by Peter Barta/St. Jude
Children’s Research Hospital
Researchers say they have developed a tool that may advance our understanding of the mutations that drive pediatric cancers.
The tool, called ProteinPaint, is a web application that allows the user to visualize genetic lesions and RNA expression in pediatric cancers.
ProteinPaint’s infographics let users see all mutations in individual genes and their corresponding proteins, including detailed information about mutation type, frequency in cancer subtype, and location in the protein domain.
That information provides clues about how a change might contribute to cancer’s start, progression, or relapse.
Jinghui Zhang, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and her colleagues described ProteinPaint in a letter to Nature Genetics.
ProteinPaint currently integrates information from 5 studies, but Dr Zhang and her colleagues said the data will be updated as new studies are published.
ProteinPaint now includes information on almost 27,500 mutations discovered in more than 1000 pediatric patients with 21 cancer subtypes. The application also includes RNA-sequencing data from 928 pediatric tumors belonging to 36 different subtypes.
Xin Zhou, PhD, also of St. Jude, developed ProteinPaint’s infographics to display the genomic information in an interactive format. A click of the mouse gives users additional details about the mutations listed, including the pediatric cancer subtype where the change has been validated and a link to the publication.
“ProteinPaint’s focus on pediatric cancer and presentation of mutations at the gene level complements existing cancer genome data portals,” Dr Zhang said. “For St. Jude, the application is the foundation for developing a global reference database for information about pediatric cancer.”
Dr Zhou added that the ProteinPaint software has the potential to help researchers studying other disorders, including sickle cell disease, that involve a mutation that affects protein function.
ProteinPaint is available at no cost to academic researchers who are free to use the tool to analyze their own data. The application also lets researchers compare information about pediatric and adult cancer genomes by providing a parallel view of data from COSMIC, the world’s largest database of somatic mutations, primarily from adult cancer.
ProteinPaint has already been used to study the role played by germline mutations in pediatric cancers. That research was published in NEJM in November.
More information about ProteinPaint is available on the St. Jude PeCan Data Portal.