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Behavioral sleep intervention linked to sleep improvement in infants
(BSI) in a real-world setting, Sarah M. Honaker, PhD, of Indiana University, Indianapolis, and her associates, reported in the Journal of Pediatrics.
In a study of 652 parents who participated, parents started BSI when their infants were as young as less than 1 month of age and as late as 18 months of age. Most parents started BSI at 3-5 months.
Crying generally was greatest the first night, occurring in 45% of cases when all BSI approaches were considered. It lasted a mean 43 minutes, which dropped significantly after 1 week to a mean 9 minutes (P less than .001). Crying was considered most intense (on a 1-5 scale) on the initial night of BSI, a mean 4.42, and this “was equally true for all of the BSI approaches,” Dr. Honaker and her colleagues wrote.
In most cases, the parents’ first attempt at BSI worked (83%). Success varied by BSI approach, with the highest first attempt success rate in the unmodified extinction group (90%), followed by parental presence without support (83%), modified extinction (81%), and parental presence with support (65%). Eventually, 27% of parents were successful with a different approach than the one with which they started. Most commonly, they changed from modified extinction to unmodified extinction (66% of those who changed approaches).
“The majority of parents report successfully implementing BSI at a variety of ages across infancy, primarily using extinction-based approaches,” the researchers concluded. “Few significant differences were found between approaches, suggesting that health providers should offer parents options for BSI implementation.”
SOURCE: Honaker SM et al., J Pediatr. 2018. doi: 10.1016/j.jpeds.2018.04.009.
(BSI) in a real-world setting, Sarah M. Honaker, PhD, of Indiana University, Indianapolis, and her associates, reported in the Journal of Pediatrics.
In a study of 652 parents who participated, parents started BSI when their infants were as young as less than 1 month of age and as late as 18 months of age. Most parents started BSI at 3-5 months.
Crying generally was greatest the first night, occurring in 45% of cases when all BSI approaches were considered. It lasted a mean 43 minutes, which dropped significantly after 1 week to a mean 9 minutes (P less than .001). Crying was considered most intense (on a 1-5 scale) on the initial night of BSI, a mean 4.42, and this “was equally true for all of the BSI approaches,” Dr. Honaker and her colleagues wrote.
In most cases, the parents’ first attempt at BSI worked (83%). Success varied by BSI approach, with the highest first attempt success rate in the unmodified extinction group (90%), followed by parental presence without support (83%), modified extinction (81%), and parental presence with support (65%). Eventually, 27% of parents were successful with a different approach than the one with which they started. Most commonly, they changed from modified extinction to unmodified extinction (66% of those who changed approaches).
“The majority of parents report successfully implementing BSI at a variety of ages across infancy, primarily using extinction-based approaches,” the researchers concluded. “Few significant differences were found between approaches, suggesting that health providers should offer parents options for BSI implementation.”
SOURCE: Honaker SM et al., J Pediatr. 2018. doi: 10.1016/j.jpeds.2018.04.009.
(BSI) in a real-world setting, Sarah M. Honaker, PhD, of Indiana University, Indianapolis, and her associates, reported in the Journal of Pediatrics.
In a study of 652 parents who participated, parents started BSI when their infants were as young as less than 1 month of age and as late as 18 months of age. Most parents started BSI at 3-5 months.
Crying generally was greatest the first night, occurring in 45% of cases when all BSI approaches were considered. It lasted a mean 43 minutes, which dropped significantly after 1 week to a mean 9 minutes (P less than .001). Crying was considered most intense (on a 1-5 scale) on the initial night of BSI, a mean 4.42, and this “was equally true for all of the BSI approaches,” Dr. Honaker and her colleagues wrote.
In most cases, the parents’ first attempt at BSI worked (83%). Success varied by BSI approach, with the highest first attempt success rate in the unmodified extinction group (90%), followed by parental presence without support (83%), modified extinction (81%), and parental presence with support (65%). Eventually, 27% of parents were successful with a different approach than the one with which they started. Most commonly, they changed from modified extinction to unmodified extinction (66% of those who changed approaches).
“The majority of parents report successfully implementing BSI at a variety of ages across infancy, primarily using extinction-based approaches,” the researchers concluded. “Few significant differences were found between approaches, suggesting that health providers should offer parents options for BSI implementation.”
SOURCE: Honaker SM et al., J Pediatr. 2018. doi: 10.1016/j.jpeds.2018.04.009.
FROM THE JOURNAL OF PEDIATRICS
Drug-related deaths continue to rise in United States
TORONTO – Drug-related deaths in America are rising faster than ever.
Rear Adm. Wanda D. Barfield, MD shared recent data from the U.S. National Center for Health Statistics on people aged 15 years and older at the Pediatric Academic Societies annual meeting. Between 1999 and 2016, for example, the number of drug overdose deaths rose more than threefold, from 6.1/100,000 standard population in 1999 to 19.8/100,000 in 2016. For males, the rate increased from 8.2/100,000 in 1999 to 26.2/100,000 in 2016. For females, the rate increased from 3.9/100,000 in 1999 to 13.4/100,000 in 2016.
Dr. Barfield, director of the division of reproductive health at the Centers for Disease Control and Prevention, said that in 2016, the NCHS also found that 22 states and the District of Columbia had drug overdoses that were significantly higher than the national average. The states with the highest number of drug overdose deaths were the District of Columbia, New Hampshire, Pennsylvania, and West Virginia while the states with the lowest observed rates were Nebraska, North Dakota, South Dakota, and Texas.
“Many of these drug overdose deaths are linked to opioids, but not exclusively,” Dr. Barfield said. “In the past, the overall opioid-related overdose deaths were mainly attributed to commonly prescribed opioid medications. However, in recent years, we’re seeing more deaths due to illicit drugs such as heroin and fentanyl.”
The NCHS found that the age-adjusted rate for drug overdose deaths involving synthetic opioids other than methadone doubled from 2015 to 2016, and that drug overdose deaths involving synthetic opioids other than methadone increased from 0.3/100,000 in 1999 to 6.2/100,000 in 2016. The rate increased an average of 18% per year from 1999 to 2006, remained steady from 2006 to 2013, but increased by 88% per year from 2013 to 2016. At the same time, drug overdose deaths involving heroin increased from 0.7/100,000 in 1999 to 1/100,000 in 2010, to 4.9/100,000 in 2016.
According to Dr. Barfield, the spike in opioid use since 1999 stems directly from increased prescribing rates. “In 2015, the number of opioids prescribed was enough so that every American could be medicated around the clock for 3 weeks,” she said. “In addition to the number of prescriptions, the average day’s supply of prescription opioids increased from 2006 to 2015, from 13.3 days in 2006 to 17.7 days in 2015.” What’s more, a recent CDC Vital Signs found that the amount of opioids prescribed per person varied widely among U.S. counties in 2015. “The wide variation among counties suggests a lack of consistency among providers when prescribing opioids,” Dr. Barfield said. “It’s concerning, as higher opioid prescribing puts patients at risk for addiction.”
At the same time, opioid overdose ED visits continue to rise. Data from the CDC’s National Syndromic Surveillance Program found that from July 2016 to September 2017, opioid overdose ED visits increased by 30% for men, by 24% for women, and for all adult age groups (31% among those aged 25-34 years, 36% among those aged 35-54 years, and 32% among those aged 55 years and older).
There’s a problem of prescription opioid use among pregnant women. Published estimates indicate that 14%-22% of women filled an opioid prescription during pregnancy, Dr. Barfield said. Among pregnant women, the prevalence of maternal opioid use or dependence during hospitalization for delivery has increased 127%, from 1.7 /1,000 delivery admissions in 1998 to 3.9/1,000 delivery admissions in 2011 (Anesthesiology 2014;121[6]:1158-65). There also has been a significant increase in neonatal abstinence syndrome (NAS), which is most commonly attributed to opioid exposure during pregnancy, from 1.2/1,000 U.S. hospital births in 2000 to 8/1,000 U.S. hospital births in 2014. “NAS is still on the rise,” Dr. Barfield said. “In 2012, we saw one baby with NAS born every 25 minutes. In 2014, that number jumped to one baby born with NAS every 15 minutes. That means about 96 infants with NAS are born daily,” she said. “Where do you think we’re going to be when we look at 2018 data?”
Role for pediatricians
Dr. Barfield closed her presentation by underscoring the role pediatricians play in counseling patients about opioid abuse or dependence during pregnancy. “We know that providers have a tremendous impact on patients and their families,” she said. “We also know that issues leading to a newborn having NAS are complex, so adopting a public health approach focused on prevention, expansion of treatment, and improvements in child welfare systems is vital.” Specifically, she said, health care providers can “bridge the gap” between clinical care and public health; lead in their communities, not just within their hospital or practice; work as a team member with colleagues in other fields of medicine such as obstetrics, family medicine, and addiction care when caring for infants with NAS, and by considering the social determinants of health.
“One way to adopt a public health perspective is to remember that the health of the fetus and baby rely on more than just prenatal care,” Dr. Barfield said. “We’re all part of a larger whole, surrounded by our families, communities, regions, state, and even our countries of origin. What’s going on with the mom, her family, and the larger community impacts the baby’s health. In other words, the social determinants of health matter, and are an important part of the conversation on NAS.”
She reported having no financial disclosures.
TORONTO – Drug-related deaths in America are rising faster than ever.
Rear Adm. Wanda D. Barfield, MD shared recent data from the U.S. National Center for Health Statistics on people aged 15 years and older at the Pediatric Academic Societies annual meeting. Between 1999 and 2016, for example, the number of drug overdose deaths rose more than threefold, from 6.1/100,000 standard population in 1999 to 19.8/100,000 in 2016. For males, the rate increased from 8.2/100,000 in 1999 to 26.2/100,000 in 2016. For females, the rate increased from 3.9/100,000 in 1999 to 13.4/100,000 in 2016.
Dr. Barfield, director of the division of reproductive health at the Centers for Disease Control and Prevention, said that in 2016, the NCHS also found that 22 states and the District of Columbia had drug overdoses that were significantly higher than the national average. The states with the highest number of drug overdose deaths were the District of Columbia, New Hampshire, Pennsylvania, and West Virginia while the states with the lowest observed rates were Nebraska, North Dakota, South Dakota, and Texas.
“Many of these drug overdose deaths are linked to opioids, but not exclusively,” Dr. Barfield said. “In the past, the overall opioid-related overdose deaths were mainly attributed to commonly prescribed opioid medications. However, in recent years, we’re seeing more deaths due to illicit drugs such as heroin and fentanyl.”
The NCHS found that the age-adjusted rate for drug overdose deaths involving synthetic opioids other than methadone doubled from 2015 to 2016, and that drug overdose deaths involving synthetic opioids other than methadone increased from 0.3/100,000 in 1999 to 6.2/100,000 in 2016. The rate increased an average of 18% per year from 1999 to 2006, remained steady from 2006 to 2013, but increased by 88% per year from 2013 to 2016. At the same time, drug overdose deaths involving heroin increased from 0.7/100,000 in 1999 to 1/100,000 in 2010, to 4.9/100,000 in 2016.
According to Dr. Barfield, the spike in opioid use since 1999 stems directly from increased prescribing rates. “In 2015, the number of opioids prescribed was enough so that every American could be medicated around the clock for 3 weeks,” she said. “In addition to the number of prescriptions, the average day’s supply of prescription opioids increased from 2006 to 2015, from 13.3 days in 2006 to 17.7 days in 2015.” What’s more, a recent CDC Vital Signs found that the amount of opioids prescribed per person varied widely among U.S. counties in 2015. “The wide variation among counties suggests a lack of consistency among providers when prescribing opioids,” Dr. Barfield said. “It’s concerning, as higher opioid prescribing puts patients at risk for addiction.”
At the same time, opioid overdose ED visits continue to rise. Data from the CDC’s National Syndromic Surveillance Program found that from July 2016 to September 2017, opioid overdose ED visits increased by 30% for men, by 24% for women, and for all adult age groups (31% among those aged 25-34 years, 36% among those aged 35-54 years, and 32% among those aged 55 years and older).
There’s a problem of prescription opioid use among pregnant women. Published estimates indicate that 14%-22% of women filled an opioid prescription during pregnancy, Dr. Barfield said. Among pregnant women, the prevalence of maternal opioid use or dependence during hospitalization for delivery has increased 127%, from 1.7 /1,000 delivery admissions in 1998 to 3.9/1,000 delivery admissions in 2011 (Anesthesiology 2014;121[6]:1158-65). There also has been a significant increase in neonatal abstinence syndrome (NAS), which is most commonly attributed to opioid exposure during pregnancy, from 1.2/1,000 U.S. hospital births in 2000 to 8/1,000 U.S. hospital births in 2014. “NAS is still on the rise,” Dr. Barfield said. “In 2012, we saw one baby with NAS born every 25 minutes. In 2014, that number jumped to one baby born with NAS every 15 minutes. That means about 96 infants with NAS are born daily,” she said. “Where do you think we’re going to be when we look at 2018 data?”
Role for pediatricians
Dr. Barfield closed her presentation by underscoring the role pediatricians play in counseling patients about opioid abuse or dependence during pregnancy. “We know that providers have a tremendous impact on patients and their families,” she said. “We also know that issues leading to a newborn having NAS are complex, so adopting a public health approach focused on prevention, expansion of treatment, and improvements in child welfare systems is vital.” Specifically, she said, health care providers can “bridge the gap” between clinical care and public health; lead in their communities, not just within their hospital or practice; work as a team member with colleagues in other fields of medicine such as obstetrics, family medicine, and addiction care when caring for infants with NAS, and by considering the social determinants of health.
“One way to adopt a public health perspective is to remember that the health of the fetus and baby rely on more than just prenatal care,” Dr. Barfield said. “We’re all part of a larger whole, surrounded by our families, communities, regions, state, and even our countries of origin. What’s going on with the mom, her family, and the larger community impacts the baby’s health. In other words, the social determinants of health matter, and are an important part of the conversation on NAS.”
She reported having no financial disclosures.
TORONTO – Drug-related deaths in America are rising faster than ever.
Rear Adm. Wanda D. Barfield, MD shared recent data from the U.S. National Center for Health Statistics on people aged 15 years and older at the Pediatric Academic Societies annual meeting. Between 1999 and 2016, for example, the number of drug overdose deaths rose more than threefold, from 6.1/100,000 standard population in 1999 to 19.8/100,000 in 2016. For males, the rate increased from 8.2/100,000 in 1999 to 26.2/100,000 in 2016. For females, the rate increased from 3.9/100,000 in 1999 to 13.4/100,000 in 2016.
Dr. Barfield, director of the division of reproductive health at the Centers for Disease Control and Prevention, said that in 2016, the NCHS also found that 22 states and the District of Columbia had drug overdoses that were significantly higher than the national average. The states with the highest number of drug overdose deaths were the District of Columbia, New Hampshire, Pennsylvania, and West Virginia while the states with the lowest observed rates were Nebraska, North Dakota, South Dakota, and Texas.
“Many of these drug overdose deaths are linked to opioids, but not exclusively,” Dr. Barfield said. “In the past, the overall opioid-related overdose deaths were mainly attributed to commonly prescribed opioid medications. However, in recent years, we’re seeing more deaths due to illicit drugs such as heroin and fentanyl.”
The NCHS found that the age-adjusted rate for drug overdose deaths involving synthetic opioids other than methadone doubled from 2015 to 2016, and that drug overdose deaths involving synthetic opioids other than methadone increased from 0.3/100,000 in 1999 to 6.2/100,000 in 2016. The rate increased an average of 18% per year from 1999 to 2006, remained steady from 2006 to 2013, but increased by 88% per year from 2013 to 2016. At the same time, drug overdose deaths involving heroin increased from 0.7/100,000 in 1999 to 1/100,000 in 2010, to 4.9/100,000 in 2016.
According to Dr. Barfield, the spike in opioid use since 1999 stems directly from increased prescribing rates. “In 2015, the number of opioids prescribed was enough so that every American could be medicated around the clock for 3 weeks,” she said. “In addition to the number of prescriptions, the average day’s supply of prescription opioids increased from 2006 to 2015, from 13.3 days in 2006 to 17.7 days in 2015.” What’s more, a recent CDC Vital Signs found that the amount of opioids prescribed per person varied widely among U.S. counties in 2015. “The wide variation among counties suggests a lack of consistency among providers when prescribing opioids,” Dr. Barfield said. “It’s concerning, as higher opioid prescribing puts patients at risk for addiction.”
At the same time, opioid overdose ED visits continue to rise. Data from the CDC’s National Syndromic Surveillance Program found that from July 2016 to September 2017, opioid overdose ED visits increased by 30% for men, by 24% for women, and for all adult age groups (31% among those aged 25-34 years, 36% among those aged 35-54 years, and 32% among those aged 55 years and older).
There’s a problem of prescription opioid use among pregnant women. Published estimates indicate that 14%-22% of women filled an opioid prescription during pregnancy, Dr. Barfield said. Among pregnant women, the prevalence of maternal opioid use or dependence during hospitalization for delivery has increased 127%, from 1.7 /1,000 delivery admissions in 1998 to 3.9/1,000 delivery admissions in 2011 (Anesthesiology 2014;121[6]:1158-65). There also has been a significant increase in neonatal abstinence syndrome (NAS), which is most commonly attributed to opioid exposure during pregnancy, from 1.2/1,000 U.S. hospital births in 2000 to 8/1,000 U.S. hospital births in 2014. “NAS is still on the rise,” Dr. Barfield said. “In 2012, we saw one baby with NAS born every 25 minutes. In 2014, that number jumped to one baby born with NAS every 15 minutes. That means about 96 infants with NAS are born daily,” she said. “Where do you think we’re going to be when we look at 2018 data?”
Role for pediatricians
Dr. Barfield closed her presentation by underscoring the role pediatricians play in counseling patients about opioid abuse or dependence during pregnancy. “We know that providers have a tremendous impact on patients and their families,” she said. “We also know that issues leading to a newborn having NAS are complex, so adopting a public health approach focused on prevention, expansion of treatment, and improvements in child welfare systems is vital.” Specifically, she said, health care providers can “bridge the gap” between clinical care and public health; lead in their communities, not just within their hospital or practice; work as a team member with colleagues in other fields of medicine such as obstetrics, family medicine, and addiction care when caring for infants with NAS, and by considering the social determinants of health.
“One way to adopt a public health perspective is to remember that the health of the fetus and baby rely on more than just prenatal care,” Dr. Barfield said. “We’re all part of a larger whole, surrounded by our families, communities, regions, state, and even our countries of origin. What’s going on with the mom, her family, and the larger community impacts the baby’s health. In other words, the social determinants of health matter, and are an important part of the conversation on NAS.”
She reported having no financial disclosures.
EXPERT ANALYSIS FROM PAS 2018
Trends in teen consumption of sports drinks are up and down
Although daily consumption of sports drinks decreased from 2010 to 2015 among teenagers, sugar-sweetened sports drinks still are popular, with numerous high school students drinking them at least weekly, said Kyla Cordery of the Steven and Alexandra Cohen Children’s Medical Center of New York, Lake Success, N.Y., and her associates.
Yet sports drink consumption in the previous week increased from 58% in 2010 to 60% in 2015 (P = .0002). And daily consumption of sports drinks also increased among teenagers watching television for more than 2 hours per day and among obese teens.
Boys were more than twice as likely as girls to drink one of more sports drinks daily (19% vs. 9%), as were more athletic/active children than those weren’t very athletic/active (18% vs. 10%).
“ Like many sugar-sweetened beverages, the excessive consumption of sports drinks is associated with weight gain, dental erosion, obesity, poor nutrition, and diabetes,” Ms. Cordery and her associates wrote. “The America Academy of Pediatrics’ Committee on Nutrition and Council on Sports Medicine and Fitness stated that the level of physical activity of the average child does not require the electrolyte replenishment offered by sports drinks.” Rehydration with water should be encouraged for most sports-related activities.
SOURCE: Cordery K et al. doi: 10.1542/peds.2017-2784.
Although daily consumption of sports drinks decreased from 2010 to 2015 among teenagers, sugar-sweetened sports drinks still are popular, with numerous high school students drinking them at least weekly, said Kyla Cordery of the Steven and Alexandra Cohen Children’s Medical Center of New York, Lake Success, N.Y., and her associates.
Yet sports drink consumption in the previous week increased from 58% in 2010 to 60% in 2015 (P = .0002). And daily consumption of sports drinks also increased among teenagers watching television for more than 2 hours per day and among obese teens.
Boys were more than twice as likely as girls to drink one of more sports drinks daily (19% vs. 9%), as were more athletic/active children than those weren’t very athletic/active (18% vs. 10%).
“ Like many sugar-sweetened beverages, the excessive consumption of sports drinks is associated with weight gain, dental erosion, obesity, poor nutrition, and diabetes,” Ms. Cordery and her associates wrote. “The America Academy of Pediatrics’ Committee on Nutrition and Council on Sports Medicine and Fitness stated that the level of physical activity of the average child does not require the electrolyte replenishment offered by sports drinks.” Rehydration with water should be encouraged for most sports-related activities.
SOURCE: Cordery K et al. doi: 10.1542/peds.2017-2784.
Although daily consumption of sports drinks decreased from 2010 to 2015 among teenagers, sugar-sweetened sports drinks still are popular, with numerous high school students drinking them at least weekly, said Kyla Cordery of the Steven and Alexandra Cohen Children’s Medical Center of New York, Lake Success, N.Y., and her associates.
Yet sports drink consumption in the previous week increased from 58% in 2010 to 60% in 2015 (P = .0002). And daily consumption of sports drinks also increased among teenagers watching television for more than 2 hours per day and among obese teens.
Boys were more than twice as likely as girls to drink one of more sports drinks daily (19% vs. 9%), as were more athletic/active children than those weren’t very athletic/active (18% vs. 10%).
“ Like many sugar-sweetened beverages, the excessive consumption of sports drinks is associated with weight gain, dental erosion, obesity, poor nutrition, and diabetes,” Ms. Cordery and her associates wrote. “The America Academy of Pediatrics’ Committee on Nutrition and Council on Sports Medicine and Fitness stated that the level of physical activity of the average child does not require the electrolyte replenishment offered by sports drinks.” Rehydration with water should be encouraged for most sports-related activities.
SOURCE: Cordery K et al. doi: 10.1542/peds.2017-2784.
FROM PEDIATRICS
The double-edged sword
Veterinarians and farmers have known it for decades. If you give a herd or flock antibiotics, its members grow better and have a better survival rate than an equivalent group of unmedicated animals. The economic benefits of administering antibiotics are so great that until very recently the practice has been the norm. However, the “everything organic” movement has begun to turn the tide as more consumers have become aware of the hazards inherent in the agricultural use of antibiotics.
Following this conservative and prudent party line can be difficult, and few of us can claim to have never sinned and written a less-than-defensible prescription for an antibiotic. However, for physicians who work in places where the mortality rate for children under age 5 years can be as high as 25%, the temptation to treat the entire population with an antibiotic must be very real.
When decreased early-childhood mortality was observed in several populations that had been given prophylactic azithromycin for trachoma, a group of scientists from the University of California, San Francisco, were prompted to take a longer look at the phenomenon (“Azithromycin to Reduce Childhood Mortality in Sub-Saharan Africa,” N Engl J Med. 2018 Apr 26;378[17]:1583-92). Almost 200,000 children aged 1 month to 5 years in Niger, Malawi, and Tanzania were enrolled in the study. Half received a single dose of azithromycin every 6 months for 2 years. Overall, the mortality rate was 14% lower in the experimental group (P less than .001) and 25% lower in the children aged 1-5 months. Most of the effect was observed in Niger where only one in four children live until their fifth birthday.
Like any good experiment, this study raises more questions than it answers. Will the emergence of antibiotic resistance make broader application of the strategy impractical? Keenan et al. refer to previous trachoma treatment programs in which resistance occurred but seemed to recede when the programs were halted. What conditions were being treated successfully but blindly? Respiratory disease, diarrhea illness, and malaria are most prevalent and are the likely suspects. The authors acknowledge that more studies need to be done.
And of course, we must remember that, when it comes to antibiotic resistance, ultimately we are all neighbors.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.
Veterinarians and farmers have known it for decades. If you give a herd or flock antibiotics, its members grow better and have a better survival rate than an equivalent group of unmedicated animals. The economic benefits of administering antibiotics are so great that until very recently the practice has been the norm. However, the “everything organic” movement has begun to turn the tide as more consumers have become aware of the hazards inherent in the agricultural use of antibiotics.
Following this conservative and prudent party line can be difficult, and few of us can claim to have never sinned and written a less-than-defensible prescription for an antibiotic. However, for physicians who work in places where the mortality rate for children under age 5 years can be as high as 25%, the temptation to treat the entire population with an antibiotic must be very real.
When decreased early-childhood mortality was observed in several populations that had been given prophylactic azithromycin for trachoma, a group of scientists from the University of California, San Francisco, were prompted to take a longer look at the phenomenon (“Azithromycin to Reduce Childhood Mortality in Sub-Saharan Africa,” N Engl J Med. 2018 Apr 26;378[17]:1583-92). Almost 200,000 children aged 1 month to 5 years in Niger, Malawi, and Tanzania were enrolled in the study. Half received a single dose of azithromycin every 6 months for 2 years. Overall, the mortality rate was 14% lower in the experimental group (P less than .001) and 25% lower in the children aged 1-5 months. Most of the effect was observed in Niger where only one in four children live until their fifth birthday.
Like any good experiment, this study raises more questions than it answers. Will the emergence of antibiotic resistance make broader application of the strategy impractical? Keenan et al. refer to previous trachoma treatment programs in which resistance occurred but seemed to recede when the programs were halted. What conditions were being treated successfully but blindly? Respiratory disease, diarrhea illness, and malaria are most prevalent and are the likely suspects. The authors acknowledge that more studies need to be done.
And of course, we must remember that, when it comes to antibiotic resistance, ultimately we are all neighbors.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.
Veterinarians and farmers have known it for decades. If you give a herd or flock antibiotics, its members grow better and have a better survival rate than an equivalent group of unmedicated animals. The economic benefits of administering antibiotics are so great that until very recently the practice has been the norm. However, the “everything organic” movement has begun to turn the tide as more consumers have become aware of the hazards inherent in the agricultural use of antibiotics.
Following this conservative and prudent party line can be difficult, and few of us can claim to have never sinned and written a less-than-defensible prescription for an antibiotic. However, for physicians who work in places where the mortality rate for children under age 5 years can be as high as 25%, the temptation to treat the entire population with an antibiotic must be very real.
When decreased early-childhood mortality was observed in several populations that had been given prophylactic azithromycin for trachoma, a group of scientists from the University of California, San Francisco, were prompted to take a longer look at the phenomenon (“Azithromycin to Reduce Childhood Mortality in Sub-Saharan Africa,” N Engl J Med. 2018 Apr 26;378[17]:1583-92). Almost 200,000 children aged 1 month to 5 years in Niger, Malawi, and Tanzania were enrolled in the study. Half received a single dose of azithromycin every 6 months for 2 years. Overall, the mortality rate was 14% lower in the experimental group (P less than .001) and 25% lower in the children aged 1-5 months. Most of the effect was observed in Niger where only one in four children live until their fifth birthday.
Like any good experiment, this study raises more questions than it answers. Will the emergence of antibiotic resistance make broader application of the strategy impractical? Keenan et al. refer to previous trachoma treatment programs in which resistance occurred but seemed to recede when the programs were halted. What conditions were being treated successfully but blindly? Respiratory disease, diarrhea illness, and malaria are most prevalent and are the likely suspects. The authors acknowledge that more studies need to be done.
And of course, we must remember that, when it comes to antibiotic resistance, ultimately we are all neighbors.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.
Guidelines-based intervention improves pediatrician management of acne
A guidelines-based educational program on treating acne in teenagers has led to significant improvements in pediatricians’ management of the condition and decreased referrals to dermatologists, new research suggests.
A research letter published online May in the Journal of the American Academy of Dermatology described the results of a study involving 116 pediatricians, who participated in an educational program, including brief live sessions, on how to manage acne in teenagers.
After 4 months, researchers saw that acne-coded visits to pediatricians increased by 18% (P less than .001), but this did not translate to more work for the physicians involved; instead, three-quarters of those involved said the treatment process involved “minimal to no work.”
At the same time, the intervention was associated with a 26% decrease in the percentage of acne referrals to dermatologists, reported Jenna Borok of the Rady Children’s Hospital in San Diego, and her coauthors.
The researchers saw a fivefold increase in the likelihood of pediatricians prescribing retinoids (P = .003), after controlling for confounding factors such as sex and insurance status, and significantly less topical clindamycin being prescribed.
The study was initiated to address what the authors described as a “practice gap” between pediatricians treating acne, compared with dermatologists treating acne, which included significantly lower prescribing rates of topical retinoids among pediatricians.
Ms. Borok and her coauthors wrote that their educational program and prescribing tool aimed to address this practice gap without increasing the workload for pediatricians or dermatologists. “Adherence to guidelines by pediatricians has the potential to improve treatment provided in the primary care setting, better patient satisfaction, and allow greater access to dermatologists and pediatric dermatologists for patients with more severe acne and other conditions.”
Acknowledging that the study took place over a relatively short period of time, the authors said future research would examine the impact of the educational program and ordering tool on patient acne outcomes.
No funding or conflicts of interest were declared.
SOURCE: Borok J et al. J Am Acad Dermatol. 2018 May 9. doi: 10.1016/j.jaad.2018.04.055.
A guidelines-based educational program on treating acne in teenagers has led to significant improvements in pediatricians’ management of the condition and decreased referrals to dermatologists, new research suggests.
A research letter published online May in the Journal of the American Academy of Dermatology described the results of a study involving 116 pediatricians, who participated in an educational program, including brief live sessions, on how to manage acne in teenagers.
After 4 months, researchers saw that acne-coded visits to pediatricians increased by 18% (P less than .001), but this did not translate to more work for the physicians involved; instead, three-quarters of those involved said the treatment process involved “minimal to no work.”
At the same time, the intervention was associated with a 26% decrease in the percentage of acne referrals to dermatologists, reported Jenna Borok of the Rady Children’s Hospital in San Diego, and her coauthors.
The researchers saw a fivefold increase in the likelihood of pediatricians prescribing retinoids (P = .003), after controlling for confounding factors such as sex and insurance status, and significantly less topical clindamycin being prescribed.
The study was initiated to address what the authors described as a “practice gap” between pediatricians treating acne, compared with dermatologists treating acne, which included significantly lower prescribing rates of topical retinoids among pediatricians.
Ms. Borok and her coauthors wrote that their educational program and prescribing tool aimed to address this practice gap without increasing the workload for pediatricians or dermatologists. “Adherence to guidelines by pediatricians has the potential to improve treatment provided in the primary care setting, better patient satisfaction, and allow greater access to dermatologists and pediatric dermatologists for patients with more severe acne and other conditions.”
Acknowledging that the study took place over a relatively short period of time, the authors said future research would examine the impact of the educational program and ordering tool on patient acne outcomes.
No funding or conflicts of interest were declared.
SOURCE: Borok J et al. J Am Acad Dermatol. 2018 May 9. doi: 10.1016/j.jaad.2018.04.055.
A guidelines-based educational program on treating acne in teenagers has led to significant improvements in pediatricians’ management of the condition and decreased referrals to dermatologists, new research suggests.
A research letter published online May in the Journal of the American Academy of Dermatology described the results of a study involving 116 pediatricians, who participated in an educational program, including brief live sessions, on how to manage acne in teenagers.
After 4 months, researchers saw that acne-coded visits to pediatricians increased by 18% (P less than .001), but this did not translate to more work for the physicians involved; instead, three-quarters of those involved said the treatment process involved “minimal to no work.”
At the same time, the intervention was associated with a 26% decrease in the percentage of acne referrals to dermatologists, reported Jenna Borok of the Rady Children’s Hospital in San Diego, and her coauthors.
The researchers saw a fivefold increase in the likelihood of pediatricians prescribing retinoids (P = .003), after controlling for confounding factors such as sex and insurance status, and significantly less topical clindamycin being prescribed.
The study was initiated to address what the authors described as a “practice gap” between pediatricians treating acne, compared with dermatologists treating acne, which included significantly lower prescribing rates of topical retinoids among pediatricians.
Ms. Borok and her coauthors wrote that their educational program and prescribing tool aimed to address this practice gap without increasing the workload for pediatricians or dermatologists. “Adherence to guidelines by pediatricians has the potential to improve treatment provided in the primary care setting, better patient satisfaction, and allow greater access to dermatologists and pediatric dermatologists for patients with more severe acne and other conditions.”
Acknowledging that the study took place over a relatively short period of time, the authors said future research would examine the impact of the educational program and ordering tool on patient acne outcomes.
No funding or conflicts of interest were declared.
SOURCE: Borok J et al. J Am Acad Dermatol. 2018 May 9. doi: 10.1016/j.jaad.2018.04.055.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Key clinical point:
Major finding: An education program for pediatricians on acne treatment increased retinoid prescribing but decreased referrals to dermatologists.
Study details: Interventional study in 116 pediatricians.
Disclosures: No funding or conflicts of interest were declared.
Source: Borok J et al. J Am Acad Dermatol. 2018 May 9. doi: 10.1016/j.jaad.2018.04.055.
No-shows
When a patient fails to show up for his appointment, your reaction may run the gamut from elation to anger or land somewhere on the spectrum between concern and self-doubt. If you are overbooked and running behind with a waiting room that looks like a bus station at rush hour, an unexpectedly unfilled appointment slot can provide a much needed but all too brief respite. However, if the patient who no-shows is someone whom you have been worried about, you may wonder if he has slipped further into a debilitating depression. Or maybe he found a physician that he prefers?
If you keep your finger on the economic pulse of your practice, you know that the empty slot created when a patient no-shows is valuable time that is not generating any income. Your practice administrator may have sent a practice-wide email expressing concern about what she feels is an unacceptably high and economically unsustainable no-show rate. She already may have replaced your antiquated system using postcards and personal phone call reminders with preprogrammed emails and robo-calls.
If despite these high tech targeted reminders your no-show rate continues to be unacceptably high, the problem may be with how and when your office schedules appointments. When a parent or older patient calls with what she feels is an urgent or time-sensitive complaint, is she offered an appointment that satisfies her sense of urgency? She may agree to make an appointment but as soon as she hangs up may begin searching for another source of care and neglect to cancel the appointment with you when she finds a more timely response.
On the other hand, the patient’s problem may have resolved itself. With this in mind, I asked our receptionists to not make next-day appointments for a child with ear pain if for whatever reason the child was unable to come in for a same-day appointment. I knew from experience that ear pain often resolved and appointments weren’t kept or parents would cancel at the last minute. However, we guaranteed that if the child’s pain persisted we would see them immediately in the morning.
You may be muttering to yourself that you can’t possibly give every patient an appointment as soon as they would like to be seen. True. But aren’t there some patients who could be well served by a quick same-day appointment to allay their fear and sketch out a starting point for diagnosis and management at a later visit? A skillful and calming appointment secretary or nurse may be able to provide the same level of reassurance. But sometimes a short office visit is a more effective and efficient way to depressurize the situation and avoid a longer appointment that has a high likelihood of being no-showed or canceled.
Finally, are you or other members of your group in the habit of making follow-up appointments for problems that probably don’t require follow up? Most patients have an excellent sense when a follow-up appointment is unnecessary and are likely to cancel at the last minute or no-show. They may have had more than one experience in which they took off time from work and traveled 20 miles for a 3-minute visit that didn’t seem worth the effort. A quick phone call or two from you or your staff may be a better way to make sure things are going in the right direction and avoid the cost and frustration of a no-show.
The bottom line is that no-shows happen but when appointments are thoughtfully made the patients are more likely to keep them.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.
When a patient fails to show up for his appointment, your reaction may run the gamut from elation to anger or land somewhere on the spectrum between concern and self-doubt. If you are overbooked and running behind with a waiting room that looks like a bus station at rush hour, an unexpectedly unfilled appointment slot can provide a much needed but all too brief respite. However, if the patient who no-shows is someone whom you have been worried about, you may wonder if he has slipped further into a debilitating depression. Or maybe he found a physician that he prefers?
If you keep your finger on the economic pulse of your practice, you know that the empty slot created when a patient no-shows is valuable time that is not generating any income. Your practice administrator may have sent a practice-wide email expressing concern about what she feels is an unacceptably high and economically unsustainable no-show rate. She already may have replaced your antiquated system using postcards and personal phone call reminders with preprogrammed emails and robo-calls.
If despite these high tech targeted reminders your no-show rate continues to be unacceptably high, the problem may be with how and when your office schedules appointments. When a parent or older patient calls with what she feels is an urgent or time-sensitive complaint, is she offered an appointment that satisfies her sense of urgency? She may agree to make an appointment but as soon as she hangs up may begin searching for another source of care and neglect to cancel the appointment with you when she finds a more timely response.
On the other hand, the patient’s problem may have resolved itself. With this in mind, I asked our receptionists to not make next-day appointments for a child with ear pain if for whatever reason the child was unable to come in for a same-day appointment. I knew from experience that ear pain often resolved and appointments weren’t kept or parents would cancel at the last minute. However, we guaranteed that if the child’s pain persisted we would see them immediately in the morning.
You may be muttering to yourself that you can’t possibly give every patient an appointment as soon as they would like to be seen. True. But aren’t there some patients who could be well served by a quick same-day appointment to allay their fear and sketch out a starting point for diagnosis and management at a later visit? A skillful and calming appointment secretary or nurse may be able to provide the same level of reassurance. But sometimes a short office visit is a more effective and efficient way to depressurize the situation and avoid a longer appointment that has a high likelihood of being no-showed or canceled.
Finally, are you or other members of your group in the habit of making follow-up appointments for problems that probably don’t require follow up? Most patients have an excellent sense when a follow-up appointment is unnecessary and are likely to cancel at the last minute or no-show. They may have had more than one experience in which they took off time from work and traveled 20 miles for a 3-minute visit that didn’t seem worth the effort. A quick phone call or two from you or your staff may be a better way to make sure things are going in the right direction and avoid the cost and frustration of a no-show.
The bottom line is that no-shows happen but when appointments are thoughtfully made the patients are more likely to keep them.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.
When a patient fails to show up for his appointment, your reaction may run the gamut from elation to anger or land somewhere on the spectrum between concern and self-doubt. If you are overbooked and running behind with a waiting room that looks like a bus station at rush hour, an unexpectedly unfilled appointment slot can provide a much needed but all too brief respite. However, if the patient who no-shows is someone whom you have been worried about, you may wonder if he has slipped further into a debilitating depression. Or maybe he found a physician that he prefers?
If you keep your finger on the economic pulse of your practice, you know that the empty slot created when a patient no-shows is valuable time that is not generating any income. Your practice administrator may have sent a practice-wide email expressing concern about what she feels is an unacceptably high and economically unsustainable no-show rate. She already may have replaced your antiquated system using postcards and personal phone call reminders with preprogrammed emails and robo-calls.
If despite these high tech targeted reminders your no-show rate continues to be unacceptably high, the problem may be with how and when your office schedules appointments. When a parent or older patient calls with what she feels is an urgent or time-sensitive complaint, is she offered an appointment that satisfies her sense of urgency? She may agree to make an appointment but as soon as she hangs up may begin searching for another source of care and neglect to cancel the appointment with you when she finds a more timely response.
On the other hand, the patient’s problem may have resolved itself. With this in mind, I asked our receptionists to not make next-day appointments for a child with ear pain if for whatever reason the child was unable to come in for a same-day appointment. I knew from experience that ear pain often resolved and appointments weren’t kept or parents would cancel at the last minute. However, we guaranteed that if the child’s pain persisted we would see them immediately in the morning.
You may be muttering to yourself that you can’t possibly give every patient an appointment as soon as they would like to be seen. True. But aren’t there some patients who could be well served by a quick same-day appointment to allay their fear and sketch out a starting point for diagnosis and management at a later visit? A skillful and calming appointment secretary or nurse may be able to provide the same level of reassurance. But sometimes a short office visit is a more effective and efficient way to depressurize the situation and avoid a longer appointment that has a high likelihood of being no-showed or canceled.
Finally, are you or other members of your group in the habit of making follow-up appointments for problems that probably don’t require follow up? Most patients have an excellent sense when a follow-up appointment is unnecessary and are likely to cancel at the last minute or no-show. They may have had more than one experience in which they took off time from work and traveled 20 miles for a 3-minute visit that didn’t seem worth the effort. A quick phone call or two from you or your staff may be a better way to make sure things are going in the right direction and avoid the cost and frustration of a no-show.
The bottom line is that no-shows happen but when appointments are thoughtfully made the patients are more likely to keep them.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.
Pediatric cancers are on the rise
PITTSBURGH – The incidence of many pediatric cancers are on the rise, and the increase is occurring in nearly all demographic groups studied, according to the latest data from the U.S. Centers for Disease Control and Prevention.
Pediatric cancers that increased significantly in incidence from 2001 through 2014, compared with previous time periods, include thyroid carcinoma, hepatic tumors, lymphomas, renal tumors, and brain tumors. Other cancer types remained unchanged, except malignant melanoma, which saw a significant decline in incidence over the same period, reported David A. Siegel, MD, of the Epidemic Intelligence Service at the CDC in Atlanta.
Recent studies of trends in pediatric cancer have either used data from before 2010 or covered less than a third of the U.S. population, the investigators noted.
To get a more accurate estimate of current trends, the investigators relied on the United States Cancer Statistics, which combines data from the Surveillance, Epidemiology, and End Results (SEER) program and the National Program of Cancer Registries. Together, the combined databases cover 100% of the U.S. population.
Dr. Siegel and his colleagues looked at cancer incidence rates and trends among individuals younger than 20 years of age from across 48 states from 2001 to 2014 – Mississippi, Nevada, and the District of Columbia were not included.
They used a joinpoint regression method to calculate average annual percent change (AAPC) in rates, then stratified rates and trends by sex, age, and race/ethnicity; location; economic status; and cancer type.
During the 14-year period of the study, there were a total of 196,200 incident cases of pediatric cancer, for an overall cancer incidence rate of 173 per million. The pediatric cancer with the highest incident rate was leukemia of any type (45.6 per million), brain tumors (30.8), and lymphomas (26.0).
Incidence rates were highest among males, patients from infancy through age 4, non-Hispanic whites, children who live in the Northeast region, those who live in the wealthiest counties, and those who live in urban/metropolitan counties. The overall pediatric cancer incidence rate increased, with an AAPC of 0.7 (95% confidence interval, 0.5-0.8).
“Rates increased in each stratum of sex, age, and race/ethnicity (except non-Hispanic American Indian/Alaska Native), region, economic status, and rural/urban classification,” the investigators wrote.
Cancers with significantly increased AAPC included thyroid carcinomas (AAPC, 4.8), hepatic tumors (2.5), lymphomas (1.7), renal tumors (0.6), and brain tumors (all types, 0.4).
There were no significant changes in the incidence of either germ cell cancer, retinoblastoma, leukemia, neuroblastoma, soft-tissue sarcomas, or bone tumors.
The only significant decrease over the study period was in the incidence of melanoma in children (–2.6).
“Possible causes of increasing rates might include changes in diagnostic, coding, and reporting standards, increased detection, population-based changes (such as increasing obesity), and environmental exposures,” they wrote.
Public health campaigns about the dangers of UV exposure and promoting the use of sunscreens may account for the decline in the incidence of malignant melanoma, they suggested.
The study was supported by the CDC. Dr. Siegel and coauthors are CDC employees. They reported having no conflicts of interest.
SOURCE: Siegel DA et al. ASPHO 2018, Abstract 605.
PITTSBURGH – The incidence of many pediatric cancers are on the rise, and the increase is occurring in nearly all demographic groups studied, according to the latest data from the U.S. Centers for Disease Control and Prevention.
Pediatric cancers that increased significantly in incidence from 2001 through 2014, compared with previous time periods, include thyroid carcinoma, hepatic tumors, lymphomas, renal tumors, and brain tumors. Other cancer types remained unchanged, except malignant melanoma, which saw a significant decline in incidence over the same period, reported David A. Siegel, MD, of the Epidemic Intelligence Service at the CDC in Atlanta.
Recent studies of trends in pediatric cancer have either used data from before 2010 or covered less than a third of the U.S. population, the investigators noted.
To get a more accurate estimate of current trends, the investigators relied on the United States Cancer Statistics, which combines data from the Surveillance, Epidemiology, and End Results (SEER) program and the National Program of Cancer Registries. Together, the combined databases cover 100% of the U.S. population.
Dr. Siegel and his colleagues looked at cancer incidence rates and trends among individuals younger than 20 years of age from across 48 states from 2001 to 2014 – Mississippi, Nevada, and the District of Columbia were not included.
They used a joinpoint regression method to calculate average annual percent change (AAPC) in rates, then stratified rates and trends by sex, age, and race/ethnicity; location; economic status; and cancer type.
During the 14-year period of the study, there were a total of 196,200 incident cases of pediatric cancer, for an overall cancer incidence rate of 173 per million. The pediatric cancer with the highest incident rate was leukemia of any type (45.6 per million), brain tumors (30.8), and lymphomas (26.0).
Incidence rates were highest among males, patients from infancy through age 4, non-Hispanic whites, children who live in the Northeast region, those who live in the wealthiest counties, and those who live in urban/metropolitan counties. The overall pediatric cancer incidence rate increased, with an AAPC of 0.7 (95% confidence interval, 0.5-0.8).
“Rates increased in each stratum of sex, age, and race/ethnicity (except non-Hispanic American Indian/Alaska Native), region, economic status, and rural/urban classification,” the investigators wrote.
Cancers with significantly increased AAPC included thyroid carcinomas (AAPC, 4.8), hepatic tumors (2.5), lymphomas (1.7), renal tumors (0.6), and brain tumors (all types, 0.4).
There were no significant changes in the incidence of either germ cell cancer, retinoblastoma, leukemia, neuroblastoma, soft-tissue sarcomas, or bone tumors.
The only significant decrease over the study period was in the incidence of melanoma in children (–2.6).
“Possible causes of increasing rates might include changes in diagnostic, coding, and reporting standards, increased detection, population-based changes (such as increasing obesity), and environmental exposures,” they wrote.
Public health campaigns about the dangers of UV exposure and promoting the use of sunscreens may account for the decline in the incidence of malignant melanoma, they suggested.
The study was supported by the CDC. Dr. Siegel and coauthors are CDC employees. They reported having no conflicts of interest.
SOURCE: Siegel DA et al. ASPHO 2018, Abstract 605.
PITTSBURGH – The incidence of many pediatric cancers are on the rise, and the increase is occurring in nearly all demographic groups studied, according to the latest data from the U.S. Centers for Disease Control and Prevention.
Pediatric cancers that increased significantly in incidence from 2001 through 2014, compared with previous time periods, include thyroid carcinoma, hepatic tumors, lymphomas, renal tumors, and brain tumors. Other cancer types remained unchanged, except malignant melanoma, which saw a significant decline in incidence over the same period, reported David A. Siegel, MD, of the Epidemic Intelligence Service at the CDC in Atlanta.
Recent studies of trends in pediatric cancer have either used data from before 2010 or covered less than a third of the U.S. population, the investigators noted.
To get a more accurate estimate of current trends, the investigators relied on the United States Cancer Statistics, which combines data from the Surveillance, Epidemiology, and End Results (SEER) program and the National Program of Cancer Registries. Together, the combined databases cover 100% of the U.S. population.
Dr. Siegel and his colleagues looked at cancer incidence rates and trends among individuals younger than 20 years of age from across 48 states from 2001 to 2014 – Mississippi, Nevada, and the District of Columbia were not included.
They used a joinpoint regression method to calculate average annual percent change (AAPC) in rates, then stratified rates and trends by sex, age, and race/ethnicity; location; economic status; and cancer type.
During the 14-year period of the study, there were a total of 196,200 incident cases of pediatric cancer, for an overall cancer incidence rate of 173 per million. The pediatric cancer with the highest incident rate was leukemia of any type (45.6 per million), brain tumors (30.8), and lymphomas (26.0).
Incidence rates were highest among males, patients from infancy through age 4, non-Hispanic whites, children who live in the Northeast region, those who live in the wealthiest counties, and those who live in urban/metropolitan counties. The overall pediatric cancer incidence rate increased, with an AAPC of 0.7 (95% confidence interval, 0.5-0.8).
“Rates increased in each stratum of sex, age, and race/ethnicity (except non-Hispanic American Indian/Alaska Native), region, economic status, and rural/urban classification,” the investigators wrote.
Cancers with significantly increased AAPC included thyroid carcinomas (AAPC, 4.8), hepatic tumors (2.5), lymphomas (1.7), renal tumors (0.6), and brain tumors (all types, 0.4).
There were no significant changes in the incidence of either germ cell cancer, retinoblastoma, leukemia, neuroblastoma, soft-tissue sarcomas, or bone tumors.
The only significant decrease over the study period was in the incidence of melanoma in children (–2.6).
“Possible causes of increasing rates might include changes in diagnostic, coding, and reporting standards, increased detection, population-based changes (such as increasing obesity), and environmental exposures,” they wrote.
Public health campaigns about the dangers of UV exposure and promoting the use of sunscreens may account for the decline in the incidence of malignant melanoma, they suggested.
The study was supported by the CDC. Dr. Siegel and coauthors are CDC employees. They reported having no conflicts of interest.
SOURCE: Siegel DA et al. ASPHO 2018, Abstract 605.
REPORTING FROM ASPHO 2018
Key clinical point: Major finding: From 2001 to 2014, there were 196,200 incident cases of pediatric cancer for an overall cancer incidence rate of 173 per 1 million.
Study details: A review of data from the United States Cancer Statistics for children under age 20.
Disclosures: The CDC supported the study. Dr. Siegel and his coauthors are CDC employees. They reported having no conflicts of interest.
Source: Siegel DA et al. ASPHO 2018, Abstract 605.
Multiple solid tumors targeted by concept CAR T
PITTSBURGH – Call it the CAR of the future – an investigational chimeric antigen receptor–T cell construct targeted against an antigen highly expressed on pediatric solid tumors has shown promising efficacy in preclinical studies.
Investigators found that the antigen, labeled B7-H3, was expressed on 84% of microarrays of pediatric solid tumors. More importantly, a single dose of CAR targeted to B7-H3 caused complete regression of osteosarcoma and Ewing sarcoma xenografts and improved survival over an untransduced, CD19-targeted CAR in mice, Robbie Majzner, MD, reported at the annual meeting of the American Society of Pediatric Hematology/Oncology.
Dr. Majzner was the recipient of an ASPHO young investigator award for his team’s research into developing a CAR T that could be as effective against solid tumors as other CAR Ts have been against hematologic malignancies such as acute lymphoblastic leukemia.
Solid tumors are more challenging to target than leukemias or lymphomas because of the small number of antigens expressed on most pediatric tumors, he said.
“Over 95% of tumors have a very low rate of mutations, which means that they have very few neoantigens which the immune system can recognize in order to attack,” he said.
In the Children’s Oncology Group ADVL1412 trial, single-agent immunotherapy with the anti–programmed death protein 1 (PD-1) inhibitor nivolumab (Opdivo) showed no evidence of efficacy against either Ewing sarcoma, osteosarcoma, rhabdomyosarcoma, or measurable neuroblastoma. PD–ligand 1 was found to be expressed in only a few of the 43 tumors studied, suggesting that checkpoint inhibitor therapy is unlikely to work in these solid tumors, he said.
In contrast, B7-H3 is highly expressed on many different pediatric solid tumors, including rhabdomyosarcoma (95% of tumors stained), Ewing sarcoma (89%), Wilms tumor (100%), neuroblastoma (82%), ganglioneuroblastoma and ganglioneuroma (53%), medulloblastoma (96%), glioblastoma multiforme (84%), and diffuse intrinsic pontine glioma (100%).
To see whether CAR T therapy might have better efficacy than checkpoint inhibitors in this population, the investigators created a B7-H3 CAR using the B7-H3 tumor–specific monoclonal antibody MGA271, which has been shown to be safe in both adults and children in early clinical trials.
In human tumor xenograft models of osteosarcoma, all mice who received a single dose of the B7-H3 CAR survived at least 70 days after tumor engraftment, whereas all control mice, who received the CD19 CAR, died by day 60 (P = .0067). Similarly, in a model of Ewing sarcoma, all mice treated with B7-H3 survived at least 100 days, whereas all controls were dead by day 50 (P = .0015).
The B7-H3 construct also showed good activity against a model of medulloblastoma, showing that it was capable of crossing the blood-brain barrier.
Since B7-H3 has been reported to be expressed on both myeloid and lymphoid leukemia cells, the investigators also tested the CAR against a murine model of leukemia generated by injection of K562, a well-characterized line of myeloid leukemia cells.
“While we found some increase in survival in the mice that received the B7-H3 CAR T cells, compared to mice that received untransduced CAR T cells, this clearly is not as effective as in our solid tumor models,” Dr. Majzner said.
Going back to the cell line, they discovered that expression of B7-H3 was considerably lower in the K562 cells than in either the osteosarcoma or medulloblastoma cell lines used in their other models.
They found that both in vitro and in vivo, high levels of B7-H3 expression were necessary to provoke the immune system into releasing cytokines necessary for an adequate antitumor response.
The investigators are currently planning clinical trials using the B7-H3 CAR T-cell construct in patients with solid tumors.
The work is supported by the Sarcoma Alliance for Research through Collaboration, the St. Baldrick’s Foundation, and Stand Up to Cancer. Dr. Majzner reported having no financial disclosures.
SOURCE: Majzner RG et al. ASPHO 2018, Abstract #PS2003.
PITTSBURGH – Call it the CAR of the future – an investigational chimeric antigen receptor–T cell construct targeted against an antigen highly expressed on pediatric solid tumors has shown promising efficacy in preclinical studies.
Investigators found that the antigen, labeled B7-H3, was expressed on 84% of microarrays of pediatric solid tumors. More importantly, a single dose of CAR targeted to B7-H3 caused complete regression of osteosarcoma and Ewing sarcoma xenografts and improved survival over an untransduced, CD19-targeted CAR in mice, Robbie Majzner, MD, reported at the annual meeting of the American Society of Pediatric Hematology/Oncology.
Dr. Majzner was the recipient of an ASPHO young investigator award for his team’s research into developing a CAR T that could be as effective against solid tumors as other CAR Ts have been against hematologic malignancies such as acute lymphoblastic leukemia.
Solid tumors are more challenging to target than leukemias or lymphomas because of the small number of antigens expressed on most pediatric tumors, he said.
“Over 95% of tumors have a very low rate of mutations, which means that they have very few neoantigens which the immune system can recognize in order to attack,” he said.
In the Children’s Oncology Group ADVL1412 trial, single-agent immunotherapy with the anti–programmed death protein 1 (PD-1) inhibitor nivolumab (Opdivo) showed no evidence of efficacy against either Ewing sarcoma, osteosarcoma, rhabdomyosarcoma, or measurable neuroblastoma. PD–ligand 1 was found to be expressed in only a few of the 43 tumors studied, suggesting that checkpoint inhibitor therapy is unlikely to work in these solid tumors, he said.
In contrast, B7-H3 is highly expressed on many different pediatric solid tumors, including rhabdomyosarcoma (95% of tumors stained), Ewing sarcoma (89%), Wilms tumor (100%), neuroblastoma (82%), ganglioneuroblastoma and ganglioneuroma (53%), medulloblastoma (96%), glioblastoma multiforme (84%), and diffuse intrinsic pontine glioma (100%).
To see whether CAR T therapy might have better efficacy than checkpoint inhibitors in this population, the investigators created a B7-H3 CAR using the B7-H3 tumor–specific monoclonal antibody MGA271, which has been shown to be safe in both adults and children in early clinical trials.
In human tumor xenograft models of osteosarcoma, all mice who received a single dose of the B7-H3 CAR survived at least 70 days after tumor engraftment, whereas all control mice, who received the CD19 CAR, died by day 60 (P = .0067). Similarly, in a model of Ewing sarcoma, all mice treated with B7-H3 survived at least 100 days, whereas all controls were dead by day 50 (P = .0015).
The B7-H3 construct also showed good activity against a model of medulloblastoma, showing that it was capable of crossing the blood-brain barrier.
Since B7-H3 has been reported to be expressed on both myeloid and lymphoid leukemia cells, the investigators also tested the CAR against a murine model of leukemia generated by injection of K562, a well-characterized line of myeloid leukemia cells.
“While we found some increase in survival in the mice that received the B7-H3 CAR T cells, compared to mice that received untransduced CAR T cells, this clearly is not as effective as in our solid tumor models,” Dr. Majzner said.
Going back to the cell line, they discovered that expression of B7-H3 was considerably lower in the K562 cells than in either the osteosarcoma or medulloblastoma cell lines used in their other models.
They found that both in vitro and in vivo, high levels of B7-H3 expression were necessary to provoke the immune system into releasing cytokines necessary for an adequate antitumor response.
The investigators are currently planning clinical trials using the B7-H3 CAR T-cell construct in patients with solid tumors.
The work is supported by the Sarcoma Alliance for Research through Collaboration, the St. Baldrick’s Foundation, and Stand Up to Cancer. Dr. Majzner reported having no financial disclosures.
SOURCE: Majzner RG et al. ASPHO 2018, Abstract #PS2003.
PITTSBURGH – Call it the CAR of the future – an investigational chimeric antigen receptor–T cell construct targeted against an antigen highly expressed on pediatric solid tumors has shown promising efficacy in preclinical studies.
Investigators found that the antigen, labeled B7-H3, was expressed on 84% of microarrays of pediatric solid tumors. More importantly, a single dose of CAR targeted to B7-H3 caused complete regression of osteosarcoma and Ewing sarcoma xenografts and improved survival over an untransduced, CD19-targeted CAR in mice, Robbie Majzner, MD, reported at the annual meeting of the American Society of Pediatric Hematology/Oncology.
Dr. Majzner was the recipient of an ASPHO young investigator award for his team’s research into developing a CAR T that could be as effective against solid tumors as other CAR Ts have been against hematologic malignancies such as acute lymphoblastic leukemia.
Solid tumors are more challenging to target than leukemias or lymphomas because of the small number of antigens expressed on most pediatric tumors, he said.
“Over 95% of tumors have a very low rate of mutations, which means that they have very few neoantigens which the immune system can recognize in order to attack,” he said.
In the Children’s Oncology Group ADVL1412 trial, single-agent immunotherapy with the anti–programmed death protein 1 (PD-1) inhibitor nivolumab (Opdivo) showed no evidence of efficacy against either Ewing sarcoma, osteosarcoma, rhabdomyosarcoma, or measurable neuroblastoma. PD–ligand 1 was found to be expressed in only a few of the 43 tumors studied, suggesting that checkpoint inhibitor therapy is unlikely to work in these solid tumors, he said.
In contrast, B7-H3 is highly expressed on many different pediatric solid tumors, including rhabdomyosarcoma (95% of tumors stained), Ewing sarcoma (89%), Wilms tumor (100%), neuroblastoma (82%), ganglioneuroblastoma and ganglioneuroma (53%), medulloblastoma (96%), glioblastoma multiforme (84%), and diffuse intrinsic pontine glioma (100%).
To see whether CAR T therapy might have better efficacy than checkpoint inhibitors in this population, the investigators created a B7-H3 CAR using the B7-H3 tumor–specific monoclonal antibody MGA271, which has been shown to be safe in both adults and children in early clinical trials.
In human tumor xenograft models of osteosarcoma, all mice who received a single dose of the B7-H3 CAR survived at least 70 days after tumor engraftment, whereas all control mice, who received the CD19 CAR, died by day 60 (P = .0067). Similarly, in a model of Ewing sarcoma, all mice treated with B7-H3 survived at least 100 days, whereas all controls were dead by day 50 (P = .0015).
The B7-H3 construct also showed good activity against a model of medulloblastoma, showing that it was capable of crossing the blood-brain barrier.
Since B7-H3 has been reported to be expressed on both myeloid and lymphoid leukemia cells, the investigators also tested the CAR against a murine model of leukemia generated by injection of K562, a well-characterized line of myeloid leukemia cells.
“While we found some increase in survival in the mice that received the B7-H3 CAR T cells, compared to mice that received untransduced CAR T cells, this clearly is not as effective as in our solid tumor models,” Dr. Majzner said.
Going back to the cell line, they discovered that expression of B7-H3 was considerably lower in the K562 cells than in either the osteosarcoma or medulloblastoma cell lines used in their other models.
They found that both in vitro and in vivo, high levels of B7-H3 expression were necessary to provoke the immune system into releasing cytokines necessary for an adequate antitumor response.
The investigators are currently planning clinical trials using the B7-H3 CAR T-cell construct in patients with solid tumors.
The work is supported by the Sarcoma Alliance for Research through Collaboration, the St. Baldrick’s Foundation, and Stand Up to Cancer. Dr. Majzner reported having no financial disclosures.
SOURCE: Majzner RG et al. ASPHO 2018, Abstract #PS2003.
REPORTING FROM ASPHO 2018
Key clinical point:
Major finding: A single dose of the B7-H3 CAR caused complete regression of osteosarcoma and Ewing sarcoma xenografts and extended survival in mice.
Study details: Preclinical research.
Disclosures: The work is supported by the Sarcoma Alliance for Research through Collaboration, St. Baldrick’s Foundation, and Stand Up to Cancer. Dr. Majzner reported having no financial disclosures.
Source: Majzner RG et al. ASPHO 2018, Abstract #PS2003.
Myelin antibody predicts ADEM relapse
LOS ANGELES – There’s substantially higher risk of relapse and epilepsy after acute disseminated encephalomyelitis when children present with serum antibodies against myelin oligodendrocyte glycoprotein, according to British investigators.
“Traditionally, we told parents that ADEM [acute disseminated encephalomyelitis] is typically monophasic. I do tell parents now that the risk of relapse is higher if we see” myelin oligodendrocyte glycoprotein antibodies (MOG-Ab), said senior investigator Yael Hacohen, MBBS, DPhil, a pediatric neurology lecturer at University College London.
There was also a strong trend for relapsing disease when children presented with seizures, and an increased risk of post-ADEM epilepsy with oligoclonal bands on cerebrospinal fluid analysis, a marker of inflammation.
ADEM is an acute CNS demyelinating disorder primarily affecting young children, often after upper respiratory tract infections and occasionally after measles, mumps, and rubella vaccination. Signs can include limb weakness, stumbling, and coma. Many children recover without incident, but some don’t.
There’s been an increasing number of reports of children – and adults – presenting with antibodies against MOG, a glycoprotein on the outermost layer of the myelin sheath. Its exact function is unknown, but antibodies have been found in a number of inflammatory CNS conditions, and its role in pathogenesis is being explored. Testing is available for clinical use, but it isn’t standardized. For now, titer levels aren’t being used to guide treatment at University College London, Dr. Hacohen said at the American Academy of Neurology annual meeting.
The team reviewed 74 children with ADEM who presented at three pediatric neurology centers during 2005-2017, at a median age of 4.5 years. There were about equal numbers of boys and girls, and all had MRI abnormalities consistent with ADEM. Fifty children (68%) were MOG-ab positive.
Twenty-seven antibody-positive children (54%) relapsed, versus 3 of the 24 negative children (13%). Relapse was almost six times more likely with MOB-Ab (95% confidence interval [CI], 1.8-19.7; P = .002). The overall relapse rate of 42% (31/74) was higher than in previous studies, probably because of longer follow-up, lasting years in some cases.
Sixteen children (22%) presented with seizures, which nearly tripled the risk of relapse, although the finding wasn’t statistically significant (95% CI, 0.9-9.2; P = .06). There was a trend toward more seizures at onset in the MOG-Ab group.
Twelve children (16.2%) developed post-ADEM epilepsy, all but one MOG-Ab positive. The median time to seizure onset was 3 months. All of the children remained on antiepileptic medications at 2-year follow-up.
Oligoclonal bands were found in 8 of 37 children tested (22%), and also markedly increased the risk of post-ADEM seizures (odds ratio, 8.7; 95% CI, 1.5-54; P = .01).
“The majority of the children that we’ve looked at remain MOG-Ab positive. There may be a trend in antibody titers going down, but overall we didn’t find titers clinically useful. I know two children where titers went down. They relapsed,” and the titers went “up again, so we don’t’ really use them clinically for treatment,” Dr. Hacohen said.
“I think there is more to do” when it comes to optimizing ADEM management. “It’s a very heterogeneous [condition, and] I don’t want to put [everyone] on immunosuppression for years. I’ve got one patient who had an event, and 7 years later had a second event, and then was back to normal in a week.” On the other hand, “10%-20% of our patients do quite poorly and relapse on all treatments,” she said.
The investigators didn’t have any disclosures and there was no industry funding for the work.
SOURCE: Rossor T et al. Neurology. 2018 Apr 90(15 Suppl.):S35.004.
LOS ANGELES – There’s substantially higher risk of relapse and epilepsy after acute disseminated encephalomyelitis when children present with serum antibodies against myelin oligodendrocyte glycoprotein, according to British investigators.
“Traditionally, we told parents that ADEM [acute disseminated encephalomyelitis] is typically monophasic. I do tell parents now that the risk of relapse is higher if we see” myelin oligodendrocyte glycoprotein antibodies (MOG-Ab), said senior investigator Yael Hacohen, MBBS, DPhil, a pediatric neurology lecturer at University College London.
There was also a strong trend for relapsing disease when children presented with seizures, and an increased risk of post-ADEM epilepsy with oligoclonal bands on cerebrospinal fluid analysis, a marker of inflammation.
ADEM is an acute CNS demyelinating disorder primarily affecting young children, often after upper respiratory tract infections and occasionally after measles, mumps, and rubella vaccination. Signs can include limb weakness, stumbling, and coma. Many children recover without incident, but some don’t.
There’s been an increasing number of reports of children – and adults – presenting with antibodies against MOG, a glycoprotein on the outermost layer of the myelin sheath. Its exact function is unknown, but antibodies have been found in a number of inflammatory CNS conditions, and its role in pathogenesis is being explored. Testing is available for clinical use, but it isn’t standardized. For now, titer levels aren’t being used to guide treatment at University College London, Dr. Hacohen said at the American Academy of Neurology annual meeting.
The team reviewed 74 children with ADEM who presented at three pediatric neurology centers during 2005-2017, at a median age of 4.5 years. There were about equal numbers of boys and girls, and all had MRI abnormalities consistent with ADEM. Fifty children (68%) were MOG-ab positive.
Twenty-seven antibody-positive children (54%) relapsed, versus 3 of the 24 negative children (13%). Relapse was almost six times more likely with MOB-Ab (95% confidence interval [CI], 1.8-19.7; P = .002). The overall relapse rate of 42% (31/74) was higher than in previous studies, probably because of longer follow-up, lasting years in some cases.
Sixteen children (22%) presented with seizures, which nearly tripled the risk of relapse, although the finding wasn’t statistically significant (95% CI, 0.9-9.2; P = .06). There was a trend toward more seizures at onset in the MOG-Ab group.
Twelve children (16.2%) developed post-ADEM epilepsy, all but one MOG-Ab positive. The median time to seizure onset was 3 months. All of the children remained on antiepileptic medications at 2-year follow-up.
Oligoclonal bands were found in 8 of 37 children tested (22%), and also markedly increased the risk of post-ADEM seizures (odds ratio, 8.7; 95% CI, 1.5-54; P = .01).
“The majority of the children that we’ve looked at remain MOG-Ab positive. There may be a trend in antibody titers going down, but overall we didn’t find titers clinically useful. I know two children where titers went down. They relapsed,” and the titers went “up again, so we don’t’ really use them clinically for treatment,” Dr. Hacohen said.
“I think there is more to do” when it comes to optimizing ADEM management. “It’s a very heterogeneous [condition, and] I don’t want to put [everyone] on immunosuppression for years. I’ve got one patient who had an event, and 7 years later had a second event, and then was back to normal in a week.” On the other hand, “10%-20% of our patients do quite poorly and relapse on all treatments,” she said.
The investigators didn’t have any disclosures and there was no industry funding for the work.
SOURCE: Rossor T et al. Neurology. 2018 Apr 90(15 Suppl.):S35.004.
LOS ANGELES – There’s substantially higher risk of relapse and epilepsy after acute disseminated encephalomyelitis when children present with serum antibodies against myelin oligodendrocyte glycoprotein, according to British investigators.
“Traditionally, we told parents that ADEM [acute disseminated encephalomyelitis] is typically monophasic. I do tell parents now that the risk of relapse is higher if we see” myelin oligodendrocyte glycoprotein antibodies (MOG-Ab), said senior investigator Yael Hacohen, MBBS, DPhil, a pediatric neurology lecturer at University College London.
There was also a strong trend for relapsing disease when children presented with seizures, and an increased risk of post-ADEM epilepsy with oligoclonal bands on cerebrospinal fluid analysis, a marker of inflammation.
ADEM is an acute CNS demyelinating disorder primarily affecting young children, often after upper respiratory tract infections and occasionally after measles, mumps, and rubella vaccination. Signs can include limb weakness, stumbling, and coma. Many children recover without incident, but some don’t.
There’s been an increasing number of reports of children – and adults – presenting with antibodies against MOG, a glycoprotein on the outermost layer of the myelin sheath. Its exact function is unknown, but antibodies have been found in a number of inflammatory CNS conditions, and its role in pathogenesis is being explored. Testing is available for clinical use, but it isn’t standardized. For now, titer levels aren’t being used to guide treatment at University College London, Dr. Hacohen said at the American Academy of Neurology annual meeting.
The team reviewed 74 children with ADEM who presented at three pediatric neurology centers during 2005-2017, at a median age of 4.5 years. There were about equal numbers of boys and girls, and all had MRI abnormalities consistent with ADEM. Fifty children (68%) were MOG-ab positive.
Twenty-seven antibody-positive children (54%) relapsed, versus 3 of the 24 negative children (13%). Relapse was almost six times more likely with MOB-Ab (95% confidence interval [CI], 1.8-19.7; P = .002). The overall relapse rate of 42% (31/74) was higher than in previous studies, probably because of longer follow-up, lasting years in some cases.
Sixteen children (22%) presented with seizures, which nearly tripled the risk of relapse, although the finding wasn’t statistically significant (95% CI, 0.9-9.2; P = .06). There was a trend toward more seizures at onset in the MOG-Ab group.
Twelve children (16.2%) developed post-ADEM epilepsy, all but one MOG-Ab positive. The median time to seizure onset was 3 months. All of the children remained on antiepileptic medications at 2-year follow-up.
Oligoclonal bands were found in 8 of 37 children tested (22%), and also markedly increased the risk of post-ADEM seizures (odds ratio, 8.7; 95% CI, 1.5-54; P = .01).
“The majority of the children that we’ve looked at remain MOG-Ab positive. There may be a trend in antibody titers going down, but overall we didn’t find titers clinically useful. I know two children where titers went down. They relapsed,” and the titers went “up again, so we don’t’ really use them clinically for treatment,” Dr. Hacohen said.
“I think there is more to do” when it comes to optimizing ADEM management. “It’s a very heterogeneous [condition, and] I don’t want to put [everyone] on immunosuppression for years. I’ve got one patient who had an event, and 7 years later had a second event, and then was back to normal in a week.” On the other hand, “10%-20% of our patients do quite poorly and relapse on all treatments,” she said.
The investigators didn’t have any disclosures and there was no industry funding for the work.
SOURCE: Rossor T et al. Neurology. 2018 Apr 90(15 Suppl.):S35.004.
REPORTING FROM AAN 2018
Key clinical point: Myelin oligodendrocyte glycoprotein antibodies help to identify children who will have relapsing ADEM.
Major finding: Twenty-seven out of 50 antibody-positive children (54%) relapsed, versus 3 of 24 negative children (13%).
Study details: Review of 74 children with ADEM
Disclosures: There was no industry funding, and the investigators had no disclosures.
Source: Rossor T et al. Neurology. 2018 Apr 90(15 Suppl.):S35.004.
Guidance coming for mTOR inhibitors in infantile TSC
LOS ANGELES – Someday soon, physicians will probably have solid, evidence-based guidelines on how to use mTOR inhibitors in infants with tuberous sclerosis complex.
They couldn’t come soon enough. Everolimus (Afinitor) is being used off label more and more often in children under 2 years old for seizures and other manifestations of the genetic disorder, often with a decent response.
“I get emails all the time saying ‘how would you start treatment at this age?’ and we say there are no data,” he said at the American Academy of Neurology annual meeting.
Dr. Krueger presented a survey of 19 TSC centers to get the ball rolling. They reported on treating 45 children under 2 years old, at least one child at each center. The goal of the survey was to establish a baseline “to allow us to move forward with what proper studies would look like, and what needs to be done. Two-thirds of patients have seizures before their first birthday; we need to establish a safety [and efficacy] profile well before 2 years of age,” and evidence-based guidelines, he said.
On average, everolimus treatment started at 11.7 months, and continued for 27 months. Sirolimus treatment started at a mean of 16 months and continued for 16 months. Dosing ranged from once a week to daily. In contrast to case reports that skew heavily toward rhabdomyomas, most of the children were treated for epilepsy and subependymal giant cell astrocytoma (SEGA). Almost all the centers had participated in a clinical evaluation of everolimus for TSC epilepsy and SEGAs in older children, “so there was familiarity and a comfort level” for those indications, Dr. Krueger said.
Everolimus was used much more often than was sirolimus, which probably reflects ongoing clinical development of the drug. A handful of children switched between the two, probably because of side effects. Most centers reported a favorable response. The average initial daily dose of everolimus was 1.05 mg/m2; the average initial daily dose of sirolimus was 0.42 mg/m2.
Thirty-five children (78%) had an adverse event (AE), usually infections or lipid problems. Most were mild or moderate and didn’t affect treatment. Seven children (16%) had severe grade 3 events.
“The frequency of these AEs and the severity and type were not different from the earlier trials,” but almost 40% of the children discontinued treatment due to AEs, which was “much higher” than in past trials. “I think this represents the lack of real data with which to guide clinical judgment. There was a high tendency with any AE for discontinuation,” Dr. Krueger said.
There were more boys than girls among the 45 children. The majority were from the United States, and predominantly Cincinnati Children’s Hospital. Most had TSC2 mutations, which are associated with worse disease than TSC1 mutations.
Dr. Krueger reported research funding and personal compensation from Novartis, maker of everolimus. Almost all of his coinvestigators reported ties to the company. The work was supported by the Tuberous Sclerosis Alliance, which is funded in part by Novartis.
SOURCE: Krueger D et al. Neurology. 2018 Apr 90(15 Suppl.):S35.003.
LOS ANGELES – Someday soon, physicians will probably have solid, evidence-based guidelines on how to use mTOR inhibitors in infants with tuberous sclerosis complex.
They couldn’t come soon enough. Everolimus (Afinitor) is being used off label more and more often in children under 2 years old for seizures and other manifestations of the genetic disorder, often with a decent response.
“I get emails all the time saying ‘how would you start treatment at this age?’ and we say there are no data,” he said at the American Academy of Neurology annual meeting.
Dr. Krueger presented a survey of 19 TSC centers to get the ball rolling. They reported on treating 45 children under 2 years old, at least one child at each center. The goal of the survey was to establish a baseline “to allow us to move forward with what proper studies would look like, and what needs to be done. Two-thirds of patients have seizures before their first birthday; we need to establish a safety [and efficacy] profile well before 2 years of age,” and evidence-based guidelines, he said.
On average, everolimus treatment started at 11.7 months, and continued for 27 months. Sirolimus treatment started at a mean of 16 months and continued for 16 months. Dosing ranged from once a week to daily. In contrast to case reports that skew heavily toward rhabdomyomas, most of the children were treated for epilepsy and subependymal giant cell astrocytoma (SEGA). Almost all the centers had participated in a clinical evaluation of everolimus for TSC epilepsy and SEGAs in older children, “so there was familiarity and a comfort level” for those indications, Dr. Krueger said.
Everolimus was used much more often than was sirolimus, which probably reflects ongoing clinical development of the drug. A handful of children switched between the two, probably because of side effects. Most centers reported a favorable response. The average initial daily dose of everolimus was 1.05 mg/m2; the average initial daily dose of sirolimus was 0.42 mg/m2.
Thirty-five children (78%) had an adverse event (AE), usually infections or lipid problems. Most were mild or moderate and didn’t affect treatment. Seven children (16%) had severe grade 3 events.
“The frequency of these AEs and the severity and type were not different from the earlier trials,” but almost 40% of the children discontinued treatment due to AEs, which was “much higher” than in past trials. “I think this represents the lack of real data with which to guide clinical judgment. There was a high tendency with any AE for discontinuation,” Dr. Krueger said.
There were more boys than girls among the 45 children. The majority were from the United States, and predominantly Cincinnati Children’s Hospital. Most had TSC2 mutations, which are associated with worse disease than TSC1 mutations.
Dr. Krueger reported research funding and personal compensation from Novartis, maker of everolimus. Almost all of his coinvestigators reported ties to the company. The work was supported by the Tuberous Sclerosis Alliance, which is funded in part by Novartis.
SOURCE: Krueger D et al. Neurology. 2018 Apr 90(15 Suppl.):S35.003.
LOS ANGELES – Someday soon, physicians will probably have solid, evidence-based guidelines on how to use mTOR inhibitors in infants with tuberous sclerosis complex.
They couldn’t come soon enough. Everolimus (Afinitor) is being used off label more and more often in children under 2 years old for seizures and other manifestations of the genetic disorder, often with a decent response.
“I get emails all the time saying ‘how would you start treatment at this age?’ and we say there are no data,” he said at the American Academy of Neurology annual meeting.
Dr. Krueger presented a survey of 19 TSC centers to get the ball rolling. They reported on treating 45 children under 2 years old, at least one child at each center. The goal of the survey was to establish a baseline “to allow us to move forward with what proper studies would look like, and what needs to be done. Two-thirds of patients have seizures before their first birthday; we need to establish a safety [and efficacy] profile well before 2 years of age,” and evidence-based guidelines, he said.
On average, everolimus treatment started at 11.7 months, and continued for 27 months. Sirolimus treatment started at a mean of 16 months and continued for 16 months. Dosing ranged from once a week to daily. In contrast to case reports that skew heavily toward rhabdomyomas, most of the children were treated for epilepsy and subependymal giant cell astrocytoma (SEGA). Almost all the centers had participated in a clinical evaluation of everolimus for TSC epilepsy and SEGAs in older children, “so there was familiarity and a comfort level” for those indications, Dr. Krueger said.
Everolimus was used much more often than was sirolimus, which probably reflects ongoing clinical development of the drug. A handful of children switched between the two, probably because of side effects. Most centers reported a favorable response. The average initial daily dose of everolimus was 1.05 mg/m2; the average initial daily dose of sirolimus was 0.42 mg/m2.
Thirty-five children (78%) had an adverse event (AE), usually infections or lipid problems. Most were mild or moderate and didn’t affect treatment. Seven children (16%) had severe grade 3 events.
“The frequency of these AEs and the severity and type were not different from the earlier trials,” but almost 40% of the children discontinued treatment due to AEs, which was “much higher” than in past trials. “I think this represents the lack of real data with which to guide clinical judgment. There was a high tendency with any AE for discontinuation,” Dr. Krueger said.
There were more boys than girls among the 45 children. The majority were from the United States, and predominantly Cincinnati Children’s Hospital. Most had TSC2 mutations, which are associated with worse disease than TSC1 mutations.
Dr. Krueger reported research funding and personal compensation from Novartis, maker of everolimus. Almost all of his coinvestigators reported ties to the company. The work was supported by the Tuberous Sclerosis Alliance, which is funded in part by Novartis.
SOURCE: Krueger D et al. Neurology. 2018 Apr 90(15 Suppl.):S35.003.
REPORTING FROM AAN 2018
Key clinical point: A survey of treatment centers has begun to plug the evidence gap for using mTOR inhibitors in infants with tuberous sclerosis.
Major finding: Adverse events don’t seem more common than in trials of adults and older children, but the discontinuation rate is much higher, at about 40%.
Study details: Review of 45 children under 2 years old.
Disclosures: The lead investigator reported research funding and personal compensation from Novartis, maker of everolimus.
Source: Krueger D et al. Neurology. 2018 Apr 90(15 Suppl.):S35.003.