Pediatrics

 

Six in ten teens now have had at least one dose of the human papillomavirus (HPV) vaccine, but many still are not receiving the second dose, according to 2016 data on vaccination coverage among adolescents published in the Morbidity and Mortality Weekly Report.

Researchers analyzed data from 20,475 adolescents aged 13-17 years in the 2016 National Immunization Survey–Teen, which showed that coverage for at least one dose of the HPV vaccine had increased from 56% in 2015 to 60% in 2016. However only 43% of adolescents – 50% of females and 38% of males – were up to date with the full two-dose vaccination series, in accordance with the updated vaccine recommendations (MMWR. 2017 Aug 25;66:874-82).

Choreograph/Thinkstock

Vaccinations rates were similar between females and males aged 13 years, but among those aged 17 years, coverage was 14-23 percentage points higher in females than in males.

“Since HPV vaccine was introduced for females in 2006 and for males in 2011, coverage has increased gradu­ally among females and more rapidly among males,” wrote Tanja Y. Walker and her colleagues from the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, Atlanta. “Coverage with 1 or more doses HPV vaccine among males continues to approach that among females, particularly for adolescents aged 13 years, suggesting that HPV vaccination of both female and male adolescents has been integrated into vaccination practices.”

HPV vaccine coverage with at least one dose was highest in central cities (66%) and lowest among adolescents in nonmetropolitan areas (50%). However, HPV coverage also was higher among adolescents living below the federal poverty line, compared with those living at or above the poverty line.

There was also significant geographic variation in HPV vaccine coverage, ranging from coverage with at least one dose among 90% of females and 88% of males in Rhode Island, to just 37% of males in Indiana and Wyoming and 48% of females in Mississippi. New York City showed the greatest average annual increase in coverage of one or more doses of the HPV vaccine from 2015 to 2016 (7.7 percentage point).

The analysis also looked at coverage for the Tdap vaccine, which increased for one or more doses from 86% to 88% from 2015 to 2016, respectively, while coverage with two or more doses of the meningococcal conjugate vaccine among 17-year-olds increased from 33% to 39%, respectively.

The authors pointed out that coverage for HPV immunization was still 22-28 percentage points below coverage for Tdap and the meningococcal conjugate vaccine, suggesting there was substantial opportunity for improvement.

“Potential contributing factors might include dif­ferences in parental acceptance of certain vaccines and provider participation in, and adolescents’ eligibility for, the Vaccines for Children program,” Ms. Walker and her colleagues said.

No conflicts of interest were declared.

 

Six in ten teens now have had at least one dose of the human papillomavirus (HPV) vaccine, but many still are not receiving the second dose, according to 2016 data on vaccination coverage among adolescents published in the Morbidity and Mortality Weekly Report.

Researchers analyzed data from 20,475 adolescents aged 13-17 years in the 2016 National Immunization Survey–Teen, which showed that coverage for at least one dose of the HPV vaccine had increased from 56% in 2015 to 60% in 2016. However only 43% of adolescents – 50% of females and 38% of males – were up to date with the full two-dose vaccination series, in accordance with the updated vaccine recommendations (MMWR. 2017 Aug 25;66:874-82).

Choreograph/Thinkstock

Vaccinations rates were similar between females and males aged 13 years, but among those aged 17 years, coverage was 14-23 percentage points higher in females than in males.

“Since HPV vaccine was introduced for females in 2006 and for males in 2011, coverage has increased gradu­ally among females and more rapidly among males,” wrote Tanja Y. Walker and her colleagues from the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, Atlanta. “Coverage with 1 or more doses HPV vaccine among males continues to approach that among females, particularly for adolescents aged 13 years, suggesting that HPV vaccination of both female and male adolescents has been integrated into vaccination practices.”

HPV vaccine coverage with at least one dose was highest in central cities (66%) and lowest among adolescents in nonmetropolitan areas (50%). However, HPV coverage also was higher among adolescents living below the federal poverty line, compared with those living at or above the poverty line.

There was also significant geographic variation in HPV vaccine coverage, ranging from coverage with at least one dose among 90% of females and 88% of males in Rhode Island, to just 37% of males in Indiana and Wyoming and 48% of females in Mississippi. New York City showed the greatest average annual increase in coverage of one or more doses of the HPV vaccine from 2015 to 2016 (7.7 percentage point).

The analysis also looked at coverage for the Tdap vaccine, which increased for one or more doses from 86% to 88% from 2015 to 2016, respectively, while coverage with two or more doses of the meningococcal conjugate vaccine among 17-year-olds increased from 33% to 39%, respectively.

The authors pointed out that coverage for HPV immunization was still 22-28 percentage points below coverage for Tdap and the meningococcal conjugate vaccine, suggesting there was substantial opportunity for improvement.

“Potential contributing factors might include dif­ferences in parental acceptance of certain vaccines and provider participation in, and adolescents’ eligibility for, the Vaccines for Children program,” Ms. Walker and her colleagues said.

No conflicts of interest were declared.

 

Six in ten teens now have had at least one dose of the human papillomavirus (HPV) vaccine, but many still are not receiving the second dose, according to 2016 data on vaccination coverage among adolescents published in the Morbidity and Mortality Weekly Report.

Researchers analyzed data from 20,475 adolescents aged 13-17 years in the 2016 National Immunization Survey–Teen, which showed that coverage for at least one dose of the HPV vaccine had increased from 56% in 2015 to 60% in 2016. However only 43% of adolescents – 50% of females and 38% of males – were up to date with the full two-dose vaccination series, in accordance with the updated vaccine recommendations (MMWR. 2017 Aug 25;66:874-82).

Choreograph/Thinkstock

Vaccinations rates were similar between females and males aged 13 years, but among those aged 17 years, coverage was 14-23 percentage points higher in females than in males.

“Since HPV vaccine was introduced for females in 2006 and for males in 2011, coverage has increased gradu­ally among females and more rapidly among males,” wrote Tanja Y. Walker and her colleagues from the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, Atlanta. “Coverage with 1 or more doses HPV vaccine among males continues to approach that among females, particularly for adolescents aged 13 years, suggesting that HPV vaccination of both female and male adolescents has been integrated into vaccination practices.”

HPV vaccine coverage with at least one dose was highest in central cities (66%) and lowest among adolescents in nonmetropolitan areas (50%). However, HPV coverage also was higher among adolescents living below the federal poverty line, compared with those living at or above the poverty line.

There was also significant geographic variation in HPV vaccine coverage, ranging from coverage with at least one dose among 90% of females and 88% of males in Rhode Island, to just 37% of males in Indiana and Wyoming and 48% of females in Mississippi. New York City showed the greatest average annual increase in coverage of one or more doses of the HPV vaccine from 2015 to 2016 (7.7 percentage point).

The analysis also looked at coverage for the Tdap vaccine, which increased for one or more doses from 86% to 88% from 2015 to 2016, respectively, while coverage with two or more doses of the meningococcal conjugate vaccine among 17-year-olds increased from 33% to 39%, respectively.

The authors pointed out that coverage for HPV immunization was still 22-28 percentage points below coverage for Tdap and the meningococcal conjugate vaccine, suggesting there was substantial opportunity for improvement.

“Potential contributing factors might include dif­ferences in parental acceptance of certain vaccines and provider participation in, and adolescents’ eligibility for, the Vaccines for Children program,” Ms. Walker and her colleagues said.

No conflicts of interest were declared.

Global mortality due to rheumatic heart disease fell by about 48% during a recent 25-year-period, but some of the poorest areas of the world were left behind, according to a report in the New England Journal of Medicine.

Those regions included Oceania, South Asia, and central sub-Saharan Africa, where rheumatic heart disease remains endemic, wrote David A. Watkins, MD, MPH, of the University of Washington, Seattle, and his coinvestigators. “We estimate that 10 persons per 1,000 population living in South Asia and central sub-Saharan Africa and 15 persons per 1,000 population in Oceania were living with rheumatic heart disease in the year 2015,” they wrote. “Improvements in the measurement of the burden of rheumatic heart disease will assist in planning for its control and will help identify countries where further investments are needed.”

Rheumatic heart disease is a sequela of untreated streptococcal pharyngitis, which is associated with poverty, overcrowding, poor sanitation, and other social predictors of poor health. In high-income countries, treatment with penicillin G and improved sanitation had nearly eliminated rheumatic heart disease by the late 20th century, but local studies pointed to ongoing morbidity and mortality in lower-income regions.

To better define the problem, Dr. Watkins and his associates analyzed epidemiologic studies of rheumatic heart disease from 1990 through 2015. They used the Cause of Death Ensemble model, which estimates mortality more reliably than older methods, and DisMod-MR (version 2.1), which sums epidemiologic data from multiple sources and corrects for gaps and inconsistencies (N Engl J Med. 2017;377:713-22).

Worldwide, about 319,400 individuals died of rheumatic heart disease in 2015, the researchers reported. Age-adjusted death rates fell by about 48% (95% confidence interval, 45%-51%), from 9.2 deaths per 100,000 population in 1990 to 4.8 deaths per 100,000 population in 2015. But this global trend masked striking regional disparities. In 1990, 77% of deaths from rheumatic heart disease occurred in endemic areas of Africa, South Asia, Oceania, and the Caribbean; by 2015, 82% of deaths occurred in endemic regions. Oceania, South Asia, and central sub-Saharan Africa had the highest death rates and were the only regions where the 95% confidence intervals for 1990 and 2015 overlapped, the investigators noted.

In 2015, age-standardized death rates exceeded 10 deaths per 100,000 population in the Solomon Islands, Pakistan, Papua New Guinea, Kiribati, Vanuatu, Fiji, India, Federated States of Micronesia, Marshall Islands, Central African Republic, and Lesotho, they reported. Estimated fatalities were highest in India (119,100 deaths), China (72,600), and Pakistan (18,900). They estimated that in 2015, there were 33.2 million cases of rheumatic heart disease and 10.5 million associated disability-adjusted life-years globally.

The study excluded “borderline” or subclinical rheumatic heart disease, which is detected by echocardiography and whose management remains unclear. “Better data for low-income and middle-income countries are needed to guide policies for the control of rheumatic heart disease,” the investigators wrote. They recommended studying death certificate misclassifications, disease prevalence among adults, and longitudinal trends in nonfatal outcomes and excess mortality.

Funders of the study included the Bill and Melinda Gates Foundation and the Medtronic Foundation. Dr. Watkins disclosed grants from the Medtronic Foundation during the conduct of the study and grants from the Bill and Melinda Gates Foundation outside the submitted work.

Global mortality due to rheumatic heart disease fell by about 48% during a recent 25-year-period, but some of the poorest areas of the world were left behind, according to a report in the New England Journal of Medicine.

Those regions included Oceania, South Asia, and central sub-Saharan Africa, where rheumatic heart disease remains endemic, wrote David A. Watkins, MD, MPH, of the University of Washington, Seattle, and his coinvestigators. “We estimate that 10 persons per 1,000 population living in South Asia and central sub-Saharan Africa and 15 persons per 1,000 population in Oceania were living with rheumatic heart disease in the year 2015,” they wrote. “Improvements in the measurement of the burden of rheumatic heart disease will assist in planning for its control and will help identify countries where further investments are needed.”

Rheumatic heart disease is a sequela of untreated streptococcal pharyngitis, which is associated with poverty, overcrowding, poor sanitation, and other social predictors of poor health. In high-income countries, treatment with penicillin G and improved sanitation had nearly eliminated rheumatic heart disease by the late 20th century, but local studies pointed to ongoing morbidity and mortality in lower-income regions.

To better define the problem, Dr. Watkins and his associates analyzed epidemiologic studies of rheumatic heart disease from 1990 through 2015. They used the Cause of Death Ensemble model, which estimates mortality more reliably than older methods, and DisMod-MR (version 2.1), which sums epidemiologic data from multiple sources and corrects for gaps and inconsistencies (N Engl J Med. 2017;377:713-22).

Worldwide, about 319,400 individuals died of rheumatic heart disease in 2015, the researchers reported. Age-adjusted death rates fell by about 48% (95% confidence interval, 45%-51%), from 9.2 deaths per 100,000 population in 1990 to 4.8 deaths per 100,000 population in 2015. But this global trend masked striking regional disparities. In 1990, 77% of deaths from rheumatic heart disease occurred in endemic areas of Africa, South Asia, Oceania, and the Caribbean; by 2015, 82% of deaths occurred in endemic regions. Oceania, South Asia, and central sub-Saharan Africa had the highest death rates and were the only regions where the 95% confidence intervals for 1990 and 2015 overlapped, the investigators noted.

In 2015, age-standardized death rates exceeded 10 deaths per 100,000 population in the Solomon Islands, Pakistan, Papua New Guinea, Kiribati, Vanuatu, Fiji, India, Federated States of Micronesia, Marshall Islands, Central African Republic, and Lesotho, they reported. Estimated fatalities were highest in India (119,100 deaths), China (72,600), and Pakistan (18,900). They estimated that in 2015, there were 33.2 million cases of rheumatic heart disease and 10.5 million associated disability-adjusted life-years globally.

The study excluded “borderline” or subclinical rheumatic heart disease, which is detected by echocardiography and whose management remains unclear. “Better data for low-income and middle-income countries are needed to guide policies for the control of rheumatic heart disease,” the investigators wrote. They recommended studying death certificate misclassifications, disease prevalence among adults, and longitudinal trends in nonfatal outcomes and excess mortality.

Funders of the study included the Bill and Melinda Gates Foundation and the Medtronic Foundation. Dr. Watkins disclosed grants from the Medtronic Foundation during the conduct of the study and grants from the Bill and Melinda Gates Foundation outside the submitted work.

Global mortality due to rheumatic heart disease fell by about 48% during a recent 25-year-period, but some of the poorest areas of the world were left behind, according to a report in the New England Journal of Medicine.

Those regions included Oceania, South Asia, and central sub-Saharan Africa, where rheumatic heart disease remains endemic, wrote David A. Watkins, MD, MPH, of the University of Washington, Seattle, and his coinvestigators. “We estimate that 10 persons per 1,000 population living in South Asia and central sub-Saharan Africa and 15 persons per 1,000 population in Oceania were living with rheumatic heart disease in the year 2015,” they wrote. “Improvements in the measurement of the burden of rheumatic heart disease will assist in planning for its control and will help identify countries where further investments are needed.”

Rheumatic heart disease is a sequela of untreated streptococcal pharyngitis, which is associated with poverty, overcrowding, poor sanitation, and other social predictors of poor health. In high-income countries, treatment with penicillin G and improved sanitation had nearly eliminated rheumatic heart disease by the late 20th century, but local studies pointed to ongoing morbidity and mortality in lower-income regions.

To better define the problem, Dr. Watkins and his associates analyzed epidemiologic studies of rheumatic heart disease from 1990 through 2015. They used the Cause of Death Ensemble model, which estimates mortality more reliably than older methods, and DisMod-MR (version 2.1), which sums epidemiologic data from multiple sources and corrects for gaps and inconsistencies (N Engl J Med. 2017;377:713-22).

Worldwide, about 319,400 individuals died of rheumatic heart disease in 2015, the researchers reported. Age-adjusted death rates fell by about 48% (95% confidence interval, 45%-51%), from 9.2 deaths per 100,000 population in 1990 to 4.8 deaths per 100,000 population in 2015. But this global trend masked striking regional disparities. In 1990, 77% of deaths from rheumatic heart disease occurred in endemic areas of Africa, South Asia, Oceania, and the Caribbean; by 2015, 82% of deaths occurred in endemic regions. Oceania, South Asia, and central sub-Saharan Africa had the highest death rates and were the only regions where the 95% confidence intervals for 1990 and 2015 overlapped, the investigators noted.

In 2015, age-standardized death rates exceeded 10 deaths per 100,000 population in the Solomon Islands, Pakistan, Papua New Guinea, Kiribati, Vanuatu, Fiji, India, Federated States of Micronesia, Marshall Islands, Central African Republic, and Lesotho, they reported. Estimated fatalities were highest in India (119,100 deaths), China (72,600), and Pakistan (18,900). They estimated that in 2015, there were 33.2 million cases of rheumatic heart disease and 10.5 million associated disability-adjusted life-years globally.

The study excluded “borderline” or subclinical rheumatic heart disease, which is detected by echocardiography and whose management remains unclear. “Better data for low-income and middle-income countries are needed to guide policies for the control of rheumatic heart disease,” the investigators wrote. They recommended studying death certificate misclassifications, disease prevalence among adults, and longitudinal trends in nonfatal outcomes and excess mortality.

Funders of the study included the Bill and Melinda Gates Foundation and the Medtronic Foundation. Dr. Watkins disclosed grants from the Medtronic Foundation during the conduct of the study and grants from the Bill and Melinda Gates Foundation outside the submitted work.

DENVER – The Colorado experience with medical marijuana products for the treatment of pediatric epilepsy holds useful lessons for physicians in states where legal marijuana is a far more recent development, Amy R. Brooks-Kayal, MD, said at the annual meeting of the Teratology Society.

Medical marijuana has been legal in Colorado for nearly 20 years. But the drug’s potential role in treating intractable pediatric epilepsy started getting a lot more attention in 2013 when a CNN report by Sanjay Gupta, MD, chronicled a child’s remarkable turnaround in response to medical marijuana. The story triggered a migration to the state by what has been termed “marijuana refugees”: desperate families with children who had the most severe, complex, treatment-refractory seizure disorders, said Dr. Brooks-Kayal, professor of pediatrics and neurology and chief of pediatric neurology at the University of Colorado at Denver, Aurora.

Today, Dr. Brooks-Kayal and her colleagues at Children’s Hospital Colorado provide care for roughly 300 children on cannabinoids for refractory epilepsy. Back when the CNN story went viral, however, they were caught off guard by the patient influx. They weren’t familiar with medical marijuana, and they had to learn on the fly. They quickly discovered that there were, at that time, no reliable data on the safety, efficacy, pharmacokinetics, or drug interactions of medical marijuana products. And the products were not reliably standardized as to content, quality, or purity.

The situation, fortunately, has improved. There is now phase 3 randomized, double-blind, placebo-controlled clinical trial evidence of efficacy for an investigational proprietary cannabidiol oral solution known as Epidiolex for children and young adults with Dravet syndrome and drug-resistant seizures, as well as documentation of multiple adverse effects (N Engl J Med. 2017 May 25;376[21]:2011-20).

Dr. Brooks-Kayal, a past president of the American Epilepsy Society, said she believes this medication is potentially approvable by the Food and Drug Administration.

“In the world of new seizure medications, what is usually required by the FDA is a 50% reduction in seizures, which this agent gets close to reaching. But it does have a higher adverse event rate than many of our medications. However, this is a tough crowd. These are very, very difficult-to-treat children. So I think any addition to our armamentarium for these kids is going to be beneficial,” she said. “Unfortunately, though, it’s not going to be the panacea that I think some of our families are looking for.”

Based upon the Colorado experience, Dr. Brooks-Kayal offered the following suggestions for colleagues around the country as they begin fielding questions from families about medical marijuana for pediatric epilepsy:
 

• Provide families with the current data, discuss what’s known and still unknown, and encourage families to disclose the use of cannabinoids so the child can be monitored.
• Have the family keep a seizure diary. Get a baseline EEG and another at about 12 weeks. Do routine laboratory monitoring every 4 weeks, including liver function tests. “We think CBDs [cannabinoids] have the potential to worsen liver function,” she said.
• Stress the importance of leaving other seizure medications unchanged. “When this first started, the medical marijuana providers were recommending patients stop their other medications. The providers don’t do that anymore, fortunately,” Dr. Brooks-Kayal said. “Every week we were putting a child in a medically induced coma because they had status epilepticus, and it was the only way to stop their seizures. They started using marijuana products, they were sure it was going to be the cure, they stopped all their other medications, and they developed status epilepticus.”
• Establish policies with the hospital administration and pharmacy about how to handle marijuana products when a child is in the hospital. The Children’s Hospital Colorado pharmacy cannot store or dispense marijuana products because of federal regulations. And again, it’s unsafe to stop seizure medications abruptly, including marijuana products. Informed consent procedures need to be developed for when patients on cannabinoids are hospitalized.
• Encourage families to participate in one of the six Food and Drug Administration–approved double-blind, placebo-controlled trials of Epidiolex for Dravet syndrome, Lennox-Gastaut syndrome, tuberous sclerosis complex, and infantile spasms sponsored by GW Pharmaceuticals.

Breaking down the evidence

Here’s what’s known and what is still unknown about the safety and efficacy of cannabinoids for the treatment of refractory pediatric epilepsy, according to Dr. Brooks-Kayal.

 

The knowns

Cannabinoids show activity against seizures in animal models. Moreover, initial clinical data suggest they may decrease seizures in some children with refractory epilepsy. This evidence includes a retrospective study from Children’s Hospital Colorado reliant upon parental reports of improvement (Epilepsy Behav. 2015 Apr;45:49-52), an Israeli retrospective study (Seizure. 2016 Feb;35:41-4), a positive open-label trial of an investigational oral oil-based solution of a pharmaceutical-grade cannabidiol known as Epidiolex (Lancet Neurol. 2016 Mar;15[3]:270-8), and evidence from a Food and Drug Administration–authorized phase 3, randomized clinical trial of Epidiolex (N Engl J Med. 2017 May 25;376[21]:2011-20).

The incidence of short-term adverse events associated with cannabinoids is substantial. The rate seems to be higher with Epidiolex than with many other medical marijuana products, although the potency is greater, too. These include somnolence, fatigue, and convulsions.

In addition, gastrointestinal side effects are common with Epidiolex. “Some are probably due to the oil base; some [are] probably due to the cannabidiol itself,” said Dr. Brooks-Kayal.
 

The unknowns

What types of seizures does it work for? This is under study in a series of FDA-authorized phase 3 randomized trials.

What is the placebo-subtracted response rate to cannabidiol? In the randomized trial published in the New England Journal of Medicine, the median monthly frequency of seizures decreased from 12.4 to 5.9 with cannabidiol, compared with a reduction from 14.9 to 14.1 with placebo. This needs confirmation in additional trials.

What’s the optimal dose? The randomized trial tested just one dose – 20 mg/kg per day.

What are the drug interactions and their possible impact on cannabidiol efficacy? Outcomes appear to be better in patients on concomitant clobazam (Onfi), perhaps because of the significantly higher blood levels of clobazam’s major metabolite in children on cannabidiol.
 

Long-term effects

The jury is still out on the long-term adverse effects. “These medical marijuana products are being given by families to 2- and 3-month-olds. It will be years before we know about potential long-term cognitive and behavioral effects,” Dr. Brooks-Kayal said.

Dr. Brooks-Kayal reported having no financial conflicts of interest regarding her presentation.
 

bjancin@frontlinemedcom.com

DENVER – The Colorado experience with medical marijuana products for the treatment of pediatric epilepsy holds useful lessons for physicians in states where legal marijuana is a far more recent development, Amy R. Brooks-Kayal, MD, said at the annual meeting of the Teratology Society.

Medical marijuana has been legal in Colorado for nearly 20 years. But the drug’s potential role in treating intractable pediatric epilepsy started getting a lot more attention in 2013 when a CNN report by Sanjay Gupta, MD, chronicled a child’s remarkable turnaround in response to medical marijuana. The story triggered a migration to the state by what has been termed “marijuana refugees”: desperate families with children who had the most severe, complex, treatment-refractory seizure disorders, said Dr. Brooks-Kayal, professor of pediatrics and neurology and chief of pediatric neurology at the University of Colorado at Denver, Aurora.

Today, Dr. Brooks-Kayal and her colleagues at Children’s Hospital Colorado provide care for roughly 300 children on cannabinoids for refractory epilepsy. Back when the CNN story went viral, however, they were caught off guard by the patient influx. They weren’t familiar with medical marijuana, and they had to learn on the fly. They quickly discovered that there were, at that time, no reliable data on the safety, efficacy, pharmacokinetics, or drug interactions of medical marijuana products. And the products were not reliably standardized as to content, quality, or purity.

The situation, fortunately, has improved. There is now phase 3 randomized, double-blind, placebo-controlled clinical trial evidence of efficacy for an investigational proprietary cannabidiol oral solution known as Epidiolex for children and young adults with Dravet syndrome and drug-resistant seizures, as well as documentation of multiple adverse effects (N Engl J Med. 2017 May 25;376[21]:2011-20).

Dr. Brooks-Kayal, a past president of the American Epilepsy Society, said she believes this medication is potentially approvable by the Food and Drug Administration.

“In the world of new seizure medications, what is usually required by the FDA is a 50% reduction in seizures, which this agent gets close to reaching. But it does have a higher adverse event rate than many of our medications. However, this is a tough crowd. These are very, very difficult-to-treat children. So I think any addition to our armamentarium for these kids is going to be beneficial,” she said. “Unfortunately, though, it’s not going to be the panacea that I think some of our families are looking for.”

Based upon the Colorado experience, Dr. Brooks-Kayal offered the following suggestions for colleagues around the country as they begin fielding questions from families about medical marijuana for pediatric epilepsy:
 

• Provide families with the current data, discuss what’s known and still unknown, and encourage families to disclose the use of cannabinoids so the child can be monitored.
• Have the family keep a seizure diary. Get a baseline EEG and another at about 12 weeks. Do routine laboratory monitoring every 4 weeks, including liver function tests. “We think CBDs [cannabinoids] have the potential to worsen liver function,” she said.
• Stress the importance of leaving other seizure medications unchanged. “When this first started, the medical marijuana providers were recommending patients stop their other medications. The providers don’t do that anymore, fortunately,” Dr. Brooks-Kayal said. “Every week we were putting a child in a medically induced coma because they had status epilepticus, and it was the only way to stop their seizures. They started using marijuana products, they were sure it was going to be the cure, they stopped all their other medications, and they developed status epilepticus.”
• Establish policies with the hospital administration and pharmacy about how to handle marijuana products when a child is in the hospital. The Children’s Hospital Colorado pharmacy cannot store or dispense marijuana products because of federal regulations. And again, it’s unsafe to stop seizure medications abruptly, including marijuana products. Informed consent procedures need to be developed for when patients on cannabinoids are hospitalized.
• Encourage families to participate in one of the six Food and Drug Administration–approved double-blind, placebo-controlled trials of Epidiolex for Dravet syndrome, Lennox-Gastaut syndrome, tuberous sclerosis complex, and infantile spasms sponsored by GW Pharmaceuticals.

Breaking down the evidence

Here’s what’s known and what is still unknown about the safety and efficacy of cannabinoids for the treatment of refractory pediatric epilepsy, according to Dr. Brooks-Kayal.

 

The knowns

Cannabinoids show activity against seizures in animal models. Moreover, initial clinical data suggest they may decrease seizures in some children with refractory epilepsy. This evidence includes a retrospective study from Children’s Hospital Colorado reliant upon parental reports of improvement (Epilepsy Behav. 2015 Apr;45:49-52), an Israeli retrospective study (Seizure. 2016 Feb;35:41-4), a positive open-label trial of an investigational oral oil-based solution of a pharmaceutical-grade cannabidiol known as Epidiolex (Lancet Neurol. 2016 Mar;15[3]:270-8), and evidence from a Food and Drug Administration–authorized phase 3, randomized clinical trial of Epidiolex (N Engl J Med. 2017 May 25;376[21]:2011-20).

The incidence of short-term adverse events associated with cannabinoids is substantial. The rate seems to be higher with Epidiolex than with many other medical marijuana products, although the potency is greater, too. These include somnolence, fatigue, and convulsions.

In addition, gastrointestinal side effects are common with Epidiolex. “Some are probably due to the oil base; some [are] probably due to the cannabidiol itself,” said Dr. Brooks-Kayal.
 

The unknowns

What types of seizures does it work for? This is under study in a series of FDA-authorized phase 3 randomized trials.

What is the placebo-subtracted response rate to cannabidiol? In the randomized trial published in the New England Journal of Medicine, the median monthly frequency of seizures decreased from 12.4 to 5.9 with cannabidiol, compared with a reduction from 14.9 to 14.1 with placebo. This needs confirmation in additional trials.

What’s the optimal dose? The randomized trial tested just one dose – 20 mg/kg per day.

What are the drug interactions and their possible impact on cannabidiol efficacy? Outcomes appear to be better in patients on concomitant clobazam (Onfi), perhaps because of the significantly higher blood levels of clobazam’s major metabolite in children on cannabidiol.
 

Long-term effects

The jury is still out on the long-term adverse effects. “These medical marijuana products are being given by families to 2- and 3-month-olds. It will be years before we know about potential long-term cognitive and behavioral effects,” Dr. Brooks-Kayal said.

Dr. Brooks-Kayal reported having no financial conflicts of interest regarding her presentation.
 

bjancin@frontlinemedcom.com

DENVER – The Colorado experience with medical marijuana products for the treatment of pediatric epilepsy holds useful lessons for physicians in states where legal marijuana is a far more recent development, Amy R. Brooks-Kayal, MD, said at the annual meeting of the Teratology Society.

Medical marijuana has been legal in Colorado for nearly 20 years. But the drug’s potential role in treating intractable pediatric epilepsy started getting a lot more attention in 2013 when a CNN report by Sanjay Gupta, MD, chronicled a child’s remarkable turnaround in response to medical marijuana. The story triggered a migration to the state by what has been termed “marijuana refugees”: desperate families with children who had the most severe, complex, treatment-refractory seizure disorders, said Dr. Brooks-Kayal, professor of pediatrics and neurology and chief of pediatric neurology at the University of Colorado at Denver, Aurora.

Today, Dr. Brooks-Kayal and her colleagues at Children’s Hospital Colorado provide care for roughly 300 children on cannabinoids for refractory epilepsy. Back when the CNN story went viral, however, they were caught off guard by the patient influx. They weren’t familiar with medical marijuana, and they had to learn on the fly. They quickly discovered that there were, at that time, no reliable data on the safety, efficacy, pharmacokinetics, or drug interactions of medical marijuana products. And the products were not reliably standardized as to content, quality, or purity.

The situation, fortunately, has improved. There is now phase 3 randomized, double-blind, placebo-controlled clinical trial evidence of efficacy for an investigational proprietary cannabidiol oral solution known as Epidiolex for children and young adults with Dravet syndrome and drug-resistant seizures, as well as documentation of multiple adverse effects (N Engl J Med. 2017 May 25;376[21]:2011-20).

Dr. Brooks-Kayal, a past president of the American Epilepsy Society, said she believes this medication is potentially approvable by the Food and Drug Administration.

“In the world of new seizure medications, what is usually required by the FDA is a 50% reduction in seizures, which this agent gets close to reaching. But it does have a higher adverse event rate than many of our medications. However, this is a tough crowd. These are very, very difficult-to-treat children. So I think any addition to our armamentarium for these kids is going to be beneficial,” she said. “Unfortunately, though, it’s not going to be the panacea that I think some of our families are looking for.”

Based upon the Colorado experience, Dr. Brooks-Kayal offered the following suggestions for colleagues around the country as they begin fielding questions from families about medical marijuana for pediatric epilepsy:
 

• Provide families with the current data, discuss what’s known and still unknown, and encourage families to disclose the use of cannabinoids so the child can be monitored.
• Have the family keep a seizure diary. Get a baseline EEG and another at about 12 weeks. Do routine laboratory monitoring every 4 weeks, including liver function tests. “We think CBDs [cannabinoids] have the potential to worsen liver function,” she said.
• Stress the importance of leaving other seizure medications unchanged. “When this first started, the medical marijuana providers were recommending patients stop their other medications. The providers don’t do that anymore, fortunately,” Dr. Brooks-Kayal said. “Every week we were putting a child in a medically induced coma because they had status epilepticus, and it was the only way to stop their seizures. They started using marijuana products, they were sure it was going to be the cure, they stopped all their other medications, and they developed status epilepticus.”
• Establish policies with the hospital administration and pharmacy about how to handle marijuana products when a child is in the hospital. The Children’s Hospital Colorado pharmacy cannot store or dispense marijuana products because of federal regulations. And again, it’s unsafe to stop seizure medications abruptly, including marijuana products. Informed consent procedures need to be developed for when patients on cannabinoids are hospitalized.
• Encourage families to participate in one of the six Food and Drug Administration–approved double-blind, placebo-controlled trials of Epidiolex for Dravet syndrome, Lennox-Gastaut syndrome, tuberous sclerosis complex, and infantile spasms sponsored by GW Pharmaceuticals.

Breaking down the evidence

Here’s what’s known and what is still unknown about the safety and efficacy of cannabinoids for the treatment of refractory pediatric epilepsy, according to Dr. Brooks-Kayal.

 

The knowns

Cannabinoids show activity against seizures in animal models. Moreover, initial clinical data suggest they may decrease seizures in some children with refractory epilepsy. This evidence includes a retrospective study from Children’s Hospital Colorado reliant upon parental reports of improvement (Epilepsy Behav. 2015 Apr;45:49-52), an Israeli retrospective study (Seizure. 2016 Feb;35:41-4), a positive open-label trial of an investigational oral oil-based solution of a pharmaceutical-grade cannabidiol known as Epidiolex (Lancet Neurol. 2016 Mar;15[3]:270-8), and evidence from a Food and Drug Administration–authorized phase 3, randomized clinical trial of Epidiolex (N Engl J Med. 2017 May 25;376[21]:2011-20).

The incidence of short-term adverse events associated with cannabinoids is substantial. The rate seems to be higher with Epidiolex than with many other medical marijuana products, although the potency is greater, too. These include somnolence, fatigue, and convulsions.

In addition, gastrointestinal side effects are common with Epidiolex. “Some are probably due to the oil base; some [are] probably due to the cannabidiol itself,” said Dr. Brooks-Kayal.
 

The unknowns

What types of seizures does it work for? This is under study in a series of FDA-authorized phase 3 randomized trials.

What is the placebo-subtracted response rate to cannabidiol? In the randomized trial published in the New England Journal of Medicine, the median monthly frequency of seizures decreased from 12.4 to 5.9 with cannabidiol, compared with a reduction from 14.9 to 14.1 with placebo. This needs confirmation in additional trials.

What’s the optimal dose? The randomized trial tested just one dose – 20 mg/kg per day.

What are the drug interactions and their possible impact on cannabidiol efficacy? Outcomes appear to be better in patients on concomitant clobazam (Onfi), perhaps because of the significantly higher blood levels of clobazam’s major metabolite in children on cannabidiol.
 

Long-term effects

The jury is still out on the long-term adverse effects. “These medical marijuana products are being given by families to 2- and 3-month-olds. It will be years before we know about potential long-term cognitive and behavioral effects,” Dr. Brooks-Kayal said.

Dr. Brooks-Kayal reported having no financial conflicts of interest regarding her presentation.
 

bjancin@frontlinemedcom.com

Photo by Bill Branson

New research suggests survivors of childhood cancer can incur high out-of-pocket medical costs into adulthood and may forgo healthcare to lessen this financial burden.

The study showed that childhood cancer survivors (CCSs) were more likely than non-CCSs to have out-of-pocket medical costs that were at least 10% of their annual income.

And these high costs were associated with delaying care or skipping it altogether.

These findings were published in the Journal of Clinical Oncology.

“Survivors who reported spending a higher percentage of their income on out-of-pocket medical costs were not only more likely to report financial burden, they also were at risk for undertaking behaviors potentially detrimental to their health in order to save money,” said study author Ryan Nipp, MD, of Massachusetts General Hospital Cancer Center in Boston.

“While studies have identified associations between financial burden and patients’ treatment outcomes, quality of life, and even survival among adults with cancer, as far as we know, this is the first to report these associations in survivors of childhood cancer.”

For this research, Dr Nipp and his colleagues surveyed participants in the Childhood Cancer Survivor Study. This included adults who had been treated for childhood cancers between 1970 and 1986 along with a control group of siblings not affected by cancer.

In 2011 and 2012, participants were asked to provide information about their health insurance, the out-of-pocket healthcare costs they paid during the previous year, and sociodemographic information such as annual income and employment status.

The researchers also asked participants whether medical costs posed a financial burden and, if so, what measures they had taken to deal with that burden.

Study population

The researchers received complete responses from 580 CCSs and 173 of their siblings without a history of cancer. The most common cancer diagnosis was leukemia (33%), followed by Hodgkin lymphoma (14%), while non-Hodgkin lymphoma was less common (7%).

CCSs were a mean of 30.2 years from diagnosis. Use of chemotherapy (77%), radiation (66%), and surgery (81%) were common. Few patients had cancer recurrence (13%) or second cancers (5%).

There was no significant difference between CCSs and their siblings with regard to age at the time of the survey (P=0.071), household income (P=0.053), education (P=0.345), health insurance status (P=0.317), or having at least 1 hospitalization in the past year (P=0.270).

However, CCSs were significantly more likely than siblings to have chronic health conditions (P<0.001). Forty percent of CCSs had severe or life-threatening chronic conditions, compared to 17% of siblings.

Seventy-six percent of CCSs and 80% of siblings were employed. Twenty-nine percent of CCSs and 39% of siblings had household incomes exceeding $100,000. Twelve percent of CCSs and 5% of siblings had household incomes below $20,000.

Ninety-one percent of CCSs and 93% of siblings were insured. Most subjects in both groups (81% and 87%, respectively) had employer-sponsored insurance.

Results

CCSs were significantly more likely than their siblings to have out-of-pocket medical costs that were at least 10% of their annual income—10% and 3%, respectively (P<0.001).

Among CCSs, those with higher out-of-pocket costs (≥10% vs <10% of income) were more likely to have household incomes below $50,000 (odds ratio [OR]=5.5) and to report being hospitalized in the past year (OR=2.3).

CCSs with a higher percentage of their income spent on out-of-pocket costs were also more likely to:

• Have problems paying their medical bills (OR=8.8)
• Report inability to pay for basic costs of living such as food, heat, or rent (OR=6.1)
• Defer healthcare for a medical problem (OR=3.1)
• Skip a test, treatment, or follow-up (OR=2.1)
• Consider filing for bankruptcy (OR=6.4).

 

“A more comprehensive understanding of the relationship between high out-of-pocket medical costs and the adverse effects of increased financial burden on cancer survivors could be instrumental in helping us identify those at risk for higher costs to help us address their financial challenges and improve health outcomes,” Dr Nipp said.

“It could also help inform policy changes to help meet the unique needs of cancer survivors and improve our understanding of how both higher costs and resulting financial burden influence patients’ approach to their medical care and decision-making.”

Photo by Bill Branson

New research suggests survivors of childhood cancer can incur high out-of-pocket medical costs into adulthood and may forgo healthcare to lessen this financial burden.

The study showed that childhood cancer survivors (CCSs) were more likely than non-CCSs to have out-of-pocket medical costs that were at least 10% of their annual income.

And these high costs were associated with delaying care or skipping it altogether.

These findings were published in the Journal of Clinical Oncology.

“Survivors who reported spending a higher percentage of their income on out-of-pocket medical costs were not only more likely to report financial burden, they also were at risk for undertaking behaviors potentially detrimental to their health in order to save money,” said study author Ryan Nipp, MD, of Massachusetts General Hospital Cancer Center in Boston.

“While studies have identified associations between financial burden and patients’ treatment outcomes, quality of life, and even survival among adults with cancer, as far as we know, this is the first to report these associations in survivors of childhood cancer.”

For this research, Dr Nipp and his colleagues surveyed participants in the Childhood Cancer Survivor Study. This included adults who had been treated for childhood cancers between 1970 and 1986 along with a control group of siblings not affected by cancer.

In 2011 and 2012, participants were asked to provide information about their health insurance, the out-of-pocket healthcare costs they paid during the previous year, and sociodemographic information such as annual income and employment status.

The researchers also asked participants whether medical costs posed a financial burden and, if so, what measures they had taken to deal with that burden.

Study population

The researchers received complete responses from 580 CCSs and 173 of their siblings without a history of cancer. The most common cancer diagnosis was leukemia (33%), followed by Hodgkin lymphoma (14%), while non-Hodgkin lymphoma was less common (7%).

CCSs were a mean of 30.2 years from diagnosis. Use of chemotherapy (77%), radiation (66%), and surgery (81%) were common. Few patients had cancer recurrence (13%) or second cancers (5%).

There was no significant difference between CCSs and their siblings with regard to age at the time of the survey (P=0.071), household income (P=0.053), education (P=0.345), health insurance status (P=0.317), or having at least 1 hospitalization in the past year (P=0.270).

However, CCSs were significantly more likely than siblings to have chronic health conditions (P<0.001). Forty percent of CCSs had severe or life-threatening chronic conditions, compared to 17% of siblings.

Seventy-six percent of CCSs and 80% of siblings were employed. Twenty-nine percent of CCSs and 39% of siblings had household incomes exceeding $100,000. Twelve percent of CCSs and 5% of siblings had household incomes below $20,000.

Ninety-one percent of CCSs and 93% of siblings were insured. Most subjects in both groups (81% and 87%, respectively) had employer-sponsored insurance.

Results

CCSs were significantly more likely than their siblings to have out-of-pocket medical costs that were at least 10% of their annual income—10% and 3%, respectively (P<0.001).

Among CCSs, those with higher out-of-pocket costs (≥10% vs <10% of income) were more likely to have household incomes below $50,000 (odds ratio [OR]=5.5) and to report being hospitalized in the past year (OR=2.3).

CCSs with a higher percentage of their income spent on out-of-pocket costs were also more likely to:

• Have problems paying their medical bills (OR=8.8)
• Report inability to pay for basic costs of living such as food, heat, or rent (OR=6.1)
• Defer healthcare for a medical problem (OR=3.1)
• Skip a test, treatment, or follow-up (OR=2.1)
• Consider filing for bankruptcy (OR=6.4).

 

“A more comprehensive understanding of the relationship between high out-of-pocket medical costs and the adverse effects of increased financial burden on cancer survivors could be instrumental in helping us identify those at risk for higher costs to help us address their financial challenges and improve health outcomes,” Dr Nipp said.

“It could also help inform policy changes to help meet the unique needs of cancer survivors and improve our understanding of how both higher costs and resulting financial burden influence patients’ approach to their medical care and decision-making.”

Photo by Bill Branson

New research suggests survivors of childhood cancer can incur high out-of-pocket medical costs into adulthood and may forgo healthcare to lessen this financial burden.

The study showed that childhood cancer survivors (CCSs) were more likely than non-CCSs to have out-of-pocket medical costs that were at least 10% of their annual income.

And these high costs were associated with delaying care or skipping it altogether.

These findings were published in the Journal of Clinical Oncology.

“Survivors who reported spending a higher percentage of their income on out-of-pocket medical costs were not only more likely to report financial burden, they also were at risk for undertaking behaviors potentially detrimental to their health in order to save money,” said study author Ryan Nipp, MD, of Massachusetts General Hospital Cancer Center in Boston.

“While studies have identified associations between financial burden and patients’ treatment outcomes, quality of life, and even survival among adults with cancer, as far as we know, this is the first to report these associations in survivors of childhood cancer.”

For this research, Dr Nipp and his colleagues surveyed participants in the Childhood Cancer Survivor Study. This included adults who had been treated for childhood cancers between 1970 and 1986 along with a control group of siblings not affected by cancer.

In 2011 and 2012, participants were asked to provide information about their health insurance, the out-of-pocket healthcare costs they paid during the previous year, and sociodemographic information such as annual income and employment status.

The researchers also asked participants whether medical costs posed a financial burden and, if so, what measures they had taken to deal with that burden.

Study population

The researchers received complete responses from 580 CCSs and 173 of their siblings without a history of cancer. The most common cancer diagnosis was leukemia (33%), followed by Hodgkin lymphoma (14%), while non-Hodgkin lymphoma was less common (7%).

CCSs were a mean of 30.2 years from diagnosis. Use of chemotherapy (77%), radiation (66%), and surgery (81%) were common. Few patients had cancer recurrence (13%) or second cancers (5%).

There was no significant difference between CCSs and their siblings with regard to age at the time of the survey (P=0.071), household income (P=0.053), education (P=0.345), health insurance status (P=0.317), or having at least 1 hospitalization in the past year (P=0.270).

However, CCSs were significantly more likely than siblings to have chronic health conditions (P<0.001). Forty percent of CCSs had severe or life-threatening chronic conditions, compared to 17% of siblings.

Seventy-six percent of CCSs and 80% of siblings were employed. Twenty-nine percent of CCSs and 39% of siblings had household incomes exceeding $100,000. Twelve percent of CCSs and 5% of siblings had household incomes below $20,000.

Ninety-one percent of CCSs and 93% of siblings were insured. Most subjects in both groups (81% and 87%, respectively) had employer-sponsored insurance.

Results

CCSs were significantly more likely than their siblings to have out-of-pocket medical costs that were at least 10% of their annual income—10% and 3%, respectively (P<0.001).

Among CCSs, those with higher out-of-pocket costs (≥10% vs <10% of income) were more likely to have household incomes below $50,000 (odds ratio [OR]=5.5) and to report being hospitalized in the past year (OR=2.3).

CCSs with a higher percentage of their income spent on out-of-pocket costs were also more likely to:

• Have problems paying their medical bills (OR=8.8)
• Report inability to pay for basic costs of living such as food, heat, or rent (OR=6.1)
• Defer healthcare for a medical problem (OR=3.1)
• Skip a test, treatment, or follow-up (OR=2.1)
• Consider filing for bankruptcy (OR=6.4).

 

“A more comprehensive understanding of the relationship between high out-of-pocket medical costs and the adverse effects of increased financial burden on cancer survivors could be instrumental in helping us identify those at risk for higher costs to help us address their financial challenges and improve health outcomes,” Dr Nipp said.

“It could also help inform policy changes to help meet the unique needs of cancer survivors and improve our understanding of how both higher costs and resulting financial burden influence patients’ approach to their medical care and decision-making.”

 

CHICAGO – If severe eczema persists in a pediatric patient despite your best treatment efforts, think allergic contact dermatitis.

“Or, if your eczema patients tell you that they have a cream that’s making things worse, you should think about a contact allergen,” Catalina Matiz, MD, said at the World Congress of Pediatric Dermatology.

Allergic contact dermatitis (ACD) is a type IV delayed-type hypersensitivity reaction to haptens that come into contact with the skin. Poison ivy is a common plant-based culprit, while nickel is the most common metal allergen in adults and children. “The skin barrier also plays a role,” said Dr. Matiz of the department of dermatology at Rady Children’s Hospital–San Diego, and the University of California, San Diego. “Compared with adults, children have a thinner stratum corneum, and some haptens can penetrate the skin. Some studies suggest that patients with atopic dermatitis may have increased rates of allergic sensitization, and filaggrin mutations have been found in patients with atopic dermatitis and in patients with ACD to nickel. Filaggrin helps to aggregate the cytoskeletal proteins that form the cornified cell envelope. Without filaggrin, the skin barrier is defective.”

Atypical locations for atopic dermatitis (AD) that should make you think of allergic contact dermatitis include the eyelids, perioral area, scalp, neck, extensor surfaces, hands and feet, and genitalia. First-line treatment involves an adequate potency of corticosteroids. “Most of the time, you need mid- to high-strength corticosteroids for body lesions,” Dr. Matiz said. “If you suspect poison ivy or severe contact reactions, you may need to treat with systemic corticosteroids with a slow taper of 3-4 weeks. It’s important to improve the skin barriers with the use of moisturizers and you want to limit the use of irritant products as well. These include fragrances, formaldehyde, and cocamidopropyl betaine. Avoidance of the suspected culprit is very important.”

The top 10 pediatric allergens found in personal hygiene products across five studies in the medical literature include neomycin, balsam of Peru, fragrance mix, benzalkonium chloride, lanolin, cocamidopropyl betaine, formaldehyde, methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), propylene glycol, and corticosteroids. Dr. Matiz makes it practice to patch test as a last resort. “I always try to get a history, try to improve their symptoms, and have them start avoidance first, following the preemptive avoidance list,” she said (Expert Rev Clin Immunol. 2016;12[5]:551-61).

The T.R.U.E. test includes 35 allergens. “The T.R.U.E test is a good tool, which can capture up to 70% of relevant reactions in children with the inconvenience that some of the allergens in the test are not that relevant in children, and it’s not yet [Food and Drug Administration] approved to use in children,” she noted. The comprehensive chamber test allows you to select from unlimited number of allergens, “but that’s difficult. You have to have specialized staff to help you make the cells.”

A list of the minimum 20 allergens you should test for in children and the recommended supplemental allergens depending on history and locations of their dermatitis can be found in the following article: Curr Allergy Asthma Rep 2014;14[6]:444. “I always tell patients when they come for consultations to bring in everything they’re using: their shampoos, creams, and medications, because we want to see what they’re exposed to, so we can select the right allergens and also test their own products,” Dr. Matiz said. She recommends avoiding testing for strong sensitizers such as paraphenylenediamine, in children younger than 12 years of age who don’t have a history of exposure.

Testing tips for children younger than age 5 include decreasing concentrations to half for nickel, formaldehyde, and rubber accelerators. “Don’t test for paraphenylenediamine unless there is high suspicion,” she said. “Consider removing patches by 24 hours in the very young.”

The best antidote to contact dermatitis is avoidance of the known trigger. “You want to spend a lot of time with patients and parents on this,” she advised. “Give a list of safe products to use from the American Contact Dermatitis Society’s Contact Allergen Management Program [www.contactderm.org], and provide handouts about the location and history of positive allergens [www.truetest.com].” And, she added, “make a plan of treatment and follow-up in 6 weeks.”

Dr. Matiz disclosed that she is a subinvestigator in the Clinical Evaluation of T.R.U.E Test Panel 3.3 in Children and Adolescents study.
 

dbrunk@frontlinemedcom.com

 

CHICAGO – If severe eczema persists in a pediatric patient despite your best treatment efforts, think allergic contact dermatitis.

“Or, if your eczema patients tell you that they have a cream that’s making things worse, you should think about a contact allergen,” Catalina Matiz, MD, said at the World Congress of Pediatric Dermatology.

Allergic contact dermatitis (ACD) is a type IV delayed-type hypersensitivity reaction to haptens that come into contact with the skin. Poison ivy is a common plant-based culprit, while nickel is the most common metal allergen in adults and children. “The skin barrier also plays a role,” said Dr. Matiz of the department of dermatology at Rady Children’s Hospital–San Diego, and the University of California, San Diego. “Compared with adults, children have a thinner stratum corneum, and some haptens can penetrate the skin. Some studies suggest that patients with atopic dermatitis may have increased rates of allergic sensitization, and filaggrin mutations have been found in patients with atopic dermatitis and in patients with ACD to nickel. Filaggrin helps to aggregate the cytoskeletal proteins that form the cornified cell envelope. Without filaggrin, the skin barrier is defective.”

Atypical locations for atopic dermatitis (AD) that should make you think of allergic contact dermatitis include the eyelids, perioral area, scalp, neck, extensor surfaces, hands and feet, and genitalia. First-line treatment involves an adequate potency of corticosteroids. “Most of the time, you need mid- to high-strength corticosteroids for body lesions,” Dr. Matiz said. “If you suspect poison ivy or severe contact reactions, you may need to treat with systemic corticosteroids with a slow taper of 3-4 weeks. It’s important to improve the skin barriers with the use of moisturizers and you want to limit the use of irritant products as well. These include fragrances, formaldehyde, and cocamidopropyl betaine. Avoidance of the suspected culprit is very important.”

The top 10 pediatric allergens found in personal hygiene products across five studies in the medical literature include neomycin, balsam of Peru, fragrance mix, benzalkonium chloride, lanolin, cocamidopropyl betaine, formaldehyde, methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), propylene glycol, and corticosteroids. Dr. Matiz makes it practice to patch test as a last resort. “I always try to get a history, try to improve their symptoms, and have them start avoidance first, following the preemptive avoidance list,” she said (Expert Rev Clin Immunol. 2016;12[5]:551-61).

The T.R.U.E. test includes 35 allergens. “The T.R.U.E test is a good tool, which can capture up to 70% of relevant reactions in children with the inconvenience that some of the allergens in the test are not that relevant in children, and it’s not yet [Food and Drug Administration] approved to use in children,” she noted. The comprehensive chamber test allows you to select from unlimited number of allergens, “but that’s difficult. You have to have specialized staff to help you make the cells.”

A list of the minimum 20 allergens you should test for in children and the recommended supplemental allergens depending on history and locations of their dermatitis can be found in the following article: Curr Allergy Asthma Rep 2014;14[6]:444. “I always tell patients when they come for consultations to bring in everything they’re using: their shampoos, creams, and medications, because we want to see what they’re exposed to, so we can select the right allergens and also test their own products,” Dr. Matiz said. She recommends avoiding testing for strong sensitizers such as paraphenylenediamine, in children younger than 12 years of age who don’t have a history of exposure.

Testing tips for children younger than age 5 include decreasing concentrations to half for nickel, formaldehyde, and rubber accelerators. “Don’t test for paraphenylenediamine unless there is high suspicion,” she said. “Consider removing patches by 24 hours in the very young.”

The best antidote to contact dermatitis is avoidance of the known trigger. “You want to spend a lot of time with patients and parents on this,” she advised. “Give a list of safe products to use from the American Contact Dermatitis Society’s Contact Allergen Management Program [www.contactderm.org], and provide handouts about the location and history of positive allergens [www.truetest.com].” And, she added, “make a plan of treatment and follow-up in 6 weeks.”

Dr. Matiz disclosed that she is a subinvestigator in the Clinical Evaluation of T.R.U.E Test Panel 3.3 in Children and Adolescents study.
 

dbrunk@frontlinemedcom.com

 

CHICAGO – If severe eczema persists in a pediatric patient despite your best treatment efforts, think allergic contact dermatitis.

“Or, if your eczema patients tell you that they have a cream that’s making things worse, you should think about a contact allergen,” Catalina Matiz, MD, said at the World Congress of Pediatric Dermatology.

Allergic contact dermatitis (ACD) is a type IV delayed-type hypersensitivity reaction to haptens that come into contact with the skin. Poison ivy is a common plant-based culprit, while nickel is the most common metal allergen in adults and children. “The skin barrier also plays a role,” said Dr. Matiz of the department of dermatology at Rady Children’s Hospital–San Diego, and the University of California, San Diego. “Compared with adults, children have a thinner stratum corneum, and some haptens can penetrate the skin. Some studies suggest that patients with atopic dermatitis may have increased rates of allergic sensitization, and filaggrin mutations have been found in patients with atopic dermatitis and in patients with ACD to nickel. Filaggrin helps to aggregate the cytoskeletal proteins that form the cornified cell envelope. Without filaggrin, the skin barrier is defective.”

Atypical locations for atopic dermatitis (AD) that should make you think of allergic contact dermatitis include the eyelids, perioral area, scalp, neck, extensor surfaces, hands and feet, and genitalia. First-line treatment involves an adequate potency of corticosteroids. “Most of the time, you need mid- to high-strength corticosteroids for body lesions,” Dr. Matiz said. “If you suspect poison ivy or severe contact reactions, you may need to treat with systemic corticosteroids with a slow taper of 3-4 weeks. It’s important to improve the skin barriers with the use of moisturizers and you want to limit the use of irritant products as well. These include fragrances, formaldehyde, and cocamidopropyl betaine. Avoidance of the suspected culprit is very important.”

The top 10 pediatric allergens found in personal hygiene products across five studies in the medical literature include neomycin, balsam of Peru, fragrance mix, benzalkonium chloride, lanolin, cocamidopropyl betaine, formaldehyde, methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), propylene glycol, and corticosteroids. Dr. Matiz makes it practice to patch test as a last resort. “I always try to get a history, try to improve their symptoms, and have them start avoidance first, following the preemptive avoidance list,” she said (Expert Rev Clin Immunol. 2016;12[5]:551-61).

The T.R.U.E. test includes 35 allergens. “The T.R.U.E test is a good tool, which can capture up to 70% of relevant reactions in children with the inconvenience that some of the allergens in the test are not that relevant in children, and it’s not yet [Food and Drug Administration] approved to use in children,” she noted. The comprehensive chamber test allows you to select from unlimited number of allergens, “but that’s difficult. You have to have specialized staff to help you make the cells.”

A list of the minimum 20 allergens you should test for in children and the recommended supplemental allergens depending on history and locations of their dermatitis can be found in the following article: Curr Allergy Asthma Rep 2014;14[6]:444. “I always tell patients when they come for consultations to bring in everything they’re using: their shampoos, creams, and medications, because we want to see what they’re exposed to, so we can select the right allergens and also test their own products,” Dr. Matiz said. She recommends avoiding testing for strong sensitizers such as paraphenylenediamine, in children younger than 12 years of age who don’t have a history of exposure.

Testing tips for children younger than age 5 include decreasing concentrations to half for nickel, formaldehyde, and rubber accelerators. “Don’t test for paraphenylenediamine unless there is high suspicion,” she said. “Consider removing patches by 24 hours in the very young.”

The best antidote to contact dermatitis is avoidance of the known trigger. “You want to spend a lot of time with patients and parents on this,” she advised. “Give a list of safe products to use from the American Contact Dermatitis Society’s Contact Allergen Management Program [www.contactderm.org], and provide handouts about the location and history of positive allergens [www.truetest.com].” And, she added, “make a plan of treatment and follow-up in 6 weeks.”

Dr. Matiz disclosed that she is a subinvestigator in the Clinical Evaluation of T.R.U.E Test Panel 3.3 in Children and Adolescents study.
 

dbrunk@frontlinemedcom.com

Musculoskeletal ultrasound (MSUS) fellowship opportunities are growing among rheumatology programs across the country as professionals push for more standardized education, according to a survey of fellowship program directors.

Rise in use of MSUS among rheumatologists is spurring more comprehensive education for providers to acquire these skill sets, which researchers have gathered will only become more prevalent.

Bogdanhoda/Thinkstock

“Our specialty has seen a dramatic increase in the use of point-of-care MSUS among rheumatologists as evidenced by delineation of MSUS standards of use, inclusion of MSUS-related criteria into disease classification systems, increased attendance by rheumatologists at training courses, provision of the RhMSUS certification, and the almost universal desire among fellowship training programs to integrate MSUS education into the curriculum,” wrote Karina Torralba, MD, of Loma Linda (Calif.) University, and her coinvestigators.

The investigators sent two surveys to 113 rheumatology fellowship program directors. In the first survey, responses from the directors of 108 programs indicated that 101 (94%) offered MSUS programs (Arthritis Care Res. 2017 Aug 4. doi: 10.1002/acr.23336).

While this number has increased dramatically since a 2013 survey showed that 60% offered MSUS programs, the new survey found that 66% of respondents would prefer for the program to be optional, as opposed to a formal part of the fellowship program.

This sentiment for nonformal education programs was mirrored in the second survey specifically targeting the 101 programs that were known to provide some sort of MSUS education.

Among the 74 program directors who responded, 30 (41%) reported having a formal curriculum, while 44 (59%) did not, citing a major barrier being a lack of interested fellows to learn the material (P = .012)

Another major barrier, according to Dr. Torralba and her colleagues, is access to faculty with enough teaching experience to properly teach MSUS skills, with 62 (84%) reporting having no or only one faculty member with MSUS certification (P = .049).

Programs without proper faculty available and even those with available faculty are choosing to outsource lessons to expensive teaching programs such as the Ultrasound School of North American Rheumatologists (USSONAR) fellowship course, according to Dr. Torralba and her associates.

“While cost of external courses can be prohibitive, (expenses for a 2- to 4-day course costs between $1,500 and $4,000), programs may augment MSUS teaching using these courses for several reasons,” according to Dr. Torralba and her colleagues. [These include] insufficient number of teaching faculty, limited time or support for faculty to deliver all educational content, inadequate confidence or competency for faculty to teach content, and utilization of external materials to bolster resources.”

While these barriers will still need addressing, according to Dr. Torralba and her colleagues, half of responders noted previous barriers such as political pushback and lack of fellow interest are starting to recede, giving more room for programs to start developing MSUS programs that researchers assert are necessary for future developing rheumatologists.

“A standardized MSUS curriculum developed and endorsed by program directors and MSUS lead educators is now reasonably within sights,” the investigators wrote. “We need to work together to proactively champion MSUS education for both faculty and fellows who desire to attain this skill set.”

This study was limited by the self-reporting nature of the survey sent, as well as the small population of the sample. Researchers were also forced to rely on program directors’ perception of how effective their MSUS programs were instead of asking those participating in the programs directly.

The researchers reported no relevant financial disclosures.

ezimmerman@frontlinemedcom.com

On Twitter @eaztweets

Musculoskeletal ultrasound (MSUS) fellowship opportunities are growing among rheumatology programs across the country as professionals push for more standardized education, according to a survey of fellowship program directors.

Rise in use of MSUS among rheumatologists is spurring more comprehensive education for providers to acquire these skill sets, which researchers have gathered will only become more prevalent.

Bogdanhoda/Thinkstock

“Our specialty has seen a dramatic increase in the use of point-of-care MSUS among rheumatologists as evidenced by delineation of MSUS standards of use, inclusion of MSUS-related criteria into disease classification systems, increased attendance by rheumatologists at training courses, provision of the RhMSUS certification, and the almost universal desire among fellowship training programs to integrate MSUS education into the curriculum,” wrote Karina Torralba, MD, of Loma Linda (Calif.) University, and her coinvestigators.

The investigators sent two surveys to 113 rheumatology fellowship program directors. In the first survey, responses from the directors of 108 programs indicated that 101 (94%) offered MSUS programs (Arthritis Care Res. 2017 Aug 4. doi: 10.1002/acr.23336).

While this number has increased dramatically since a 2013 survey showed that 60% offered MSUS programs, the new survey found that 66% of respondents would prefer for the program to be optional, as opposed to a formal part of the fellowship program.

This sentiment for nonformal education programs was mirrored in the second survey specifically targeting the 101 programs that were known to provide some sort of MSUS education.

Among the 74 program directors who responded, 30 (41%) reported having a formal curriculum, while 44 (59%) did not, citing a major barrier being a lack of interested fellows to learn the material (P = .012)

Another major barrier, according to Dr. Torralba and her colleagues, is access to faculty with enough teaching experience to properly teach MSUS skills, with 62 (84%) reporting having no or only one faculty member with MSUS certification (P = .049).

Programs without proper faculty available and even those with available faculty are choosing to outsource lessons to expensive teaching programs such as the Ultrasound School of North American Rheumatologists (USSONAR) fellowship course, according to Dr. Torralba and her associates.

“While cost of external courses can be prohibitive, (expenses for a 2- to 4-day course costs between $1,500 and $4,000), programs may augment MSUS teaching using these courses for several reasons,” according to Dr. Torralba and her colleagues. [These include] insufficient number of teaching faculty, limited time or support for faculty to deliver all educational content, inadequate confidence or competency for faculty to teach content, and utilization of external materials to bolster resources.”

While these barriers will still need addressing, according to Dr. Torralba and her colleagues, half of responders noted previous barriers such as political pushback and lack of fellow interest are starting to recede, giving more room for programs to start developing MSUS programs that researchers assert are necessary for future developing rheumatologists.

“A standardized MSUS curriculum developed and endorsed by program directors and MSUS lead educators is now reasonably within sights,” the investigators wrote. “We need to work together to proactively champion MSUS education for both faculty and fellows who desire to attain this skill set.”

This study was limited by the self-reporting nature of the survey sent, as well as the small population of the sample. Researchers were also forced to rely on program directors’ perception of how effective their MSUS programs were instead of asking those participating in the programs directly.

The researchers reported no relevant financial disclosures.

ezimmerman@frontlinemedcom.com

On Twitter @eaztweets

Musculoskeletal ultrasound (MSUS) fellowship opportunities are growing among rheumatology programs across the country as professionals push for more standardized education, according to a survey of fellowship program directors.

Rise in use of MSUS among rheumatologists is spurring more comprehensive education for providers to acquire these skill sets, which researchers have gathered will only become more prevalent.

Bogdanhoda/Thinkstock

“Our specialty has seen a dramatic increase in the use of point-of-care MSUS among rheumatologists as evidenced by delineation of MSUS standards of use, inclusion of MSUS-related criteria into disease classification systems, increased attendance by rheumatologists at training courses, provision of the RhMSUS certification, and the almost universal desire among fellowship training programs to integrate MSUS education into the curriculum,” wrote Karina Torralba, MD, of Loma Linda (Calif.) University, and her coinvestigators.

The investigators sent two surveys to 113 rheumatology fellowship program directors. In the first survey, responses from the directors of 108 programs indicated that 101 (94%) offered MSUS programs (Arthritis Care Res. 2017 Aug 4. doi: 10.1002/acr.23336).

While this number has increased dramatically since a 2013 survey showed that 60% offered MSUS programs, the new survey found that 66% of respondents would prefer for the program to be optional, as opposed to a formal part of the fellowship program.

This sentiment for nonformal education programs was mirrored in the second survey specifically targeting the 101 programs that were known to provide some sort of MSUS education.

Among the 74 program directors who responded, 30 (41%) reported having a formal curriculum, while 44 (59%) did not, citing a major barrier being a lack of interested fellows to learn the material (P = .012)

Another major barrier, according to Dr. Torralba and her colleagues, is access to faculty with enough teaching experience to properly teach MSUS skills, with 62 (84%) reporting having no or only one faculty member with MSUS certification (P = .049).

Programs without proper faculty available and even those with available faculty are choosing to outsource lessons to expensive teaching programs such as the Ultrasound School of North American Rheumatologists (USSONAR) fellowship course, according to Dr. Torralba and her associates.

“While cost of external courses can be prohibitive, (expenses for a 2- to 4-day course costs between $1,500 and $4,000), programs may augment MSUS teaching using these courses for several reasons,” according to Dr. Torralba and her colleagues. [These include] insufficient number of teaching faculty, limited time or support for faculty to deliver all educational content, inadequate confidence or competency for faculty to teach content, and utilization of external materials to bolster resources.”

While these barriers will still need addressing, according to Dr. Torralba and her colleagues, half of responders noted previous barriers such as political pushback and lack of fellow interest are starting to recede, giving more room for programs to start developing MSUS programs that researchers assert are necessary for future developing rheumatologists.

“A standardized MSUS curriculum developed and endorsed by program directors and MSUS lead educators is now reasonably within sights,” the investigators wrote. “We need to work together to proactively champion MSUS education for both faculty and fellows who desire to attain this skill set.”

This study was limited by the self-reporting nature of the survey sent, as well as the small population of the sample. Researchers were also forced to rely on program directors’ perception of how effective their MSUS programs were instead of asking those participating in the programs directly.

The researchers reported no relevant financial disclosures.

ezimmerman@frontlinemedcom.com

On Twitter @eaztweets

 

It has been a remarkable summer of milestones and crises for high-technology medicine.

An FDA panel has unanimously approved a gene therapy: The patient’s own immune cells are taken from his or her body, genetically modified, and reinfused to attack cancer. While the treatment has some dangers, it can be worth trying when conventional therapy has failed, and it appears to be curative when it works. Final FDA approval is expected in September.

Scientists have also announced the first use of gene therapy to effectively treat a human embryo. They successfully replaced a defective gene with an engineered correction. The in vitro embryos were not implanted.

While those breakthroughs were occurring, the parents of Charlie Gard, an infant in England with a very rare and devastating mitochondrial disease, were seeking experimental therapy for their child. The medical staff disagreed with the parents: They recommended that the best thing for Charlie would be to stop the ventilator and allow him to die, rather than let him to continue to suffer. Three British courts reviewed Charlie’s case and concurred with the medical staff; on appeal, the European Court of Human Rights also denied the parents’ wishes.

End of life cases similar to Charlie’s are not rare. In modern medicine, parents sometimes must make the heart-wrenching decision to stop aggressive therapies and accept that death is imminent and unavoidable. Many factors go into making that decision. Both the courts and medical staff presume that parents are the best decision makers. Generally, medical staff provide emotional and spiritual support to the parents, along with a tincture of time. In the vast majority of cases, parents and physicians come to agree on the course of care, but sometimes, there are irreconcilable disagreements.

It is rare for courts to overrule parents. The government typically intervenes only when the harm from a parent’s choice exceeds some threshold. For instance, it is not in a child’s best interest to be put in a car during a blizzard and driven to the store to get cigarettes. But neither is it wise to have an intrusive government reviewing every choice a parent makes. The potential harm must be large enough, likely enough, and imminent enough before most judges will intervene. The law will insist the child be in a car seat at least.

In Charlie’s case, the medical staff and the judges all explicitly said that the cost of therapy did not factor into their decision making; they looked solely at what was best for Charlie. The focus was on whether the unproven potential benefits of experimental therapy outweighed the risk of suffering caused by the therapy and continued intensive medical care.

Even when a bedside decision ignores the financial impact, money often structures which therapeutic choices are available. There are also issues of equitable access to be raised and weighed. Expenditures impact other social choices.

Money influenced the actions of Martin Shkreli, who is best known as the pharmacy company executive who markedly increased the price of a drug. Mr. Shkreli was recently convicted on three of eight charges for securities fraud, and sentencing is pending; the convictions were not related to the price increase.

Money also appears to have played a key role in the tragic deaths of more than 30 infants in northern India, who died when the hospital’s oxygen tanks went empty. The company responsible for refilling the oxygen tanks didn’t do so because, it claimed, the hospital wasn’t paying its bills. Public outrage has the government investigating the situation.

The United States has created some amazing technologies to save individual, identifiable lives, but they come at a high price that often costs lives in ways more subtle than the incident in India. At some point, the government and the public are responsible for either financing or rationing care, but that doesn’t absolve the scientists completely. The Russell-Einstein (Pugwash) Manifesto established that scientists have a moral accountability for the negative consequences of creating new technology, and that includes the financial aspects.

 

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at pdnews@frontlinemedcom.com

 

It has been a remarkable summer of milestones and crises for high-technology medicine.

An FDA panel has unanimously approved a gene therapy: The patient’s own immune cells are taken from his or her body, genetically modified, and reinfused to attack cancer. While the treatment has some dangers, it can be worth trying when conventional therapy has failed, and it appears to be curative when it works. Final FDA approval is expected in September.

Scientists have also announced the first use of gene therapy to effectively treat a human embryo. They successfully replaced a defective gene with an engineered correction. The in vitro embryos were not implanted.

While those breakthroughs were occurring, the parents of Charlie Gard, an infant in England with a very rare and devastating mitochondrial disease, were seeking experimental therapy for their child. The medical staff disagreed with the parents: They recommended that the best thing for Charlie would be to stop the ventilator and allow him to die, rather than let him to continue to suffer. Three British courts reviewed Charlie’s case and concurred with the medical staff; on appeal, the European Court of Human Rights also denied the parents’ wishes.

End of life cases similar to Charlie’s are not rare. In modern medicine, parents sometimes must make the heart-wrenching decision to stop aggressive therapies and accept that death is imminent and unavoidable. Many factors go into making that decision. Both the courts and medical staff presume that parents are the best decision makers. Generally, medical staff provide emotional and spiritual support to the parents, along with a tincture of time. In the vast majority of cases, parents and physicians come to agree on the course of care, but sometimes, there are irreconcilable disagreements.

It is rare for courts to overrule parents. The government typically intervenes only when the harm from a parent’s choice exceeds some threshold. For instance, it is not in a child’s best interest to be put in a car during a blizzard and driven to the store to get cigarettes. But neither is it wise to have an intrusive government reviewing every choice a parent makes. The potential harm must be large enough, likely enough, and imminent enough before most judges will intervene. The law will insist the child be in a car seat at least.

In Charlie’s case, the medical staff and the judges all explicitly said that the cost of therapy did not factor into their decision making; they looked solely at what was best for Charlie. The focus was on whether the unproven potential benefits of experimental therapy outweighed the risk of suffering caused by the therapy and continued intensive medical care.

Even when a bedside decision ignores the financial impact, money often structures which therapeutic choices are available. There are also issues of equitable access to be raised and weighed. Expenditures impact other social choices.

Money influenced the actions of Martin Shkreli, who is best known as the pharmacy company executive who markedly increased the price of a drug. Mr. Shkreli was recently convicted on three of eight charges for securities fraud, and sentencing is pending; the convictions were not related to the price increase.

Money also appears to have played a key role in the tragic deaths of more than 30 infants in northern India, who died when the hospital’s oxygen tanks went empty. The company responsible for refilling the oxygen tanks didn’t do so because, it claimed, the hospital wasn’t paying its bills. Public outrage has the government investigating the situation.

The United States has created some amazing technologies to save individual, identifiable lives, but they come at a high price that often costs lives in ways more subtle than the incident in India. At some point, the government and the public are responsible for either financing or rationing care, but that doesn’t absolve the scientists completely. The Russell-Einstein (Pugwash) Manifesto established that scientists have a moral accountability for the negative consequences of creating new technology, and that includes the financial aspects.

 

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at pdnews@frontlinemedcom.com

 

It has been a remarkable summer of milestones and crises for high-technology medicine.

An FDA panel has unanimously approved a gene therapy: The patient’s own immune cells are taken from his or her body, genetically modified, and reinfused to attack cancer. While the treatment has some dangers, it can be worth trying when conventional therapy has failed, and it appears to be curative when it works. Final FDA approval is expected in September.

Scientists have also announced the first use of gene therapy to effectively treat a human embryo. They successfully replaced a defective gene with an engineered correction. The in vitro embryos were not implanted.

While those breakthroughs were occurring, the parents of Charlie Gard, an infant in England with a very rare and devastating mitochondrial disease, were seeking experimental therapy for their child. The medical staff disagreed with the parents: They recommended that the best thing for Charlie would be to stop the ventilator and allow him to die, rather than let him to continue to suffer. Three British courts reviewed Charlie’s case and concurred with the medical staff; on appeal, the European Court of Human Rights also denied the parents’ wishes.

End of life cases similar to Charlie’s are not rare. In modern medicine, parents sometimes must make the heart-wrenching decision to stop aggressive therapies and accept that death is imminent and unavoidable. Many factors go into making that decision. Both the courts and medical staff presume that parents are the best decision makers. Generally, medical staff provide emotional and spiritual support to the parents, along with a tincture of time. In the vast majority of cases, parents and physicians come to agree on the course of care, but sometimes, there are irreconcilable disagreements.

It is rare for courts to overrule parents. The government typically intervenes only when the harm from a parent’s choice exceeds some threshold. For instance, it is not in a child’s best interest to be put in a car during a blizzard and driven to the store to get cigarettes. But neither is it wise to have an intrusive government reviewing every choice a parent makes. The potential harm must be large enough, likely enough, and imminent enough before most judges will intervene. The law will insist the child be in a car seat at least.

In Charlie’s case, the medical staff and the judges all explicitly said that the cost of therapy did not factor into their decision making; they looked solely at what was best for Charlie. The focus was on whether the unproven potential benefits of experimental therapy outweighed the risk of suffering caused by the therapy and continued intensive medical care.

Even when a bedside decision ignores the financial impact, money often structures which therapeutic choices are available. There are also issues of equitable access to be raised and weighed. Expenditures impact other social choices.

Money influenced the actions of Martin Shkreli, who is best known as the pharmacy company executive who markedly increased the price of a drug. Mr. Shkreli was recently convicted on three of eight charges for securities fraud, and sentencing is pending; the convictions were not related to the price increase.

Money also appears to have played a key role in the tragic deaths of more than 30 infants in northern India, who died when the hospital’s oxygen tanks went empty. The company responsible for refilling the oxygen tanks didn’t do so because, it claimed, the hospital wasn’t paying its bills. Public outrage has the government investigating the situation.

The United States has created some amazing technologies to save individual, identifiable lives, but they come at a high price that often costs lives in ways more subtle than the incident in India. At some point, the government and the public are responsible for either financing or rationing care, but that doesn’t absolve the scientists completely. The Russell-Einstein (Pugwash) Manifesto established that scientists have a moral accountability for the negative consequences of creating new technology, and that includes the financial aspects.

 

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at pdnews@frontlinemedcom.com

Photo by Bill Branson

The US Food and Drug Administration (FDA) has granted orphan drug designation to SENS-401 to be used for the prevention of platinum-induced ototoxicity in pediatric patients.

Platinum-based chemotherapies, particularly cisplatin, can induce severe hearing loss in cancer patients, but there is no pharmaceutical agent approved to treat this side effect.

“Hearing loss in pediatric oncology patients is one of the most frequent side effects of cisplatin treatment and may disable them for the rest of their lives,” said Nawal Ouzren, CEO of Sensorion, the company developing SENS-401.

“Based on its unique profile and the data generated to date, we believe SENS-401 has the potential to be a safe and effective treatment for this serious medical condition where a significant unmet need exists. As such, we look forward to working with the FDA and EMA [European Medicines Agency] to set up an IND [investigational new drug application] and design a phase 2 clinical trial in order to evaluate SENS-401 in this indication.”

About SENS-401

SENS-401 (R-azasetron besylate) is a small molecule intended to protect and preserve inner ear tissue when lesions cause progressive or sequelar hearing impairments. The drug can be taken orally or via an injection.

SENS-401 is one of the two enantiomer forms of SENS-218 (azasetron), a racemic molecule belonging to the family of setrons marketed in Asia under the name Serotone. Pharmacological and pharmacokinetic tests have shown a superior profile for SENS-401 compared with the other enantiomer or the racemic form.

Healthy subjects demonstrated a “very good clinical tolerance” to SENS-401 in a phase 1 study, according to Sensorion. The company is planning to launch a phase 2 trial of the drug for platinum-induced ototoxicity in 2018.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Photo by Bill Branson

The US Food and Drug Administration (FDA) has granted orphan drug designation to SENS-401 to be used for the prevention of platinum-induced ototoxicity in pediatric patients.

Platinum-based chemotherapies, particularly cisplatin, can induce severe hearing loss in cancer patients, but there is no pharmaceutical agent approved to treat this side effect.

“Hearing loss in pediatric oncology patients is one of the most frequent side effects of cisplatin treatment and may disable them for the rest of their lives,” said Nawal Ouzren, CEO of Sensorion, the company developing SENS-401.

“Based on its unique profile and the data generated to date, we believe SENS-401 has the potential to be a safe and effective treatment for this serious medical condition where a significant unmet need exists. As such, we look forward to working with the FDA and EMA [European Medicines Agency] to set up an IND [investigational new drug application] and design a phase 2 clinical trial in order to evaluate SENS-401 in this indication.”

About SENS-401

SENS-401 (R-azasetron besylate) is a small molecule intended to protect and preserve inner ear tissue when lesions cause progressive or sequelar hearing impairments. The drug can be taken orally or via an injection.

SENS-401 is one of the two enantiomer forms of SENS-218 (azasetron), a racemic molecule belonging to the family of setrons marketed in Asia under the name Serotone. Pharmacological and pharmacokinetic tests have shown a superior profile for SENS-401 compared with the other enantiomer or the racemic form.

Healthy subjects demonstrated a “very good clinical tolerance” to SENS-401 in a phase 1 study, according to Sensorion. The company is planning to launch a phase 2 trial of the drug for platinum-induced ototoxicity in 2018.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Photo by Bill Branson

The US Food and Drug Administration (FDA) has granted orphan drug designation to SENS-401 to be used for the prevention of platinum-induced ototoxicity in pediatric patients.

Platinum-based chemotherapies, particularly cisplatin, can induce severe hearing loss in cancer patients, but there is no pharmaceutical agent approved to treat this side effect.

“Hearing loss in pediatric oncology patients is one of the most frequent side effects of cisplatin treatment and may disable them for the rest of their lives,” said Nawal Ouzren, CEO of Sensorion, the company developing SENS-401.

“Based on its unique profile and the data generated to date, we believe SENS-401 has the potential to be a safe and effective treatment for this serious medical condition where a significant unmet need exists. As such, we look forward to working with the FDA and EMA [European Medicines Agency] to set up an IND [investigational new drug application] and design a phase 2 clinical trial in order to evaluate SENS-401 in this indication.”

About SENS-401

SENS-401 (R-azasetron besylate) is a small molecule intended to protect and preserve inner ear tissue when lesions cause progressive or sequelar hearing impairments. The drug can be taken orally or via an injection.

SENS-401 is one of the two enantiomer forms of SENS-218 (azasetron), a racemic molecule belonging to the family of setrons marketed in Asia under the name Serotone. Pharmacological and pharmacokinetic tests have shown a superior profile for SENS-401 compared with the other enantiomer or the racemic form.

Healthy subjects demonstrated a “very good clinical tolerance” to SENS-401 in a phase 1 study, according to Sensorion. The company is planning to launch a phase 2 trial of the drug for platinum-induced ototoxicity in 2018.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

 

New studies raise doubts on the reliability of physical exam findings in suspected pediatric community-acquired pneumonia cases and on the value of blood cultures in hospitalized pediatric CAP cases.

In one study, 128 cases of suspected CAP in children aged 3 months to 18 years presenting to an ED from July 2013 to May 2016 underwent paired assessments within 20 minutes of each other. Only 3 of 19 exam findings used to diagnose CAP – wheezing, retractions, and respiratory rate – had acceptable levels of inter-rater reliability, with the lower end of the 95% confidential interval at a Fleiss’ kappa value of 0.4 or higher.

CDC/Amanda Mills

Eight exam findings – capillary refill time, cough, rhonchi, head bobbing, behavior, grunting, general appearance, and decreased breath sounds – had poor to fair reliability, with a kappa of 0-0.4, the investigators found. These results came from an ongoing prospective cohort study of children with suspected CAP called Catalyzing Ambulatory Research in Pneumonia Etiology and Diagnostic Innovations in Emergency Medicine, or CARPE DIEM.

“The reliability of these findings must be considered in the clinical management and research of children with CAP,” said lead author Todd Florin, MD, associate research director in emergency medicine at Cincinnati Children’s Hospital Medical Center and his associates. (Pediatrics. 2017;140[3]:e20170310)

In a retrospective cohort analysis, researchers found that just 2.5% of 2,568 hospitalized children with CAP who had a blood culture performed actually grew a pathogen. And of the detected pathogens, 82% were susceptible to penicillin. Streptococcus pneumoniae accounted for 78% of all the pathogens that were found; it was detected in only 2% of all children who had blood cultures taken.

Just 11 children – or 0.43% of the children with a blood culture performed – had growth of a pathogen that was not treatable with penicillin, said lead author Mark Neuman, MD, director of research at Boston Children’s Hospital and his associates (Pediatrics. 2017;140[3]:e20171013).

The analysis was drawn from a cohort of 7,509 children hospitalized from 2007 to 2011, with children with complex chronic conditions excluded. Data for the analysis came from the Pediatric Health Information System Plus database, in which administrative, billing, laboratory, and radiographic information is stored from six tertiary children’s hospitals.

The investigators said that one challenge is that when blood cultures are drawn early in the course of evaluation and treatment, the severity of the child’s CAP might not be apparent, which makes it difficult to know which children would benefit from a blood culture.

“The routine performance of blood cultures in these children may not be indicated,” Dr. Neuman and his associates said. “Researchers in future studies should seek to identify the clinical characteristics of children in whom obtaining blood cultures would lead to changes in clinical management, especially when identifying those patients at risk for CAP caused by organisms not susceptible to guideline-recommended, narrow-spectrum antibiotics.”

 

Both studies were funded by the National Institutes of Health. For the physician exam study, additional funding was provided by individual grants from the Gerber Foundation, the National Center for Research Resources and the National Center for Advancing Translational Sciences, the National Institute for Allergy and Infectious Diseases and the National Institutes of Health, and a Trustee Award from Cincinnati Children’s Hospital Medical Center. For the blood cultures study, individual researchers received funding from the National Institute of Allergy and Infectious Diseases and the Agency for Healthcare Research and Quality. For the physician exam study, no financial disclosures were reported. For the blood cultures study, Anne Blaschke, MD, PhD, reported receiving research funding from and other financial relationships with BioFire Diagnostics.

 

New studies raise doubts on the reliability of physical exam findings in suspected pediatric community-acquired pneumonia cases and on the value of blood cultures in hospitalized pediatric CAP cases.

In one study, 128 cases of suspected CAP in children aged 3 months to 18 years presenting to an ED from July 2013 to May 2016 underwent paired assessments within 20 minutes of each other. Only 3 of 19 exam findings used to diagnose CAP – wheezing, retractions, and respiratory rate – had acceptable levels of inter-rater reliability, with the lower end of the 95% confidential interval at a Fleiss’ kappa value of 0.4 or higher.

CDC/Amanda Mills

Eight exam findings – capillary refill time, cough, rhonchi, head bobbing, behavior, grunting, general appearance, and decreased breath sounds – had poor to fair reliability, with a kappa of 0-0.4, the investigators found. These results came from an ongoing prospective cohort study of children with suspected CAP called Catalyzing Ambulatory Research in Pneumonia Etiology and Diagnostic Innovations in Emergency Medicine, or CARPE DIEM.

“The reliability of these findings must be considered in the clinical management and research of children with CAP,” said lead author Todd Florin, MD, associate research director in emergency medicine at Cincinnati Children’s Hospital Medical Center and his associates. (Pediatrics. 2017;140[3]:e20170310)

In a retrospective cohort analysis, researchers found that just 2.5% of 2,568 hospitalized children with CAP who had a blood culture performed actually grew a pathogen. And of the detected pathogens, 82% were susceptible to penicillin. Streptococcus pneumoniae accounted for 78% of all the pathogens that were found; it was detected in only 2% of all children who had blood cultures taken.

Just 11 children – or 0.43% of the children with a blood culture performed – had growth of a pathogen that was not treatable with penicillin, said lead author Mark Neuman, MD, director of research at Boston Children’s Hospital and his associates (Pediatrics. 2017;140[3]:e20171013).

The analysis was drawn from a cohort of 7,509 children hospitalized from 2007 to 2011, with children with complex chronic conditions excluded. Data for the analysis came from the Pediatric Health Information System Plus database, in which administrative, billing, laboratory, and radiographic information is stored from six tertiary children’s hospitals.

The investigators said that one challenge is that when blood cultures are drawn early in the course of evaluation and treatment, the severity of the child’s CAP might not be apparent, which makes it difficult to know which children would benefit from a blood culture.

“The routine performance of blood cultures in these children may not be indicated,” Dr. Neuman and his associates said. “Researchers in future studies should seek to identify the clinical characteristics of children in whom obtaining blood cultures would lead to changes in clinical management, especially when identifying those patients at risk for CAP caused by organisms not susceptible to guideline-recommended, narrow-spectrum antibiotics.”

 

Both studies were funded by the National Institutes of Health. For the physician exam study, additional funding was provided by individual grants from the Gerber Foundation, the National Center for Research Resources and the National Center for Advancing Translational Sciences, the National Institute for Allergy and Infectious Diseases and the National Institutes of Health, and a Trustee Award from Cincinnati Children’s Hospital Medical Center. For the blood cultures study, individual researchers received funding from the National Institute of Allergy and Infectious Diseases and the Agency for Healthcare Research and Quality. For the physician exam study, no financial disclosures were reported. For the blood cultures study, Anne Blaschke, MD, PhD, reported receiving research funding from and other financial relationships with BioFire Diagnostics.

 

New studies raise doubts on the reliability of physical exam findings in suspected pediatric community-acquired pneumonia cases and on the value of blood cultures in hospitalized pediatric CAP cases.

In one study, 128 cases of suspected CAP in children aged 3 months to 18 years presenting to an ED from July 2013 to May 2016 underwent paired assessments within 20 minutes of each other. Only 3 of 19 exam findings used to diagnose CAP – wheezing, retractions, and respiratory rate – had acceptable levels of inter-rater reliability, with the lower end of the 95% confidential interval at a Fleiss’ kappa value of 0.4 or higher.

CDC/Amanda Mills

Eight exam findings – capillary refill time, cough, rhonchi, head bobbing, behavior, grunting, general appearance, and decreased breath sounds – had poor to fair reliability, with a kappa of 0-0.4, the investigators found. These results came from an ongoing prospective cohort study of children with suspected CAP called Catalyzing Ambulatory Research in Pneumonia Etiology and Diagnostic Innovations in Emergency Medicine, or CARPE DIEM.

“The reliability of these findings must be considered in the clinical management and research of children with CAP,” said lead author Todd Florin, MD, associate research director in emergency medicine at Cincinnati Children’s Hospital Medical Center and his associates. (Pediatrics. 2017;140[3]:e20170310)

In a retrospective cohort analysis, researchers found that just 2.5% of 2,568 hospitalized children with CAP who had a blood culture performed actually grew a pathogen. And of the detected pathogens, 82% were susceptible to penicillin. Streptococcus pneumoniae accounted for 78% of all the pathogens that were found; it was detected in only 2% of all children who had blood cultures taken.

Just 11 children – or 0.43% of the children with a blood culture performed – had growth of a pathogen that was not treatable with penicillin, said lead author Mark Neuman, MD, director of research at Boston Children’s Hospital and his associates (Pediatrics. 2017;140[3]:e20171013).

The analysis was drawn from a cohort of 7,509 children hospitalized from 2007 to 2011, with children with complex chronic conditions excluded. Data for the analysis came from the Pediatric Health Information System Plus database, in which administrative, billing, laboratory, and radiographic information is stored from six tertiary children’s hospitals.

The investigators said that one challenge is that when blood cultures are drawn early in the course of evaluation and treatment, the severity of the child’s CAP might not be apparent, which makes it difficult to know which children would benefit from a blood culture.

“The routine performance of blood cultures in these children may not be indicated,” Dr. Neuman and his associates said. “Researchers in future studies should seek to identify the clinical characteristics of children in whom obtaining blood cultures would lead to changes in clinical management, especially when identifying those patients at risk for CAP caused by organisms not susceptible to guideline-recommended, narrow-spectrum antibiotics.”

 

Both studies were funded by the National Institutes of Health. For the physician exam study, additional funding was provided by individual grants from the Gerber Foundation, the National Center for Research Resources and the National Center for Advancing Translational Sciences, the National Institute for Allergy and Infectious Diseases and the National Institutes of Health, and a Trustee Award from Cincinnati Children’s Hospital Medical Center. For the blood cultures study, individual researchers received funding from the National Institute of Allergy and Infectious Diseases and the Agency for Healthcare Research and Quality. For the physician exam study, no financial disclosures were reported. For the blood cultures study, Anne Blaschke, MD, PhD, reported receiving research funding from and other financial relationships with BioFire Diagnostics.

 

Body mass index z scores fall short for tracking children with severe obesity, based on data from nearly 7,000 children in the Bogalusa Heart Study.

The current parameters used in the Centers for Disease Control and Prevention growth charts for children with high body mass index (BMI) “can result in estimates that differ substantially from those that are observed and constrains the maximum BMI z that is attainable at a given sex and age,” wrote David S. Freedman, PhD, of the Centers for Disease Control and Prevention in Atlanta, and Gerald S. Berenson, MD, of Louisiana State University Health Sciences Center, New Orleans, (Pediatrics. 2017;140:e20171072).

The BMI adjusted z score (BMIaz) or the BMI expressed as a percentage of the 95th percentile (%BMI_p95) “will provide more accurate information on body size over time among children with very high BMIs,” they said.

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To compare different BMI metrics, the researchers reviewed data from 6,977 children aged 2-17 years participating in the longitudinal Bogalusa Heart Study who were examined in two or more cross-sectional studies. Among the 247 who met criteria for severe obesity, the average BMI was 32 kg/m², the average BMI z score was 2.4 standard deviation (SD), and the average BMI adjusted z score (BMIaz) was +3.0 SD. Correlations for BMI z scores were “consistently weaker than those for BMI, BMIaz, and %BMI_p95,” for children with obesity or severe obesity over an average of 2.8 years. Obesity was defined as BMI in the 95th percentile or higher.

In children with severe obesity, BMI z was a weaker measure (r = 0.46) than were measures of %BMI_p95 (r = 0.61) or BMIaz scores with no upper boundary (r = 0.65).

BMI z scores were weakest when applied to children younger than 10 years, with correlations of r = 0.36 for BMI z vs. correlations of 0.60 and 0.57 for BMIaz and %BMI_p95, respectively.

The results were limited by several factors including the age of the data (40 years ago, when the prevalence of severe obesity was lower, 2% compared with approximately 6% now) and long intervals between exams in some cases (5 years or more), the researchers noted. However, the results suggest that BMI z values “can differ substantially from empirical estimates, have an effective upper limit, and are strongly influenced by sex and age,” they said. As an alternative, the researchers recommended that “very high BMIs should be should expressed as z scores on the basis of linear extrapolations of a fixed SD or as percentage of the CDC 95th percentile,” or using multilevel models that adjust for age and sex.

The researchers had no financial conflicts to disclose. The National Institute on Aging, the National Heart, Lung, and Blood Institute, and the National Institutes of Health funded the study.

 

Body mass index z scores fall short for tracking children with severe obesity, based on data from nearly 7,000 children in the Bogalusa Heart Study.

The current parameters used in the Centers for Disease Control and Prevention growth charts for children with high body mass index (BMI) “can result in estimates that differ substantially from those that are observed and constrains the maximum BMI z that is attainable at a given sex and age,” wrote David S. Freedman, PhD, of the Centers for Disease Control and Prevention in Atlanta, and Gerald S. Berenson, MD, of Louisiana State University Health Sciences Center, New Orleans, (Pediatrics. 2017;140:e20171072).

The BMI adjusted z score (BMIaz) or the BMI expressed as a percentage of the 95th percentile (%BMI_p95) “will provide more accurate information on body size over time among children with very high BMIs,” they said.

iStockphoto

To compare different BMI metrics, the researchers reviewed data from 6,977 children aged 2-17 years participating in the longitudinal Bogalusa Heart Study who were examined in two or more cross-sectional studies. Among the 247 who met criteria for severe obesity, the average BMI was 32 kg/m², the average BMI z score was 2.4 standard deviation (SD), and the average BMI adjusted z score (BMIaz) was +3.0 SD. Correlations for BMI z scores were “consistently weaker than those for BMI, BMIaz, and %BMI_p95,” for children with obesity or severe obesity over an average of 2.8 years. Obesity was defined as BMI in the 95th percentile or higher.

In children with severe obesity, BMI z was a weaker measure (r = 0.46) than were measures of %BMI_p95 (r = 0.61) or BMIaz scores with no upper boundary (r = 0.65).

BMI z scores were weakest when applied to children younger than 10 years, with correlations of r = 0.36 for BMI z vs. correlations of 0.60 and 0.57 for BMIaz and %BMI_p95, respectively.

The results were limited by several factors including the age of the data (40 years ago, when the prevalence of severe obesity was lower, 2% compared with approximately 6% now) and long intervals between exams in some cases (5 years or more), the researchers noted. However, the results suggest that BMI z values “can differ substantially from empirical estimates, have an effective upper limit, and are strongly influenced by sex and age,” they said. As an alternative, the researchers recommended that “very high BMIs should be should expressed as z scores on the basis of linear extrapolations of a fixed SD or as percentage of the CDC 95th percentile,” or using multilevel models that adjust for age and sex.

The researchers had no financial conflicts to disclose. The National Institute on Aging, the National Heart, Lung, and Blood Institute, and the National Institutes of Health funded the study.

 

Body mass index z scores fall short for tracking children with severe obesity, based on data from nearly 7,000 children in the Bogalusa Heart Study.

The current parameters used in the Centers for Disease Control and Prevention growth charts for children with high body mass index (BMI) “can result in estimates that differ substantially from those that are observed and constrains the maximum BMI z that is attainable at a given sex and age,” wrote David S. Freedman, PhD, of the Centers for Disease Control and Prevention in Atlanta, and Gerald S. Berenson, MD, of Louisiana State University Health Sciences Center, New Orleans, (Pediatrics. 2017;140:e20171072).

The BMI adjusted z score (BMIaz) or the BMI expressed as a percentage of the 95th percentile (%BMI_p95) “will provide more accurate information on body size over time among children with very high BMIs,” they said.

iStockphoto

To compare different BMI metrics, the researchers reviewed data from 6,977 children aged 2-17 years participating in the longitudinal Bogalusa Heart Study who were examined in two or more cross-sectional studies. Among the 247 who met criteria for severe obesity, the average BMI was 32 kg/m², the average BMI z score was 2.4 standard deviation (SD), and the average BMI adjusted z score (BMIaz) was +3.0 SD. Correlations for BMI z scores were “consistently weaker than those for BMI, BMIaz, and %BMI_p95,” for children with obesity or severe obesity over an average of 2.8 years. Obesity was defined as BMI in the 95th percentile or higher.

In children with severe obesity, BMI z was a weaker measure (r = 0.46) than were measures of %BMI_p95 (r = 0.61) or BMIaz scores with no upper boundary (r = 0.65).

BMI z scores were weakest when applied to children younger than 10 years, with correlations of r = 0.36 for BMI z vs. correlations of 0.60 and 0.57 for BMIaz and %BMI_p95, respectively.

The results were limited by several factors including the age of the data (40 years ago, when the prevalence of severe obesity was lower, 2% compared with approximately 6% now) and long intervals between exams in some cases (5 years or more), the researchers noted. However, the results suggest that BMI z values “can differ substantially from empirical estimates, have an effective upper limit, and are strongly influenced by sex and age,” they said. As an alternative, the researchers recommended that “very high BMIs should be should expressed as z scores on the basis of linear extrapolations of a fixed SD or as percentage of the CDC 95th percentile,” or using multilevel models that adjust for age and sex.

The researchers had no financial conflicts to disclose. The National Institute on Aging, the National Heart, Lung, and Blood Institute, and the National Institutes of Health funded the study.