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Cannabis crimps teen cognitive development
BARCELONA – What would you predict has a greater detrimental effect on adolescent cognitive development: alcohol or cannabis use?
The evidence-based answer may come as a surprise. It certainly did for Patricia Conrod, PhD, who led the large population-based study that addressed the question.
“Generally, we found no effect of alcohol on cognitive development, which was a huge surprise to us. It might be related to the fact that the quantity of alcohol consumption in this young sample just wasn’t high enough to produce significant effects on cognitive development. But, to our surprise, we found rather significant effects of cannabis use on cognitive development,” she said at the annual congress of the European College of Neuropsychopharmacology.
Indeed, cannabis use proved to have detrimental effects on all four cognitive domains assessed in the study: working memory, perceptual reasoning, delayed recall, and inhibitory control, reported Dr. Conrod, professor of psychiatry at the University of Montreal.
Her recently study, published in the American Journal of Psychiatry, included 3,826 seventh-grade students at 31 Montreal-area schools. They constituted 5% of all students entering that grade in the greater Montreal area. Participants were prospectively assessed annually for 4 years regarding their use or nonuse of alcohol or cannabis and also underwent neurocognitive testing on the four domains of interest. The assessments were done on school computers with preservation of student confidentiality. Investigators used a Big Data approach to model the relationship between the extent of substance use and neurocognitive function variables over time.
Abstinent students were the best performers on the neurocognitive testing. Cannabis use, but not alcohol, in a given year was associated with concurrent adverse effects on all four cognitive domains. In addition, cannabis use showed evidence of having a neurotoxic lag effect on inhibitory control and working memory. This took the form of a lasting effect: A student who reported using cannabis 1 year but not the next showed impairment of inhibitory control and working memory during both years. And a student who used cannabis both years was even more impaired in those domains.
Dr. Conrod found the evidence of a neurotoxic effect of cannabis use on inhibitory control to be of particular concern because in earlier studies she established that impaired inhibitory control is a strong independent risk factor for subsequent substance use disorders.
”So what we’re seeing is indeed that early onset substance use is interfering with cognitive development, which now sets us up to be able to answer the question of whether evidence-based prevention protects cognitive development by delaying early onset of substance use. And over the longer term, does that protect young people against addiction?”
Dr. Conrod and her coworkers are now in the process of obtaining answers to those questions in the large ongoing Canadian Institutes of Health Research-funded Co-Venture Trial. This randomized trial involving thousands of adolescent students used the investigators’ Preventure Program, a school-based, personality-targeted intervention for prevention of substance use and abuse.
The Preventure Program involves two 90-minute group sessions of manual-based cognitive-behavioral therapy. Students are invited to participate if they score at least one standard deviation above the school mean on one of four personality traits that have been shown to increase the risk of substance misuse and psychiatric disorders. The four personality traits are sensation seeking, impulsivity, anxiety sensitivity, and hopelessness. Typically, about 45% of students met that threshold, and 85% of those invited to participate in the program volunteered to do so. Students of similar personality type are grouped together for the targeted therapy sessions.
This brief coping skills intervention has been shown in multiple randomized trials around the world to reduce the likelihood of substance use in at-risk adolescents. For example, in an early trial involving 732 high school students in London, participation in the Preventure Program was associated with a 30% reduction in the likelihood of taking up the use of cannabis within the next 2 years, an 80% reduction in the likelihood of taking up cocaine, and a 50% reduction in the use of other drugs (Arch Gen Psychiatry. 2010 Jan;67[1]:85-93).
bjancin@mdedge.com
SOURCE: Conrod P. Am J Psychiatry. 2018 Oct 3. doi: 10.1176/appi.ajp.2018.18020202.
BARCELONA – What would you predict has a greater detrimental effect on adolescent cognitive development: alcohol or cannabis use?
The evidence-based answer may come as a surprise. It certainly did for Patricia Conrod, PhD, who led the large population-based study that addressed the question.
“Generally, we found no effect of alcohol on cognitive development, which was a huge surprise to us. It might be related to the fact that the quantity of alcohol consumption in this young sample just wasn’t high enough to produce significant effects on cognitive development. But, to our surprise, we found rather significant effects of cannabis use on cognitive development,” she said at the annual congress of the European College of Neuropsychopharmacology.
Indeed, cannabis use proved to have detrimental effects on all four cognitive domains assessed in the study: working memory, perceptual reasoning, delayed recall, and inhibitory control, reported Dr. Conrod, professor of psychiatry at the University of Montreal.
Her recently study, published in the American Journal of Psychiatry, included 3,826 seventh-grade students at 31 Montreal-area schools. They constituted 5% of all students entering that grade in the greater Montreal area. Participants were prospectively assessed annually for 4 years regarding their use or nonuse of alcohol or cannabis and also underwent neurocognitive testing on the four domains of interest. The assessments were done on school computers with preservation of student confidentiality. Investigators used a Big Data approach to model the relationship between the extent of substance use and neurocognitive function variables over time.
Abstinent students were the best performers on the neurocognitive testing. Cannabis use, but not alcohol, in a given year was associated with concurrent adverse effects on all four cognitive domains. In addition, cannabis use showed evidence of having a neurotoxic lag effect on inhibitory control and working memory. This took the form of a lasting effect: A student who reported using cannabis 1 year but not the next showed impairment of inhibitory control and working memory during both years. And a student who used cannabis both years was even more impaired in those domains.
Dr. Conrod found the evidence of a neurotoxic effect of cannabis use on inhibitory control to be of particular concern because in earlier studies she established that impaired inhibitory control is a strong independent risk factor for subsequent substance use disorders.
”So what we’re seeing is indeed that early onset substance use is interfering with cognitive development, which now sets us up to be able to answer the question of whether evidence-based prevention protects cognitive development by delaying early onset of substance use. And over the longer term, does that protect young people against addiction?”
Dr. Conrod and her coworkers are now in the process of obtaining answers to those questions in the large ongoing Canadian Institutes of Health Research-funded Co-Venture Trial. This randomized trial involving thousands of adolescent students used the investigators’ Preventure Program, a school-based, personality-targeted intervention for prevention of substance use and abuse.
The Preventure Program involves two 90-minute group sessions of manual-based cognitive-behavioral therapy. Students are invited to participate if they score at least one standard deviation above the school mean on one of four personality traits that have been shown to increase the risk of substance misuse and psychiatric disorders. The four personality traits are sensation seeking, impulsivity, anxiety sensitivity, and hopelessness. Typically, about 45% of students met that threshold, and 85% of those invited to participate in the program volunteered to do so. Students of similar personality type are grouped together for the targeted therapy sessions.
This brief coping skills intervention has been shown in multiple randomized trials around the world to reduce the likelihood of substance use in at-risk adolescents. For example, in an early trial involving 732 high school students in London, participation in the Preventure Program was associated with a 30% reduction in the likelihood of taking up the use of cannabis within the next 2 years, an 80% reduction in the likelihood of taking up cocaine, and a 50% reduction in the use of other drugs (Arch Gen Psychiatry. 2010 Jan;67[1]:85-93).
bjancin@mdedge.com
SOURCE: Conrod P. Am J Psychiatry. 2018 Oct 3. doi: 10.1176/appi.ajp.2018.18020202.
BARCELONA – What would you predict has a greater detrimental effect on adolescent cognitive development: alcohol or cannabis use?
The evidence-based answer may come as a surprise. It certainly did for Patricia Conrod, PhD, who led the large population-based study that addressed the question.
“Generally, we found no effect of alcohol on cognitive development, which was a huge surprise to us. It might be related to the fact that the quantity of alcohol consumption in this young sample just wasn’t high enough to produce significant effects on cognitive development. But, to our surprise, we found rather significant effects of cannabis use on cognitive development,” she said at the annual congress of the European College of Neuropsychopharmacology.
Indeed, cannabis use proved to have detrimental effects on all four cognitive domains assessed in the study: working memory, perceptual reasoning, delayed recall, and inhibitory control, reported Dr. Conrod, professor of psychiatry at the University of Montreal.
Her recently study, published in the American Journal of Psychiatry, included 3,826 seventh-grade students at 31 Montreal-area schools. They constituted 5% of all students entering that grade in the greater Montreal area. Participants were prospectively assessed annually for 4 years regarding their use or nonuse of alcohol or cannabis and also underwent neurocognitive testing on the four domains of interest. The assessments were done on school computers with preservation of student confidentiality. Investigators used a Big Data approach to model the relationship between the extent of substance use and neurocognitive function variables over time.
Abstinent students were the best performers on the neurocognitive testing. Cannabis use, but not alcohol, in a given year was associated with concurrent adverse effects on all four cognitive domains. In addition, cannabis use showed evidence of having a neurotoxic lag effect on inhibitory control and working memory. This took the form of a lasting effect: A student who reported using cannabis 1 year but not the next showed impairment of inhibitory control and working memory during both years. And a student who used cannabis both years was even more impaired in those domains.
Dr. Conrod found the evidence of a neurotoxic effect of cannabis use on inhibitory control to be of particular concern because in earlier studies she established that impaired inhibitory control is a strong independent risk factor for subsequent substance use disorders.
”So what we’re seeing is indeed that early onset substance use is interfering with cognitive development, which now sets us up to be able to answer the question of whether evidence-based prevention protects cognitive development by delaying early onset of substance use. And over the longer term, does that protect young people against addiction?”
Dr. Conrod and her coworkers are now in the process of obtaining answers to those questions in the large ongoing Canadian Institutes of Health Research-funded Co-Venture Trial. This randomized trial involving thousands of adolescent students used the investigators’ Preventure Program, a school-based, personality-targeted intervention for prevention of substance use and abuse.
The Preventure Program involves two 90-minute group sessions of manual-based cognitive-behavioral therapy. Students are invited to participate if they score at least one standard deviation above the school mean on one of four personality traits that have been shown to increase the risk of substance misuse and psychiatric disorders. The four personality traits are sensation seeking, impulsivity, anxiety sensitivity, and hopelessness. Typically, about 45% of students met that threshold, and 85% of those invited to participate in the program volunteered to do so. Students of similar personality type are grouped together for the targeted therapy sessions.
This brief coping skills intervention has been shown in multiple randomized trials around the world to reduce the likelihood of substance use in at-risk adolescents. For example, in an early trial involving 732 high school students in London, participation in the Preventure Program was associated with a 30% reduction in the likelihood of taking up the use of cannabis within the next 2 years, an 80% reduction in the likelihood of taking up cocaine, and a 50% reduction in the use of other drugs (Arch Gen Psychiatry. 2010 Jan;67[1]:85-93).
bjancin@mdedge.com
SOURCE: Conrod P. Am J Psychiatry. 2018 Oct 3. doi: 10.1176/appi.ajp.2018.18020202.
REPORTING FROM THE ECNP CONGRESS
Key clinical point:
Major finding: The observed neurotoxic effect on impulse control may spell future trouble.
Study details: This population-based study included 3,826 Montreal-area seventh graders who were prospectively assessed annually for 4 years regarding their cannabis and alcohol use and also underwent neurocognitive testing.
Disclosures: The study was funded by the Canadian Institutes of Health Research.
Source: Conrod P. Am J Psychiatry. 2018 Oct 3. doi: 10.1176/appi.ajp.2018.18020202.
Age limits restrict AYA participation in relevant trials
MUNICH—Age limits imposed in European countries can prevent adolescents and young adults (AYAs) from enrolling in appropriate clinical trials, a new study suggests.
Investigators reviewed phase 1 and 2 trials conducted over a 6-year period at a single center in France.
The results showed that adolescents were prevented from enrolling in potentially beneficial adult trials, and young adults were unable to enroll in potentially beneficial pediatric trials.
These results were presented at the ESMO 2018 Congress (abstract 424P_PR).
In Europe, the legal minimum age to participate in adult clinical trials is typically 18.
“We know, however, that certain girls will develop genetically driven breast cancers very early in life,” said Dr. Aurore Vozy, of Gustave Roussy Institut de Cancérologie in Villejuif, France.
“There are no pediatric trials for this disease, yet these patients are systematically barred from participating in the relevant adult trials. The situation is similar for some adolescents with lymphomas or sarcomas, whose tumors often resemble those of adults much more closely than those found in children.”
On the other hand, adults in their early twenties may be diagnosed with cancers most commonly seen in children. And pediatric clinical trials typically set an upper age limit of 18 or 21.
To assess the availability and accessibility of new treatments to AYA cancer patients, Dr. Vozy and her colleagues conducted a review of all phase 1 and 2 trials opened at Gustave Roussy from 2012 through 2017 for patients with solid tumors or lymphomas.
Over the 6-year period, 465 trials were open—403 adult trials and 62 pediatric trials.
Only 65 of the trials (14%) included patients between the ages of 12 and 17.
“In other words, patients in this age group had access to less than 15% of all the early phase trials at our institute,” Dr. Vozy said.
In all, there were 389 trials that were not open to adolescents, and the investigators found that 55% of these trials could have been relevant for underage patients. Twenty-eight of the trials targeted tumor types that are particularly common among teenagers.
“This means that patients have been denied access to innovative medicines which were available at the very center where they were being treated, and to which they may have had a better response than to conventional therapy,” Dr. Vozy said.
She and her colleagues also found that young adults were often unable to enroll in pediatric trials.
There were 62 pediatric trials open over the period studied, and more than half of them (n=36, 58%) did not recruit patients aged 19 to 25, even though 10 of these trials targeted tumor types that also occur in this age group.
“Raising the age bar in pediatric trials to 25 years would clearly make sense in certain cases,” Dr. Vozy said.
She argued, however, that the more pressing issue is the current age limit in adult trials.
“We know that the diseases, toxicities, and pharmacology seen in 12- to 17-year-olds are similar to what we find in adults, so it would be feasible to include these patients in adult trials at no additional risk to them,” Dr. Vozy said.
This has already been done successfully in the United States, where the minimum age for trial participation has been lowered to 12 years.
An additional measure to consider, Dr. Vozy said, is creating dedicated trial cohorts for adolescents within adult trials.
“In a context where, today, most phase 1 trials in oncology are launched with multiple study populations for different tumor types, it would be easy to cater to the specific needs of adolescents by including them in cohorts of their own,” she said.
“The main constraint is that trials which include underage patients should only be conducted in centers that also have pediatric services onsite. Adolescents may be affected by disease similarly to adults, but they still need to be treated and followed up on by pediatric specialists.”
One investigator involved in this study reported relationships with Amgen, Astellas, Astra Zeneca, Bayer, Celgene, Genentech, Ipsen, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, and Orion. All other investigators declared no conflicts of interest.
MUNICH—Age limits imposed in European countries can prevent adolescents and young adults (AYAs) from enrolling in appropriate clinical trials, a new study suggests.
Investigators reviewed phase 1 and 2 trials conducted over a 6-year period at a single center in France.
The results showed that adolescents were prevented from enrolling in potentially beneficial adult trials, and young adults were unable to enroll in potentially beneficial pediatric trials.
These results were presented at the ESMO 2018 Congress (abstract 424P_PR).
In Europe, the legal minimum age to participate in adult clinical trials is typically 18.
“We know, however, that certain girls will develop genetically driven breast cancers very early in life,” said Dr. Aurore Vozy, of Gustave Roussy Institut de Cancérologie in Villejuif, France.
“There are no pediatric trials for this disease, yet these patients are systematically barred from participating in the relevant adult trials. The situation is similar for some adolescents with lymphomas or sarcomas, whose tumors often resemble those of adults much more closely than those found in children.”
On the other hand, adults in their early twenties may be diagnosed with cancers most commonly seen in children. And pediatric clinical trials typically set an upper age limit of 18 or 21.
To assess the availability and accessibility of new treatments to AYA cancer patients, Dr. Vozy and her colleagues conducted a review of all phase 1 and 2 trials opened at Gustave Roussy from 2012 through 2017 for patients with solid tumors or lymphomas.
Over the 6-year period, 465 trials were open—403 adult trials and 62 pediatric trials.
Only 65 of the trials (14%) included patients between the ages of 12 and 17.
“In other words, patients in this age group had access to less than 15% of all the early phase trials at our institute,” Dr. Vozy said.
In all, there were 389 trials that were not open to adolescents, and the investigators found that 55% of these trials could have been relevant for underage patients. Twenty-eight of the trials targeted tumor types that are particularly common among teenagers.
“This means that patients have been denied access to innovative medicines which were available at the very center where they were being treated, and to which they may have had a better response than to conventional therapy,” Dr. Vozy said.
She and her colleagues also found that young adults were often unable to enroll in pediatric trials.
There were 62 pediatric trials open over the period studied, and more than half of them (n=36, 58%) did not recruit patients aged 19 to 25, even though 10 of these trials targeted tumor types that also occur in this age group.
“Raising the age bar in pediatric trials to 25 years would clearly make sense in certain cases,” Dr. Vozy said.
She argued, however, that the more pressing issue is the current age limit in adult trials.
“We know that the diseases, toxicities, and pharmacology seen in 12- to 17-year-olds are similar to what we find in adults, so it would be feasible to include these patients in adult trials at no additional risk to them,” Dr. Vozy said.
This has already been done successfully in the United States, where the minimum age for trial participation has been lowered to 12 years.
An additional measure to consider, Dr. Vozy said, is creating dedicated trial cohorts for adolescents within adult trials.
“In a context where, today, most phase 1 trials in oncology are launched with multiple study populations for different tumor types, it would be easy to cater to the specific needs of adolescents by including them in cohorts of their own,” she said.
“The main constraint is that trials which include underage patients should only be conducted in centers that also have pediatric services onsite. Adolescents may be affected by disease similarly to adults, but they still need to be treated and followed up on by pediatric specialists.”
One investigator involved in this study reported relationships with Amgen, Astellas, Astra Zeneca, Bayer, Celgene, Genentech, Ipsen, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, and Orion. All other investigators declared no conflicts of interest.
MUNICH—Age limits imposed in European countries can prevent adolescents and young adults (AYAs) from enrolling in appropriate clinical trials, a new study suggests.
Investigators reviewed phase 1 and 2 trials conducted over a 6-year period at a single center in France.
The results showed that adolescents were prevented from enrolling in potentially beneficial adult trials, and young adults were unable to enroll in potentially beneficial pediatric trials.
These results were presented at the ESMO 2018 Congress (abstract 424P_PR).
In Europe, the legal minimum age to participate in adult clinical trials is typically 18.
“We know, however, that certain girls will develop genetically driven breast cancers very early in life,” said Dr. Aurore Vozy, of Gustave Roussy Institut de Cancérologie in Villejuif, France.
“There are no pediatric trials for this disease, yet these patients are systematically barred from participating in the relevant adult trials. The situation is similar for some adolescents with lymphomas or sarcomas, whose tumors often resemble those of adults much more closely than those found in children.”
On the other hand, adults in their early twenties may be diagnosed with cancers most commonly seen in children. And pediatric clinical trials typically set an upper age limit of 18 or 21.
To assess the availability and accessibility of new treatments to AYA cancer patients, Dr. Vozy and her colleagues conducted a review of all phase 1 and 2 trials opened at Gustave Roussy from 2012 through 2017 for patients with solid tumors or lymphomas.
Over the 6-year period, 465 trials were open—403 adult trials and 62 pediatric trials.
Only 65 of the trials (14%) included patients between the ages of 12 and 17.
“In other words, patients in this age group had access to less than 15% of all the early phase trials at our institute,” Dr. Vozy said.
In all, there were 389 trials that were not open to adolescents, and the investigators found that 55% of these trials could have been relevant for underage patients. Twenty-eight of the trials targeted tumor types that are particularly common among teenagers.
“This means that patients have been denied access to innovative medicines which were available at the very center where they were being treated, and to which they may have had a better response than to conventional therapy,” Dr. Vozy said.
She and her colleagues also found that young adults were often unable to enroll in pediatric trials.
There were 62 pediatric trials open over the period studied, and more than half of them (n=36, 58%) did not recruit patients aged 19 to 25, even though 10 of these trials targeted tumor types that also occur in this age group.
“Raising the age bar in pediatric trials to 25 years would clearly make sense in certain cases,” Dr. Vozy said.
She argued, however, that the more pressing issue is the current age limit in adult trials.
“We know that the diseases, toxicities, and pharmacology seen in 12- to 17-year-olds are similar to what we find in adults, so it would be feasible to include these patients in adult trials at no additional risk to them,” Dr. Vozy said.
This has already been done successfully in the United States, where the minimum age for trial participation has been lowered to 12 years.
An additional measure to consider, Dr. Vozy said, is creating dedicated trial cohorts for adolescents within adult trials.
“In a context where, today, most phase 1 trials in oncology are launched with multiple study populations for different tumor types, it would be easy to cater to the specific needs of adolescents by including them in cohorts of their own,” she said.
“The main constraint is that trials which include underage patients should only be conducted in centers that also have pediatric services onsite. Adolescents may be affected by disease similarly to adults, but they still need to be treated and followed up on by pediatric specialists.”
One investigator involved in this study reported relationships with Amgen, Astellas, Astra Zeneca, Bayer, Celgene, Genentech, Ipsen, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, and Orion. All other investigators declared no conflicts of interest.
Imaging of child basal ganglion lesions yields useful clinical information
NEW YORK – When paraganglionic lesions are compared with isolated basal ganglionic lesions in children, important differences in clinical manifestations were identified, according to imaging-based findings presented at the International Conference on Parkinson’s Disease and Movement Disorders.
“The percentage of children with impaired cognitive function, motor weakness, and disturbed level of consciousness were all significantly higher among the paraganglionic group,” reported Hamada I. Zehry, MD, of Al-Azhar University, Cairo, Egypt.
Conversely, “the incidence of abnormal movements and rigidity were significantly higher among the group with basal ganglion lesions alone,” he said.
The findings were based on comparisons made after MRI imaging differentiated the 23 children with basal ganglionic lesions alone (IG) from 11 children with paraganglionic lesions (PG). About half of the PG group also had lesions involving the basal ganglion as well. All patients were 18 years of age or younger. The mean ages were 9 years in the IG group and 5.7 years in the PG group (P less than .04). Both groups contained approximately 55% males.
Both the IG and PG groups were stratified by ischemic, infectious, metabolic, and toxic etiologies. For the IG relative to the PG group, the ischemic (34.8% vs. 36.4%), infectious (26.1% vs. 36.4%), and metabolic (30.4% vs. 27.2%) etiologies had a relatively similar distribution. However, there was no patient in the PG group with a toxic etiology versus 8.7% (P = .003) in the IG group.
Neurologic symptoms by lesion site differed. Cognitive dysfunction (55% vs. 26%), seizures (64% vs. 43%), muscle weakness (45% vs. 30%), and changes in level of consciousness (82% vs. 22%) were all more common in the PG than the IG group according to Dr. Zehry. However, abnormal movements (30% vs. 9%) and rigidity (17% vs. 0%) were more common in the IG group.
These differences were all significant by conventional statistical analysis (P less than .05), according to Dr. Zehry, although he did not provide the specific P values for each of the comparisons.
There were also differences in the frequency of neurologic symptoms within groups when stratified by etiology. Of the biggest differences in the IG group, cognitive dysfunction was observed in 57% of those with a metabolic etiology but only 17% of those with an infectious etiology and 13% of those with an ischemic etiology. None of those with a toxic etiology had cognitive dysfunction.
In the PG group, the rates of cognitive dysfunction were 25%, 50%, and 100% for the ischemic, infectious, and metabolic etiologies, respectively. Changed levels of consciousness were observed in 75%, 100%, and 67% of these etiologies, respectively, in the PG group, but in only 13%, 33%, and 0%, respectively, in the IG group. In those with a toxic etiology in the IG group, a changed level of consciousness was observed in 100%.
Laboratory findings also were compared between groups and between etiologies within groups. It is notable that liver dysfunction and cytopenias were confined to those with metabolic infectious etiologies in both the IG and PG patients. However, Dr. Zehry suggested that the significance of these and other differences in laboratory findings deserve confirmation and further study in a larger study.
In this series, which excluded patients with a history of trauma or tumors, Dr. Zehry emphasized that bilateral lesions were commonly found in both groups. Overall, he cautioned that distinguishing IG and PG “is not straightforward.” In addition to MRI, he suggested additional imaging tools – such as MR angiography, MR venography, and CT scans – might be useful for evaluating children suspected of pathology in the basal ganglion.
Because there is often bilateral involvement, “the careful assessment of imaging abnormalities occurring simultaneously with bilateral ganglionic injury is recommended,” he said. He added that the diagnosis can also be facilitated by correlating imaging features with clinical and laboratory data.”
NEW YORK – When paraganglionic lesions are compared with isolated basal ganglionic lesions in children, important differences in clinical manifestations were identified, according to imaging-based findings presented at the International Conference on Parkinson’s Disease and Movement Disorders.
“The percentage of children with impaired cognitive function, motor weakness, and disturbed level of consciousness were all significantly higher among the paraganglionic group,” reported Hamada I. Zehry, MD, of Al-Azhar University, Cairo, Egypt.
Conversely, “the incidence of abnormal movements and rigidity were significantly higher among the group with basal ganglion lesions alone,” he said.
The findings were based on comparisons made after MRI imaging differentiated the 23 children with basal ganglionic lesions alone (IG) from 11 children with paraganglionic lesions (PG). About half of the PG group also had lesions involving the basal ganglion as well. All patients were 18 years of age or younger. The mean ages were 9 years in the IG group and 5.7 years in the PG group (P less than .04). Both groups contained approximately 55% males.
Both the IG and PG groups were stratified by ischemic, infectious, metabolic, and toxic etiologies. For the IG relative to the PG group, the ischemic (34.8% vs. 36.4%), infectious (26.1% vs. 36.4%), and metabolic (30.4% vs. 27.2%) etiologies had a relatively similar distribution. However, there was no patient in the PG group with a toxic etiology versus 8.7% (P = .003) in the IG group.
Neurologic symptoms by lesion site differed. Cognitive dysfunction (55% vs. 26%), seizures (64% vs. 43%), muscle weakness (45% vs. 30%), and changes in level of consciousness (82% vs. 22%) were all more common in the PG than the IG group according to Dr. Zehry. However, abnormal movements (30% vs. 9%) and rigidity (17% vs. 0%) were more common in the IG group.
These differences were all significant by conventional statistical analysis (P less than .05), according to Dr. Zehry, although he did not provide the specific P values for each of the comparisons.
There were also differences in the frequency of neurologic symptoms within groups when stratified by etiology. Of the biggest differences in the IG group, cognitive dysfunction was observed in 57% of those with a metabolic etiology but only 17% of those with an infectious etiology and 13% of those with an ischemic etiology. None of those with a toxic etiology had cognitive dysfunction.
In the PG group, the rates of cognitive dysfunction were 25%, 50%, and 100% for the ischemic, infectious, and metabolic etiologies, respectively. Changed levels of consciousness were observed in 75%, 100%, and 67% of these etiologies, respectively, in the PG group, but in only 13%, 33%, and 0%, respectively, in the IG group. In those with a toxic etiology in the IG group, a changed level of consciousness was observed in 100%.
Laboratory findings also were compared between groups and between etiologies within groups. It is notable that liver dysfunction and cytopenias were confined to those with metabolic infectious etiologies in both the IG and PG patients. However, Dr. Zehry suggested that the significance of these and other differences in laboratory findings deserve confirmation and further study in a larger study.
In this series, which excluded patients with a history of trauma or tumors, Dr. Zehry emphasized that bilateral lesions were commonly found in both groups. Overall, he cautioned that distinguishing IG and PG “is not straightforward.” In addition to MRI, he suggested additional imaging tools – such as MR angiography, MR venography, and CT scans – might be useful for evaluating children suspected of pathology in the basal ganglion.
Because there is often bilateral involvement, “the careful assessment of imaging abnormalities occurring simultaneously with bilateral ganglionic injury is recommended,” he said. He added that the diagnosis can also be facilitated by correlating imaging features with clinical and laboratory data.”
NEW YORK – When paraganglionic lesions are compared with isolated basal ganglionic lesions in children, important differences in clinical manifestations were identified, according to imaging-based findings presented at the International Conference on Parkinson’s Disease and Movement Disorders.
“The percentage of children with impaired cognitive function, motor weakness, and disturbed level of consciousness were all significantly higher among the paraganglionic group,” reported Hamada I. Zehry, MD, of Al-Azhar University, Cairo, Egypt.
Conversely, “the incidence of abnormal movements and rigidity were significantly higher among the group with basal ganglion lesions alone,” he said.
The findings were based on comparisons made after MRI imaging differentiated the 23 children with basal ganglionic lesions alone (IG) from 11 children with paraganglionic lesions (PG). About half of the PG group also had lesions involving the basal ganglion as well. All patients were 18 years of age or younger. The mean ages were 9 years in the IG group and 5.7 years in the PG group (P less than .04). Both groups contained approximately 55% males.
Both the IG and PG groups were stratified by ischemic, infectious, metabolic, and toxic etiologies. For the IG relative to the PG group, the ischemic (34.8% vs. 36.4%), infectious (26.1% vs. 36.4%), and metabolic (30.4% vs. 27.2%) etiologies had a relatively similar distribution. However, there was no patient in the PG group with a toxic etiology versus 8.7% (P = .003) in the IG group.
Neurologic symptoms by lesion site differed. Cognitive dysfunction (55% vs. 26%), seizures (64% vs. 43%), muscle weakness (45% vs. 30%), and changes in level of consciousness (82% vs. 22%) were all more common in the PG than the IG group according to Dr. Zehry. However, abnormal movements (30% vs. 9%) and rigidity (17% vs. 0%) were more common in the IG group.
These differences were all significant by conventional statistical analysis (P less than .05), according to Dr. Zehry, although he did not provide the specific P values for each of the comparisons.
There were also differences in the frequency of neurologic symptoms within groups when stratified by etiology. Of the biggest differences in the IG group, cognitive dysfunction was observed in 57% of those with a metabolic etiology but only 17% of those with an infectious etiology and 13% of those with an ischemic etiology. None of those with a toxic etiology had cognitive dysfunction.
In the PG group, the rates of cognitive dysfunction were 25%, 50%, and 100% for the ischemic, infectious, and metabolic etiologies, respectively. Changed levels of consciousness were observed in 75%, 100%, and 67% of these etiologies, respectively, in the PG group, but in only 13%, 33%, and 0%, respectively, in the IG group. In those with a toxic etiology in the IG group, a changed level of consciousness was observed in 100%.
Laboratory findings also were compared between groups and between etiologies within groups. It is notable that liver dysfunction and cytopenias were confined to those with metabolic infectious etiologies in both the IG and PG patients. However, Dr. Zehry suggested that the significance of these and other differences in laboratory findings deserve confirmation and further study in a larger study.
In this series, which excluded patients with a history of trauma or tumors, Dr. Zehry emphasized that bilateral lesions were commonly found in both groups. Overall, he cautioned that distinguishing IG and PG “is not straightforward.” In addition to MRI, he suggested additional imaging tools – such as MR angiography, MR venography, and CT scans – might be useful for evaluating children suspected of pathology in the basal ganglion.
Because there is often bilateral involvement, “the careful assessment of imaging abnormalities occurring simultaneously with bilateral ganglionic injury is recommended,” he said. He added that the diagnosis can also be facilitated by correlating imaging features with clinical and laboratory data.”
REPORTING FROM ICPDMD 2018
Key clinical point: In children with basal ganglion and paraganglion lesions, injury site on imaging yields clinical distinctions.
Major finding: Relative to isolated lesions, paraganglion lesions produce more neuropathy such as cognitive dysfunction (57% vs. 26%; P less than .05)
Study details: Cross-sectional observational study.
Disclosures: Dr. Zehry reports no financial relationships relevant to this study.
Study supports sequencing in kids with cancer
SAN DIEGO—Comprehensive next-generation sequencing is both feasible and clinically useful in pediatric cancer patients, a new study suggests.
Researchers sequenced samples from 253 pediatric cancer patients and found that, in 79% of cases, there was at least one finding that could help guide care.
Scott Newman, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, presented these findings at the American Society of Human Genetics (ASHG) 2018 Annual Meeting (abstract 52).
The researchers conducted whole-genome, exome, and transcriptome sequencing of the patients’ tumors, as well as sequencing non-cancerous tissues from the same patients.
Of the 253 patients studied, 123 had hematologic malignancies.
The researchers found a mean of four pathogenic or likely pathogenic variants per patient (range, 0-18). This included prognostic (21.8%) and diagnostic (15.1%) variants as well as variants that could be targeted therapeutically (6.8%).
In all, 79% of the patients had at least one variant that was targetable, diagnostic, or prognostic. And test results were available within about 40 days, quickly enough that they could be used to guide care.
“With results available in a clinically relevant time frame, and pricing becoming increasingly comparable to the radiology and pathology tests, WGS [whole-genome sequencing] is becoming more accessible to pediatric oncology patients,” Dr. Newman said.
This work was part of the Genomes for Kids study (G4K), an effort to understand how best to use genetic data for pediatric cancer diagnosis and treatment. St. Jude has compiled the information from G4K into a publicly accessible online database.
The researchers have continued to perform sequencing on current patients, and, since the original study ended, have successfully used this method on roughly 300 additional patients. The team plans to continue studying sequencing methods in hopes of producing clinically applicable data more quickly.
G4K was sponsored by St. Jude.
SAN DIEGO—Comprehensive next-generation sequencing is both feasible and clinically useful in pediatric cancer patients, a new study suggests.
Researchers sequenced samples from 253 pediatric cancer patients and found that, in 79% of cases, there was at least one finding that could help guide care.
Scott Newman, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, presented these findings at the American Society of Human Genetics (ASHG) 2018 Annual Meeting (abstract 52).
The researchers conducted whole-genome, exome, and transcriptome sequencing of the patients’ tumors, as well as sequencing non-cancerous tissues from the same patients.
Of the 253 patients studied, 123 had hematologic malignancies.
The researchers found a mean of four pathogenic or likely pathogenic variants per patient (range, 0-18). This included prognostic (21.8%) and diagnostic (15.1%) variants as well as variants that could be targeted therapeutically (6.8%).
In all, 79% of the patients had at least one variant that was targetable, diagnostic, or prognostic. And test results were available within about 40 days, quickly enough that they could be used to guide care.
“With results available in a clinically relevant time frame, and pricing becoming increasingly comparable to the radiology and pathology tests, WGS [whole-genome sequencing] is becoming more accessible to pediatric oncology patients,” Dr. Newman said.
This work was part of the Genomes for Kids study (G4K), an effort to understand how best to use genetic data for pediatric cancer diagnosis and treatment. St. Jude has compiled the information from G4K into a publicly accessible online database.
The researchers have continued to perform sequencing on current patients, and, since the original study ended, have successfully used this method on roughly 300 additional patients. The team plans to continue studying sequencing methods in hopes of producing clinically applicable data more quickly.
G4K was sponsored by St. Jude.
SAN DIEGO—Comprehensive next-generation sequencing is both feasible and clinically useful in pediatric cancer patients, a new study suggests.
Researchers sequenced samples from 253 pediatric cancer patients and found that, in 79% of cases, there was at least one finding that could help guide care.
Scott Newman, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, presented these findings at the American Society of Human Genetics (ASHG) 2018 Annual Meeting (abstract 52).
The researchers conducted whole-genome, exome, and transcriptome sequencing of the patients’ tumors, as well as sequencing non-cancerous tissues from the same patients.
Of the 253 patients studied, 123 had hematologic malignancies.
The researchers found a mean of four pathogenic or likely pathogenic variants per patient (range, 0-18). This included prognostic (21.8%) and diagnostic (15.1%) variants as well as variants that could be targeted therapeutically (6.8%).
In all, 79% of the patients had at least one variant that was targetable, diagnostic, or prognostic. And test results were available within about 40 days, quickly enough that they could be used to guide care.
“With results available in a clinically relevant time frame, and pricing becoming increasingly comparable to the radiology and pathology tests, WGS [whole-genome sequencing] is becoming more accessible to pediatric oncology patients,” Dr. Newman said.
This work was part of the Genomes for Kids study (G4K), an effort to understand how best to use genetic data for pediatric cancer diagnosis and treatment. St. Jude has compiled the information from G4K into a publicly accessible online database.
The researchers have continued to perform sequencing on current patients, and, since the original study ended, have successfully used this method on roughly 300 additional patients. The team plans to continue studying sequencing methods in hopes of producing clinically applicable data more quickly.
G4K was sponsored by St. Jude.
Kymriah appears cost effective in analysis
The high price of chimeric antigen receptor (CAR) T-cell therapy for pediatric leukemia may prove cost effective if long-term survival benefits are realized, researchers reported.
A cost-effectiveness analysis of the CAR T-cell therapy tisagenlecleucel suggests that the $475,000 price tag is in alignment with the lifetime benefits of the treatment. The findings were published in JAMA Pediatrics.
Tisagenlecleucel – marketed as Kymriah – is a one-dose treatment for relapsed or refractory pediatric B-cell acute lymphoblastic leukemia (ALL) and the first CAR T-cell therapy approved by the Food and Drug Administration.
In this cost-effectiveness analysis, researchers used a decision analytic model that extrapolated the evidence from clinical trials over a patient’s lifetime to assess life-years gained, quality-adjusted life-years (QALYs) gained, and incremental costs per life-year and QALY gained. The comparator was the chemoimmunotherapeutic agent clofarabine.
While tisagenlecleucel has a list price of $475,000, researchers discounted the price by 3% and added several additional costs, such as hospital administration, pretreatment, and potential adverse events, to get to a total discounted cost of about $667,000. They estimated that 42.6% of patients were considered to be long-term survivors with tisagenlecleucel, 10.34 life-years would be gained, and 9.28 QALYs would be gained.
In comparison, clofarabine had a total discounted cost of approximately $337,000 (including an initial discounted price of $164,000 plus additional treatment and administrative costs), 10.8% of patients were long-term survivors, 2.43 life-years were gained, and 2.10 QALYs were gained in the model.
Overall, the mean incremental cost-effectiveness ratio was about $46,000 per QALY gained in this base-case model.
In analyses of different scenarios, such as a deeper discount, a different treatment start, or a different calculation of future treatment costs, the cost-effectiveness ratio varied from $37,000 to $78,000 per QALY gained.
“We acknowledge that considerable uncertainty remains around the long-term benefit of tisagenlecleucel owing to limited available evidence; however, with current evidence and assumptions, tisagenlecleucel meets commonly cited value thresholds over a patient lifetime horizon, assuming payment for treatment acquisition for responders at 1 month,” wrote Melanie D. Whittington, PhD, from the University of Colorado at Denver, Aurora, and her colleagues.
The authors noted that the clinical trial evidence for tisagenlecleucel came from single-arm trials, which made selection of a comparator challenging. Clofarabine was chosen because it had the most similar baseline population characteristics, but they acknowledged that blinatumomab was also frequently used as a treatment for these patients.
“We suspect that tisagenlecleucel would remain cost effective, compared with blinatumomab,” they wrote. “A study conducted by other researchers found the incremental cost-effectiveness ratio of tisagenlecleucel versus blinatumomab was similar to the incremental cost-effectiveness ratio of tisagenlecleucel versus clofarabine [i.e., $3,000 more per QALY].”
The authors suggested that uncertainties in the evidence should be considered as payers are negotiating coverage and payment for tisagenlecleucel.
“Novel payment models consistent with the present evidence may reduce the risk and uncertainty in long-term value and be more closely aligned with ensuring high-value care,” they wrote. “Financing cures in the United States is challenging, owing to the high up-front price, rapid uptake, and uncertainty in long-term outcomes; however, innovative payment models are an opportunity to address some of these challenges and to promote patient access to novel and promising therapies.”
The study was funded by the Institute for Clinical and Economic Review, which receives some funding from the pharmaceutical industry. Four authors are employees of the Institute for Clinical and Economic Review.
SOURCE: Whittington MD et al. JAMA Pediatr. 2018 Oct 8. doi: 10.1001/jamapediatrics.2018.2530.
The high price of chimeric antigen receptor (CAR) T-cell therapy for pediatric leukemia may prove cost effective if long-term survival benefits are realized, researchers reported.
A cost-effectiveness analysis of the CAR T-cell therapy tisagenlecleucel suggests that the $475,000 price tag is in alignment with the lifetime benefits of the treatment. The findings were published in JAMA Pediatrics.
Tisagenlecleucel – marketed as Kymriah – is a one-dose treatment for relapsed or refractory pediatric B-cell acute lymphoblastic leukemia (ALL) and the first CAR T-cell therapy approved by the Food and Drug Administration.
In this cost-effectiveness analysis, researchers used a decision analytic model that extrapolated the evidence from clinical trials over a patient’s lifetime to assess life-years gained, quality-adjusted life-years (QALYs) gained, and incremental costs per life-year and QALY gained. The comparator was the chemoimmunotherapeutic agent clofarabine.
While tisagenlecleucel has a list price of $475,000, researchers discounted the price by 3% and added several additional costs, such as hospital administration, pretreatment, and potential adverse events, to get to a total discounted cost of about $667,000. They estimated that 42.6% of patients were considered to be long-term survivors with tisagenlecleucel, 10.34 life-years would be gained, and 9.28 QALYs would be gained.
In comparison, clofarabine had a total discounted cost of approximately $337,000 (including an initial discounted price of $164,000 plus additional treatment and administrative costs), 10.8% of patients were long-term survivors, 2.43 life-years were gained, and 2.10 QALYs were gained in the model.
Overall, the mean incremental cost-effectiveness ratio was about $46,000 per QALY gained in this base-case model.
In analyses of different scenarios, such as a deeper discount, a different treatment start, or a different calculation of future treatment costs, the cost-effectiveness ratio varied from $37,000 to $78,000 per QALY gained.
“We acknowledge that considerable uncertainty remains around the long-term benefit of tisagenlecleucel owing to limited available evidence; however, with current evidence and assumptions, tisagenlecleucel meets commonly cited value thresholds over a patient lifetime horizon, assuming payment for treatment acquisition for responders at 1 month,” wrote Melanie D. Whittington, PhD, from the University of Colorado at Denver, Aurora, and her colleagues.
The authors noted that the clinical trial evidence for tisagenlecleucel came from single-arm trials, which made selection of a comparator challenging. Clofarabine was chosen because it had the most similar baseline population characteristics, but they acknowledged that blinatumomab was also frequently used as a treatment for these patients.
“We suspect that tisagenlecleucel would remain cost effective, compared with blinatumomab,” they wrote. “A study conducted by other researchers found the incremental cost-effectiveness ratio of tisagenlecleucel versus blinatumomab was similar to the incremental cost-effectiveness ratio of tisagenlecleucel versus clofarabine [i.e., $3,000 more per QALY].”
The authors suggested that uncertainties in the evidence should be considered as payers are negotiating coverage and payment for tisagenlecleucel.
“Novel payment models consistent with the present evidence may reduce the risk and uncertainty in long-term value and be more closely aligned with ensuring high-value care,” they wrote. “Financing cures in the United States is challenging, owing to the high up-front price, rapid uptake, and uncertainty in long-term outcomes; however, innovative payment models are an opportunity to address some of these challenges and to promote patient access to novel and promising therapies.”
The study was funded by the Institute for Clinical and Economic Review, which receives some funding from the pharmaceutical industry. Four authors are employees of the Institute for Clinical and Economic Review.
SOURCE: Whittington MD et al. JAMA Pediatr. 2018 Oct 8. doi: 10.1001/jamapediatrics.2018.2530.
The high price of chimeric antigen receptor (CAR) T-cell therapy for pediatric leukemia may prove cost effective if long-term survival benefits are realized, researchers reported.
A cost-effectiveness analysis of the CAR T-cell therapy tisagenlecleucel suggests that the $475,000 price tag is in alignment with the lifetime benefits of the treatment. The findings were published in JAMA Pediatrics.
Tisagenlecleucel – marketed as Kymriah – is a one-dose treatment for relapsed or refractory pediatric B-cell acute lymphoblastic leukemia (ALL) and the first CAR T-cell therapy approved by the Food and Drug Administration.
In this cost-effectiveness analysis, researchers used a decision analytic model that extrapolated the evidence from clinical trials over a patient’s lifetime to assess life-years gained, quality-adjusted life-years (QALYs) gained, and incremental costs per life-year and QALY gained. The comparator was the chemoimmunotherapeutic agent clofarabine.
While tisagenlecleucel has a list price of $475,000, researchers discounted the price by 3% and added several additional costs, such as hospital administration, pretreatment, and potential adverse events, to get to a total discounted cost of about $667,000. They estimated that 42.6% of patients were considered to be long-term survivors with tisagenlecleucel, 10.34 life-years would be gained, and 9.28 QALYs would be gained.
In comparison, clofarabine had a total discounted cost of approximately $337,000 (including an initial discounted price of $164,000 plus additional treatment and administrative costs), 10.8% of patients were long-term survivors, 2.43 life-years were gained, and 2.10 QALYs were gained in the model.
Overall, the mean incremental cost-effectiveness ratio was about $46,000 per QALY gained in this base-case model.
In analyses of different scenarios, such as a deeper discount, a different treatment start, or a different calculation of future treatment costs, the cost-effectiveness ratio varied from $37,000 to $78,000 per QALY gained.
“We acknowledge that considerable uncertainty remains around the long-term benefit of tisagenlecleucel owing to limited available evidence; however, with current evidence and assumptions, tisagenlecleucel meets commonly cited value thresholds over a patient lifetime horizon, assuming payment for treatment acquisition for responders at 1 month,” wrote Melanie D. Whittington, PhD, from the University of Colorado at Denver, Aurora, and her colleagues.
The authors noted that the clinical trial evidence for tisagenlecleucel came from single-arm trials, which made selection of a comparator challenging. Clofarabine was chosen because it had the most similar baseline population characteristics, but they acknowledged that blinatumomab was also frequently used as a treatment for these patients.
“We suspect that tisagenlecleucel would remain cost effective, compared with blinatumomab,” they wrote. “A study conducted by other researchers found the incremental cost-effectiveness ratio of tisagenlecleucel versus blinatumomab was similar to the incremental cost-effectiveness ratio of tisagenlecleucel versus clofarabine [i.e., $3,000 more per QALY].”
The authors suggested that uncertainties in the evidence should be considered as payers are negotiating coverage and payment for tisagenlecleucel.
“Novel payment models consistent with the present evidence may reduce the risk and uncertainty in long-term value and be more closely aligned with ensuring high-value care,” they wrote. “Financing cures in the United States is challenging, owing to the high up-front price, rapid uptake, and uncertainty in long-term outcomes; however, innovative payment models are an opportunity to address some of these challenges and to promote patient access to novel and promising therapies.”
The study was funded by the Institute for Clinical and Economic Review, which receives some funding from the pharmaceutical industry. Four authors are employees of the Institute for Clinical and Economic Review.
SOURCE: Whittington MD et al. JAMA Pediatr. 2018 Oct 8. doi: 10.1001/jamapediatrics.2018.2530.
FROM JAMA PEDIATRICS
Key clinical point:
Major finding: The incremental cost-effectiveness ratio for tisagenlecleucel versus clofarabine ranged from $37,000 to $78,000 per quality-adjusted life year gained.
Study details: A cost-effectiveness analysis comparing tisagenlecleucel with clofarabine monotherapy.
Disclosures: The study was funded by the Institute for Clinical and Economic Review, which receives some funding from the pharmaceutical industry. Four authors are employees of the Institute for Clinical and Economic Review.
Source: Whittington MD et al. JAMA Pediatr. 2018 Oct 8. doi: 10.1001/jamapediatrics.2018.2530.
Mysterious polio-like illness baffles medical experts while frightening parents
A spike in the number of children with a rare neurological disease that causes polio-like symptoms has health officials across the country scrambling to understand the illness. Yet, more than 4 years after health officials first recorded the most recent uptick in cases, much about the national outbreak remains a mystery.
Acute flaccid myelitis (AFM) affects the gray matter in the spinal cord, causing sudden muscle weakness and a loss of reflexes. The illness can lead to serious complications – including paralysis or respiratory failure – and requires immediate medical attention.
The Centers for Disease Control and Prevention is investigating 127 cases of possible AFM, including 62 that have been confirmed in 22 states this year. At least 90% of the cases are among patients 18 years old and younger. The average age of a patient is 4 years old.
AFM remains extremely rare, even with the recent increase. The CDC estimates fewer than 1 in a million Americans will get the disease. Officials advised parents not to panic but remain vigilant for any sudden onset of symptoms. They also suggested that children stay up to date with their vaccines and practice good hand washing habits.
This year’s outbreak marks the third spike of AFM in 4 years. From August 2014 to September 2018, 386 cases have been confirmed. Yet, experts still do not understand crucial aspects of the disease, including its origins and who is most at risk.
“There is a lot we don’t know about AFM,” said Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases. Here’s what puzzles health officials about AFM:
The cause is still unknown
Acute flaccid myelitis can be caused by viruses, such as polio or West Nile. But federal officials said that those viruses have not been linked to the U.S. outbreak over the past 4 years. They have not isolated the cause of these cases.
Despite symptoms reminiscent of polio, no AFM cases have tested positive for that virus, according to the CDC. Investigators have also ruled out a variety of germs. Environmental agents, viruses, and other pathogens are still being considered.
The 2014 outbreak of AFM coincided with a surge of another virus that caused severe respiratory problems, called EV-D68. However, the CDC could not establish a causal link between AFM and the virus. Since then, no large outbreaks of the virus have occurred, according to the CDC.
Carlos Pardo-Villamizar, MD, a neurologist and director of the Johns Hopkins Transverse Myelitis Center, said that the mystery lies in whether the damage seen in AFM is caused by an external agent or the body’s own defenses.
“At this moment, we don’t know if it’s a virus that is coming and producing direct damage of the gray matter in the spinal cord,” he said, “or if a virus is triggering immunological responses that produce a secondary damage in the spinal cord.”
It’s not clear who is at risk
Although the disease appears to target a certain age group, federal disease experts do not know who is likely to get acute flaccid myelitis.
Dr. Pardo-Villamizar said identifying vulnerable populations is “a work in progress.”
Mary Anne Jackson, MD, a pediatric infectious disease specialist and interim dean of the school of medicine at the University of Missouri–Kansas City, said many of the patients she saw were healthy children before falling ill with the disease. She suspects that a host of factors play a role in the likelihood of getting AFM, but more cases must be reviewed in order to find an answer.
The long-term effects are unknown
The CDC said it doesn’t know how long symptoms of the disease will last for patients. However, experts say that initial indications from a small number of cases suggest a grim outlook.
A study published last year found six of eight children in Colorado with acute flaccid myelitis still struggled with motor skills 1 year after their diagnosis. Nonetheless, the researchers found that the patients and families “demonstrated a high degree of resilience and recovery.”
“The majority of these patients are left with extensive problems,” said Dr. Pardo-Villamizar, who was not involved in the study.
Dr. Jackson, who also saw persistent muscle weakness in her patients, said she believes the CDC may be hesitant to specify the long-term effects of the disease because existing studies have included only small numbers of patients. More studies that include a larger proportion of confirmed cases are needed to better understand long-term outcomes, she said.
KHN’s coverage of children’s health care issues is supported in part by the Heising-Simons Foundation. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
A spike in the number of children with a rare neurological disease that causes polio-like symptoms has health officials across the country scrambling to understand the illness. Yet, more than 4 years after health officials first recorded the most recent uptick in cases, much about the national outbreak remains a mystery.
Acute flaccid myelitis (AFM) affects the gray matter in the spinal cord, causing sudden muscle weakness and a loss of reflexes. The illness can lead to serious complications – including paralysis or respiratory failure – and requires immediate medical attention.
The Centers for Disease Control and Prevention is investigating 127 cases of possible AFM, including 62 that have been confirmed in 22 states this year. At least 90% of the cases are among patients 18 years old and younger. The average age of a patient is 4 years old.
AFM remains extremely rare, even with the recent increase. The CDC estimates fewer than 1 in a million Americans will get the disease. Officials advised parents not to panic but remain vigilant for any sudden onset of symptoms. They also suggested that children stay up to date with their vaccines and practice good hand washing habits.
This year’s outbreak marks the third spike of AFM in 4 years. From August 2014 to September 2018, 386 cases have been confirmed. Yet, experts still do not understand crucial aspects of the disease, including its origins and who is most at risk.
“There is a lot we don’t know about AFM,” said Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases. Here’s what puzzles health officials about AFM:
The cause is still unknown
Acute flaccid myelitis can be caused by viruses, such as polio or West Nile. But federal officials said that those viruses have not been linked to the U.S. outbreak over the past 4 years. They have not isolated the cause of these cases.
Despite symptoms reminiscent of polio, no AFM cases have tested positive for that virus, according to the CDC. Investigators have also ruled out a variety of germs. Environmental agents, viruses, and other pathogens are still being considered.
The 2014 outbreak of AFM coincided with a surge of another virus that caused severe respiratory problems, called EV-D68. However, the CDC could not establish a causal link between AFM and the virus. Since then, no large outbreaks of the virus have occurred, according to the CDC.
Carlos Pardo-Villamizar, MD, a neurologist and director of the Johns Hopkins Transverse Myelitis Center, said that the mystery lies in whether the damage seen in AFM is caused by an external agent or the body’s own defenses.
“At this moment, we don’t know if it’s a virus that is coming and producing direct damage of the gray matter in the spinal cord,” he said, “or if a virus is triggering immunological responses that produce a secondary damage in the spinal cord.”
It’s not clear who is at risk
Although the disease appears to target a certain age group, federal disease experts do not know who is likely to get acute flaccid myelitis.
Dr. Pardo-Villamizar said identifying vulnerable populations is “a work in progress.”
Mary Anne Jackson, MD, a pediatric infectious disease specialist and interim dean of the school of medicine at the University of Missouri–Kansas City, said many of the patients she saw were healthy children before falling ill with the disease. She suspects that a host of factors play a role in the likelihood of getting AFM, but more cases must be reviewed in order to find an answer.
The long-term effects are unknown
The CDC said it doesn’t know how long symptoms of the disease will last for patients. However, experts say that initial indications from a small number of cases suggest a grim outlook.
A study published last year found six of eight children in Colorado with acute flaccid myelitis still struggled with motor skills 1 year after their diagnosis. Nonetheless, the researchers found that the patients and families “demonstrated a high degree of resilience and recovery.”
“The majority of these patients are left with extensive problems,” said Dr. Pardo-Villamizar, who was not involved in the study.
Dr. Jackson, who also saw persistent muscle weakness in her patients, said she believes the CDC may be hesitant to specify the long-term effects of the disease because existing studies have included only small numbers of patients. More studies that include a larger proportion of confirmed cases are needed to better understand long-term outcomes, she said.
KHN’s coverage of children’s health care issues is supported in part by the Heising-Simons Foundation. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
A spike in the number of children with a rare neurological disease that causes polio-like symptoms has health officials across the country scrambling to understand the illness. Yet, more than 4 years after health officials first recorded the most recent uptick in cases, much about the national outbreak remains a mystery.
Acute flaccid myelitis (AFM) affects the gray matter in the spinal cord, causing sudden muscle weakness and a loss of reflexes. The illness can lead to serious complications – including paralysis or respiratory failure – and requires immediate medical attention.
The Centers for Disease Control and Prevention is investigating 127 cases of possible AFM, including 62 that have been confirmed in 22 states this year. At least 90% of the cases are among patients 18 years old and younger. The average age of a patient is 4 years old.
AFM remains extremely rare, even with the recent increase. The CDC estimates fewer than 1 in a million Americans will get the disease. Officials advised parents not to panic but remain vigilant for any sudden onset of symptoms. They also suggested that children stay up to date with their vaccines and practice good hand washing habits.
This year’s outbreak marks the third spike of AFM in 4 years. From August 2014 to September 2018, 386 cases have been confirmed. Yet, experts still do not understand crucial aspects of the disease, including its origins and who is most at risk.
“There is a lot we don’t know about AFM,” said Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases. Here’s what puzzles health officials about AFM:
The cause is still unknown
Acute flaccid myelitis can be caused by viruses, such as polio or West Nile. But federal officials said that those viruses have not been linked to the U.S. outbreak over the past 4 years. They have not isolated the cause of these cases.
Despite symptoms reminiscent of polio, no AFM cases have tested positive for that virus, according to the CDC. Investigators have also ruled out a variety of germs. Environmental agents, viruses, and other pathogens are still being considered.
The 2014 outbreak of AFM coincided with a surge of another virus that caused severe respiratory problems, called EV-D68. However, the CDC could not establish a causal link between AFM and the virus. Since then, no large outbreaks of the virus have occurred, according to the CDC.
Carlos Pardo-Villamizar, MD, a neurologist and director of the Johns Hopkins Transverse Myelitis Center, said that the mystery lies in whether the damage seen in AFM is caused by an external agent or the body’s own defenses.
“At this moment, we don’t know if it’s a virus that is coming and producing direct damage of the gray matter in the spinal cord,” he said, “or if a virus is triggering immunological responses that produce a secondary damage in the spinal cord.”
It’s not clear who is at risk
Although the disease appears to target a certain age group, federal disease experts do not know who is likely to get acute flaccid myelitis.
Dr. Pardo-Villamizar said identifying vulnerable populations is “a work in progress.”
Mary Anne Jackson, MD, a pediatric infectious disease specialist and interim dean of the school of medicine at the University of Missouri–Kansas City, said many of the patients she saw were healthy children before falling ill with the disease. She suspects that a host of factors play a role in the likelihood of getting AFM, but more cases must be reviewed in order to find an answer.
The long-term effects are unknown
The CDC said it doesn’t know how long symptoms of the disease will last for patients. However, experts say that initial indications from a small number of cases suggest a grim outlook.
A study published last year found six of eight children in Colorado with acute flaccid myelitis still struggled with motor skills 1 year after their diagnosis. Nonetheless, the researchers found that the patients and families “demonstrated a high degree of resilience and recovery.”
“The majority of these patients are left with extensive problems,” said Dr. Pardo-Villamizar, who was not involved in the study.
Dr. Jackson, who also saw persistent muscle weakness in her patients, said she believes the CDC may be hesitant to specify the long-term effects of the disease because existing studies have included only small numbers of patients. More studies that include a larger proportion of confirmed cases are needed to better understand long-term outcomes, she said.
KHN’s coverage of children’s health care issues is supported in part by the Heising-Simons Foundation. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
Pediatric Skin Care: Survey of the Cutis Editorial Board
To improve patient care and outcomes, leading dermatologists from the Cutis Editorial Board answered 5 questions on pediatric skin care. Here’s what we found.
Do you recommend sunscreen in babies younger than 6 months?
More than half (64%) of dermatologists we surveyed do not recommend using sunscreens in babies younger than 6 months; they should stay out of the sun. They recommended sun-protective clothing, hats, and sunglasses in this age group.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
Babies younger than 6 months are still developing barrier functionality and have a higher surface area to body weight ratio compared to older children and adults. There is decreased UV light barrier protection and increased risk for systemic drug absorption. Therefore, it is best to avoid sunscreen in babies younger than 6 months. Instead, I recommend avoiding sunlight during peak hours, keeping babies in the shade, and dressing them in sun-protective clothing and hats.
Next page: Bathing and eczema
What advice do you give parents/guardians on bathing for babies with eczema?
Two-thirds of dermatologists (68%) indicated that moisturizers should be applied after bathing babies with eczema. More than half (64%) suggested using fragrance-free cleansers. Results varied on the frequency of bathing; 32% said bathe once daily for short periods with warm water, and 41% suggested to reduce bathing to a few nights a week.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
Dry skin is a characteristic feature of atopic dermatitis. We now know that skin barrier dysfunction, such as filaggrin deficiency, contributes to the pathophysiology in some patients. In addition, a paucity of stratum corneum and intercellular lipids increases transepidermal water loss. Therefore, emollients containing humectants to augment stratum corneum hydration and occludents to reduce evaporation are extremely helpful in maintenance treatment of atopic dermatitis.
Next page: Nonsteroidal agents
Do you prescribe nonsteroidal agents for children younger than 2 years?
Almost two-thirds (64%) of dermatologists do prescribe nonsteroidal agents for children younger than 2 years.
If yes, which nonsteroidal agents do you prescribe for children?
Of those dermatologists who indicated that they do prescribe nonsteroidal agents for children younger than 2 years, almost half (45%) prescribe pimecrolimus, while 36% prescribe crisaborole or tacrolimus.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
We have limited options for US Food and Drug Administration (FDA)–approved therapies for atopic dermatitis in children younger than 2 years. The risks of adverse effects also are higher in younger children compared to older children and adults, particularly hypothalamic-pituitary-adrenal suppression with corticosteroids. Pimecrolimus was the most common nonsteroidal prescribed in this group. It should be noted that pimecrolimus is not FDA approved for use in children younger than 2 years; however, 2 phase 3 studies were conducted with 436 infants aged 3 months to 23 months and they demonstrated safety and efficacy.
Next page: Procedures in adolescents
Which procedures do you perform on adolescents?
Forty-one percent of dermatologists surveyed indicated that they do not perform procedures on adolescents. Of those that do, 32% use laser hair removal or chemical peels in adolescents, while only 23% each use light therapy for acne or onabotulinumtoxinA for hyperhidrosis. Pulsed dye laser use was reported in only 18% of dermatologists.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
The results of this survey are a reflection of the relatively recent trends in dermatology training. Now that there is board certification in pediatric dermatology, many dermatologists now refer to pediatric dermatologists for children who need or want procedures.
Next page: More tips from derms
More Tips From Dermatologists
The dermatologists we polled had the following advice for their peers:
Keep the regimen as simple as possible and make sure your skin care advice is culturally relevant.—Craig Burkhart, MD (Chapel Hill, North Carolina)
Please, avoid direct sun exposure as much as possible by wearing protective garments and finding shades in the outside.—Jisun Cha, MD (New Brunswick, New Jersey)
Good habits start early. Teach children how to care for their skin and they will carry that practice with them over the course of their lifetime, and hopefully pass it on.—James Q. Del Rosso, DO (Las Vegas, Nevada)
About This Survey
The survey was fielded electronically to Cutis Editorial Board Members within the United States from September 13, 2018, to October 4, 2018. A total of 22 usable responses were received.
To improve patient care and outcomes, leading dermatologists from the Cutis Editorial Board answered 5 questions on pediatric skin care. Here’s what we found.
Do you recommend sunscreen in babies younger than 6 months?
More than half (64%) of dermatologists we surveyed do not recommend using sunscreens in babies younger than 6 months; they should stay out of the sun. They recommended sun-protective clothing, hats, and sunglasses in this age group.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
Babies younger than 6 months are still developing barrier functionality and have a higher surface area to body weight ratio compared to older children and adults. There is decreased UV light barrier protection and increased risk for systemic drug absorption. Therefore, it is best to avoid sunscreen in babies younger than 6 months. Instead, I recommend avoiding sunlight during peak hours, keeping babies in the shade, and dressing them in sun-protective clothing and hats.
Next page: Bathing and eczema
What advice do you give parents/guardians on bathing for babies with eczema?
Two-thirds of dermatologists (68%) indicated that moisturizers should be applied after bathing babies with eczema. More than half (64%) suggested using fragrance-free cleansers. Results varied on the frequency of bathing; 32% said bathe once daily for short periods with warm water, and 41% suggested to reduce bathing to a few nights a week.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
Dry skin is a characteristic feature of atopic dermatitis. We now know that skin barrier dysfunction, such as filaggrin deficiency, contributes to the pathophysiology in some patients. In addition, a paucity of stratum corneum and intercellular lipids increases transepidermal water loss. Therefore, emollients containing humectants to augment stratum corneum hydration and occludents to reduce evaporation are extremely helpful in maintenance treatment of atopic dermatitis.
Next page: Nonsteroidal agents
Do you prescribe nonsteroidal agents for children younger than 2 years?
Almost two-thirds (64%) of dermatologists do prescribe nonsteroidal agents for children younger than 2 years.
If yes, which nonsteroidal agents do you prescribe for children?
Of those dermatologists who indicated that they do prescribe nonsteroidal agents for children younger than 2 years, almost half (45%) prescribe pimecrolimus, while 36% prescribe crisaborole or tacrolimus.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
We have limited options for US Food and Drug Administration (FDA)–approved therapies for atopic dermatitis in children younger than 2 years. The risks of adverse effects also are higher in younger children compared to older children and adults, particularly hypothalamic-pituitary-adrenal suppression with corticosteroids. Pimecrolimus was the most common nonsteroidal prescribed in this group. It should be noted that pimecrolimus is not FDA approved for use in children younger than 2 years; however, 2 phase 3 studies were conducted with 436 infants aged 3 months to 23 months and they demonstrated safety and efficacy.
Next page: Procedures in adolescents
Which procedures do you perform on adolescents?
Forty-one percent of dermatologists surveyed indicated that they do not perform procedures on adolescents. Of those that do, 32% use laser hair removal or chemical peels in adolescents, while only 23% each use light therapy for acne or onabotulinumtoxinA for hyperhidrosis. Pulsed dye laser use was reported in only 18% of dermatologists.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
The results of this survey are a reflection of the relatively recent trends in dermatology training. Now that there is board certification in pediatric dermatology, many dermatologists now refer to pediatric dermatologists for children who need or want procedures.
Next page: More tips from derms
More Tips From Dermatologists
The dermatologists we polled had the following advice for their peers:
Keep the regimen as simple as possible and make sure your skin care advice is culturally relevant.—Craig Burkhart, MD (Chapel Hill, North Carolina)
Please, avoid direct sun exposure as much as possible by wearing protective garments and finding shades in the outside.—Jisun Cha, MD (New Brunswick, New Jersey)
Good habits start early. Teach children how to care for their skin and they will carry that practice with them over the course of their lifetime, and hopefully pass it on.—James Q. Del Rosso, DO (Las Vegas, Nevada)
About This Survey
The survey was fielded electronically to Cutis Editorial Board Members within the United States from September 13, 2018, to October 4, 2018. A total of 22 usable responses were received.
To improve patient care and outcomes, leading dermatologists from the Cutis Editorial Board answered 5 questions on pediatric skin care. Here’s what we found.
Do you recommend sunscreen in babies younger than 6 months?
More than half (64%) of dermatologists we surveyed do not recommend using sunscreens in babies younger than 6 months; they should stay out of the sun. They recommended sun-protective clothing, hats, and sunglasses in this age group.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
Babies younger than 6 months are still developing barrier functionality and have a higher surface area to body weight ratio compared to older children and adults. There is decreased UV light barrier protection and increased risk for systemic drug absorption. Therefore, it is best to avoid sunscreen in babies younger than 6 months. Instead, I recommend avoiding sunlight during peak hours, keeping babies in the shade, and dressing them in sun-protective clothing and hats.
Next page: Bathing and eczema
What advice do you give parents/guardians on bathing for babies with eczema?
Two-thirds of dermatologists (68%) indicated that moisturizers should be applied after bathing babies with eczema. More than half (64%) suggested using fragrance-free cleansers. Results varied on the frequency of bathing; 32% said bathe once daily for short periods with warm water, and 41% suggested to reduce bathing to a few nights a week.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
Dry skin is a characteristic feature of atopic dermatitis. We now know that skin barrier dysfunction, such as filaggrin deficiency, contributes to the pathophysiology in some patients. In addition, a paucity of stratum corneum and intercellular lipids increases transepidermal water loss. Therefore, emollients containing humectants to augment stratum corneum hydration and occludents to reduce evaporation are extremely helpful in maintenance treatment of atopic dermatitis.
Next page: Nonsteroidal agents
Do you prescribe nonsteroidal agents for children younger than 2 years?
Almost two-thirds (64%) of dermatologists do prescribe nonsteroidal agents for children younger than 2 years.
If yes, which nonsteroidal agents do you prescribe for children?
Of those dermatologists who indicated that they do prescribe nonsteroidal agents for children younger than 2 years, almost half (45%) prescribe pimecrolimus, while 36% prescribe crisaborole or tacrolimus.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
We have limited options for US Food and Drug Administration (FDA)–approved therapies for atopic dermatitis in children younger than 2 years. The risks of adverse effects also are higher in younger children compared to older children and adults, particularly hypothalamic-pituitary-adrenal suppression with corticosteroids. Pimecrolimus was the most common nonsteroidal prescribed in this group. It should be noted that pimecrolimus is not FDA approved for use in children younger than 2 years; however, 2 phase 3 studies were conducted with 436 infants aged 3 months to 23 months and they demonstrated safety and efficacy.
Next page: Procedures in adolescents
Which procedures do you perform on adolescents?
Forty-one percent of dermatologists surveyed indicated that they do not perform procedures on adolescents. Of those that do, 32% use laser hair removal or chemical peels in adolescents, while only 23% each use light therapy for acne or onabotulinumtoxinA for hyperhidrosis. Pulsed dye laser use was reported in only 18% of dermatologists.
Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)
The results of this survey are a reflection of the relatively recent trends in dermatology training. Now that there is board certification in pediatric dermatology, many dermatologists now refer to pediatric dermatologists for children who need or want procedures.
Next page: More tips from derms
More Tips From Dermatologists
The dermatologists we polled had the following advice for their peers:
Keep the regimen as simple as possible and make sure your skin care advice is culturally relevant.—Craig Burkhart, MD (Chapel Hill, North Carolina)
Please, avoid direct sun exposure as much as possible by wearing protective garments and finding shades in the outside.—Jisun Cha, MD (New Brunswick, New Jersey)
Good habits start early. Teach children how to care for their skin and they will carry that practice with them over the course of their lifetime, and hopefully pass it on.—James Q. Del Rosso, DO (Las Vegas, Nevada)
About This Survey
The survey was fielded electronically to Cutis Editorial Board Members within the United States from September 13, 2018, to October 4, 2018. A total of 22 usable responses were received.
Gene-Replacement Therapy for SMA1 May Necessitate New Rating Measures to Capture Patients’ Motor Function Gains
CHOP-INTEND scores plateaued in a phase I trial of AVXS-101 even as patients reached new motor milestones.
CHICAGO—The Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) was designed to track motor function in patients with spinal muscular atrophy type 1 (SMA1), but the test may not be sensitive to advances in motor function made by patients who receive an investigational gene-replacement therapy, researchers said at the 47th Annual Meeting of the Child Neurology Society.
AVXS-101 is an adeno-associated virus serotype 9 (AAV9)-based gene-replacement therapy that contains a copy of the SMN1 gene. AVXS-101 crosses the blood–brain barrier and is meant to treat the deletion or loss of function of the SMN1 gene in patients with SMA. The treatment may result in sustained SMN protein expression with a one-time dose.
Researchers conducted a phase I, open-label, dose-escalation study to study the treatment. Fifteen patients received AVXS-101 intravenously, and 12 participants received the proposed therapeutic dose.
“Patients treated with AVXS-101 achieved and maintained motor milestones unprecedented in the natural history of SMA1,” said Linda P. Lowes, PT, PhD, Principal Investigator for the Center for Gene Therapy at Nationwide Children’s Hospital in Columbus, Ohio, and Associate Professor of Pediatrics at Ohio State University, and colleagues. “CHOP-INTEND is a reliable tool for detecting early treatment impact, but appears insensitive to further motor function gains among AVXS-101–treated children as they age and develop.”
For example, the scale did not capture skills such as independent rolling and sitting that had not been seen in patients with SMA1, the researchers said.
CHOP-INTEND uses a 0–64-point scale where higher scores indicate better motor function. By six months, essentially no untreated patients with SMA1 achieve a score of 40 or greater points on the CHOP-INTEND, and scores may decrease between age 6 and 12 months. In the phase I trial of AVXS-101, CHOP-INTEND score increased from baseline by a mean of 9.8 points at one month postdose, 15.4 points at three months postdose, and 25.4 points at 24 months (n = 12 at all time points). Eleven of the 12 patients maintained a CHOP-INTEND score greater than 40 points for a mean of 19.5 months. Two children were able to crawl, pull to a stand, and stand and walk independently.
In the study, patients who achieved additional sitting milestones did not have accompanying increases on their CHOP-INTEND scores. For example, the 11 patients who sat for at least 5 seconds had a mean CHOP-INTEND plateau score of 56.9, while the 10 patients who sat for at least 10 seconds had a mean CHOP-INTEND plateau score of 57.0 and the nine patients who sat for at least 30 seconds had a mean CHOP-INTEND plateau score of 57.7.
The investigators suggested that the addition of scoring items such as supported sitting, head lifting, and walking could “mitigate the artificial ceiling effect” with the current scoring system. Other modifications to CHOP-INTEND, such as assessing one side of a patient instead of both sides, could reduce test administration time without affecting scores.
Furthermore, several CHOP-INTEND items may not perform well in assessing patients treated with AVXS-101 because they test primitive reflexes that fade as children live longer (eg, spinal incurvation) or children may become too heavy for the tests (eg, ventral suspension).
The study was sponsored by AveXis.
CHOP-INTEND scores plateaued in a phase I trial of AVXS-101 even as patients reached new motor milestones.
CHOP-INTEND scores plateaued in a phase I trial of AVXS-101 even as patients reached new motor milestones.
CHICAGO—The Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) was designed to track motor function in patients with spinal muscular atrophy type 1 (SMA1), but the test may not be sensitive to advances in motor function made by patients who receive an investigational gene-replacement therapy, researchers said at the 47th Annual Meeting of the Child Neurology Society.
AVXS-101 is an adeno-associated virus serotype 9 (AAV9)-based gene-replacement therapy that contains a copy of the SMN1 gene. AVXS-101 crosses the blood–brain barrier and is meant to treat the deletion or loss of function of the SMN1 gene in patients with SMA. The treatment may result in sustained SMN protein expression with a one-time dose.
Researchers conducted a phase I, open-label, dose-escalation study to study the treatment. Fifteen patients received AVXS-101 intravenously, and 12 participants received the proposed therapeutic dose.
“Patients treated with AVXS-101 achieved and maintained motor milestones unprecedented in the natural history of SMA1,” said Linda P. Lowes, PT, PhD, Principal Investigator for the Center for Gene Therapy at Nationwide Children’s Hospital in Columbus, Ohio, and Associate Professor of Pediatrics at Ohio State University, and colleagues. “CHOP-INTEND is a reliable tool for detecting early treatment impact, but appears insensitive to further motor function gains among AVXS-101–treated children as they age and develop.”
For example, the scale did not capture skills such as independent rolling and sitting that had not been seen in patients with SMA1, the researchers said.
CHOP-INTEND uses a 0–64-point scale where higher scores indicate better motor function. By six months, essentially no untreated patients with SMA1 achieve a score of 40 or greater points on the CHOP-INTEND, and scores may decrease between age 6 and 12 months. In the phase I trial of AVXS-101, CHOP-INTEND score increased from baseline by a mean of 9.8 points at one month postdose, 15.4 points at three months postdose, and 25.4 points at 24 months (n = 12 at all time points). Eleven of the 12 patients maintained a CHOP-INTEND score greater than 40 points for a mean of 19.5 months. Two children were able to crawl, pull to a stand, and stand and walk independently.
In the study, patients who achieved additional sitting milestones did not have accompanying increases on their CHOP-INTEND scores. For example, the 11 patients who sat for at least 5 seconds had a mean CHOP-INTEND plateau score of 56.9, while the 10 patients who sat for at least 10 seconds had a mean CHOP-INTEND plateau score of 57.0 and the nine patients who sat for at least 30 seconds had a mean CHOP-INTEND plateau score of 57.7.
The investigators suggested that the addition of scoring items such as supported sitting, head lifting, and walking could “mitigate the artificial ceiling effect” with the current scoring system. Other modifications to CHOP-INTEND, such as assessing one side of a patient instead of both sides, could reduce test administration time without affecting scores.
Furthermore, several CHOP-INTEND items may not perform well in assessing patients treated with AVXS-101 because they test primitive reflexes that fade as children live longer (eg, spinal incurvation) or children may become too heavy for the tests (eg, ventral suspension).
The study was sponsored by AveXis.
CHICAGO—The Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) was designed to track motor function in patients with spinal muscular atrophy type 1 (SMA1), but the test may not be sensitive to advances in motor function made by patients who receive an investigational gene-replacement therapy, researchers said at the 47th Annual Meeting of the Child Neurology Society.
AVXS-101 is an adeno-associated virus serotype 9 (AAV9)-based gene-replacement therapy that contains a copy of the SMN1 gene. AVXS-101 crosses the blood–brain barrier and is meant to treat the deletion or loss of function of the SMN1 gene in patients with SMA. The treatment may result in sustained SMN protein expression with a one-time dose.
Researchers conducted a phase I, open-label, dose-escalation study to study the treatment. Fifteen patients received AVXS-101 intravenously, and 12 participants received the proposed therapeutic dose.
“Patients treated with AVXS-101 achieved and maintained motor milestones unprecedented in the natural history of SMA1,” said Linda P. Lowes, PT, PhD, Principal Investigator for the Center for Gene Therapy at Nationwide Children’s Hospital in Columbus, Ohio, and Associate Professor of Pediatrics at Ohio State University, and colleagues. “CHOP-INTEND is a reliable tool for detecting early treatment impact, but appears insensitive to further motor function gains among AVXS-101–treated children as they age and develop.”
For example, the scale did not capture skills such as independent rolling and sitting that had not been seen in patients with SMA1, the researchers said.
CHOP-INTEND uses a 0–64-point scale where higher scores indicate better motor function. By six months, essentially no untreated patients with SMA1 achieve a score of 40 or greater points on the CHOP-INTEND, and scores may decrease between age 6 and 12 months. In the phase I trial of AVXS-101, CHOP-INTEND score increased from baseline by a mean of 9.8 points at one month postdose, 15.4 points at three months postdose, and 25.4 points at 24 months (n = 12 at all time points). Eleven of the 12 patients maintained a CHOP-INTEND score greater than 40 points for a mean of 19.5 months. Two children were able to crawl, pull to a stand, and stand and walk independently.
In the study, patients who achieved additional sitting milestones did not have accompanying increases on their CHOP-INTEND scores. For example, the 11 patients who sat for at least 5 seconds had a mean CHOP-INTEND plateau score of 56.9, while the 10 patients who sat for at least 10 seconds had a mean CHOP-INTEND plateau score of 57.0 and the nine patients who sat for at least 30 seconds had a mean CHOP-INTEND plateau score of 57.7.
The investigators suggested that the addition of scoring items such as supported sitting, head lifting, and walking could “mitigate the artificial ceiling effect” with the current scoring system. Other modifications to CHOP-INTEND, such as assessing one side of a patient instead of both sides, could reduce test administration time without affecting scores.
Furthermore, several CHOP-INTEND items may not perform well in assessing patients treated with AVXS-101 because they test primitive reflexes that fade as children live longer (eg, spinal incurvation) or children may become too heavy for the tests (eg, ventral suspension).
The study was sponsored by AveXis.
Transfusion errors more common in kids than adults, study suggests
BOSTON—Even the most vigilant hospitals experience transfusion errors and problems with blood storage, according to researchers.
A review of data from 32 U.S. hospitals showed that pediatric transfusions were associated with a higher rate of safety problems than adult transfusions, with errors differing by age group.
The most common error in the pediatric population was failure to follow protocol, and the most common error in the adult population was that scheduled transfusions were not performed.
Sarah Vossoughi, MD, of Columbia University and New York–Presbyterian Hospital in New York, described these findings at AABB 2018 (abstract QT4).
To evaluate patient safety events related to blood transfusions, Dr. Vossoughi and her colleagues reviewed data on events reported by three children’s hospitals and 29 adult hospitals. Events were reported to either the AABB Center for Patient Safety or the medical center’s own adverse event reporting system from January 2010 through September 2017.
The researchers identified a total of 1,806 reports associated with approximately 1,088,884 transfusions.
There were 249 reports associated with 99,064 pediatric transfusions and 1,577 reports associated with 989,820 adult transfusions. So the reporting rate was 251 per 100,000 transfusions for the pediatric population and 157 per 100,000 transfusions for the adult population (P<0.001).
The most common error for pediatric patients—failure to follow the transfusion protocol—made up 31% of the pediatric errors.
“In a lot of the pediatric hospitals, it’s kind of like the Wild West,” Dr. Vossoughi said. “People say, ‘Well, I know it’s the hospital policy, but this child is special, so I’m going to do it this way, this time.’ That seems to be a culture in pediatrics, whereas, on the adult side, [clinicians] seem to be much less likely to just deviate from the protocol.”
Among adults, the most common error was “transfusion not performed,” which accounted for 43% of the adult errors. Dr. Vossoughi said transfusions may be skipped due to a bungled patient hand-off during a shift change or when a patient is being moved from one unit to another.
“The next day, they’ll check the patient’s CBC [complete blood count] and realize that the patient didn’t respond to the infusion that it turned out they never got, and then the product will be found on the floor, expired,” Dr. Vossoughi said.
She and her colleagues also found that 20% of pediatric errors and 24% of adult errors were associated with incorrect storage of blood products on the patient floor.
“It’s very common for blood banks to find platelets in the refrigerator,” Dr. Vossoughi said. “It doesn’t matter how old you are or what type of hospital you’re at. Everyone’s putting platelets in the fridge.”
Dr. Vossoughi and her colleagues believe these findings could help inpatient blood management programs target education and interventions to providers who commit similar errors.
“If you know that a particular provider group has problems following the protocol, maybe you can make the protocol a little simpler to follow or make the checklist less cumbersome, and then maybe they’ll follow them more often,” Dr. Vossoughi said.
This research was supported by the AABB Center for Patient Safety and University of Vermont Medical Center. The researchers reported no conflicts of interest.
BOSTON—Even the most vigilant hospitals experience transfusion errors and problems with blood storage, according to researchers.
A review of data from 32 U.S. hospitals showed that pediatric transfusions were associated with a higher rate of safety problems than adult transfusions, with errors differing by age group.
The most common error in the pediatric population was failure to follow protocol, and the most common error in the adult population was that scheduled transfusions were not performed.
Sarah Vossoughi, MD, of Columbia University and New York–Presbyterian Hospital in New York, described these findings at AABB 2018 (abstract QT4).
To evaluate patient safety events related to blood transfusions, Dr. Vossoughi and her colleagues reviewed data on events reported by three children’s hospitals and 29 adult hospitals. Events were reported to either the AABB Center for Patient Safety or the medical center’s own adverse event reporting system from January 2010 through September 2017.
The researchers identified a total of 1,806 reports associated with approximately 1,088,884 transfusions.
There were 249 reports associated with 99,064 pediatric transfusions and 1,577 reports associated with 989,820 adult transfusions. So the reporting rate was 251 per 100,000 transfusions for the pediatric population and 157 per 100,000 transfusions for the adult population (P<0.001).
The most common error for pediatric patients—failure to follow the transfusion protocol—made up 31% of the pediatric errors.
“In a lot of the pediatric hospitals, it’s kind of like the Wild West,” Dr. Vossoughi said. “People say, ‘Well, I know it’s the hospital policy, but this child is special, so I’m going to do it this way, this time.’ That seems to be a culture in pediatrics, whereas, on the adult side, [clinicians] seem to be much less likely to just deviate from the protocol.”
Among adults, the most common error was “transfusion not performed,” which accounted for 43% of the adult errors. Dr. Vossoughi said transfusions may be skipped due to a bungled patient hand-off during a shift change or when a patient is being moved from one unit to another.
“The next day, they’ll check the patient’s CBC [complete blood count] and realize that the patient didn’t respond to the infusion that it turned out they never got, and then the product will be found on the floor, expired,” Dr. Vossoughi said.
She and her colleagues also found that 20% of pediatric errors and 24% of adult errors were associated with incorrect storage of blood products on the patient floor.
“It’s very common for blood banks to find platelets in the refrigerator,” Dr. Vossoughi said. “It doesn’t matter how old you are or what type of hospital you’re at. Everyone’s putting platelets in the fridge.”
Dr. Vossoughi and her colleagues believe these findings could help inpatient blood management programs target education and interventions to providers who commit similar errors.
“If you know that a particular provider group has problems following the protocol, maybe you can make the protocol a little simpler to follow or make the checklist less cumbersome, and then maybe they’ll follow them more often,” Dr. Vossoughi said.
This research was supported by the AABB Center for Patient Safety and University of Vermont Medical Center. The researchers reported no conflicts of interest.
BOSTON—Even the most vigilant hospitals experience transfusion errors and problems with blood storage, according to researchers.
A review of data from 32 U.S. hospitals showed that pediatric transfusions were associated with a higher rate of safety problems than adult transfusions, with errors differing by age group.
The most common error in the pediatric population was failure to follow protocol, and the most common error in the adult population was that scheduled transfusions were not performed.
Sarah Vossoughi, MD, of Columbia University and New York–Presbyterian Hospital in New York, described these findings at AABB 2018 (abstract QT4).
To evaluate patient safety events related to blood transfusions, Dr. Vossoughi and her colleagues reviewed data on events reported by three children’s hospitals and 29 adult hospitals. Events were reported to either the AABB Center for Patient Safety or the medical center’s own adverse event reporting system from January 2010 through September 2017.
The researchers identified a total of 1,806 reports associated with approximately 1,088,884 transfusions.
There were 249 reports associated with 99,064 pediatric transfusions and 1,577 reports associated with 989,820 adult transfusions. So the reporting rate was 251 per 100,000 transfusions for the pediatric population and 157 per 100,000 transfusions for the adult population (P<0.001).
The most common error for pediatric patients—failure to follow the transfusion protocol—made up 31% of the pediatric errors.
“In a lot of the pediatric hospitals, it’s kind of like the Wild West,” Dr. Vossoughi said. “People say, ‘Well, I know it’s the hospital policy, but this child is special, so I’m going to do it this way, this time.’ That seems to be a culture in pediatrics, whereas, on the adult side, [clinicians] seem to be much less likely to just deviate from the protocol.”
Among adults, the most common error was “transfusion not performed,” which accounted for 43% of the adult errors. Dr. Vossoughi said transfusions may be skipped due to a bungled patient hand-off during a shift change or when a patient is being moved from one unit to another.
“The next day, they’ll check the patient’s CBC [complete blood count] and realize that the patient didn’t respond to the infusion that it turned out they never got, and then the product will be found on the floor, expired,” Dr. Vossoughi said.
She and her colleagues also found that 20% of pediatric errors and 24% of adult errors were associated with incorrect storage of blood products on the patient floor.
“It’s very common for blood banks to find platelets in the refrigerator,” Dr. Vossoughi said. “It doesn’t matter how old you are or what type of hospital you’re at. Everyone’s putting platelets in the fridge.”
Dr. Vossoughi and her colleagues believe these findings could help inpatient blood management programs target education and interventions to providers who commit similar errors.
“If you know that a particular provider group has problems following the protocol, maybe you can make the protocol a little simpler to follow or make the checklist less cumbersome, and then maybe they’ll follow them more often,” Dr. Vossoughi said.
This research was supported by the AABB Center for Patient Safety and University of Vermont Medical Center. The researchers reported no conflicts of interest.
How much more proof do you need?
One piece of wisdom I was given in medical school was to never be the first nor the last to adopt a new treatment. The history of medicine is full of new discoveries that don’t work out as well as the first report. It also is full of long standing dogmas that later were proven false. This balancing act is part of being a professional and being an advocate for your patient. There is science behind this art. Everett Rogers identified innovators, early adopters, and laggards as new ideas are diffused into practice.1
A 2007 French study2 that investigated oral amoxicillin for early-onset group B streptococcal (GBS) disease is one of the few times in the past 3 decades in which I changed my practice based on a single article. It was a large, conclusive study with 222 patients, so it doesn’t need a meta-analysis like American research often requires. The research showed that most of what I had been taught about oral amoxicillin was false. Amoxicillin is absorbed well even at doses above 50 mg/kg per day. It is absorbed reliably by full term neonates, even mildly sick ones. It does adequately cross the blood-brain barrier. The French researchers measured serum levels and proved all this using both scientific principles and through a clinical trial.
I have used this oral protocol (10 days total after 2-3 days IV therapy) on two occasions to treat GBS sepsis when I had informed consent of the parents and buy-in from the primary care pediatrician to be early adopters. I expected the Red Book would update its recommendations. That didn’t happen.
Meanwhile, I have seen other babies kept for 10 days in the hospital for IV therapy with resultant wasted costs (about $20 million/year in the United States) and income loss for the parents. I’ve treated complications and readmissions caused by peripherally inserted central catheter (PICC) line issues. One baby at home got a syringe of gentamicin given as an IV push instead of a normal saline flush. Mistakes happen at home and in the hospital.
Because late-onset GBS can be acquired environmentally, there always will be recurrences. Unless you are practicing defensive medicine, the issue isn’t the rate of recurrence; it is whether the more invasive intervention of prolonged IV therapy reduces that rate. Then balance any measured reduction (which apparently is zero) against the adverse effects of the invasive intervention, such as PICC line infections. This Bayesian decision making is hard for some risk-averse humans to assimilate. (I’m part Borg.)
Coon et al.3 have confirmed, using big data, that prolonged IV therapy of uncomplicated, late-onset GBS bacteremia does not generate a clinically significant benefit. It certainly is possible to sow doubt by asking for proof in a variety of subpopulations. Even in the era of intrapartum antibiotic prophylaxis, which has halved the incidence of GBS disease, GBS disease occurs in about 2,000 babies per year in the United States. However, most are treated in community hospitals and are not included in the database used in this new report. With fewer than 2-3 cases of GBS bacteremia per year per hospital, a multicenter, randomized controlled trial would be an unprecedented undertaking, is ethically problematic, and is not realistically happening soon. So these observational data, skillfully acquired and analyzed, are and will remain the best available data.
This new article is in the context of multiple articles over the past decade that have disproven the myth of the superiority of IV therapy. Given the known risks and costs of PICC lines and prolonged IV therapy, the default should be, absent a credible rationale to the contrary, that oral therapy at home is better.
Coon et al. show that, by 2015, 5 of 49 children’s hospitals (10%) were early adopters and had already made the switch to mostly using short treatment courses for uncomplicated GBS bacteremia; 14 of 49 (29%) hadn’t changed at all from the obsolete Red Book recommendation. Given this new analysis, what are you laggards4 waiting for?
Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at pdnews@mdedge.com.
References
1. “Diffusion of Innovations,” 5th ed. (New York: Free Press, 2003).
2. Eur J Clin Pharmacol. 2007 Jul;63(7):657-62.
3. Pediatrics. 2018;142(5):e20180345.
4. https://en.wikipedia.org/wiki/Diffusion_of_innovations.
One piece of wisdom I was given in medical school was to never be the first nor the last to adopt a new treatment. The history of medicine is full of new discoveries that don’t work out as well as the first report. It also is full of long standing dogmas that later were proven false. This balancing act is part of being a professional and being an advocate for your patient. There is science behind this art. Everett Rogers identified innovators, early adopters, and laggards as new ideas are diffused into practice.1
A 2007 French study2 that investigated oral amoxicillin for early-onset group B streptococcal (GBS) disease is one of the few times in the past 3 decades in which I changed my practice based on a single article. It was a large, conclusive study with 222 patients, so it doesn’t need a meta-analysis like American research often requires. The research showed that most of what I had been taught about oral amoxicillin was false. Amoxicillin is absorbed well even at doses above 50 mg/kg per day. It is absorbed reliably by full term neonates, even mildly sick ones. It does adequately cross the blood-brain barrier. The French researchers measured serum levels and proved all this using both scientific principles and through a clinical trial.
I have used this oral protocol (10 days total after 2-3 days IV therapy) on two occasions to treat GBS sepsis when I had informed consent of the parents and buy-in from the primary care pediatrician to be early adopters. I expected the Red Book would update its recommendations. That didn’t happen.
Meanwhile, I have seen other babies kept for 10 days in the hospital for IV therapy with resultant wasted costs (about $20 million/year in the United States) and income loss for the parents. I’ve treated complications and readmissions caused by peripherally inserted central catheter (PICC) line issues. One baby at home got a syringe of gentamicin given as an IV push instead of a normal saline flush. Mistakes happen at home and in the hospital.
Because late-onset GBS can be acquired environmentally, there always will be recurrences. Unless you are practicing defensive medicine, the issue isn’t the rate of recurrence; it is whether the more invasive intervention of prolonged IV therapy reduces that rate. Then balance any measured reduction (which apparently is zero) against the adverse effects of the invasive intervention, such as PICC line infections. This Bayesian decision making is hard for some risk-averse humans to assimilate. (I’m part Borg.)
Coon et al.3 have confirmed, using big data, that prolonged IV therapy of uncomplicated, late-onset GBS bacteremia does not generate a clinically significant benefit. It certainly is possible to sow doubt by asking for proof in a variety of subpopulations. Even in the era of intrapartum antibiotic prophylaxis, which has halved the incidence of GBS disease, GBS disease occurs in about 2,000 babies per year in the United States. However, most are treated in community hospitals and are not included in the database used in this new report. With fewer than 2-3 cases of GBS bacteremia per year per hospital, a multicenter, randomized controlled trial would be an unprecedented undertaking, is ethically problematic, and is not realistically happening soon. So these observational data, skillfully acquired and analyzed, are and will remain the best available data.
This new article is in the context of multiple articles over the past decade that have disproven the myth of the superiority of IV therapy. Given the known risks and costs of PICC lines and prolonged IV therapy, the default should be, absent a credible rationale to the contrary, that oral therapy at home is better.
Coon et al. show that, by 2015, 5 of 49 children’s hospitals (10%) were early adopters and had already made the switch to mostly using short treatment courses for uncomplicated GBS bacteremia; 14 of 49 (29%) hadn’t changed at all from the obsolete Red Book recommendation. Given this new analysis, what are you laggards4 waiting for?
Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at pdnews@mdedge.com.
References
1. “Diffusion of Innovations,” 5th ed. (New York: Free Press, 2003).
2. Eur J Clin Pharmacol. 2007 Jul;63(7):657-62.
3. Pediatrics. 2018;142(5):e20180345.
4. https://en.wikipedia.org/wiki/Diffusion_of_innovations.
One piece of wisdom I was given in medical school was to never be the first nor the last to adopt a new treatment. The history of medicine is full of new discoveries that don’t work out as well as the first report. It also is full of long standing dogmas that later were proven false. This balancing act is part of being a professional and being an advocate for your patient. There is science behind this art. Everett Rogers identified innovators, early adopters, and laggards as new ideas are diffused into practice.1
A 2007 French study2 that investigated oral amoxicillin for early-onset group B streptococcal (GBS) disease is one of the few times in the past 3 decades in which I changed my practice based on a single article. It was a large, conclusive study with 222 patients, so it doesn’t need a meta-analysis like American research often requires. The research showed that most of what I had been taught about oral amoxicillin was false. Amoxicillin is absorbed well even at doses above 50 mg/kg per day. It is absorbed reliably by full term neonates, even mildly sick ones. It does adequately cross the blood-brain barrier. The French researchers measured serum levels and proved all this using both scientific principles and through a clinical trial.
I have used this oral protocol (10 days total after 2-3 days IV therapy) on two occasions to treat GBS sepsis when I had informed consent of the parents and buy-in from the primary care pediatrician to be early adopters. I expected the Red Book would update its recommendations. That didn’t happen.
Meanwhile, I have seen other babies kept for 10 days in the hospital for IV therapy with resultant wasted costs (about $20 million/year in the United States) and income loss for the parents. I’ve treated complications and readmissions caused by peripherally inserted central catheter (PICC) line issues. One baby at home got a syringe of gentamicin given as an IV push instead of a normal saline flush. Mistakes happen at home and in the hospital.
Because late-onset GBS can be acquired environmentally, there always will be recurrences. Unless you are practicing defensive medicine, the issue isn’t the rate of recurrence; it is whether the more invasive intervention of prolonged IV therapy reduces that rate. Then balance any measured reduction (which apparently is zero) against the adverse effects of the invasive intervention, such as PICC line infections. This Bayesian decision making is hard for some risk-averse humans to assimilate. (I’m part Borg.)
Coon et al.3 have confirmed, using big data, that prolonged IV therapy of uncomplicated, late-onset GBS bacteremia does not generate a clinically significant benefit. It certainly is possible to sow doubt by asking for proof in a variety of subpopulations. Even in the era of intrapartum antibiotic prophylaxis, which has halved the incidence of GBS disease, GBS disease occurs in about 2,000 babies per year in the United States. However, most are treated in community hospitals and are not included in the database used in this new report. With fewer than 2-3 cases of GBS bacteremia per year per hospital, a multicenter, randomized controlled trial would be an unprecedented undertaking, is ethically problematic, and is not realistically happening soon. So these observational data, skillfully acquired and analyzed, are and will remain the best available data.
This new article is in the context of multiple articles over the past decade that have disproven the myth of the superiority of IV therapy. Given the known risks and costs of PICC lines and prolonged IV therapy, the default should be, absent a credible rationale to the contrary, that oral therapy at home is better.
Coon et al. show that, by 2015, 5 of 49 children’s hospitals (10%) were early adopters and had already made the switch to mostly using short treatment courses for uncomplicated GBS bacteremia; 14 of 49 (29%) hadn’t changed at all from the obsolete Red Book recommendation. Given this new analysis, what are you laggards4 waiting for?
Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at pdnews@mdedge.com.
References
1. “Diffusion of Innovations,” 5th ed. (New York: Free Press, 2003).
2. Eur J Clin Pharmacol. 2007 Jul;63(7):657-62.
3. Pediatrics. 2018;142(5):e20180345.
4. https://en.wikipedia.org/wiki/Diffusion_of_innovations.