User login
Kids may have higher rate of AdV infection after HSCT
LISBON—Results of a large study revealed a higher incidence of adenovirus (AdV) infection after allogeneic hematopoietic stem cell transplant (allo-HSCT) in children than adults.
The rate of AdV infection in the 6 months after allo-HSCT was 32% in children and 6% in adults.
However, researchers believe this data may be influenced by a lack of routine AdV screening in adults.
These findings—from the AdVance study—were reported at the 44th Annual Meeting of the EBMT as abstracts OS9-7 and B043.*
Other results from AdVance were also presented at the meeting, with mortality data reported as abstract OS9-8 and hospitalization data reported as abstract B073. The AdVance study was sponsored by Chimerix, Inc.
“The robust findings of the AdVance study are extremely important for transplant clinicians, as we seek to better understand the rates and clinical outcomes of adenovirus infection and assess ways to evaluate antiviral therapies,” said study investigator Marco Zecca, MD, of Fondazione IRCCS Policlinico San Matteo in Pavia, Italy.
AdVance is a multi-center, retrospective study of 4276 allo-HSCT recipients—1738 pediatric patients and 2538 adults. The patients underwent transplants at 50 centers in Europe from January 2013 to September 2015.
Abstract OS9-7: Incidence
Thirty-two percent (n=558) of pediatric patients developed an AdV infection in the first 6 months after allo-HSCT, and 23% (n=395) developed detectable AdV viremia. Fourteen percent (n=241) had AdV viremia ≥ 1000 copies/mL, a level previously associated with negative clinical outcomes.
Meanwhile, 6% (n=141) of adults had an AdV infection in the 6 months after transplant, 3% (n=77) developed AdV viremia, and 2% (n=39) had ≥ 1000 copies /mL.
Further analysis revealed that age, donor type, and use of T-cell depletion were independent predictors of AdV viremia ≥ 1000 copies/mL.
Older age was associated with a lower risk of AdV viremia ≥ 1000 copies/mL. There was a stepwise reduction in risk with increasing age (compared to ages 0-2, P=0.104 for ages 2-12, P=0.001 for ages 13-17, and P<0.0001 for ages 18-65+).
T-cell depletion was associated with an increased risk of AdV viremia ≥ 1000 copies/mL. Compared to no T-cell depletion, there was an increased risk for depletion with antithymocyte globulin (P=0.036) or alemtuzumab (P<0.0001) and for ex vivo depletion (P=0.002).
Compared to patients who received a matched related transplant, recipients of other transplants had an increased risk of AdV viremia ≥ 1000 copies/mL. This includes matched unrelated (P=0.016), cord blood (P=0.011), haploidentical (P=0.007), and mismatched (P<0.001) transplants.
Abstract B043: Screening
Dr Zecca and his colleagues believe the difference in AdV incidence between children and adults may have been affected by a lack of routine screening in adults.
To assess the use of screening, the investigators analyzed practice surveys from physicians at centers included in the AdVance study. There were 28 survey respondents who treat pediatric patients and 14 who treat adults.
All 28 physicians treating pediatric patients said there is routine AdV screening at their center. Ninety-three percent of these doctors said they routinely screen all pediatric allo-HSCT recipients for AdV infection. The remaining 7% said they screen patients considered to be at high-risk of AdV infection.
Thirty-six percent of the physicians treating adults (5/14) said they routinely screen for AdV, and 21% (3/14) said they routinely screen all of their adult allo-HSCT recipients for AdV infection.
Of the 11 doctors who said they did not routinely screen adult allo-HSCT recipients, some said they would screen recipients with a high-risk of AdV infection, such as those with graft-versus-host disease (4/11) or those who received haploidentical, mismatched, or cord blood transplants (3/11).
*Data in the abstracts differ from the presentations.
LISBON—Results of a large study revealed a higher incidence of adenovirus (AdV) infection after allogeneic hematopoietic stem cell transplant (allo-HSCT) in children than adults.
The rate of AdV infection in the 6 months after allo-HSCT was 32% in children and 6% in adults.
However, researchers believe this data may be influenced by a lack of routine AdV screening in adults.
These findings—from the AdVance study—were reported at the 44th Annual Meeting of the EBMT as abstracts OS9-7 and B043.*
Other results from AdVance were also presented at the meeting, with mortality data reported as abstract OS9-8 and hospitalization data reported as abstract B073. The AdVance study was sponsored by Chimerix, Inc.
“The robust findings of the AdVance study are extremely important for transplant clinicians, as we seek to better understand the rates and clinical outcomes of adenovirus infection and assess ways to evaluate antiviral therapies,” said study investigator Marco Zecca, MD, of Fondazione IRCCS Policlinico San Matteo in Pavia, Italy.
AdVance is a multi-center, retrospective study of 4276 allo-HSCT recipients—1738 pediatric patients and 2538 adults. The patients underwent transplants at 50 centers in Europe from January 2013 to September 2015.
Abstract OS9-7: Incidence
Thirty-two percent (n=558) of pediatric patients developed an AdV infection in the first 6 months after allo-HSCT, and 23% (n=395) developed detectable AdV viremia. Fourteen percent (n=241) had AdV viremia ≥ 1000 copies/mL, a level previously associated with negative clinical outcomes.
Meanwhile, 6% (n=141) of adults had an AdV infection in the 6 months after transplant, 3% (n=77) developed AdV viremia, and 2% (n=39) had ≥ 1000 copies /mL.
Further analysis revealed that age, donor type, and use of T-cell depletion were independent predictors of AdV viremia ≥ 1000 copies/mL.
Older age was associated with a lower risk of AdV viremia ≥ 1000 copies/mL. There was a stepwise reduction in risk with increasing age (compared to ages 0-2, P=0.104 for ages 2-12, P=0.001 for ages 13-17, and P<0.0001 for ages 18-65+).
T-cell depletion was associated with an increased risk of AdV viremia ≥ 1000 copies/mL. Compared to no T-cell depletion, there was an increased risk for depletion with antithymocyte globulin (P=0.036) or alemtuzumab (P<0.0001) and for ex vivo depletion (P=0.002).
Compared to patients who received a matched related transplant, recipients of other transplants had an increased risk of AdV viremia ≥ 1000 copies/mL. This includes matched unrelated (P=0.016), cord blood (P=0.011), haploidentical (P=0.007), and mismatched (P<0.001) transplants.
Abstract B043: Screening
Dr Zecca and his colleagues believe the difference in AdV incidence between children and adults may have been affected by a lack of routine screening in adults.
To assess the use of screening, the investigators analyzed practice surveys from physicians at centers included in the AdVance study. There were 28 survey respondents who treat pediatric patients and 14 who treat adults.
All 28 physicians treating pediatric patients said there is routine AdV screening at their center. Ninety-three percent of these doctors said they routinely screen all pediatric allo-HSCT recipients for AdV infection. The remaining 7% said they screen patients considered to be at high-risk of AdV infection.
Thirty-six percent of the physicians treating adults (5/14) said they routinely screen for AdV, and 21% (3/14) said they routinely screen all of their adult allo-HSCT recipients for AdV infection.
Of the 11 doctors who said they did not routinely screen adult allo-HSCT recipients, some said they would screen recipients with a high-risk of AdV infection, such as those with graft-versus-host disease (4/11) or those who received haploidentical, mismatched, or cord blood transplants (3/11).
*Data in the abstracts differ from the presentations.
LISBON—Results of a large study revealed a higher incidence of adenovirus (AdV) infection after allogeneic hematopoietic stem cell transplant (allo-HSCT) in children than adults.
The rate of AdV infection in the 6 months after allo-HSCT was 32% in children and 6% in adults.
However, researchers believe this data may be influenced by a lack of routine AdV screening in adults.
These findings—from the AdVance study—were reported at the 44th Annual Meeting of the EBMT as abstracts OS9-7 and B043.*
Other results from AdVance were also presented at the meeting, with mortality data reported as abstract OS9-8 and hospitalization data reported as abstract B073. The AdVance study was sponsored by Chimerix, Inc.
“The robust findings of the AdVance study are extremely important for transplant clinicians, as we seek to better understand the rates and clinical outcomes of adenovirus infection and assess ways to evaluate antiviral therapies,” said study investigator Marco Zecca, MD, of Fondazione IRCCS Policlinico San Matteo in Pavia, Italy.
AdVance is a multi-center, retrospective study of 4276 allo-HSCT recipients—1738 pediatric patients and 2538 adults. The patients underwent transplants at 50 centers in Europe from January 2013 to September 2015.
Abstract OS9-7: Incidence
Thirty-two percent (n=558) of pediatric patients developed an AdV infection in the first 6 months after allo-HSCT, and 23% (n=395) developed detectable AdV viremia. Fourteen percent (n=241) had AdV viremia ≥ 1000 copies/mL, a level previously associated with negative clinical outcomes.
Meanwhile, 6% (n=141) of adults had an AdV infection in the 6 months after transplant, 3% (n=77) developed AdV viremia, and 2% (n=39) had ≥ 1000 copies /mL.
Further analysis revealed that age, donor type, and use of T-cell depletion were independent predictors of AdV viremia ≥ 1000 copies/mL.
Older age was associated with a lower risk of AdV viremia ≥ 1000 copies/mL. There was a stepwise reduction in risk with increasing age (compared to ages 0-2, P=0.104 for ages 2-12, P=0.001 for ages 13-17, and P<0.0001 for ages 18-65+).
T-cell depletion was associated with an increased risk of AdV viremia ≥ 1000 copies/mL. Compared to no T-cell depletion, there was an increased risk for depletion with antithymocyte globulin (P=0.036) or alemtuzumab (P<0.0001) and for ex vivo depletion (P=0.002).
Compared to patients who received a matched related transplant, recipients of other transplants had an increased risk of AdV viremia ≥ 1000 copies/mL. This includes matched unrelated (P=0.016), cord blood (P=0.011), haploidentical (P=0.007), and mismatched (P<0.001) transplants.
Abstract B043: Screening
Dr Zecca and his colleagues believe the difference in AdV incidence between children and adults may have been affected by a lack of routine screening in adults.
To assess the use of screening, the investigators analyzed practice surveys from physicians at centers included in the AdVance study. There were 28 survey respondents who treat pediatric patients and 14 who treat adults.
All 28 physicians treating pediatric patients said there is routine AdV screening at their center. Ninety-three percent of these doctors said they routinely screen all pediatric allo-HSCT recipients for AdV infection. The remaining 7% said they screen patients considered to be at high-risk of AdV infection.
Thirty-six percent of the physicians treating adults (5/14) said they routinely screen for AdV, and 21% (3/14) said they routinely screen all of their adult allo-HSCT recipients for AdV infection.
Of the 11 doctors who said they did not routinely screen adult allo-HSCT recipients, some said they would screen recipients with a high-risk of AdV infection, such as those with graft-versus-host disease (4/11) or those who received haploidentical, mismatched, or cord blood transplants (3/11).
*Data in the abstracts differ from the presentations.
AdV viral burden linked to mortality in kids
LISBON—Data from the AdVance study revealed a “strong correlation” between adenovirus (AdV) viral load and mortality in pediatric recipients of allogeneic hematopoietic stem cell transplant (allo-HSCT), according to researchers.
The team found that patients with the highest AdV viral burden had roughly 12 times the risk of all-cause mortality as patients with the lowest viral burden.
These findings were presented at the 44th Annual Meeting of the EBMT (abstract OS9-8).*
Other findings from AdVance were also reported at the meeting (abstracts OS9-7 and B043 as well as B073). The study was sponsored by Chimerix, Inc.
AdVance is a multi-center, retrospective study of 4276 allo-HSCT recipients, including 1738 pediatric patients. The patients underwent transplants at 50 centers in Europe from January 2013 to September 2015.
Thirty-two percent (n=558) of pediatric patients developed an AdV infection in the first 6 months after allo-HSCT. Twenty-three percent (n=395) developed detectable AdV viremia, and 14% (n=241) had AdV viremia ≥ 1000 copies/mL.
The researchers assessed AdV plasma viral burden, measured by time-averaged area under the curve (AAUC) over 16 weeks from the time of viremia ≥ 1000 copies/mL, and its correlation with all-cause mortality.
“[T]he highest mortality was observed in those with the greatest adenovirus burden,” said AdVance investigator Marco Zecca, MD, of Fondazione IRCCS Policlinico San Matteo in Pavia, Italy.
He and his colleagues divided patients into 4 quartiles according to AdV AAUC, with the third and fourth quartiles reflecting higher, more prolonged AdV viremia.
Rates of all-cause mortality at 6 months (from the first viremia ≥ 1000 copies/mL) were 52% in the fourth quartile, 10% in the third, 7% in the second, and 3% in the first quartile.
Forty percent of patients in the fourth quartile died within 2 months of transplant.
The hazard ratio for mortality was 11.7 in the fourth quartile, 2.7 in the third, and 1.5 in the second, with the first quartile as the reference.
“These data suggest that AdV AAUC is an appropriate endpoint to assess the potential benefits of antiviral therapies for the treatment of adenovirus,” Dr Zecca concluded.
*Data in the abstract differ from the presentation.
LISBON—Data from the AdVance study revealed a “strong correlation” between adenovirus (AdV) viral load and mortality in pediatric recipients of allogeneic hematopoietic stem cell transplant (allo-HSCT), according to researchers.
The team found that patients with the highest AdV viral burden had roughly 12 times the risk of all-cause mortality as patients with the lowest viral burden.
These findings were presented at the 44th Annual Meeting of the EBMT (abstract OS9-8).*
Other findings from AdVance were also reported at the meeting (abstracts OS9-7 and B043 as well as B073). The study was sponsored by Chimerix, Inc.
AdVance is a multi-center, retrospective study of 4276 allo-HSCT recipients, including 1738 pediatric patients. The patients underwent transplants at 50 centers in Europe from January 2013 to September 2015.
Thirty-two percent (n=558) of pediatric patients developed an AdV infection in the first 6 months after allo-HSCT. Twenty-three percent (n=395) developed detectable AdV viremia, and 14% (n=241) had AdV viremia ≥ 1000 copies/mL.
The researchers assessed AdV plasma viral burden, measured by time-averaged area under the curve (AAUC) over 16 weeks from the time of viremia ≥ 1000 copies/mL, and its correlation with all-cause mortality.
“[T]he highest mortality was observed in those with the greatest adenovirus burden,” said AdVance investigator Marco Zecca, MD, of Fondazione IRCCS Policlinico San Matteo in Pavia, Italy.
He and his colleagues divided patients into 4 quartiles according to AdV AAUC, with the third and fourth quartiles reflecting higher, more prolonged AdV viremia.
Rates of all-cause mortality at 6 months (from the first viremia ≥ 1000 copies/mL) were 52% in the fourth quartile, 10% in the third, 7% in the second, and 3% in the first quartile.
Forty percent of patients in the fourth quartile died within 2 months of transplant.
The hazard ratio for mortality was 11.7 in the fourth quartile, 2.7 in the third, and 1.5 in the second, with the first quartile as the reference.
“These data suggest that AdV AAUC is an appropriate endpoint to assess the potential benefits of antiviral therapies for the treatment of adenovirus,” Dr Zecca concluded.
*Data in the abstract differ from the presentation.
LISBON—Data from the AdVance study revealed a “strong correlation” between adenovirus (AdV) viral load and mortality in pediatric recipients of allogeneic hematopoietic stem cell transplant (allo-HSCT), according to researchers.
The team found that patients with the highest AdV viral burden had roughly 12 times the risk of all-cause mortality as patients with the lowest viral burden.
These findings were presented at the 44th Annual Meeting of the EBMT (abstract OS9-8).*
Other findings from AdVance were also reported at the meeting (abstracts OS9-7 and B043 as well as B073). The study was sponsored by Chimerix, Inc.
AdVance is a multi-center, retrospective study of 4276 allo-HSCT recipients, including 1738 pediatric patients. The patients underwent transplants at 50 centers in Europe from January 2013 to September 2015.
Thirty-two percent (n=558) of pediatric patients developed an AdV infection in the first 6 months after allo-HSCT. Twenty-three percent (n=395) developed detectable AdV viremia, and 14% (n=241) had AdV viremia ≥ 1000 copies/mL.
The researchers assessed AdV plasma viral burden, measured by time-averaged area under the curve (AAUC) over 16 weeks from the time of viremia ≥ 1000 copies/mL, and its correlation with all-cause mortality.
“[T]he highest mortality was observed in those with the greatest adenovirus burden,” said AdVance investigator Marco Zecca, MD, of Fondazione IRCCS Policlinico San Matteo in Pavia, Italy.
He and his colleagues divided patients into 4 quartiles according to AdV AAUC, with the third and fourth quartiles reflecting higher, more prolonged AdV viremia.
Rates of all-cause mortality at 6 months (from the first viremia ≥ 1000 copies/mL) were 52% in the fourth quartile, 10% in the third, 7% in the second, and 3% in the first quartile.
Forty percent of patients in the fourth quartile died within 2 months of transplant.
The hazard ratio for mortality was 11.7 in the fourth quartile, 2.7 in the third, and 1.5 in the second, with the first quartile as the reference.
“These data suggest that AdV AAUC is an appropriate endpoint to assess the potential benefits of antiviral therapies for the treatment of adenovirus,” Dr Zecca concluded.
*Data in the abstract differ from the presentation.
Parents surveyed about underage drinking
Most parents of children aged 10-17 years have talked to them about alcohol consumption, but many do not consider brain health to be an important reason to avoid underage drinking, according to a recent survey of 1,000 parents.
The 76% of parents who reported having at least one conversation about alcohol was up by 7% from a survey conducted in 2003, the Foundation for Advancing Alcohol Responsibility said.
As for the most important reasons to avoid alcohol, 79% said that it interferes with judgment and the ability to make good decisions, and 77% mentioned the unintended consequences of consuming too much. Slightly more than 40% did not include its effects on brain development, the report said.
“Adolescence includes critical phases in brain development. The area of the brain that controls reasoning – helps us think before we act – matures later in the third decade of life. The sooner that parents speak with their children about the dangers of drinking alcohol underage, the better,” said Deborah Gilboa, MD, a Pittsburgh family physician who serves on the foundation’s education advisory board.
The survey was conducted online by GfK between Nov. 10 and 12, 2017, among adults aged 18 years and over with at least one child aged 10-17 years. The margin of error is plus or minus 3 percentage points for the full sample.
Most parents of children aged 10-17 years have talked to them about alcohol consumption, but many do not consider brain health to be an important reason to avoid underage drinking, according to a recent survey of 1,000 parents.
The 76% of parents who reported having at least one conversation about alcohol was up by 7% from a survey conducted in 2003, the Foundation for Advancing Alcohol Responsibility said.
As for the most important reasons to avoid alcohol, 79% said that it interferes with judgment and the ability to make good decisions, and 77% mentioned the unintended consequences of consuming too much. Slightly more than 40% did not include its effects on brain development, the report said.
“Adolescence includes critical phases in brain development. The area of the brain that controls reasoning – helps us think before we act – matures later in the third decade of life. The sooner that parents speak with their children about the dangers of drinking alcohol underage, the better,” said Deborah Gilboa, MD, a Pittsburgh family physician who serves on the foundation’s education advisory board.
The survey was conducted online by GfK between Nov. 10 and 12, 2017, among adults aged 18 years and over with at least one child aged 10-17 years. The margin of error is plus or minus 3 percentage points for the full sample.
Most parents of children aged 10-17 years have talked to them about alcohol consumption, but many do not consider brain health to be an important reason to avoid underage drinking, according to a recent survey of 1,000 parents.
The 76% of parents who reported having at least one conversation about alcohol was up by 7% from a survey conducted in 2003, the Foundation for Advancing Alcohol Responsibility said.
As for the most important reasons to avoid alcohol, 79% said that it interferes with judgment and the ability to make good decisions, and 77% mentioned the unintended consequences of consuming too much. Slightly more than 40% did not include its effects on brain development, the report said.
“Adolescence includes critical phases in brain development. The area of the brain that controls reasoning – helps us think before we act – matures later in the third decade of life. The sooner that parents speak with their children about the dangers of drinking alcohol underage, the better,” said Deborah Gilboa, MD, a Pittsburgh family physician who serves on the foundation’s education advisory board.
The survey was conducted online by GfK between Nov. 10 and 12, 2017, among adults aged 18 years and over with at least one child aged 10-17 years. The margin of error is plus or minus 3 percentage points for the full sample.
Bleeding episodes more common in boys with VWD
SAN DIEGO – Among children with types 1 and 2 von Willebrand disease (VWD), a higher proportion of boys than girls reported ever having a bleeding episode and using more treatment products. But the trend did not continue among children with type 3 disease.
Those are some of the key findings from a never-before-published analysis of surveillance data from the Centers for Disease Control and Prevention presented by Karon Abe, PhD, during a poster session at the biennial summit of the Thrombosis & Hemostasis Societies of North America.
The researchers retrieved data from the UDC (Universal Data Collection System), a federally funded surveillance system of people with hemophilia and other bleeding disorders treated at 130 U.S. Hemophilia Treatment Centers (HTCs) during 1998-2011. Although UDC data collection ended in 2011, a current CDC bleeding surveillance project called Community Counts continues and expands on the work of the UDC.
Between 1998 and 2011, data were collected on 2,413 children with VWD aged 2-12 years. Of these, 2,070 had type 1, 224 had type 2, and 119 had type 3 VWD. The researchers used chi-square analysis and Wilcoxon rank sum tests to assess differences in bleeding characteristics by sex and by type of VWD. Next, they used a multivariate regression model to examine the association between demographic and clinical characteristics and a history of ever having had a bleeding episode among type 1 VWD patients.
Nearly two-thirds of children (65%) were non-Hispanic, 17% were Hispanic, 8% were black, and the remainder were from other ethnicities. In addition, 40% of the children had no family history of a bleeding disorder.
The median age of first bleed was lower among children with type 3 VWD, compared with other VWD types, and was lower among boys than girls with type 1 VWD (36 months vs. 48 months, respectively; P less than .001) and type 3 VWD (9 months vs. 12 months; P = .04), Dr. Abe reported.
A higher proportion of boys than girls reported ever having a bleeding episode among children with type 1 VWD (78% vs. 73%; P = .01) and type 2 VWD (90% vs. 75%; P = .01), but not among children with type 3 VWD (97% vs. 96%; P = .77).
A higher prevalence of treatment-product use was reported among children with type 3 VWD, compared with those with the other VWD types (a mean of 95% vs. 79% and 71% among types 2 and 1, respectively). A significantly higher prevalence of the use of treatment product was seen among boys than girls with type 1 VWD (73% vs. 68%, P = .03) and type 2 VWD (87% vs. 72%, P =.01), but not type 3 VWD (94% vs. 96%, P = .87).
The most common sites of the first bleed among all patients regardless of gender or VWD type were epistaxis and oral cavity bleeding.
“To our surprise, the boys were showing more bleeding and were receiving more product than the females,” Dr. Abe said in an interview. “This is a fairly large population.”
Multivariate regression analysis revealed independent associations between the following patient characteristics and ever having a bleed among children with type 1 VWD: male gender (adjusted odds ratio, 1.23); being aged 7-9 years at registration, compared with being aged 2-6 years (aOR, 1.5); being black (aOR, 1.7); being Asian, Native Hawaiian or Pacific Islander (aOR, 2.4), being Hispanic (aOR, 2.8), and being some other race/ethnicity (aOR, 1.8). However, family history of a bleeding disorder was protective (aOR, 0.721).
Dr. Abe said she hopes that the findings will raise awareness and help physicians to educate families about bleeding symptoms and intervene to treat bleeding episodes appropriately. She and her associates are planning to compare the data with Community Counts, “so it’s more up to date,” she said.
Dr. Abe reported having no financial disclosures.
SOURCE: Abe K et al. THSNA 2018, Poster 145.
SAN DIEGO – Among children with types 1 and 2 von Willebrand disease (VWD), a higher proportion of boys than girls reported ever having a bleeding episode and using more treatment products. But the trend did not continue among children with type 3 disease.
Those are some of the key findings from a never-before-published analysis of surveillance data from the Centers for Disease Control and Prevention presented by Karon Abe, PhD, during a poster session at the biennial summit of the Thrombosis & Hemostasis Societies of North America.
The researchers retrieved data from the UDC (Universal Data Collection System), a federally funded surveillance system of people with hemophilia and other bleeding disorders treated at 130 U.S. Hemophilia Treatment Centers (HTCs) during 1998-2011. Although UDC data collection ended in 2011, a current CDC bleeding surveillance project called Community Counts continues and expands on the work of the UDC.
Between 1998 and 2011, data were collected on 2,413 children with VWD aged 2-12 years. Of these, 2,070 had type 1, 224 had type 2, and 119 had type 3 VWD. The researchers used chi-square analysis and Wilcoxon rank sum tests to assess differences in bleeding characteristics by sex and by type of VWD. Next, they used a multivariate regression model to examine the association between demographic and clinical characteristics and a history of ever having had a bleeding episode among type 1 VWD patients.
Nearly two-thirds of children (65%) were non-Hispanic, 17% were Hispanic, 8% were black, and the remainder were from other ethnicities. In addition, 40% of the children had no family history of a bleeding disorder.
The median age of first bleed was lower among children with type 3 VWD, compared with other VWD types, and was lower among boys than girls with type 1 VWD (36 months vs. 48 months, respectively; P less than .001) and type 3 VWD (9 months vs. 12 months; P = .04), Dr. Abe reported.
A higher proportion of boys than girls reported ever having a bleeding episode among children with type 1 VWD (78% vs. 73%; P = .01) and type 2 VWD (90% vs. 75%; P = .01), but not among children with type 3 VWD (97% vs. 96%; P = .77).
A higher prevalence of treatment-product use was reported among children with type 3 VWD, compared with those with the other VWD types (a mean of 95% vs. 79% and 71% among types 2 and 1, respectively). A significantly higher prevalence of the use of treatment product was seen among boys than girls with type 1 VWD (73% vs. 68%, P = .03) and type 2 VWD (87% vs. 72%, P =.01), but not type 3 VWD (94% vs. 96%, P = .87).
The most common sites of the first bleed among all patients regardless of gender or VWD type were epistaxis and oral cavity bleeding.
“To our surprise, the boys were showing more bleeding and were receiving more product than the females,” Dr. Abe said in an interview. “This is a fairly large population.”
Multivariate regression analysis revealed independent associations between the following patient characteristics and ever having a bleed among children with type 1 VWD: male gender (adjusted odds ratio, 1.23); being aged 7-9 years at registration, compared with being aged 2-6 years (aOR, 1.5); being black (aOR, 1.7); being Asian, Native Hawaiian or Pacific Islander (aOR, 2.4), being Hispanic (aOR, 2.8), and being some other race/ethnicity (aOR, 1.8). However, family history of a bleeding disorder was protective (aOR, 0.721).
Dr. Abe said she hopes that the findings will raise awareness and help physicians to educate families about bleeding symptoms and intervene to treat bleeding episodes appropriately. She and her associates are planning to compare the data with Community Counts, “so it’s more up to date,” she said.
Dr. Abe reported having no financial disclosures.
SOURCE: Abe K et al. THSNA 2018, Poster 145.
SAN DIEGO – Among children with types 1 and 2 von Willebrand disease (VWD), a higher proportion of boys than girls reported ever having a bleeding episode and using more treatment products. But the trend did not continue among children with type 3 disease.
Those are some of the key findings from a never-before-published analysis of surveillance data from the Centers for Disease Control and Prevention presented by Karon Abe, PhD, during a poster session at the biennial summit of the Thrombosis & Hemostasis Societies of North America.
The researchers retrieved data from the UDC (Universal Data Collection System), a federally funded surveillance system of people with hemophilia and other bleeding disorders treated at 130 U.S. Hemophilia Treatment Centers (HTCs) during 1998-2011. Although UDC data collection ended in 2011, a current CDC bleeding surveillance project called Community Counts continues and expands on the work of the UDC.
Between 1998 and 2011, data were collected on 2,413 children with VWD aged 2-12 years. Of these, 2,070 had type 1, 224 had type 2, and 119 had type 3 VWD. The researchers used chi-square analysis and Wilcoxon rank sum tests to assess differences in bleeding characteristics by sex and by type of VWD. Next, they used a multivariate regression model to examine the association between demographic and clinical characteristics and a history of ever having had a bleeding episode among type 1 VWD patients.
Nearly two-thirds of children (65%) were non-Hispanic, 17% were Hispanic, 8% were black, and the remainder were from other ethnicities. In addition, 40% of the children had no family history of a bleeding disorder.
The median age of first bleed was lower among children with type 3 VWD, compared with other VWD types, and was lower among boys than girls with type 1 VWD (36 months vs. 48 months, respectively; P less than .001) and type 3 VWD (9 months vs. 12 months; P = .04), Dr. Abe reported.
A higher proportion of boys than girls reported ever having a bleeding episode among children with type 1 VWD (78% vs. 73%; P = .01) and type 2 VWD (90% vs. 75%; P = .01), but not among children with type 3 VWD (97% vs. 96%; P = .77).
A higher prevalence of treatment-product use was reported among children with type 3 VWD, compared with those with the other VWD types (a mean of 95% vs. 79% and 71% among types 2 and 1, respectively). A significantly higher prevalence of the use of treatment product was seen among boys than girls with type 1 VWD (73% vs. 68%, P = .03) and type 2 VWD (87% vs. 72%, P =.01), but not type 3 VWD (94% vs. 96%, P = .87).
The most common sites of the first bleed among all patients regardless of gender or VWD type were epistaxis and oral cavity bleeding.
“To our surprise, the boys were showing more bleeding and were receiving more product than the females,” Dr. Abe said in an interview. “This is a fairly large population.”
Multivariate regression analysis revealed independent associations between the following patient characteristics and ever having a bleed among children with type 1 VWD: male gender (adjusted odds ratio, 1.23); being aged 7-9 years at registration, compared with being aged 2-6 years (aOR, 1.5); being black (aOR, 1.7); being Asian, Native Hawaiian or Pacific Islander (aOR, 2.4), being Hispanic (aOR, 2.8), and being some other race/ethnicity (aOR, 1.8). However, family history of a bleeding disorder was protective (aOR, 0.721).
Dr. Abe said she hopes that the findings will raise awareness and help physicians to educate families about bleeding symptoms and intervene to treat bleeding episodes appropriately. She and her associates are planning to compare the data with Community Counts, “so it’s more up to date,” she said.
Dr. Abe reported having no financial disclosures.
SOURCE: Abe K et al. THSNA 2018, Poster 145.
REPORTING FROM THSNA 2018
Key clinical point:
Major finding: A higher proportion of boys than girls reported ever having a bleeding episode among children with type 1 VWD (78% vs. 73%; P= .01) and type 2 VWD (90% vs. 75%; P= .01), but not among children with type 3 VWD (97% vs. 96%; P= .77).
Study details: An analysis of 2,413 children with VWD aged 2-12 years.
Disclosures: Dr. Abe reported having no financial disclosures.
Source: Abe K et al. THSNA 2018, Poster 145.
Alternative oxygen therapy reduces treatment failure in bronchiolitis
High-flow oxygen therapy outside the ICU boosts the likelihood that infants with bronchiolitis will avoid treatment failure and an escalation of treatment, a study finds.
“High flow can be safely used in general emergency wards and general pediatric ward settings in regional and metropolitan hospitals that have no immediate direct access to dedicated pediatric intensive care facilities,” study coauthor Andreas Schibler, MD, of University of Queensland in Australia, said in an interview. The findings were published March 22 in the New England Journal of Medicine.
“The typical treatment for bronchiolitis is supportive therapy, providing nutrition, fluids, and if needed respiratory support including provision of oxygen,” Dr. Schibler said.
The prognosis is generally goods thanks to improvements in intensive care, he said, which some infants need because the standard oxygen therapy provided in general pediatric wards is insufficient. The new study examines whether high-flow oxygen therapy through a cannula – which he said has become more common – reduces the risk of treatment failure in non-ICU therapy, compared with standard oxygen treatment.
Dr. Schibler and his colleagues tracked 1,472 patients under 12 months with bronchiolitis and a need for oxygen treatment who were randomly assigned to high-flow or standard oxygen therapy to maintain their oxygen saturation at 92%-98% or 94%-98%, depending on policy at the hospital. The subjects were patients at 17 hospitals in Australia and New Zealand.
A total of 739 infants received high-flow treatment that provided heated and humidified oxygen at a rate of 2 liters per kilogram of body weight per minute. The other 733 infants received standard oxygen therapy up to a maximum 2 liters per minute.
The treatment failed, requiring an escalation of care, in 87 of 739 patients (12%) in the high-flow group and 167 of 733 (23%) in the standard-therapy group. (risk difference = –11% points; 95% confidence interval, –15 to –7; P less than .001).
“The ease to use and simplicity of high flow made us recognize and think that this level of respiratory care can be provided outside intensive care,” Dr. Schibler said. “This was further supported by the observational fact that most of these infants with bronchiolitis showed a dramatically improved respiratory condition once on high flow.”
Dr. Schibler said there haven’t been any signs of adverse effects from high-flow oxygen therapy. As for the cost of the treatment, he said it is “likely offset by a reduced need for intensive care therapy or costs associated with transferring to a children’s hospital.”
What should physicians and hospitals take from the study findings? “If a hospital explores the option to use high flow in bronchiolitis, then start the therapy early in the disease process or once an oxygen requirement is recognized,” Dr. Schibler said. “Implementation of a solid and structured training program with a clear hospital guideline based on the evidence will ensure the staff who care for these patients will be empowered and comfortable to adjust the oxygen levels given by the high-flow equipment. The greater the confidence and comfort level for the nursing and respiratory technician staff the better for these infants, as they will sooner observe those infants who are not responding well and may require a higher level of care such as intensive care or they will recognize the infant who responds well.”
The National Health and Medical Research Council (Australia) and the Queensland Emergency Medical Research Fund provided funding, and sites received grant funding from various sources. Fisher & Paykel Healthcare, a respiratory care company based in Auckland, New Zealand, donated high-flow equipment and consumables and travel/accommodation support. Study authors reported various grants and other support.
SOURCE: Franklin D et al. N Engl J Med. 2018;378(12):1112-31.
High-flow oxygen therapy outside the ICU boosts the likelihood that infants with bronchiolitis will avoid treatment failure and an escalation of treatment, a study finds.
“High flow can be safely used in general emergency wards and general pediatric ward settings in regional and metropolitan hospitals that have no immediate direct access to dedicated pediatric intensive care facilities,” study coauthor Andreas Schibler, MD, of University of Queensland in Australia, said in an interview. The findings were published March 22 in the New England Journal of Medicine.
“The typical treatment for bronchiolitis is supportive therapy, providing nutrition, fluids, and if needed respiratory support including provision of oxygen,” Dr. Schibler said.
The prognosis is generally goods thanks to improvements in intensive care, he said, which some infants need because the standard oxygen therapy provided in general pediatric wards is insufficient. The new study examines whether high-flow oxygen therapy through a cannula – which he said has become more common – reduces the risk of treatment failure in non-ICU therapy, compared with standard oxygen treatment.
Dr. Schibler and his colleagues tracked 1,472 patients under 12 months with bronchiolitis and a need for oxygen treatment who were randomly assigned to high-flow or standard oxygen therapy to maintain their oxygen saturation at 92%-98% or 94%-98%, depending on policy at the hospital. The subjects were patients at 17 hospitals in Australia and New Zealand.
A total of 739 infants received high-flow treatment that provided heated and humidified oxygen at a rate of 2 liters per kilogram of body weight per minute. The other 733 infants received standard oxygen therapy up to a maximum 2 liters per minute.
The treatment failed, requiring an escalation of care, in 87 of 739 patients (12%) in the high-flow group and 167 of 733 (23%) in the standard-therapy group. (risk difference = –11% points; 95% confidence interval, –15 to –7; P less than .001).
“The ease to use and simplicity of high flow made us recognize and think that this level of respiratory care can be provided outside intensive care,” Dr. Schibler said. “This was further supported by the observational fact that most of these infants with bronchiolitis showed a dramatically improved respiratory condition once on high flow.”
Dr. Schibler said there haven’t been any signs of adverse effects from high-flow oxygen therapy. As for the cost of the treatment, he said it is “likely offset by a reduced need for intensive care therapy or costs associated with transferring to a children’s hospital.”
What should physicians and hospitals take from the study findings? “If a hospital explores the option to use high flow in bronchiolitis, then start the therapy early in the disease process or once an oxygen requirement is recognized,” Dr. Schibler said. “Implementation of a solid and structured training program with a clear hospital guideline based on the evidence will ensure the staff who care for these patients will be empowered and comfortable to adjust the oxygen levels given by the high-flow equipment. The greater the confidence and comfort level for the nursing and respiratory technician staff the better for these infants, as they will sooner observe those infants who are not responding well and may require a higher level of care such as intensive care or they will recognize the infant who responds well.”
The National Health and Medical Research Council (Australia) and the Queensland Emergency Medical Research Fund provided funding, and sites received grant funding from various sources. Fisher & Paykel Healthcare, a respiratory care company based in Auckland, New Zealand, donated high-flow equipment and consumables and travel/accommodation support. Study authors reported various grants and other support.
SOURCE: Franklin D et al. N Engl J Med. 2018;378(12):1112-31.
High-flow oxygen therapy outside the ICU boosts the likelihood that infants with bronchiolitis will avoid treatment failure and an escalation of treatment, a study finds.
“High flow can be safely used in general emergency wards and general pediatric ward settings in regional and metropolitan hospitals that have no immediate direct access to dedicated pediatric intensive care facilities,” study coauthor Andreas Schibler, MD, of University of Queensland in Australia, said in an interview. The findings were published March 22 in the New England Journal of Medicine.
“The typical treatment for bronchiolitis is supportive therapy, providing nutrition, fluids, and if needed respiratory support including provision of oxygen,” Dr. Schibler said.
The prognosis is generally goods thanks to improvements in intensive care, he said, which some infants need because the standard oxygen therapy provided in general pediatric wards is insufficient. The new study examines whether high-flow oxygen therapy through a cannula – which he said has become more common – reduces the risk of treatment failure in non-ICU therapy, compared with standard oxygen treatment.
Dr. Schibler and his colleagues tracked 1,472 patients under 12 months with bronchiolitis and a need for oxygen treatment who were randomly assigned to high-flow or standard oxygen therapy to maintain their oxygen saturation at 92%-98% or 94%-98%, depending on policy at the hospital. The subjects were patients at 17 hospitals in Australia and New Zealand.
A total of 739 infants received high-flow treatment that provided heated and humidified oxygen at a rate of 2 liters per kilogram of body weight per minute. The other 733 infants received standard oxygen therapy up to a maximum 2 liters per minute.
The treatment failed, requiring an escalation of care, in 87 of 739 patients (12%) in the high-flow group and 167 of 733 (23%) in the standard-therapy group. (risk difference = –11% points; 95% confidence interval, –15 to –7; P less than .001).
“The ease to use and simplicity of high flow made us recognize and think that this level of respiratory care can be provided outside intensive care,” Dr. Schibler said. “This was further supported by the observational fact that most of these infants with bronchiolitis showed a dramatically improved respiratory condition once on high flow.”
Dr. Schibler said there haven’t been any signs of adverse effects from high-flow oxygen therapy. As for the cost of the treatment, he said it is “likely offset by a reduced need for intensive care therapy or costs associated with transferring to a children’s hospital.”
What should physicians and hospitals take from the study findings? “If a hospital explores the option to use high flow in bronchiolitis, then start the therapy early in the disease process or once an oxygen requirement is recognized,” Dr. Schibler said. “Implementation of a solid and structured training program with a clear hospital guideline based on the evidence will ensure the staff who care for these patients will be empowered and comfortable to adjust the oxygen levels given by the high-flow equipment. The greater the confidence and comfort level for the nursing and respiratory technician staff the better for these infants, as they will sooner observe those infants who are not responding well and may require a higher level of care such as intensive care or they will recognize the infant who responds well.”
The National Health and Medical Research Council (Australia) and the Queensland Emergency Medical Research Fund provided funding, and sites received grant funding from various sources. Fisher & Paykel Healthcare, a respiratory care company based in Auckland, New Zealand, donated high-flow equipment and consumables and travel/accommodation support. Study authors reported various grants and other support.
SOURCE: Franklin D et al. N Engl J Med. 2018;378(12):1112-31.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: In non-ICUs, infants under 12 months with bronchiolitis are less likely to fail treatment if they are given high-flow oxygen therapy instead of standard oxygen therapy.
Major finding: Treatment failure occurred in 8 of 739 (12%) patients in the high-flow oxygen therapy group and 167 of 733 (23%) in the standard-therapy group.
Study details: Multicenter, randomized, controlled trial of 1,472 infants.
Disclosures: The National Health and Medical Research Council (Australia) and the Queensland Emergency Medical Research Fund provided funding, and sites received grant funding from various sources. Fisher & Paykel Healthcare, a respiratory care company based in Auckland, New Zealand, donated high-flow equipment/consumables and travel/accommodation support. Study authors reported various grants and other support.
Source: Franklin D et al. N Engl J Med 2018;378(12):1112-31.
Novel oral immunotherapy increased peanut tolerance in children, adults
ORLANDO – compared with those receiving placebo, according to research results.
Stacie M. Jones, MD, of the University of Arkansas and Arkansas Children’s Hospital, Little Rock, presented the late-breaking results from the pivotal PALISADE trial at the joint congress of the American Academy of Allergy, Asthma, and Immunology and the World Asthma Organization, in which Dr. Jones and her colleagues sought to examine the safety and efficacy of the novel oral immunotherapy AR101 for patients with peanut allergy.
At 12 months, 67% of patients who received AR101 tolerated 600 mg or more of peanut protein, compared with 4% of control patients (P less than .00001). The tolerance benefit for AR101 appeared to continue when the researchers evaluated 1,000 mg of peanut protein. A dose of 1,000 mg or more was tolerated by 50% of patients in the AR101 group, compared with 2.4% of patients in the control group (P less than .00001).
“Tolerance at 600 mg should indicate, not prove, but indicate that this therapy should be able to provide protection for the vast majority of individuals treated,” Dr. Jones said in an interview.
The majority of patients in the study experienced an adverse event; however, those who received AR101 experienced more events, and more events that were considered serious, she said. Patients in the treatment arm also experienced more treatment-related hypersensitivity, compared with patients in the placebo arm (14.5% vs. 3.2%), nearly all of which were mild to moderate.
It is important to note two key safety outcomes regarding AR101, Dr. Jones said. First, that one patient was diagnosed with eosinophilic esophagitis (EoE) during the study. “EoE has been a recurring theme with oral immunotherapy. Previous data showed EoE diagnoses in as many as 2%-5% of patients, and although one is certainly less than that, it is still important.”
Secondly, she pointed out that 6.7% of patients in the treatment group withdrew as a result of gastrointestinal adverse events. “This is a lower percentage than previously published data, but I don’t think you can understate this safety concern,” Dr. Jones said.
The efficacy of AR101 has prompted energy and hope for children with a peanut allergy. In the weeks following her presentation at AAAAI/WAO, Dr. Jones said she has been inundated with emails and calls from allergists asking for these data. However, she called for caution and patience, saying that it is important for the therapy to clear the appropriate steps in the process.
“This should not change clinical care that much in the next 12-18 months,” Dr. Jones said. “But it is very hopeful that this will be a new therapy on the market.”
The PALISADE trial was funded by Aimmune Therapeutics, and Dr. Jones reported holding an advisory board position for Aimmune Therapeutics, as well as having received other forms of support from biotech, pharmaceutical, and governmental organizations.
SOURCE: Jones SM et al. AAAAI/WAO Joint Congress, Abstract L6.
ORLANDO – compared with those receiving placebo, according to research results.
Stacie M. Jones, MD, of the University of Arkansas and Arkansas Children’s Hospital, Little Rock, presented the late-breaking results from the pivotal PALISADE trial at the joint congress of the American Academy of Allergy, Asthma, and Immunology and the World Asthma Organization, in which Dr. Jones and her colleagues sought to examine the safety and efficacy of the novel oral immunotherapy AR101 for patients with peanut allergy.
At 12 months, 67% of patients who received AR101 tolerated 600 mg or more of peanut protein, compared with 4% of control patients (P less than .00001). The tolerance benefit for AR101 appeared to continue when the researchers evaluated 1,000 mg of peanut protein. A dose of 1,000 mg or more was tolerated by 50% of patients in the AR101 group, compared with 2.4% of patients in the control group (P less than .00001).
“Tolerance at 600 mg should indicate, not prove, but indicate that this therapy should be able to provide protection for the vast majority of individuals treated,” Dr. Jones said in an interview.
The majority of patients in the study experienced an adverse event; however, those who received AR101 experienced more events, and more events that were considered serious, she said. Patients in the treatment arm also experienced more treatment-related hypersensitivity, compared with patients in the placebo arm (14.5% vs. 3.2%), nearly all of which were mild to moderate.
It is important to note two key safety outcomes regarding AR101, Dr. Jones said. First, that one patient was diagnosed with eosinophilic esophagitis (EoE) during the study. “EoE has been a recurring theme with oral immunotherapy. Previous data showed EoE diagnoses in as many as 2%-5% of patients, and although one is certainly less than that, it is still important.”
Secondly, she pointed out that 6.7% of patients in the treatment group withdrew as a result of gastrointestinal adverse events. “This is a lower percentage than previously published data, but I don’t think you can understate this safety concern,” Dr. Jones said.
The efficacy of AR101 has prompted energy and hope for children with a peanut allergy. In the weeks following her presentation at AAAAI/WAO, Dr. Jones said she has been inundated with emails and calls from allergists asking for these data. However, she called for caution and patience, saying that it is important for the therapy to clear the appropriate steps in the process.
“This should not change clinical care that much in the next 12-18 months,” Dr. Jones said. “But it is very hopeful that this will be a new therapy on the market.”
The PALISADE trial was funded by Aimmune Therapeutics, and Dr. Jones reported holding an advisory board position for Aimmune Therapeutics, as well as having received other forms of support from biotech, pharmaceutical, and governmental organizations.
SOURCE: Jones SM et al. AAAAI/WAO Joint Congress, Abstract L6.
ORLANDO – compared with those receiving placebo, according to research results.
Stacie M. Jones, MD, of the University of Arkansas and Arkansas Children’s Hospital, Little Rock, presented the late-breaking results from the pivotal PALISADE trial at the joint congress of the American Academy of Allergy, Asthma, and Immunology and the World Asthma Organization, in which Dr. Jones and her colleagues sought to examine the safety and efficacy of the novel oral immunotherapy AR101 for patients with peanut allergy.
At 12 months, 67% of patients who received AR101 tolerated 600 mg or more of peanut protein, compared with 4% of control patients (P less than .00001). The tolerance benefit for AR101 appeared to continue when the researchers evaluated 1,000 mg of peanut protein. A dose of 1,000 mg or more was tolerated by 50% of patients in the AR101 group, compared with 2.4% of patients in the control group (P less than .00001).
“Tolerance at 600 mg should indicate, not prove, but indicate that this therapy should be able to provide protection for the vast majority of individuals treated,” Dr. Jones said in an interview.
The majority of patients in the study experienced an adverse event; however, those who received AR101 experienced more events, and more events that were considered serious, she said. Patients in the treatment arm also experienced more treatment-related hypersensitivity, compared with patients in the placebo arm (14.5% vs. 3.2%), nearly all of which were mild to moderate.
It is important to note two key safety outcomes regarding AR101, Dr. Jones said. First, that one patient was diagnosed with eosinophilic esophagitis (EoE) during the study. “EoE has been a recurring theme with oral immunotherapy. Previous data showed EoE diagnoses in as many as 2%-5% of patients, and although one is certainly less than that, it is still important.”
Secondly, she pointed out that 6.7% of patients in the treatment group withdrew as a result of gastrointestinal adverse events. “This is a lower percentage than previously published data, but I don’t think you can understate this safety concern,” Dr. Jones said.
The efficacy of AR101 has prompted energy and hope for children with a peanut allergy. In the weeks following her presentation at AAAAI/WAO, Dr. Jones said she has been inundated with emails and calls from allergists asking for these data. However, she called for caution and patience, saying that it is important for the therapy to clear the appropriate steps in the process.
“This should not change clinical care that much in the next 12-18 months,” Dr. Jones said. “But it is very hopeful that this will be a new therapy on the market.”
The PALISADE trial was funded by Aimmune Therapeutics, and Dr. Jones reported holding an advisory board position for Aimmune Therapeutics, as well as having received other forms of support from biotech, pharmaceutical, and governmental organizations.
SOURCE: Jones SM et al. AAAAI/WAO Joint Congress, Abstract L6.
FROM AAAAI/WAO JOINT CONGRESS 2018
Key clinical point: A novel oral immunotherapy significantly improved peanut tolerance in children and adults with peanut allergy.
Major finding: Two-thirds of patients who received AR101 tolerated 600 mg or more of peanut protein, compared with 4% of patients who did not receive the novel oral immunotherapy.
Data source: The randomized, phase 3, double-blind, placebo-controlled PALISADE trial.
Disclosures: The study was funded by Aimmune Therapeutics. Dr. Jones reported holding an advisory board position with Aimmune Therapeutics.
Source: Jones SM et al. AAAAI/WAO Joint Congress, Abstract L6.
Early family intervention tied to reduced AUDs in Mexican American youth
A family-focused middle school intervention can help reduce alcohol abuse and alcohol use disorders (AUD) in Mexican American adolescents who are at heightened risk for problem drinking, according to Nancy A. Gonzales, PhD, and her associates.
The report was published March 21 in JAMA Psychiatry.
The investigators examined 5-year follow-up results of a randomized controlled trial, Bridges/Puentes, a 9-week, evidence-based intervention aimed at helping urban, low-income Mexican American teens succeed at school. Among other features, the Bridges/Puentes intervention promoted cultural strengths that had been identified in previous interventions aimed at Latino youth.
“This blend of evidence-based practices and good recruitment rates, retention, and fidelity provided a strong foundation for testing the sustained results of middle school prevention for Latinos,” wrote Dr. Gonzales of the department of psychology and the REACH Institute at Arizona State University, Tempe, and her associates.
The study’s focus on Mexican American youth, which makes it difficult to generalize the results to other populations, was a limitation, the authors noted. Nevertheless, the intervention “is a viable method to not only reduce substance use initiation in the short-term ... but also to reduce later rates of AUDs and alcohol misuse among Mexican American adolescents at heightened risk for problem drinking,” they wrote.
The study was funded by the National Institute of Mental Health. No conflicts of interest were reported.
SOURCE: Gonzales NA et al. doi: 10.1001/jamapsychiatry.2018.0058.
A family-focused middle school intervention can help reduce alcohol abuse and alcohol use disorders (AUD) in Mexican American adolescents who are at heightened risk for problem drinking, according to Nancy A. Gonzales, PhD, and her associates.
The report was published March 21 in JAMA Psychiatry.
The investigators examined 5-year follow-up results of a randomized controlled trial, Bridges/Puentes, a 9-week, evidence-based intervention aimed at helping urban, low-income Mexican American teens succeed at school. Among other features, the Bridges/Puentes intervention promoted cultural strengths that had been identified in previous interventions aimed at Latino youth.
“This blend of evidence-based practices and good recruitment rates, retention, and fidelity provided a strong foundation for testing the sustained results of middle school prevention for Latinos,” wrote Dr. Gonzales of the department of psychology and the REACH Institute at Arizona State University, Tempe, and her associates.
The study’s focus on Mexican American youth, which makes it difficult to generalize the results to other populations, was a limitation, the authors noted. Nevertheless, the intervention “is a viable method to not only reduce substance use initiation in the short-term ... but also to reduce later rates of AUDs and alcohol misuse among Mexican American adolescents at heightened risk for problem drinking,” they wrote.
The study was funded by the National Institute of Mental Health. No conflicts of interest were reported.
SOURCE: Gonzales NA et al. doi: 10.1001/jamapsychiatry.2018.0058.
A family-focused middle school intervention can help reduce alcohol abuse and alcohol use disorders (AUD) in Mexican American adolescents who are at heightened risk for problem drinking, according to Nancy A. Gonzales, PhD, and her associates.
The report was published March 21 in JAMA Psychiatry.
The investigators examined 5-year follow-up results of a randomized controlled trial, Bridges/Puentes, a 9-week, evidence-based intervention aimed at helping urban, low-income Mexican American teens succeed at school. Among other features, the Bridges/Puentes intervention promoted cultural strengths that had been identified in previous interventions aimed at Latino youth.
“This blend of evidence-based practices and good recruitment rates, retention, and fidelity provided a strong foundation for testing the sustained results of middle school prevention for Latinos,” wrote Dr. Gonzales of the department of psychology and the REACH Institute at Arizona State University, Tempe, and her associates.
The study’s focus on Mexican American youth, which makes it difficult to generalize the results to other populations, was a limitation, the authors noted. Nevertheless, the intervention “is a viable method to not only reduce substance use initiation in the short-term ... but also to reduce later rates of AUDs and alcohol misuse among Mexican American adolescents at heightened risk for problem drinking,” they wrote.
The study was funded by the National Institute of Mental Health. No conflicts of interest were reported.
SOURCE: Gonzales NA et al. doi: 10.1001/jamapsychiatry.2018.0058.
FROM JAMA PSYCHIATRY
Docs worry there’s ‘nowhere to send’ new and expectant moms with depression
Lawmakers in California will begin debate next month on a bill that would require doctors to screen new moms for mental health problems – once while they’re pregnant and again after they give birth.
But many obstetricians and pediatricians bristle at the idea, saying they are afraid to screen new moms for depression and anxiety.
“What are you going to do with those people who screen positive?” asked Laura L. Sirott, MD, an ob.gyn. who practices in Pasadena. “Some providers have nowhere to send them.”
Nationally, depression affects up to one in seven women during or after pregnancy, according to the American Psychological Association.
And, of women who screen positive for the condition, 78% don’t get mental health treatment, according to a 2015 research review published in the journal Obstetrics & Gynecology.
Dr. Sirott said her patients give a range of reasons why they don’t take her up on a referral to a psychologist: “ ‘Oh, they don’t take my insurance.’ Or ‘my insurance pays for three visits.’ ‘I can’t take time off work to go to those visits.’ ‘It’s a 3-month wait to get in to that person.’ ”
She said it’s also hard to find a psychiatrist who is willing to treat them and who is trained in the complexities of prescribing medications to pregnant or breastfeeding women, especially in rural areas.
“So it’s very frustrating,” Dr. Sirott said, “to ask patients about a problem and then not have any way to solve that problem.”
Moms are frustrated, too. After the baby comes, no one asks about the baby’s mother anymore.
Wendy Root Askew struggled for years to get pregnant, and when she finally did, her anxiety got worse. She couldn’t stop worrying that something would go wrong.
“And then, after I had my son, I would have these dreams where someone would come to the door and they would say, ‘Well, you know, we’re just going to wait 2 weeks to see if you get to keep your baby or not,’ ” Ms. Root Askew said. “And it really impacted my ability to bond with him.”
She likes California’s bill, AB 2193, because it goes beyond mandated screening. It would require health insurance companies to set up case management programs to help moms find a therapist, and connect obstetricians or pediatricians to a psychiatric specialist.
“Just like we have case-management programs for patients who have diabetes or sleep issues or back pain, a case-management program requires the insurance company to take some ownership of making sure their patients are getting the treatment they need to be healthy,” said Ms. Root Askew, who is now advocating for the bill on behalf of the group 2020 Mom.
Health insurance companies haven’t taken a position on the legislation. It’s unclear how much it would cost them to comply, because some already have infrastructure in place for case-management programs, and some do not. But there is consensus among insurers and health advocates that such programs save money in the long run.
“The sooner that you can get good treatment for a mom, the less expensive that condition will be to manage over the course of the woman’s life and over the course of that child’s life,” Ms. Root Askew said.
Some doctors still have their objections. Under the bill, they could be disciplined for not screening. Some have said they worry about how much time it would take.
The health care system, and the incentives, aren’t set up for this sort of screening, Dr. Sirott said.
“Currently, I get $6 for screening a patient,” she said. “By the time I put it on a piece of paper and print it, it’s not worth it.”
It’s not clear whether the direct and indirect costs of screening would be worth it to the patients, either. Four other states – Illinois, Massachusetts, New Jersey, and West Virginia – have tried mandated screening, and it did not result in more women getting treatment, according to a 2015 study published in Psychiatric Services.
Even with California’s extra requirement that insurance companies facilitate care, women could still face high copays or limits on the number of therapy sessions. Or, a new mother might be so overwhelmed with care for her newborn that it would be difficult to add anything to her busy schedule.
What does seem to work, according to the study of mandated screening in other states, is when nurses or mental health providers visit new moms at home.
“Despite abundant goodwill, there is no evidence that state policies are addressing this great need,” the study’s authors report.
Supporters of California’s proposed bill, however, say doctors need to start somewhere. Screening is the first step in recognizing the full scope of the problem, said Nirmaljit Dhami, MD, a Mountain View, Calif., psychiatrist. Women should be screened on an ongoing basis throughout pregnancy and for a year after birth, Dr. Dhami said, not just once or twice as the bill requires.
“I often tell doctors that if you don’t know that somebody is suicidal, it doesn’t mean that their suicidality will go away,” she said. “If you don’t ask, the risk is the same.”
This story is part of a partnership that includes KQED, NPR, and Kaiser Health News. KHN’s coverage of women’s health care issues is supported in part by The David and Lucile Packard Foundation. KHN is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
Lawmakers in California will begin debate next month on a bill that would require doctors to screen new moms for mental health problems – once while they’re pregnant and again after they give birth.
But many obstetricians and pediatricians bristle at the idea, saying they are afraid to screen new moms for depression and anxiety.
“What are you going to do with those people who screen positive?” asked Laura L. Sirott, MD, an ob.gyn. who practices in Pasadena. “Some providers have nowhere to send them.”
Nationally, depression affects up to one in seven women during or after pregnancy, according to the American Psychological Association.
And, of women who screen positive for the condition, 78% don’t get mental health treatment, according to a 2015 research review published in the journal Obstetrics & Gynecology.
Dr. Sirott said her patients give a range of reasons why they don’t take her up on a referral to a psychologist: “ ‘Oh, they don’t take my insurance.’ Or ‘my insurance pays for three visits.’ ‘I can’t take time off work to go to those visits.’ ‘It’s a 3-month wait to get in to that person.’ ”
She said it’s also hard to find a psychiatrist who is willing to treat them and who is trained in the complexities of prescribing medications to pregnant or breastfeeding women, especially in rural areas.
“So it’s very frustrating,” Dr. Sirott said, “to ask patients about a problem and then not have any way to solve that problem.”
Moms are frustrated, too. After the baby comes, no one asks about the baby’s mother anymore.
Wendy Root Askew struggled for years to get pregnant, and when she finally did, her anxiety got worse. She couldn’t stop worrying that something would go wrong.
“And then, after I had my son, I would have these dreams where someone would come to the door and they would say, ‘Well, you know, we’re just going to wait 2 weeks to see if you get to keep your baby or not,’ ” Ms. Root Askew said. “And it really impacted my ability to bond with him.”
She likes California’s bill, AB 2193, because it goes beyond mandated screening. It would require health insurance companies to set up case management programs to help moms find a therapist, and connect obstetricians or pediatricians to a psychiatric specialist.
“Just like we have case-management programs for patients who have diabetes or sleep issues or back pain, a case-management program requires the insurance company to take some ownership of making sure their patients are getting the treatment they need to be healthy,” said Ms. Root Askew, who is now advocating for the bill on behalf of the group 2020 Mom.
Health insurance companies haven’t taken a position on the legislation. It’s unclear how much it would cost them to comply, because some already have infrastructure in place for case-management programs, and some do not. But there is consensus among insurers and health advocates that such programs save money in the long run.
“The sooner that you can get good treatment for a mom, the less expensive that condition will be to manage over the course of the woman’s life and over the course of that child’s life,” Ms. Root Askew said.
Some doctors still have their objections. Under the bill, they could be disciplined for not screening. Some have said they worry about how much time it would take.
The health care system, and the incentives, aren’t set up for this sort of screening, Dr. Sirott said.
“Currently, I get $6 for screening a patient,” she said. “By the time I put it on a piece of paper and print it, it’s not worth it.”
It’s not clear whether the direct and indirect costs of screening would be worth it to the patients, either. Four other states – Illinois, Massachusetts, New Jersey, and West Virginia – have tried mandated screening, and it did not result in more women getting treatment, according to a 2015 study published in Psychiatric Services.
Even with California’s extra requirement that insurance companies facilitate care, women could still face high copays or limits on the number of therapy sessions. Or, a new mother might be so overwhelmed with care for her newborn that it would be difficult to add anything to her busy schedule.
What does seem to work, according to the study of mandated screening in other states, is when nurses or mental health providers visit new moms at home.
“Despite abundant goodwill, there is no evidence that state policies are addressing this great need,” the study’s authors report.
Supporters of California’s proposed bill, however, say doctors need to start somewhere. Screening is the first step in recognizing the full scope of the problem, said Nirmaljit Dhami, MD, a Mountain View, Calif., psychiatrist. Women should be screened on an ongoing basis throughout pregnancy and for a year after birth, Dr. Dhami said, not just once or twice as the bill requires.
“I often tell doctors that if you don’t know that somebody is suicidal, it doesn’t mean that their suicidality will go away,” she said. “If you don’t ask, the risk is the same.”
This story is part of a partnership that includes KQED, NPR, and Kaiser Health News. KHN’s coverage of women’s health care issues is supported in part by The David and Lucile Packard Foundation. KHN is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
Lawmakers in California will begin debate next month on a bill that would require doctors to screen new moms for mental health problems – once while they’re pregnant and again after they give birth.
But many obstetricians and pediatricians bristle at the idea, saying they are afraid to screen new moms for depression and anxiety.
“What are you going to do with those people who screen positive?” asked Laura L. Sirott, MD, an ob.gyn. who practices in Pasadena. “Some providers have nowhere to send them.”
Nationally, depression affects up to one in seven women during or after pregnancy, according to the American Psychological Association.
And, of women who screen positive for the condition, 78% don’t get mental health treatment, according to a 2015 research review published in the journal Obstetrics & Gynecology.
Dr. Sirott said her patients give a range of reasons why they don’t take her up on a referral to a psychologist: “ ‘Oh, they don’t take my insurance.’ Or ‘my insurance pays for three visits.’ ‘I can’t take time off work to go to those visits.’ ‘It’s a 3-month wait to get in to that person.’ ”
She said it’s also hard to find a psychiatrist who is willing to treat them and who is trained in the complexities of prescribing medications to pregnant or breastfeeding women, especially in rural areas.
“So it’s very frustrating,” Dr. Sirott said, “to ask patients about a problem and then not have any way to solve that problem.”
Moms are frustrated, too. After the baby comes, no one asks about the baby’s mother anymore.
Wendy Root Askew struggled for years to get pregnant, and when she finally did, her anxiety got worse. She couldn’t stop worrying that something would go wrong.
“And then, after I had my son, I would have these dreams where someone would come to the door and they would say, ‘Well, you know, we’re just going to wait 2 weeks to see if you get to keep your baby or not,’ ” Ms. Root Askew said. “And it really impacted my ability to bond with him.”
She likes California’s bill, AB 2193, because it goes beyond mandated screening. It would require health insurance companies to set up case management programs to help moms find a therapist, and connect obstetricians or pediatricians to a psychiatric specialist.
“Just like we have case-management programs for patients who have diabetes or sleep issues or back pain, a case-management program requires the insurance company to take some ownership of making sure their patients are getting the treatment they need to be healthy,” said Ms. Root Askew, who is now advocating for the bill on behalf of the group 2020 Mom.
Health insurance companies haven’t taken a position on the legislation. It’s unclear how much it would cost them to comply, because some already have infrastructure in place for case-management programs, and some do not. But there is consensus among insurers and health advocates that such programs save money in the long run.
“The sooner that you can get good treatment for a mom, the less expensive that condition will be to manage over the course of the woman’s life and over the course of that child’s life,” Ms. Root Askew said.
Some doctors still have their objections. Under the bill, they could be disciplined for not screening. Some have said they worry about how much time it would take.
The health care system, and the incentives, aren’t set up for this sort of screening, Dr. Sirott said.
“Currently, I get $6 for screening a patient,” she said. “By the time I put it on a piece of paper and print it, it’s not worth it.”
It’s not clear whether the direct and indirect costs of screening would be worth it to the patients, either. Four other states – Illinois, Massachusetts, New Jersey, and West Virginia – have tried mandated screening, and it did not result in more women getting treatment, according to a 2015 study published in Psychiatric Services.
Even with California’s extra requirement that insurance companies facilitate care, women could still face high copays or limits on the number of therapy sessions. Or, a new mother might be so overwhelmed with care for her newborn that it would be difficult to add anything to her busy schedule.
What does seem to work, according to the study of mandated screening in other states, is when nurses or mental health providers visit new moms at home.
“Despite abundant goodwill, there is no evidence that state policies are addressing this great need,” the study’s authors report.
Supporters of California’s proposed bill, however, say doctors need to start somewhere. Screening is the first step in recognizing the full scope of the problem, said Nirmaljit Dhami, MD, a Mountain View, Calif., psychiatrist. Women should be screened on an ongoing basis throughout pregnancy and for a year after birth, Dr. Dhami said, not just once or twice as the bill requires.
“I often tell doctors that if you don’t know that somebody is suicidal, it doesn’t mean that their suicidality will go away,” she said. “If you don’t ask, the risk is the same.”
This story is part of a partnership that includes KQED, NPR, and Kaiser Health News. KHN’s coverage of women’s health care issues is supported in part by The David and Lucile Packard Foundation. KHN is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
Metabolic changes in T cells may limit CAR potential in kids
Researchers analyzed peripheral blood T cells from 157 pediatric cancer patients at diagnosis and after chemotherapy and found the potential to produce effective chimeric antigen receptor (CAR) T cells declined with each cycle of chemotherapy.
This was also true for acute lymphoblastic leukemia (ALL) and Wilms’ tumor, which had high CAR T-cell manufacturing potential in the pre-chemotherapy samples.
Children younger than 3 years particularly showed a significant decline in CAR T-cell potential with cumulative cycles of chemotherapy.
“Everybody knows that chemotherapy is really bad for your T cells, and the more chemo you get, the less likely you are to have healthy T cells,” David M. Barrett, MD, PhD, of Children’s Hospital of Philadelphia in Pennsylvania, said at a press preview of research to be presented at the AACR Annual Meeting 2018.
“We know a lot about what a highly active, highly successful CAR T cell looks like right before it goes back into the patient after it’s finished manufacturing,” Dr Barrett added.
But he and his colleagues wanted to determine what goes into producing high-quality cells from a patient and the difference between cells that were good starting material and cells that weren’t.
The investigators analyzed blood samples from pediatric patients with ALL, non-Hodgkin lymphoma, neuroblastoma, osteosarcoma, rhabdomyosarcoma, Wilms’ tumor, Hodgkin lymphoma, chronic myeloid leukemia, and Ewing sarcoma. The team collected samples at diagnosis and after every cycle of chemotherapy.
Using flow cytometry, they quantified the CD3+ cell population and expanded the T cells using CD3 and CD28 stimulatory beads, “the backbone of pretty much every center’s way to make CAR T cells in the lab,” Dr Barrett said.
And the researchers found poor CAR T-cell manufacturing potential in all tumor types at diagnosis except for ALL and Wilms’ tumor. In standard-risk and high-risk ALL, more than 90% of patients had high-quality T cells at diagnosis.
The team report the findings in abstract 1631, which is scheduled to be presented at the AACR Annual Meeting on April 15.
“This may have played into why pediatric ALL is one of the great successes with CAR T-cell therapy,” Dr Barrett explained. “We may have actually been working with uniquely well-suited, good starting material to build a CAR T cell.”
T cells from lymphoma patients—Burkitt lymphoma, diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, and Hodgkin lymphoma—were actually quite poor in their potential to become good CAR T cells, Dr Barrett noted.
“This may be reflected clinically in pediatrics at Children’s Hospital of Philadelphia,” he said. “We’ve only been able to successfully treat 3 children with lymphoma, as opposed to more than 200 children with leukemia.”
The only other type of tumor that seemed to have good CAR T potential was Wilms’ tumor.
“I don’t have a CAR T cell for Wilms’ tumor yet,” Dr Barrett said, “but, if I wanted to make one, I would at least have a degree of confidence that the cells gotten from a patient would at least be able to be successfully made into a highly functional T cell that can go back into a patient.”
The investigators also observed that cumulative chemotherapy alters the metabolic profile in T cells, “gradually turning them by cycle 6 into something that doesn’t work anymore,” Dr Barrett said.
The researchers then looked into what differences there were in the quality of collected T cells and found that metabolic changes varied with tumor and treatment.
T cells with poor CAR T-cell potential were biased toward using glycolysis as their energy source instead of using fatty acids.
“Normal, healthy donor T cells cluster together in terms of metabolic pathways that are active or inactive,” Dr Barrett explained.
“[P]atients who had leukemia and the Wilms’ tumor patients could make successful CAR T cells from those samples. On the other hand, solid tumors and a Hodgkin disease patient look like they have a very different metabolic profile. And that is associated with failure to make a good CAR T cell.”
The investigators were able to get the T cells to shift metabolic pathways by “essentially force-feeding T cells things like fatty acids so they don’t use as much glucose,” Dr Barrett said.
“We’ve had some success in force-feeding them essentially neutral amino acids and others like arginine. And so you can actually potentially provide a T cell with an attractive alternative fuel source.”
Dr Barrett noted that the findings have already altered practice for children at his institution.
They now collect T cells early even if the patient is not eligible for a CAR trial, “simply because we know that cumulative chemotherapy is going to progressively deteriorate the likelihood that those cells will make a functional CAR product, and we’ve been recommending that to other centers,” Dr Barrett said.
“We’re trying to understand what goes into making the best starting material so that we can alter our approaches to make sure that we make a highly functional CAR T-cell product not only for kids with leukemia and CART19, but also potentially for solid tumor CARs as we try to develop those in the future.”
Researchers analyzed peripheral blood T cells from 157 pediatric cancer patients at diagnosis and after chemotherapy and found the potential to produce effective chimeric antigen receptor (CAR) T cells declined with each cycle of chemotherapy.
This was also true for acute lymphoblastic leukemia (ALL) and Wilms’ tumor, which had high CAR T-cell manufacturing potential in the pre-chemotherapy samples.
Children younger than 3 years particularly showed a significant decline in CAR T-cell potential with cumulative cycles of chemotherapy.
“Everybody knows that chemotherapy is really bad for your T cells, and the more chemo you get, the less likely you are to have healthy T cells,” David M. Barrett, MD, PhD, of Children’s Hospital of Philadelphia in Pennsylvania, said at a press preview of research to be presented at the AACR Annual Meeting 2018.
“We know a lot about what a highly active, highly successful CAR T cell looks like right before it goes back into the patient after it’s finished manufacturing,” Dr Barrett added.
But he and his colleagues wanted to determine what goes into producing high-quality cells from a patient and the difference between cells that were good starting material and cells that weren’t.
The investigators analyzed blood samples from pediatric patients with ALL, non-Hodgkin lymphoma, neuroblastoma, osteosarcoma, rhabdomyosarcoma, Wilms’ tumor, Hodgkin lymphoma, chronic myeloid leukemia, and Ewing sarcoma. The team collected samples at diagnosis and after every cycle of chemotherapy.
Using flow cytometry, they quantified the CD3+ cell population and expanded the T cells using CD3 and CD28 stimulatory beads, “the backbone of pretty much every center’s way to make CAR T cells in the lab,” Dr Barrett said.
And the researchers found poor CAR T-cell manufacturing potential in all tumor types at diagnosis except for ALL and Wilms’ tumor. In standard-risk and high-risk ALL, more than 90% of patients had high-quality T cells at diagnosis.
The team report the findings in abstract 1631, which is scheduled to be presented at the AACR Annual Meeting on April 15.
“This may have played into why pediatric ALL is one of the great successes with CAR T-cell therapy,” Dr Barrett explained. “We may have actually been working with uniquely well-suited, good starting material to build a CAR T cell.”
T cells from lymphoma patients—Burkitt lymphoma, diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, and Hodgkin lymphoma—were actually quite poor in their potential to become good CAR T cells, Dr Barrett noted.
“This may be reflected clinically in pediatrics at Children’s Hospital of Philadelphia,” he said. “We’ve only been able to successfully treat 3 children with lymphoma, as opposed to more than 200 children with leukemia.”
The only other type of tumor that seemed to have good CAR T potential was Wilms’ tumor.
“I don’t have a CAR T cell for Wilms’ tumor yet,” Dr Barrett said, “but, if I wanted to make one, I would at least have a degree of confidence that the cells gotten from a patient would at least be able to be successfully made into a highly functional T cell that can go back into a patient.”
The investigators also observed that cumulative chemotherapy alters the metabolic profile in T cells, “gradually turning them by cycle 6 into something that doesn’t work anymore,” Dr Barrett said.
The researchers then looked into what differences there were in the quality of collected T cells and found that metabolic changes varied with tumor and treatment.
T cells with poor CAR T-cell potential were biased toward using glycolysis as their energy source instead of using fatty acids.
“Normal, healthy donor T cells cluster together in terms of metabolic pathways that are active or inactive,” Dr Barrett explained.
“[P]atients who had leukemia and the Wilms’ tumor patients could make successful CAR T cells from those samples. On the other hand, solid tumors and a Hodgkin disease patient look like they have a very different metabolic profile. And that is associated with failure to make a good CAR T cell.”
The investigators were able to get the T cells to shift metabolic pathways by “essentially force-feeding T cells things like fatty acids so they don’t use as much glucose,” Dr Barrett said.
“We’ve had some success in force-feeding them essentially neutral amino acids and others like arginine. And so you can actually potentially provide a T cell with an attractive alternative fuel source.”
Dr Barrett noted that the findings have already altered practice for children at his institution.
They now collect T cells early even if the patient is not eligible for a CAR trial, “simply because we know that cumulative chemotherapy is going to progressively deteriorate the likelihood that those cells will make a functional CAR product, and we’ve been recommending that to other centers,” Dr Barrett said.
“We’re trying to understand what goes into making the best starting material so that we can alter our approaches to make sure that we make a highly functional CAR T-cell product not only for kids with leukemia and CART19, but also potentially for solid tumor CARs as we try to develop those in the future.”
Researchers analyzed peripheral blood T cells from 157 pediatric cancer patients at diagnosis and after chemotherapy and found the potential to produce effective chimeric antigen receptor (CAR) T cells declined with each cycle of chemotherapy.
This was also true for acute lymphoblastic leukemia (ALL) and Wilms’ tumor, which had high CAR T-cell manufacturing potential in the pre-chemotherapy samples.
Children younger than 3 years particularly showed a significant decline in CAR T-cell potential with cumulative cycles of chemotherapy.
“Everybody knows that chemotherapy is really bad for your T cells, and the more chemo you get, the less likely you are to have healthy T cells,” David M. Barrett, MD, PhD, of Children’s Hospital of Philadelphia in Pennsylvania, said at a press preview of research to be presented at the AACR Annual Meeting 2018.
“We know a lot about what a highly active, highly successful CAR T cell looks like right before it goes back into the patient after it’s finished manufacturing,” Dr Barrett added.
But he and his colleagues wanted to determine what goes into producing high-quality cells from a patient and the difference between cells that were good starting material and cells that weren’t.
The investigators analyzed blood samples from pediatric patients with ALL, non-Hodgkin lymphoma, neuroblastoma, osteosarcoma, rhabdomyosarcoma, Wilms’ tumor, Hodgkin lymphoma, chronic myeloid leukemia, and Ewing sarcoma. The team collected samples at diagnosis and after every cycle of chemotherapy.
Using flow cytometry, they quantified the CD3+ cell population and expanded the T cells using CD3 and CD28 stimulatory beads, “the backbone of pretty much every center’s way to make CAR T cells in the lab,” Dr Barrett said.
And the researchers found poor CAR T-cell manufacturing potential in all tumor types at diagnosis except for ALL and Wilms’ tumor. In standard-risk and high-risk ALL, more than 90% of patients had high-quality T cells at diagnosis.
The team report the findings in abstract 1631, which is scheduled to be presented at the AACR Annual Meeting on April 15.
“This may have played into why pediatric ALL is one of the great successes with CAR T-cell therapy,” Dr Barrett explained. “We may have actually been working with uniquely well-suited, good starting material to build a CAR T cell.”
T cells from lymphoma patients—Burkitt lymphoma, diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, and Hodgkin lymphoma—were actually quite poor in their potential to become good CAR T cells, Dr Barrett noted.
“This may be reflected clinically in pediatrics at Children’s Hospital of Philadelphia,” he said. “We’ve only been able to successfully treat 3 children with lymphoma, as opposed to more than 200 children with leukemia.”
The only other type of tumor that seemed to have good CAR T potential was Wilms’ tumor.
“I don’t have a CAR T cell for Wilms’ tumor yet,” Dr Barrett said, “but, if I wanted to make one, I would at least have a degree of confidence that the cells gotten from a patient would at least be able to be successfully made into a highly functional T cell that can go back into a patient.”
The investigators also observed that cumulative chemotherapy alters the metabolic profile in T cells, “gradually turning them by cycle 6 into something that doesn’t work anymore,” Dr Barrett said.
The researchers then looked into what differences there were in the quality of collected T cells and found that metabolic changes varied with tumor and treatment.
T cells with poor CAR T-cell potential were biased toward using glycolysis as their energy source instead of using fatty acids.
“Normal, healthy donor T cells cluster together in terms of metabolic pathways that are active or inactive,” Dr Barrett explained.
“[P]atients who had leukemia and the Wilms’ tumor patients could make successful CAR T cells from those samples. On the other hand, solid tumors and a Hodgkin disease patient look like they have a very different metabolic profile. And that is associated with failure to make a good CAR T cell.”
The investigators were able to get the T cells to shift metabolic pathways by “essentially force-feeding T cells things like fatty acids so they don’t use as much glucose,” Dr Barrett said.
“We’ve had some success in force-feeding them essentially neutral amino acids and others like arginine. And so you can actually potentially provide a T cell with an attractive alternative fuel source.”
Dr Barrett noted that the findings have already altered practice for children at his institution.
They now collect T cells early even if the patient is not eligible for a CAR trial, “simply because we know that cumulative chemotherapy is going to progressively deteriorate the likelihood that those cells will make a functional CAR product, and we’ve been recommending that to other centers,” Dr Barrett said.
“We’re trying to understand what goes into making the best starting material so that we can alter our approaches to make sure that we make a highly functional CAR T-cell product not only for kids with leukemia and CART19, but also potentially for solid tumor CARs as we try to develop those in the future.”
Tanning addiction associated with multiple behavioral comorbidities
said Kimberly A. Miller, PhD, of the University of Southern California, Los Angeles, and her associates.
Of a multiethnic sample of 2,637 high school students aged 16-17 years from Los Angeles, 7% met the modified CAGE criteria for tanning addiction, a compulsive drive to use indoor tanning beds frequently. The rate was similar in Hispanic teens and non-Hispanic white adolescents (7.6% versus 7.9%, respectively). Asian and Asian American teens had the lowest prevalence of tanning addiction (4.3%), while Native Hawaiian/Pacific Islanders had the highest (10.5%). Slightly more females than males met the criteria (9% vs. 5%), Dr. Miller and her associates reported in the Journal of Investigative Dermatology.
Past 30-day tobacco and marijuana use was significantly associated with tanning addiction, and teens with problem drinking were 3.4 times as likely to meet tanning addiction criteria as were those without problem drinking. Adolescents with panic disorder symptoms were two times more likely to meet tanning addiction criteria than were those without symptoms, and those with obsessive-compulsive disorder symptoms were three times more likely, Dr. Miller and associates said.
“ for each additional psychological symptom, this figure was 30%,” the researchers said.
Dr. Miller and her associates cited several limitations. One was the cross-sectional design of the study. Another was the study’s focus on adolescents from Los Angeles, which limits the generalizability of the findings.
The authors declared no conflicts of interest.
SOURCE: Miller KA et al. J Investig Dermatol. 2018. doi: 10.1016/j.jid.2018.02.018.
said Kimberly A. Miller, PhD, of the University of Southern California, Los Angeles, and her associates.
Of a multiethnic sample of 2,637 high school students aged 16-17 years from Los Angeles, 7% met the modified CAGE criteria for tanning addiction, a compulsive drive to use indoor tanning beds frequently. The rate was similar in Hispanic teens and non-Hispanic white adolescents (7.6% versus 7.9%, respectively). Asian and Asian American teens had the lowest prevalence of tanning addiction (4.3%), while Native Hawaiian/Pacific Islanders had the highest (10.5%). Slightly more females than males met the criteria (9% vs. 5%), Dr. Miller and her associates reported in the Journal of Investigative Dermatology.
Past 30-day tobacco and marijuana use was significantly associated with tanning addiction, and teens with problem drinking were 3.4 times as likely to meet tanning addiction criteria as were those without problem drinking. Adolescents with panic disorder symptoms were two times more likely to meet tanning addiction criteria than were those without symptoms, and those with obsessive-compulsive disorder symptoms were three times more likely, Dr. Miller and associates said.
“ for each additional psychological symptom, this figure was 30%,” the researchers said.
Dr. Miller and her associates cited several limitations. One was the cross-sectional design of the study. Another was the study’s focus on adolescents from Los Angeles, which limits the generalizability of the findings.
The authors declared no conflicts of interest.
SOURCE: Miller KA et al. J Investig Dermatol. 2018. doi: 10.1016/j.jid.2018.02.018.
said Kimberly A. Miller, PhD, of the University of Southern California, Los Angeles, and her associates.
Of a multiethnic sample of 2,637 high school students aged 16-17 years from Los Angeles, 7% met the modified CAGE criteria for tanning addiction, a compulsive drive to use indoor tanning beds frequently. The rate was similar in Hispanic teens and non-Hispanic white adolescents (7.6% versus 7.9%, respectively). Asian and Asian American teens had the lowest prevalence of tanning addiction (4.3%), while Native Hawaiian/Pacific Islanders had the highest (10.5%). Slightly more females than males met the criteria (9% vs. 5%), Dr. Miller and her associates reported in the Journal of Investigative Dermatology.
Past 30-day tobacco and marijuana use was significantly associated with tanning addiction, and teens with problem drinking were 3.4 times as likely to meet tanning addiction criteria as were those without problem drinking. Adolescents with panic disorder symptoms were two times more likely to meet tanning addiction criteria than were those without symptoms, and those with obsessive-compulsive disorder symptoms were three times more likely, Dr. Miller and associates said.
“ for each additional psychological symptom, this figure was 30%,” the researchers said.
Dr. Miller and her associates cited several limitations. One was the cross-sectional design of the study. Another was the study’s focus on adolescents from Los Angeles, which limits the generalizability of the findings.
The authors declared no conflicts of interest.
SOURCE: Miller KA et al. J Investig Dermatol. 2018. doi: 10.1016/j.jid.2018.02.018.
FROM THE JOURNAL OF INVESTIGATIVE DERMATOLOGY