BOSTON – Carla E. Small, MBA, senior director of innovation at Boston Children’s Hospital, addressed digital health care in a video interview at the AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology. It is really just providing health care to patients in a digital world, she said, adding that she prefers the term “tech-enabled health care.” One up-and-coming example of this is the use of Alexa-type voice devices to do work and solve small clinical problems. Her program did a nationwide survey of pediatricians and found that half were interested in using voice technology. Artificial intelligence is another area of technology that Boston Children’s is using – in particular, they have created algorithms that help pediatricians analyze brain scans of young children, because so few pediatricians are trained in this area. The innovation program also has taken the digital world to pediatric patients in a program called Health Voyager in which children can take a virtual journey through their own diseased intestinal system.

lmcglade@mdedge.com

BOSTON – Carla E. Small, MBA, senior director of innovation at Boston Children’s Hospital, addressed digital health care in a video interview at the AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology. It is really just providing health care to patients in a digital world, she said, adding that she prefers the term “tech-enabled health care.” One up-and-coming example of this is the use of Alexa-type voice devices to do work and solve small clinical problems. Her program did a nationwide survey of pediatricians and found that half were interested in using voice technology. Artificial intelligence is another area of technology that Boston Children’s is using – in particular, they have created algorithms that help pediatricians analyze brain scans of young children, because so few pediatricians are trained in this area. The innovation program also has taken the digital world to pediatric patients in a program called Health Voyager in which children can take a virtual journey through their own diseased intestinal system.

lmcglade@mdedge.com

BOSTON – Carla E. Small, MBA, senior director of innovation at Boston Children’s Hospital, addressed digital health care in a video interview at the AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology. It is really just providing health care to patients in a digital world, she said, adding that she prefers the term “tech-enabled health care.” One up-and-coming example of this is the use of Alexa-type voice devices to do work and solve small clinical problems. Her program did a nationwide survey of pediatricians and found that half were interested in using voice technology. Artificial intelligence is another area of technology that Boston Children’s is using – in particular, they have created algorithms that help pediatricians analyze brain scans of young children, because so few pediatricians are trained in this area. The innovation program also has taken the digital world to pediatric patients in a program called Health Voyager in which children can take a virtual journey through their own diseased intestinal system.

lmcglade@mdedge.com

California signed up an estimated 450,000 people under Medicaid expansion who may not have been eligible for coverage, according to a report by the Health & Human Services’ chief watchdog.

In a Feb. 21 report, the HHS’s inspector general estimated that California spent $738.2 million on 366,078 expansion beneficiaries who were ineligible. It spent an additional $416.5 million for 79,055 expansion enrollees who were “potentially” ineligible, auditors found.

Auditors said nearly 90% of the $1.15 billion in questionable payments involved federal money, while the rest came from the state’s Medicaid program, known as Medi-Cal. They examined a 6-month period from Oct. 1, 2014, to March 31, 2015, when Medicaid payments of $6.2 billion were made related to 1.9 million newly eligible enrollees.

There were limitations to the California review, however. The audit extrapolated from a sample of 150 beneficiaries. The authors reported a 90% confidence level in their results – whereas 95% would be more common. That meant that the number of those ineligible could have been as low as 260,000 or as high as 630,000.

“If HHS has a strong reason to believe that California is systematically making enrollment errors, it would be helpful to show that in a more robust analysis,” said Ben Ippolito, a health care economist at the American Enterprise Institute, a conservative think tank. “The federal government should ensure that states are being good stewards of federal money.”

Nonetheless, the audit highlighted weaknesses in California’s Medicaid program, the largest in the nation with 13.4 million enrollees and an annual budget topping $100 billion, counting federal and state money. Medicaid covers one in three Californians.

The inspector general found deficiencies in the state’s computer system for verifying eligibility and discovered errors by caseworkers. The Medicaid payments cited in the report covered people in the state’s fee-for-service system, managed-care plans, drug treatment programs, and those receiving mental health services.

California’s Department of Health Care Services, which runs Medi-Cal, said in a statement that it agreed with nearly all of the auditors’ recommendations and that the agency “has taken steps to address all of the findings.”

In a written response to the inspector general, California officials said several computer upgrades were made after the audit period and before publication of the report that should improve the accuracy of eligibility decisions.

Among the 150 expansion enrollees analyzed in detail, 75%, or 112, were deemed eligible for the Medicaid program in California. Auditors discovered a variety of problems with the other 38 enrollees.

During the audit period, 12 enrollees in the sample group had incomes above 138% of the federal poverty level, making them ineligible financially for public assistance, according to the report.

In other instances, beneficiaries were already enrolled in Medicare, the federal health insurance for people 65 and older or who have severe disabilities, and did not qualify for Medi-Cal. One woman indicated she didn’t want Medi-Cal but was enrolled anyway.

In 2014, the state struggled to clear a massive backlog of Medi-Cal applications, which reached about 900,000 at one point. Many people complained about being mistakenly rejected for coverage or that their applications were lost in the state or county computer systems.

California was one of 31 states to expand Medicaid under the 2010 Affordable Care Act. The health law established a higher federal reimbursement for these newly eligible patients, primarily low-income adults without children. After expansion started in 2014, the HHS inspector general’s office began reviewing whether states were determining eligibility correctly and spending taxpayer dollars appropriately.

In a similar audit released in January, the inspector general estimated that New York spent $26.2 million in federal Medicaid money on 47,271 expansion enrollees who were ineligible for coverage. (The sample size there was 130 enrollees.) Overall, New York had far fewer expansion enrollees and related spending, compared with California.

Audits of other states’ records are planned

“It is inevitable that in a big rollout of new eligibility for any public program there are going to be glitches in implementation,” said Kathy Hempstead, a health-policy expert and senior adviser at the Robert Wood Johnson Foundation. “The inspector general wants to make sure that states are being sufficiently careful.”

Nationwide, Medicaid, the state-federal health insurance program designed for the poor, is the country’s largest health insurance program, covering 74 million Americans. In the past year, Republican efforts to reduce Medicaid funding and enrollment have sparked intense political debates and loud protests over the size and scope of the public program.

The federal government footed the entire cost of Medicaid expansion during the first three years, instead of taking the usual approach of splitting the costs with states. Now, states are picking up more of the bill. Their share of the costs will grow to 10 percent by 2020.

The California audit didn’t request a specific repayment from the state, but the findings were sent to the Centers for Medicare & Medicaid Services for review. CMS officials didn’t return a request for comment.

Donald White, a spokesman for the inspector general’s office, said the agency stood by the report’s findings and declined to comment further.

This story was produced by Kaiser Health News, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. Kaiser Health News 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.

California signed up an estimated 450,000 people under Medicaid expansion who may not have been eligible for coverage, according to a report by the Health & Human Services’ chief watchdog.

In a Feb. 21 report, the HHS’s inspector general estimated that California spent $738.2 million on 366,078 expansion beneficiaries who were ineligible. It spent an additional $416.5 million for 79,055 expansion enrollees who were “potentially” ineligible, auditors found.

Auditors said nearly 90% of the $1.15 billion in questionable payments involved federal money, while the rest came from the state’s Medicaid program, known as Medi-Cal. They examined a 6-month period from Oct. 1, 2014, to March 31, 2015, when Medicaid payments of $6.2 billion were made related to 1.9 million newly eligible enrollees.

There were limitations to the California review, however. The audit extrapolated from a sample of 150 beneficiaries. The authors reported a 90% confidence level in their results – whereas 95% would be more common. That meant that the number of those ineligible could have been as low as 260,000 or as high as 630,000.

“If HHS has a strong reason to believe that California is systematically making enrollment errors, it would be helpful to show that in a more robust analysis,” said Ben Ippolito, a health care economist at the American Enterprise Institute, a conservative think tank. “The federal government should ensure that states are being good stewards of federal money.”

Nonetheless, the audit highlighted weaknesses in California’s Medicaid program, the largest in the nation with 13.4 million enrollees and an annual budget topping $100 billion, counting federal and state money. Medicaid covers one in three Californians.

The inspector general found deficiencies in the state’s computer system for verifying eligibility and discovered errors by caseworkers. The Medicaid payments cited in the report covered people in the state’s fee-for-service system, managed-care plans, drug treatment programs, and those receiving mental health services.

California’s Department of Health Care Services, which runs Medi-Cal, said in a statement that it agreed with nearly all of the auditors’ recommendations and that the agency “has taken steps to address all of the findings.”

In a written response to the inspector general, California officials said several computer upgrades were made after the audit period and before publication of the report that should improve the accuracy of eligibility decisions.

Among the 150 expansion enrollees analyzed in detail, 75%, or 112, were deemed eligible for the Medicaid program in California. Auditors discovered a variety of problems with the other 38 enrollees.

During the audit period, 12 enrollees in the sample group had incomes above 138% of the federal poverty level, making them ineligible financially for public assistance, according to the report.

In other instances, beneficiaries were already enrolled in Medicare, the federal health insurance for people 65 and older or who have severe disabilities, and did not qualify for Medi-Cal. One woman indicated she didn’t want Medi-Cal but was enrolled anyway.

In 2014, the state struggled to clear a massive backlog of Medi-Cal applications, which reached about 900,000 at one point. Many people complained about being mistakenly rejected for coverage or that their applications were lost in the state or county computer systems.

California was one of 31 states to expand Medicaid under the 2010 Affordable Care Act. The health law established a higher federal reimbursement for these newly eligible patients, primarily low-income adults without children. After expansion started in 2014, the HHS inspector general’s office began reviewing whether states were determining eligibility correctly and spending taxpayer dollars appropriately.

In a similar audit released in January, the inspector general estimated that New York spent $26.2 million in federal Medicaid money on 47,271 expansion enrollees who were ineligible for coverage. (The sample size there was 130 enrollees.) Overall, New York had far fewer expansion enrollees and related spending, compared with California.

Audits of other states’ records are planned

“It is inevitable that in a big rollout of new eligibility for any public program there are going to be glitches in implementation,” said Kathy Hempstead, a health-policy expert and senior adviser at the Robert Wood Johnson Foundation. “The inspector general wants to make sure that states are being sufficiently careful.”

Nationwide, Medicaid, the state-federal health insurance program designed for the poor, is the country’s largest health insurance program, covering 74 million Americans. In the past year, Republican efforts to reduce Medicaid funding and enrollment have sparked intense political debates and loud protests over the size and scope of the public program.

The federal government footed the entire cost of Medicaid expansion during the first three years, instead of taking the usual approach of splitting the costs with states. Now, states are picking up more of the bill. Their share of the costs will grow to 10 percent by 2020.

The California audit didn’t request a specific repayment from the state, but the findings were sent to the Centers for Medicare & Medicaid Services for review. CMS officials didn’t return a request for comment.

Donald White, a spokesman for the inspector general’s office, said the agency stood by the report’s findings and declined to comment further.

This story was produced by Kaiser Health News, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. Kaiser Health News 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.

California signed up an estimated 450,000 people under Medicaid expansion who may not have been eligible for coverage, according to a report by the Health & Human Services’ chief watchdog.

In a Feb. 21 report, the HHS’s inspector general estimated that California spent $738.2 million on 366,078 expansion beneficiaries who were ineligible. It spent an additional $416.5 million for 79,055 expansion enrollees who were “potentially” ineligible, auditors found.

Auditors said nearly 90% of the $1.15 billion in questionable payments involved federal money, while the rest came from the state’s Medicaid program, known as Medi-Cal. They examined a 6-month period from Oct. 1, 2014, to March 31, 2015, when Medicaid payments of $6.2 billion were made related to 1.9 million newly eligible enrollees.

There were limitations to the California review, however. The audit extrapolated from a sample of 150 beneficiaries. The authors reported a 90% confidence level in their results – whereas 95% would be more common. That meant that the number of those ineligible could have been as low as 260,000 or as high as 630,000.

“If HHS has a strong reason to believe that California is systematically making enrollment errors, it would be helpful to show that in a more robust analysis,” said Ben Ippolito, a health care economist at the American Enterprise Institute, a conservative think tank. “The federal government should ensure that states are being good stewards of federal money.”

Nonetheless, the audit highlighted weaknesses in California’s Medicaid program, the largest in the nation with 13.4 million enrollees and an annual budget topping $100 billion, counting federal and state money. Medicaid covers one in three Californians.

The inspector general found deficiencies in the state’s computer system for verifying eligibility and discovered errors by caseworkers. The Medicaid payments cited in the report covered people in the state’s fee-for-service system, managed-care plans, drug treatment programs, and those receiving mental health services.

California’s Department of Health Care Services, which runs Medi-Cal, said in a statement that it agreed with nearly all of the auditors’ recommendations and that the agency “has taken steps to address all of the findings.”

In a written response to the inspector general, California officials said several computer upgrades were made after the audit period and before publication of the report that should improve the accuracy of eligibility decisions.

Among the 150 expansion enrollees analyzed in detail, 75%, or 112, were deemed eligible for the Medicaid program in California. Auditors discovered a variety of problems with the other 38 enrollees.

During the audit period, 12 enrollees in the sample group had incomes above 138% of the federal poverty level, making them ineligible financially for public assistance, according to the report.

In other instances, beneficiaries were already enrolled in Medicare, the federal health insurance for people 65 and older or who have severe disabilities, and did not qualify for Medi-Cal. One woman indicated she didn’t want Medi-Cal but was enrolled anyway.

In 2014, the state struggled to clear a massive backlog of Medi-Cal applications, which reached about 900,000 at one point. Many people complained about being mistakenly rejected for coverage or that their applications were lost in the state or county computer systems.

California was one of 31 states to expand Medicaid under the 2010 Affordable Care Act. The health law established a higher federal reimbursement for these newly eligible patients, primarily low-income adults without children. After expansion started in 2014, the HHS inspector general’s office began reviewing whether states were determining eligibility correctly and spending taxpayer dollars appropriately.

In a similar audit released in January, the inspector general estimated that New York spent $26.2 million in federal Medicaid money on 47,271 expansion enrollees who were ineligible for coverage. (The sample size there was 130 enrollees.) Overall, New York had far fewer expansion enrollees and related spending, compared with California.

Audits of other states’ records are planned

“It is inevitable that in a big rollout of new eligibility for any public program there are going to be glitches in implementation,” said Kathy Hempstead, a health-policy expert and senior adviser at the Robert Wood Johnson Foundation. “The inspector general wants to make sure that states are being sufficiently careful.”

Nationwide, Medicaid, the state-federal health insurance program designed for the poor, is the country’s largest health insurance program, covering 74 million Americans. In the past year, Republican efforts to reduce Medicaid funding and enrollment have sparked intense political debates and loud protests over the size and scope of the public program.

The federal government footed the entire cost of Medicaid expansion during the first three years, instead of taking the usual approach of splitting the costs with states. Now, states are picking up more of the bill. Their share of the costs will grow to 10 percent by 2020.

The California audit didn’t request a specific repayment from the state, but the findings were sent to the Centers for Medicare & Medicaid Services for review. CMS officials didn’t return a request for comment.

Donald White, a spokesman for the inspector general’s office, said the agency stood by the report’s findings and declined to comment further.

This story was produced by Kaiser Health News, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. Kaiser Health News 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.

BOSTON – The AGA Center for GI Innovation and Technology (CGIT) was founded 9 years ago to foster innovation in GI disease, according to Sri Komanduri, MD, AGAF, and V. Raman Muthusamy, MD, the current cochairs. The mandate is still the same, with the idea that CGIT will continue to provide support and resources to a wide variety of stakeholders throughout the daunting process of getting a new technology or product through funding and approval to reimbursement and adoption. Dr. Komanduri, the medical director of the GI laboratory and director of interventional endoscopy at Northwestern University in Chicago, emphasized the need to support the entire process from idea to adoption as a continuum that should not be handled by different silos – CGIT should be there every step of the way.

CGIT will concentrate on six main areas now, although Dr. Muthusamy, director of interventional endoscopy and general GI endoscopy at the University of California, Los Angeles, said in a video interview that they are flexible enough to work with any GI-applicable technology that will help practicing clinicians. These six areas are endoscopy for bariatric treatments, endoscopy for resection in place of surgery, endoscope reprocessing, interventional endoscopy, endoscopic reflux technology, and endoscopic diagnostic colorectal advances.

lmcglade@mdedge.com

BOSTON – The AGA Center for GI Innovation and Technology (CGIT) was founded 9 years ago to foster innovation in GI disease, according to Sri Komanduri, MD, AGAF, and V. Raman Muthusamy, MD, the current cochairs. The mandate is still the same, with the idea that CGIT will continue to provide support and resources to a wide variety of stakeholders throughout the daunting process of getting a new technology or product through funding and approval to reimbursement and adoption. Dr. Komanduri, the medical director of the GI laboratory and director of interventional endoscopy at Northwestern University in Chicago, emphasized the need to support the entire process from idea to adoption as a continuum that should not be handled by different silos – CGIT should be there every step of the way.

CGIT will concentrate on six main areas now, although Dr. Muthusamy, director of interventional endoscopy and general GI endoscopy at the University of California, Los Angeles, said in a video interview that they are flexible enough to work with any GI-applicable technology that will help practicing clinicians. These six areas are endoscopy for bariatric treatments, endoscopy for resection in place of surgery, endoscope reprocessing, interventional endoscopy, endoscopic reflux technology, and endoscopic diagnostic colorectal advances.

lmcglade@mdedge.com

BOSTON – The AGA Center for GI Innovation and Technology (CGIT) was founded 9 years ago to foster innovation in GI disease, according to Sri Komanduri, MD, AGAF, and V. Raman Muthusamy, MD, the current cochairs. The mandate is still the same, with the idea that CGIT will continue to provide support and resources to a wide variety of stakeholders throughout the daunting process of getting a new technology or product through funding and approval to reimbursement and adoption. Dr. Komanduri, the medical director of the GI laboratory and director of interventional endoscopy at Northwestern University in Chicago, emphasized the need to support the entire process from idea to adoption as a continuum that should not be handled by different silos – CGIT should be there every step of the way.

CGIT will concentrate on six main areas now, although Dr. Muthusamy, director of interventional endoscopy and general GI endoscopy at the University of California, Los Angeles, said in a video interview that they are flexible enough to work with any GI-applicable technology that will help practicing clinicians. These six areas are endoscopy for bariatric treatments, endoscopy for resection in place of surgery, endoscope reprocessing, interventional endoscopy, endoscopic reflux technology, and endoscopic diagnostic colorectal advances.

lmcglade@mdedge.com

BOSTON – “When I assess a new technology,” said V. Raman Muthusamy, MD, chair of the AGA Center for GI Innovation and Technology (CGIT), “I look for three things” – it should allow us to do something we couldn’t do before, give better outcomes and/or do the procedure less invasively, or provide cost savings. Ideally, he said during an interview at the AGA Tech Summit, it should do all three. Dr. Muthusamy, director of interventional endoscopy and general GI endoscopy at the University of California, Los Angeles, said one of the goals of the CGIT is to keep physicians up to date on new technologies, but he recommends all physicians assess the data on new technologies and weigh the advantages before incorporating a new device into their practice. Better diagnostic tools and novel therapeutics should improve the patient experience.

lmcglade@mdedge.com

BOSTON – “When I assess a new technology,” said V. Raman Muthusamy, MD, chair of the AGA Center for GI Innovation and Technology (CGIT), “I look for three things” – it should allow us to do something we couldn’t do before, give better outcomes and/or do the procedure less invasively, or provide cost savings. Ideally, he said during an interview at the AGA Tech Summit, it should do all three. Dr. Muthusamy, director of interventional endoscopy and general GI endoscopy at the University of California, Los Angeles, said one of the goals of the CGIT is to keep physicians up to date on new technologies, but he recommends all physicians assess the data on new technologies and weigh the advantages before incorporating a new device into their practice. Better diagnostic tools and novel therapeutics should improve the patient experience.

lmcglade@mdedge.com

BOSTON – “When I assess a new technology,” said V. Raman Muthusamy, MD, chair of the AGA Center for GI Innovation and Technology (CGIT), “I look for three things” – it should allow us to do something we couldn’t do before, give better outcomes and/or do the procedure less invasively, or provide cost savings. Ideally, he said during an interview at the AGA Tech Summit, it should do all three. Dr. Muthusamy, director of interventional endoscopy and general GI endoscopy at the University of California, Los Angeles, said one of the goals of the CGIT is to keep physicians up to date on new technologies, but he recommends all physicians assess the data on new technologies and weigh the advantages before incorporating a new device into their practice. Better diagnostic tools and novel therapeutics should improve the patient experience.

lmcglade@mdedge.com

Children who are particularly irritable, depressive, and anxious might be at greater risk of suicidality in adolescence, according to a population-based cohort study.

Researchers enrolled 1,430 participants from the Québec Longitudinal Study of Child Development, aged 6-12 years, and performed yearly or biyearly assessments over a follow-up of 5 months to 17 years, according to a study published online March 28 in JAMA Psychiatry (doi: 10.1001/jamapsychiatry.2018.0174).

They found that girls who rated highly for irritability and for the depressive/anxious mood profile on the Behavior Questionnaire, a measure created for Canada’s National Longitudinal Study of Children and Youth, had a threefold higher risk of suicidality (odds ratio, 3.07; 95% confidence interval, 1.54-6.12). Meanwhile, boys had a twofold higher risk (OR, 2.13; 95% CI, 0.95-4.78), compared with children with low irritability and depressive/anxious mood.

“Exploratory analyses by sex indicated that this association was more important for girls than boys, as indicated by the need to prevent the exposure among 5 girls to avoid 1 case of suicidality,” wrote Massimiliano Orri, PhD, and his associates.

The rates of suicidality in children with high irritability and high depressive/anxious mood were 16.4%, compared with 11% in the group with the lowest symptom levels.

Even in children with only moderate irritability and low depressive/anxious mood, a significant increase was found in the odds of showing suicidality, compared with the reference group (OR, 1.51; 95% CI, 1.02-2.25).

“Although previous studies reported associations between irritability during childhood and adolescence and later depression, anxiety, and suicidality, we found that even moderate levels of irritability may contribute to suicidal risk,” wrote Dr. Orri of Bordeaux Population Health Research Centre, at the Institut National de la Santé et de la Recherche Medicale in France. “Such results indicate that children presenting with only irritability symptoms may benefit from an assessment for suicidal behaviors.”

cpnews@mdedge.com

SOURCE: Orri M et al. JAMA Psychiatry. 2018 Mar 28. doi: 10.1001/jamapsychiatry.2018.0174.

Children who are particularly irritable, depressive, and anxious might be at greater risk of suicidality in adolescence, according to a population-based cohort study.

Researchers enrolled 1,430 participants from the Québec Longitudinal Study of Child Development, aged 6-12 years, and performed yearly or biyearly assessments over a follow-up of 5 months to 17 years, according to a study published online March 28 in JAMA Psychiatry (doi: 10.1001/jamapsychiatry.2018.0174).

They found that girls who rated highly for irritability and for the depressive/anxious mood profile on the Behavior Questionnaire, a measure created for Canada’s National Longitudinal Study of Children and Youth, had a threefold higher risk of suicidality (odds ratio, 3.07; 95% confidence interval, 1.54-6.12). Meanwhile, boys had a twofold higher risk (OR, 2.13; 95% CI, 0.95-4.78), compared with children with low irritability and depressive/anxious mood.

“Exploratory analyses by sex indicated that this association was more important for girls than boys, as indicated by the need to prevent the exposure among 5 girls to avoid 1 case of suicidality,” wrote Massimiliano Orri, PhD, and his associates.

The rates of suicidality in children with high irritability and high depressive/anxious mood were 16.4%, compared with 11% in the group with the lowest symptom levels.

Even in children with only moderate irritability and low depressive/anxious mood, a significant increase was found in the odds of showing suicidality, compared with the reference group (OR, 1.51; 95% CI, 1.02-2.25).

“Although previous studies reported associations between irritability during childhood and adolescence and later depression, anxiety, and suicidality, we found that even moderate levels of irritability may contribute to suicidal risk,” wrote Dr. Orri of Bordeaux Population Health Research Centre, at the Institut National de la Santé et de la Recherche Medicale in France. “Such results indicate that children presenting with only irritability symptoms may benefit from an assessment for suicidal behaviors.”

cpnews@mdedge.com

SOURCE: Orri M et al. JAMA Psychiatry. 2018 Mar 28. doi: 10.1001/jamapsychiatry.2018.0174.

Children who are particularly irritable, depressive, and anxious might be at greater risk of suicidality in adolescence, according to a population-based cohort study.

Researchers enrolled 1,430 participants from the Québec Longitudinal Study of Child Development, aged 6-12 years, and performed yearly or biyearly assessments over a follow-up of 5 months to 17 years, according to a study published online March 28 in JAMA Psychiatry (doi: 10.1001/jamapsychiatry.2018.0174).

They found that girls who rated highly for irritability and for the depressive/anxious mood profile on the Behavior Questionnaire, a measure created for Canada’s National Longitudinal Study of Children and Youth, had a threefold higher risk of suicidality (odds ratio, 3.07; 95% confidence interval, 1.54-6.12). Meanwhile, boys had a twofold higher risk (OR, 2.13; 95% CI, 0.95-4.78), compared with children with low irritability and depressive/anxious mood.

“Exploratory analyses by sex indicated that this association was more important for girls than boys, as indicated by the need to prevent the exposure among 5 girls to avoid 1 case of suicidality,” wrote Massimiliano Orri, PhD, and his associates.

The rates of suicidality in children with high irritability and high depressive/anxious mood were 16.4%, compared with 11% in the group with the lowest symptom levels.

Even in children with only moderate irritability and low depressive/anxious mood, a significant increase was found in the odds of showing suicidality, compared with the reference group (OR, 1.51; 95% CI, 1.02-2.25).

“Although previous studies reported associations between irritability during childhood and adolescence and later depression, anxiety, and suicidality, we found that even moderate levels of irritability may contribute to suicidal risk,” wrote Dr. Orri of Bordeaux Population Health Research Centre, at the Institut National de la Santé et de la Recherche Medicale in France. “Such results indicate that children presenting with only irritability symptoms may benefit from an assessment for suicidal behaviors.”

cpnews@mdedge.com

SOURCE: Orri M et al. JAMA Psychiatry. 2018 Mar 28. doi: 10.1001/jamapsychiatry.2018.0174.

The Carl R. Darnall Army Medical Center at Fort Hood, Texas, is named in honor of Brigadier General Carl Rogers Darnall, a Texas native and career Army physician whose active-duty service spanned 35 years. Darnall, the oldest of 7 siblings, could not have imagined the enormity of the contributions that he would make and the lives that would be saved as he pursued a career in medicine.

Born on the family farm north of Dallas on Christmas Day in 1867, Darnall attended college in nearby Bonham and graduated from Transylvania University in Kentucky. He attended Jefferson Medical College in Philadelphia, Pennsylvania, graduating in 1890. Darnall spent several years in private practice before he joined the Army Medical Corps in 1896. He completed the Army Medical School in 1897. Opened in 1893, the Army Medical School was a 4-to-6-month course for civilian physicians entering active duty. The courses introduced physicians to the duties of medical officers as well as military surgery, medicine, and hygiene. It is considered by many to be the first school of public health in the U.S.

Darnall’s first assignments in Texas were followed by deployment to Cuba during the Spanish American War and then the Philippines, where he served as an operating surgeon and pathologist aboard the hospital ship, USS Relief. Darnall later accompanied an international expeditionary force to China in response to the Boxer Rebellion. In 1902, Darnall received an assignment to the Army Medical School in Washington, DC, that would change his life and the lives of millions around the world. Detailed as instructor for sanitary chemistry and operative surgery, he also served as secretary of the faculty. Just as Major Walter Reed and others before him, Darnall used his position at the Army Medical School to pursue important clinical research.

The complete story of the purification of drinking water is beyond the scope of this short biography. In brief, as early as 1894 the addition of chlorine to water was shown to render it “germ free.” In the 1890s, there were at least 2 attempts at water purification on a large scale with chlorine in European cities. One of the first uses of chlorine in the U.S. occurred in 1908 in Jersey City, New Jersey. At the Army Medical School, Darnall discovered the value of using compressed liquefied chlorine gas to purify water. He invented a mechanical liquid chlorine purifier in 1910 that became known as a chlorinator. In November 1911, Major Darnall authored a 15-page article concerning water purification.¹ Darnall also devised and patented a water filter, which the U.S. Army used for many years.

The principles of his chlorinator and use of anhydrous liquid chlorine were later applied to municipal water supplies throughout the world. The positive benefit of clean drinking water to improving public health is beyond measure. It has been said that more lives have been saved and more sickness prevented by Darnall’s contribution to sanitary water than by any other single achievement in medicine.

During World War I, Darnall was promoted to colonel and assigned to the Finance and Supply Division in the Office of the Surgeon General. After the war, he served as department surgeon in Hawaii. In 1925, he returned to the Office of the Surgeon General as executive officer. In November 1929, he was promoted to brigadier general and became the commanding general of the Army Medical Center and Walter Reed General Hospital, a position he held for 2 years until his retirement in 1931.Darnall died on January 18, 1941, at Walter Reed General Hospital just 6 days after his wife of 48 years had died at their home in Washington, DC. He is buried in Section 3 at Arlington National Cemetery. His 3 sons, Joseph Rogers, William Major, and Carl Robert, all served in some capacity in the Army.

Darnall Army Community Hospital opened in 1965, replacing the World War II-era hospital at Fort Hood. In 1984 a 5-year reconstruction project with additional floor space was completed. On May 1, 2006, the hospital was officially renamed the Carl R. Darnall Army Medical Center.

About this column
This column provides biographical sketches of the namesakes of military and VA health care facilities. To learn more about the individual your facility was named for or to offer a topic suggestion, contact us at fedprac@frontlinemedcom.com or on Facebook.

The Carl R. Darnall Army Medical Center at Fort Hood, Texas, is named in honor of Brigadier General Carl Rogers Darnall, a Texas native and career Army physician whose active-duty service spanned 35 years. Darnall, the oldest of 7 siblings, could not have imagined the enormity of the contributions that he would make and the lives that would be saved as he pursued a career in medicine.

Born on the family farm north of Dallas on Christmas Day in 1867, Darnall attended college in nearby Bonham and graduated from Transylvania University in Kentucky. He attended Jefferson Medical College in Philadelphia, Pennsylvania, graduating in 1890. Darnall spent several years in private practice before he joined the Army Medical Corps in 1896. He completed the Army Medical School in 1897. Opened in 1893, the Army Medical School was a 4-to-6-month course for civilian physicians entering active duty. The courses introduced physicians to the duties of medical officers as well as military surgery, medicine, and hygiene. It is considered by many to be the first school of public health in the U.S.

Darnall’s first assignments in Texas were followed by deployment to Cuba during the Spanish American War and then the Philippines, where he served as an operating surgeon and pathologist aboard the hospital ship, USS Relief. Darnall later accompanied an international expeditionary force to China in response to the Boxer Rebellion. In 1902, Darnall received an assignment to the Army Medical School in Washington, DC, that would change his life and the lives of millions around the world. Detailed as instructor for sanitary chemistry and operative surgery, he also served as secretary of the faculty. Just as Major Walter Reed and others before him, Darnall used his position at the Army Medical School to pursue important clinical research.

The complete story of the purification of drinking water is beyond the scope of this short biography. In brief, as early as 1894 the addition of chlorine to water was shown to render it “germ free.” In the 1890s, there were at least 2 attempts at water purification on a large scale with chlorine in European cities. One of the first uses of chlorine in the U.S. occurred in 1908 in Jersey City, New Jersey. At the Army Medical School, Darnall discovered the value of using compressed liquefied chlorine gas to purify water. He invented a mechanical liquid chlorine purifier in 1910 that became known as a chlorinator. In November 1911, Major Darnall authored a 15-page article concerning water purification.¹ Darnall also devised and patented a water filter, which the U.S. Army used for many years.

The principles of his chlorinator and use of anhydrous liquid chlorine were later applied to municipal water supplies throughout the world. The positive benefit of clean drinking water to improving public health is beyond measure. It has been said that more lives have been saved and more sickness prevented by Darnall’s contribution to sanitary water than by any other single achievement in medicine.

During World War I, Darnall was promoted to colonel and assigned to the Finance and Supply Division in the Office of the Surgeon General. After the war, he served as department surgeon in Hawaii. In 1925, he returned to the Office of the Surgeon General as executive officer. In November 1929, he was promoted to brigadier general and became the commanding general of the Army Medical Center and Walter Reed General Hospital, a position he held for 2 years until his retirement in 1931.Darnall died on January 18, 1941, at Walter Reed General Hospital just 6 days after his wife of 48 years had died at their home in Washington, DC. He is buried in Section 3 at Arlington National Cemetery. His 3 sons, Joseph Rogers, William Major, and Carl Robert, all served in some capacity in the Army.

Darnall Army Community Hospital opened in 1965, replacing the World War II-era hospital at Fort Hood. In 1984 a 5-year reconstruction project with additional floor space was completed. On May 1, 2006, the hospital was officially renamed the Carl R. Darnall Army Medical Center.

About this column
This column provides biographical sketches of the namesakes of military and VA health care facilities. To learn more about the individual your facility was named for or to offer a topic suggestion, contact us at fedprac@frontlinemedcom.com or on Facebook.

The Carl R. Darnall Army Medical Center at Fort Hood, Texas, is named in honor of Brigadier General Carl Rogers Darnall, a Texas native and career Army physician whose active-duty service spanned 35 years. Darnall, the oldest of 7 siblings, could not have imagined the enormity of the contributions that he would make and the lives that would be saved as he pursued a career in medicine.

Born on the family farm north of Dallas on Christmas Day in 1867, Darnall attended college in nearby Bonham and graduated from Transylvania University in Kentucky. He attended Jefferson Medical College in Philadelphia, Pennsylvania, graduating in 1890. Darnall spent several years in private practice before he joined the Army Medical Corps in 1896. He completed the Army Medical School in 1897. Opened in 1893, the Army Medical School was a 4-to-6-month course for civilian physicians entering active duty. The courses introduced physicians to the duties of medical officers as well as military surgery, medicine, and hygiene. It is considered by many to be the first school of public health in the U.S.

Darnall’s first assignments in Texas were followed by deployment to Cuba during the Spanish American War and then the Philippines, where he served as an operating surgeon and pathologist aboard the hospital ship, USS Relief. Darnall later accompanied an international expeditionary force to China in response to the Boxer Rebellion. In 1902, Darnall received an assignment to the Army Medical School in Washington, DC, that would change his life and the lives of millions around the world. Detailed as instructor for sanitary chemistry and operative surgery, he also served as secretary of the faculty. Just as Major Walter Reed and others before him, Darnall used his position at the Army Medical School to pursue important clinical research.

The complete story of the purification of drinking water is beyond the scope of this short biography. In brief, as early as 1894 the addition of chlorine to water was shown to render it “germ free.” In the 1890s, there were at least 2 attempts at water purification on a large scale with chlorine in European cities. One of the first uses of chlorine in the U.S. occurred in 1908 in Jersey City, New Jersey. At the Army Medical School, Darnall discovered the value of using compressed liquefied chlorine gas to purify water. He invented a mechanical liquid chlorine purifier in 1910 that became known as a chlorinator. In November 1911, Major Darnall authored a 15-page article concerning water purification.¹ Darnall also devised and patented a water filter, which the U.S. Army used for many years.

The principles of his chlorinator and use of anhydrous liquid chlorine were later applied to municipal water supplies throughout the world. The positive benefit of clean drinking water to improving public health is beyond measure. It has been said that more lives have been saved and more sickness prevented by Darnall’s contribution to sanitary water than by any other single achievement in medicine.

During World War I, Darnall was promoted to colonel and assigned to the Finance and Supply Division in the Office of the Surgeon General. After the war, he served as department surgeon in Hawaii. In 1925, he returned to the Office of the Surgeon General as executive officer. In November 1929, he was promoted to brigadier general and became the commanding general of the Army Medical Center and Walter Reed General Hospital, a position he held for 2 years until his retirement in 1931.Darnall died on January 18, 1941, at Walter Reed General Hospital just 6 days after his wife of 48 years had died at their home in Washington, DC. He is buried in Section 3 at Arlington National Cemetery. His 3 sons, Joseph Rogers, William Major, and Carl Robert, all served in some capacity in the Army.

Darnall Army Community Hospital opened in 1965, replacing the World War II-era hospital at Fort Hood. In 1984 a 5-year reconstruction project with additional floor space was completed. On May 1, 2006, the hospital was officially renamed the Carl R. Darnall Army Medical Center.

About this column
This column provides biographical sketches of the namesakes of military and VA health care facilities. To learn more about the individual your facility was named for or to offer a topic suggestion, contact us at fedprac@frontlinemedcom.com or on Facebook.

Why most heart failure may be preventable. Statins miss the mark in familial high cholesterol. Why mumps outbreaks are on the rise. And how using epileptic drugs in pregnancy affects school test scores.

Listen to the MDedge Daily News podcast for all the details on today’s top news.
 

Why most heart failure may be preventable. Statins miss the mark in familial high cholesterol. Why mumps outbreaks are on the rise. And how using epileptic drugs in pregnancy affects school test scores.

Listen to the MDedge Daily News podcast for all the details on today’s top news.
 

Why most heart failure may be preventable. Statins miss the mark in familial high cholesterol. Why mumps outbreaks are on the rise. And how using epileptic drugs in pregnancy affects school test scores.

Listen to the MDedge Daily News podcast for all the details on today’s top news.
 

Photo courtesy of GOSH

LISBON—Early results from a phase 1, pediatric trial of UCART19 expand upon results observed in children who received the therapy via a compassionate use program.

Two patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) received UCART19, a “universal,” donor-derived chimeric antigen receptor (CAR) T-cell therapy, via the program.

Both achieved remission and were still alive at last follow-up, more than 2 years after proceeding to transplant.

In the phase 1 trial, 5 of 6 B-ALL patients have achieved remission and gone on to transplant.

Three of the patients are still alive, and 2 are still negative for minimal residual disease (MRD) at 10 months and 11 months after UCART19 infusion.

However, 2 patients died of progression, and 1 died of transplant-related complications.

Paul Veys, MBBS, of Great Ormond Street Hospital (GOSH) in London, UK, presented these results, from the PALL trial, at the 44th Annual Meeting of the EBMT (abstract OS18-5*).

The trial is sponsored by Servier. In 2015, Servier acquired exclusive rights from Cellectis for UCART19, which is being co-developed by Servier and Pfizer.

Prior experience

Researchers previously reported results with UCART19 in 2 infants with relapsed/refractory B-ALL who had exhausted all other treatment options and received UCART19 via a compassionate use program.

Both patients achieved remission after UCART19 and proceeded to allogeneic hematopoietic stem cell transplant (allo-HSCT).

When these results were published, in January 2017, both patients were still alive and leukemia-free at last follow-up—12 months and 18 months after UCART19 infusion.

Dr Veys provided an update, noting that these patients were still alive and in remission at 24 months and 30 months after allo-HSCT.

Phase 1 patients and treatment

Thus far, the phase 1 trial has enrolled and treated 6 patients with relapsed B-ALL. They had a median age of 3.75 (range, 0.8-16.4).

All patients had morphological disease or an MRD level of at least 1 x 10^-3 (via flow cytometry and/or qPCR) at baseline.

One patient had received 1 prior therapy, 2 had 3 prior therapies, and 3 had 4 or more prior therapies. Two patients had prior inotuzumab ozogamicin, and 2 had prior allo-HSCT. Both had relapsed within 6 months of allo-HSCT.

Five patients had less than 10% bone marrow blasts prior to lymphodepletion, and 1 had greater than 50% blasts.

Patients underwent lymphodepletion with fludarabine, cyclophosphamide, and alemtuzumab (n=5) or fludarabine and cyclophosphamide (n=1).

The patients received UCART19 at doses of 2 x 10⁷ total cells or 1.1 to 2.3 x 10⁶ cells/kg.

Toxicity

All 6 patients developed cytokine release syndrome (CRS), including grade 1 (n=1), grade 2 (n=4), and grade 3 (n-1) CRS. However, all 6 cases resolved completely.

Three patients had neurotoxic events, 2 grade 1 and 1 grade 2. One patient had grade 3 febrile neutropenia.

Three patients had grade 4 prolonged cytopenia. This was defined as persistent neutropenia and/or thrombocytopenia beyond day 42 after UCART19 infusion, except if the patient had >5% bone marrow blasts.

One patient had grade 1 adenovirus infection, 1 had grade 3 cytomegalovirus infection, 2 had grade 3 BK virus hemorrhagic cystitis, and 1 had grade 4 metapneumovirus infection.

One patient had grade 1 acute cutaneous graft-versus-host disease.

Efficacy

All 6 patients achieved a complete response at day 28 to 42 after UCART19 infusion. Five patients achieved MRD negativity according to flow cytometry, and 3 were MRD-negative according to PCR.

The 5 flow-MRD-negative patients went on to receive an allo-HSCT between 49 days and 62 days after UCART19 infusion. Conditioning consisted of total body irradiation and fludarabine, with or without cyclophosphamide and antithymocyte globulin. All of these patients received a dose of rituximab as well, which was intended to target any remaining UCART19 cells.

Two patients relapsed 3 months after transplant and died at 7 months and 8 months after UCART19 infusion. One of these patients was CD19-, and 1 was CD19+, but both were MRD-positive by PCR prior to receiving their transplant.

A third patient died 2.5 months after allo-HSCT from transplant-related complications, including thrombotic microangiopathy, BK hemorrhagic cystitis, and nephritis.

The remaining 3 patients are still alive at 1.5 months, 10 months, and 11 months after UCART19 infusion. Two are still MRD-negative, and 1 is MRD-positive. The MRD-positive patient has not undergone allo-HSCT.

*Data in the abstract were updated in the presentation.

Photo courtesy of GOSH

LISBON—Early results from a phase 1, pediatric trial of UCART19 expand upon results observed in children who received the therapy via a compassionate use program.

Two patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) received UCART19, a “universal,” donor-derived chimeric antigen receptor (CAR) T-cell therapy, via the program.

Both achieved remission and were still alive at last follow-up, more than 2 years after proceeding to transplant.

In the phase 1 trial, 5 of 6 B-ALL patients have achieved remission and gone on to transplant.

Three of the patients are still alive, and 2 are still negative for minimal residual disease (MRD) at 10 months and 11 months after UCART19 infusion.

However, 2 patients died of progression, and 1 died of transplant-related complications.

Paul Veys, MBBS, of Great Ormond Street Hospital (GOSH) in London, UK, presented these results, from the PALL trial, at the 44th Annual Meeting of the EBMT (abstract OS18-5*).

The trial is sponsored by Servier. In 2015, Servier acquired exclusive rights from Cellectis for UCART19, which is being co-developed by Servier and Pfizer.

Prior experience

Researchers previously reported results with UCART19 in 2 infants with relapsed/refractory B-ALL who had exhausted all other treatment options and received UCART19 via a compassionate use program.

Both patients achieved remission after UCART19 and proceeded to allogeneic hematopoietic stem cell transplant (allo-HSCT).

When these results were published, in January 2017, both patients were still alive and leukemia-free at last follow-up—12 months and 18 months after UCART19 infusion.

Dr Veys provided an update, noting that these patients were still alive and in remission at 24 months and 30 months after allo-HSCT.

Phase 1 patients and treatment

Thus far, the phase 1 trial has enrolled and treated 6 patients with relapsed B-ALL. They had a median age of 3.75 (range, 0.8-16.4).

All patients had morphological disease or an MRD level of at least 1 x 10^-3 (via flow cytometry and/or qPCR) at baseline.

One patient had received 1 prior therapy, 2 had 3 prior therapies, and 3 had 4 or more prior therapies. Two patients had prior inotuzumab ozogamicin, and 2 had prior allo-HSCT. Both had relapsed within 6 months of allo-HSCT.

Five patients had less than 10% bone marrow blasts prior to lymphodepletion, and 1 had greater than 50% blasts.

Patients underwent lymphodepletion with fludarabine, cyclophosphamide, and alemtuzumab (n=5) or fludarabine and cyclophosphamide (n=1).

The patients received UCART19 at doses of 2 x 10⁷ total cells or 1.1 to 2.3 x 10⁶ cells/kg.

Toxicity

All 6 patients developed cytokine release syndrome (CRS), including grade 1 (n=1), grade 2 (n=4), and grade 3 (n-1) CRS. However, all 6 cases resolved completely.

Three patients had neurotoxic events, 2 grade 1 and 1 grade 2. One patient had grade 3 febrile neutropenia.

Three patients had grade 4 prolonged cytopenia. This was defined as persistent neutropenia and/or thrombocytopenia beyond day 42 after UCART19 infusion, except if the patient had >5% bone marrow blasts.

One patient had grade 1 adenovirus infection, 1 had grade 3 cytomegalovirus infection, 2 had grade 3 BK virus hemorrhagic cystitis, and 1 had grade 4 metapneumovirus infection.

One patient had grade 1 acute cutaneous graft-versus-host disease.

Efficacy

All 6 patients achieved a complete response at day 28 to 42 after UCART19 infusion. Five patients achieved MRD negativity according to flow cytometry, and 3 were MRD-negative according to PCR.

The 5 flow-MRD-negative patients went on to receive an allo-HSCT between 49 days and 62 days after UCART19 infusion. Conditioning consisted of total body irradiation and fludarabine, with or without cyclophosphamide and antithymocyte globulin. All of these patients received a dose of rituximab as well, which was intended to target any remaining UCART19 cells.

Two patients relapsed 3 months after transplant and died at 7 months and 8 months after UCART19 infusion. One of these patients was CD19-, and 1 was CD19+, but both were MRD-positive by PCR prior to receiving their transplant.

A third patient died 2.5 months after allo-HSCT from transplant-related complications, including thrombotic microangiopathy, BK hemorrhagic cystitis, and nephritis.

The remaining 3 patients are still alive at 1.5 months, 10 months, and 11 months after UCART19 infusion. Two are still MRD-negative, and 1 is MRD-positive. The MRD-positive patient has not undergone allo-HSCT.

*Data in the abstract were updated in the presentation.

Photo courtesy of GOSH

LISBON—Early results from a phase 1, pediatric trial of UCART19 expand upon results observed in children who received the therapy via a compassionate use program.

Two patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) received UCART19, a “universal,” donor-derived chimeric antigen receptor (CAR) T-cell therapy, via the program.

Both achieved remission and were still alive at last follow-up, more than 2 years after proceeding to transplant.

In the phase 1 trial, 5 of 6 B-ALL patients have achieved remission and gone on to transplant.

Three of the patients are still alive, and 2 are still negative for minimal residual disease (MRD) at 10 months and 11 months after UCART19 infusion.

However, 2 patients died of progression, and 1 died of transplant-related complications.

Paul Veys, MBBS, of Great Ormond Street Hospital (GOSH) in London, UK, presented these results, from the PALL trial, at the 44th Annual Meeting of the EBMT (abstract OS18-5*).

The trial is sponsored by Servier. In 2015, Servier acquired exclusive rights from Cellectis for UCART19, which is being co-developed by Servier and Pfizer.

Prior experience

Researchers previously reported results with UCART19 in 2 infants with relapsed/refractory B-ALL who had exhausted all other treatment options and received UCART19 via a compassionate use program.

Both patients achieved remission after UCART19 and proceeded to allogeneic hematopoietic stem cell transplant (allo-HSCT).

When these results were published, in January 2017, both patients were still alive and leukemia-free at last follow-up—12 months and 18 months after UCART19 infusion.

Dr Veys provided an update, noting that these patients were still alive and in remission at 24 months and 30 months after allo-HSCT.

Phase 1 patients and treatment

Thus far, the phase 1 trial has enrolled and treated 6 patients with relapsed B-ALL. They had a median age of 3.75 (range, 0.8-16.4).

All patients had morphological disease or an MRD level of at least 1 x 10^-3 (via flow cytometry and/or qPCR) at baseline.

One patient had received 1 prior therapy, 2 had 3 prior therapies, and 3 had 4 or more prior therapies. Two patients had prior inotuzumab ozogamicin, and 2 had prior allo-HSCT. Both had relapsed within 6 months of allo-HSCT.

Five patients had less than 10% bone marrow blasts prior to lymphodepletion, and 1 had greater than 50% blasts.

Patients underwent lymphodepletion with fludarabine, cyclophosphamide, and alemtuzumab (n=5) or fludarabine and cyclophosphamide (n=1).

The patients received UCART19 at doses of 2 x 10⁷ total cells or 1.1 to 2.3 x 10⁶ cells/kg.

Toxicity

All 6 patients developed cytokine release syndrome (CRS), including grade 1 (n=1), grade 2 (n=4), and grade 3 (n-1) CRS. However, all 6 cases resolved completely.

Three patients had neurotoxic events, 2 grade 1 and 1 grade 2. One patient had grade 3 febrile neutropenia.

Three patients had grade 4 prolonged cytopenia. This was defined as persistent neutropenia and/or thrombocytopenia beyond day 42 after UCART19 infusion, except if the patient had >5% bone marrow blasts.

One patient had grade 1 adenovirus infection, 1 had grade 3 cytomegalovirus infection, 2 had grade 3 BK virus hemorrhagic cystitis, and 1 had grade 4 metapneumovirus infection.

One patient had grade 1 acute cutaneous graft-versus-host disease.

Efficacy

All 6 patients achieved a complete response at day 28 to 42 after UCART19 infusion. Five patients achieved MRD negativity according to flow cytometry, and 3 were MRD-negative according to PCR.

The 5 flow-MRD-negative patients went on to receive an allo-HSCT between 49 days and 62 days after UCART19 infusion. Conditioning consisted of total body irradiation and fludarabine, with or without cyclophosphamide and antithymocyte globulin. All of these patients received a dose of rituximab as well, which was intended to target any remaining UCART19 cells.

Two patients relapsed 3 months after transplant and died at 7 months and 8 months after UCART19 infusion. One of these patients was CD19-, and 1 was CD19+, but both were MRD-positive by PCR prior to receiving their transplant.

A third patient died 2.5 months after allo-HSCT from transplant-related complications, including thrombotic microangiopathy, BK hemorrhagic cystitis, and nephritis.

The remaining 3 patients are still alive at 1.5 months, 10 months, and 11 months after UCART19 infusion. Two are still MRD-negative, and 1 is MRD-positive. The MRD-positive patient has not undergone allo-HSCT.

*Data in the abstract were updated in the presentation.

Photo from PharmaMar

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended refusal of marketing authorization for plitidepsin (Aplidin).

PharmaMar is seeking approval for plitidepsin to treat adults with multiple myeloma (MM) who have received at least 3 prior treatments, including bortezomib and either lenalidomide or thalidomide.

Plitidepsin is intended to be used in combination with dexamethasone.

This is the second time the CHMP has recommended against authorizing plitidepsin for this indication. The first time was last December.

At that time, PharmaMar asked the CHMP to re-examine its opinion, and the CHMP obliged. The committee confirmed its negative opinion of plitidepsin last week.

The CHMP’s review

Upon its initial review, the CHMP was concerned that data from the main study of plitidepsin in MM—the phase 3 ADMYRE trial—did not demonstrate a sufficient benefit of plitidepsin plus dexamethasone, compared to dexamethasone alone, in MM patients who had received 3 to 6 prior therapies.

The CHMP noted that the data showed a modest increase in progression free-survival (PFS)—around 1 month—with plitidepsin. According to study investigators, the median PFS was 3.8 months in patients who received plitidepsin and 1.9 months in those who received dexamethasone alone. According to an independent review committee, the median PFS was 2.6 months and 1.7 months, respectively.

The CHMP also said improvement in overall survival (OS) was not sufficiently demonstrated in this trial. The median OS was 11.6 months in the plitidepsin arm and 6.4 months in the dexamethasone arm.

Finally, the CHMP noted that severe adverse events were reported more frequently in patients who received plitidepsin. The most common grade 3/4 treatment-related adverse events (in the plitidepsin and dexamethasone arms, respectively) were fatigue (10.8% vs 1.2%), myalgia (5.4% vs 0%), and nausea (3.6% vs 1.2%).

Rates of treatment discontinuation were 9% in the plitidepsin arm, 6.5% in the dexamethasone arm, and 13.5% among patients who crossed over from the dexamethasone arm to the plitidepsin arm. Patients were allowed to cross over if they progressed after at least 8 weeks of treatment.

Based on these data, the CHMP was of the opinion that the benefits of plitidepsin did not outweigh its risks, so the committee recommended refusal of marketing authorization. After re-examination, the CHMP remained of the same opinion.

The European Commission (EC) has the final say on the marketing authorization application for plitidepsin. Though it is not required to do so, the EC typically follows the CHMP’s advice. The EC makes its decision within 67 days of the CHMP’s opinion.

PharmaMar has not announced whether it plans to continue developing plitidepsin for MM patients if the EC refuses to authorize the drug, and the company did not respond to a request for comment.

About plitidepsin

Plitidepsin is an investigational anticancer agent of marine origin, originally obtained from the ascidian Aplidium albicans. The drug specifically binds to eEF1A2 and targets the non-canonical role of this protein, resulting in cancer cell death via apoptosis.

Plitidepsin is currently in clinical development for hematologic malignancies.

In a phase 1b trial (NCT02100657), researchers are evaluating plitidepsin in combination with bortezomib and dexamethasone for patients with relapsed/refractory MM.

In a phase 2 trial (NCT03117361), researchers are investigating plitidepsin in combination with bortezomib and dexamethasone for patients with MM that is refractory to both lenalidomide and bortezomib.

Plitidepsin has received orphan drug designation in the European Union and the US.

Photo from PharmaMar

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended refusal of marketing authorization for plitidepsin (Aplidin).

PharmaMar is seeking approval for plitidepsin to treat adults with multiple myeloma (MM) who have received at least 3 prior treatments, including bortezomib and either lenalidomide or thalidomide.

Plitidepsin is intended to be used in combination with dexamethasone.

This is the second time the CHMP has recommended against authorizing plitidepsin for this indication. The first time was last December.

At that time, PharmaMar asked the CHMP to re-examine its opinion, and the CHMP obliged. The committee confirmed its negative opinion of plitidepsin last week.

The CHMP’s review

Upon its initial review, the CHMP was concerned that data from the main study of plitidepsin in MM—the phase 3 ADMYRE trial—did not demonstrate a sufficient benefit of plitidepsin plus dexamethasone, compared to dexamethasone alone, in MM patients who had received 3 to 6 prior therapies.

The CHMP noted that the data showed a modest increase in progression free-survival (PFS)—around 1 month—with plitidepsin. According to study investigators, the median PFS was 3.8 months in patients who received plitidepsin and 1.9 months in those who received dexamethasone alone. According to an independent review committee, the median PFS was 2.6 months and 1.7 months, respectively.

The CHMP also said improvement in overall survival (OS) was not sufficiently demonstrated in this trial. The median OS was 11.6 months in the plitidepsin arm and 6.4 months in the dexamethasone arm.

Finally, the CHMP noted that severe adverse events were reported more frequently in patients who received plitidepsin. The most common grade 3/4 treatment-related adverse events (in the plitidepsin and dexamethasone arms, respectively) were fatigue (10.8% vs 1.2%), myalgia (5.4% vs 0%), and nausea (3.6% vs 1.2%).

Rates of treatment discontinuation were 9% in the plitidepsin arm, 6.5% in the dexamethasone arm, and 13.5% among patients who crossed over from the dexamethasone arm to the plitidepsin arm. Patients were allowed to cross over if they progressed after at least 8 weeks of treatment.

Based on these data, the CHMP was of the opinion that the benefits of plitidepsin did not outweigh its risks, so the committee recommended refusal of marketing authorization. After re-examination, the CHMP remained of the same opinion.

The European Commission (EC) has the final say on the marketing authorization application for plitidepsin. Though it is not required to do so, the EC typically follows the CHMP’s advice. The EC makes its decision within 67 days of the CHMP’s opinion.

PharmaMar has not announced whether it plans to continue developing plitidepsin for MM patients if the EC refuses to authorize the drug, and the company did not respond to a request for comment.

About plitidepsin

Plitidepsin is an investigational anticancer agent of marine origin, originally obtained from the ascidian Aplidium albicans. The drug specifically binds to eEF1A2 and targets the non-canonical role of this protein, resulting in cancer cell death via apoptosis.

Plitidepsin is currently in clinical development for hematologic malignancies.

In a phase 1b trial (NCT02100657), researchers are evaluating plitidepsin in combination with bortezomib and dexamethasone for patients with relapsed/refractory MM.

In a phase 2 trial (NCT03117361), researchers are investigating plitidepsin in combination with bortezomib and dexamethasone for patients with MM that is refractory to both lenalidomide and bortezomib.

Plitidepsin has received orphan drug designation in the European Union and the US.

Photo from PharmaMar

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended refusal of marketing authorization for plitidepsin (Aplidin).

PharmaMar is seeking approval for plitidepsin to treat adults with multiple myeloma (MM) who have received at least 3 prior treatments, including bortezomib and either lenalidomide or thalidomide.

Plitidepsin is intended to be used in combination with dexamethasone.

This is the second time the CHMP has recommended against authorizing plitidepsin for this indication. The first time was last December.

At that time, PharmaMar asked the CHMP to re-examine its opinion, and the CHMP obliged. The committee confirmed its negative opinion of plitidepsin last week.

The CHMP’s review

Upon its initial review, the CHMP was concerned that data from the main study of plitidepsin in MM—the phase 3 ADMYRE trial—did not demonstrate a sufficient benefit of plitidepsin plus dexamethasone, compared to dexamethasone alone, in MM patients who had received 3 to 6 prior therapies.

The CHMP noted that the data showed a modest increase in progression free-survival (PFS)—around 1 month—with plitidepsin. According to study investigators, the median PFS was 3.8 months in patients who received plitidepsin and 1.9 months in those who received dexamethasone alone. According to an independent review committee, the median PFS was 2.6 months and 1.7 months, respectively.

The CHMP also said improvement in overall survival (OS) was not sufficiently demonstrated in this trial. The median OS was 11.6 months in the plitidepsin arm and 6.4 months in the dexamethasone arm.

Finally, the CHMP noted that severe adverse events were reported more frequently in patients who received plitidepsin. The most common grade 3/4 treatment-related adverse events (in the plitidepsin and dexamethasone arms, respectively) were fatigue (10.8% vs 1.2%), myalgia (5.4% vs 0%), and nausea (3.6% vs 1.2%).

Rates of treatment discontinuation were 9% in the plitidepsin arm, 6.5% in the dexamethasone arm, and 13.5% among patients who crossed over from the dexamethasone arm to the plitidepsin arm. Patients were allowed to cross over if they progressed after at least 8 weeks of treatment.

Based on these data, the CHMP was of the opinion that the benefits of plitidepsin did not outweigh its risks, so the committee recommended refusal of marketing authorization. After re-examination, the CHMP remained of the same opinion.

The European Commission (EC) has the final say on the marketing authorization application for plitidepsin. Though it is not required to do so, the EC typically follows the CHMP’s advice. The EC makes its decision within 67 days of the CHMP’s opinion.

PharmaMar has not announced whether it plans to continue developing plitidepsin for MM patients if the EC refuses to authorize the drug, and the company did not respond to a request for comment.

About plitidepsin

Plitidepsin is an investigational anticancer agent of marine origin, originally obtained from the ascidian Aplidium albicans. The drug specifically binds to eEF1A2 and targets the non-canonical role of this protein, resulting in cancer cell death via apoptosis.

Plitidepsin is currently in clinical development for hematologic malignancies.

In a phase 1b trial (NCT02100657), researchers are evaluating plitidepsin in combination with bortezomib and dexamethasone for patients with relapsed/refractory MM.

In a phase 2 trial (NCT03117361), researchers are investigating plitidepsin in combination with bortezomib and dexamethasone for patients with MM that is refractory to both lenalidomide and bortezomib.

Plitidepsin has received orphan drug designation in the European Union and the US.

Photo courtesy of the CDC

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended granting marketing authorization to a generic version of prasugrel called Prasugrel Mylan.

Mylan S.A.S. is seeking approval for this product to be co-administered with acetylsalicylic acid for the prevention of atherothrombotic events in adults with acute coronary syndrome (ie, unstable angina, non-ST segment elevation myocardial infarction, or ST segment elevation myocardial infarction) undergoing primary or delayed percutaneous coronary intervention.

The CHMP’s opinion on Prasugrel Mylan will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

If approved, Prasugrel Mylan will be available as 5 mg and 10 mg film-coated tablets.

Prasugrel is an inhibitor of platelet activation and aggregation that acts through the irreversible binding of its active metabolite to the P2Y12 class of ADP receptors on platelets.

Since platelets participate in the initiation and/or evolution of thrombotic complications of atherosclerotic disease, inhibition of platelet function can reduce the risk of cardiovascular events such as death, myocardial infarction, or stroke.

Prasugrel Mylan is a generic of Efient, which has been authorized in the European Union since 2009.

According to the CHMP, studies have demonstrated that Prasugrel Mylan is of “satisfactory quality” and bioequivalent to Efient.

In the TRITON–TIMI 38 study, treatment with prasugrel (Efient) was associated with significantly reduced rates of ischemic events, including stent thrombosis, when compared to treatment with clopidogrel in patients with moderate- to high-risk acute coronary syndromes with scheduled percutaneous coronary intervention.

However, prasugrel was also associated with an increased risk of major bleeding, including fatal bleeding. Still, there was no significant difference in mortality between the treatment groups.

These results were published in NEJM in 2007.

Photo courtesy of the CDC

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended granting marketing authorization to a generic version of prasugrel called Prasugrel Mylan.

Mylan S.A.S. is seeking approval for this product to be co-administered with acetylsalicylic acid for the prevention of atherothrombotic events in adults with acute coronary syndrome (ie, unstable angina, non-ST segment elevation myocardial infarction, or ST segment elevation myocardial infarction) undergoing primary or delayed percutaneous coronary intervention.

The CHMP’s opinion on Prasugrel Mylan will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

If approved, Prasugrel Mylan will be available as 5 mg and 10 mg film-coated tablets.

Prasugrel is an inhibitor of platelet activation and aggregation that acts through the irreversible binding of its active metabolite to the P2Y12 class of ADP receptors on platelets.

Since platelets participate in the initiation and/or evolution of thrombotic complications of atherosclerotic disease, inhibition of platelet function can reduce the risk of cardiovascular events such as death, myocardial infarction, or stroke.

Prasugrel Mylan is a generic of Efient, which has been authorized in the European Union since 2009.

According to the CHMP, studies have demonstrated that Prasugrel Mylan is of “satisfactory quality” and bioequivalent to Efient.

In the TRITON–TIMI 38 study, treatment with prasugrel (Efient) was associated with significantly reduced rates of ischemic events, including stent thrombosis, when compared to treatment with clopidogrel in patients with moderate- to high-risk acute coronary syndromes with scheduled percutaneous coronary intervention.

However, prasugrel was also associated with an increased risk of major bleeding, including fatal bleeding. Still, there was no significant difference in mortality between the treatment groups.

These results were published in NEJM in 2007.

Photo courtesy of the CDC

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended granting marketing authorization to a generic version of prasugrel called Prasugrel Mylan.

Mylan S.A.S. is seeking approval for this product to be co-administered with acetylsalicylic acid for the prevention of atherothrombotic events in adults with acute coronary syndrome (ie, unstable angina, non-ST segment elevation myocardial infarction, or ST segment elevation myocardial infarction) undergoing primary or delayed percutaneous coronary intervention.

The CHMP’s opinion on Prasugrel Mylan will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

If approved, Prasugrel Mylan will be available as 5 mg and 10 mg film-coated tablets.

Prasugrel is an inhibitor of platelet activation and aggregation that acts through the irreversible binding of its active metabolite to the P2Y12 class of ADP receptors on platelets.

Since platelets participate in the initiation and/or evolution of thrombotic complications of atherosclerotic disease, inhibition of platelet function can reduce the risk of cardiovascular events such as death, myocardial infarction, or stroke.

Prasugrel Mylan is a generic of Efient, which has been authorized in the European Union since 2009.

According to the CHMP, studies have demonstrated that Prasugrel Mylan is of “satisfactory quality” and bioequivalent to Efient.

In the TRITON–TIMI 38 study, treatment with prasugrel (Efient) was associated with significantly reduced rates of ischemic events, including stent thrombosis, when compared to treatment with clopidogrel in patients with moderate- to high-risk acute coronary syndromes with scheduled percutaneous coronary intervention.

However, prasugrel was also associated with an increased risk of major bleeding, including fatal bleeding. Still, there was no significant difference in mortality between the treatment groups.

These results were published in NEJM in 2007.