Medtronic is recalling certain MiniMed600 insulin pumps as part of a class I recall, the most serious kind of recall, because of a potentially fatal risk of incorrect dosing, according to a Food and Drug Administration MedWatch release.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

A class I recall such as this indicates that there is reasonable probability that using a defective pump will cause serious adverse health consequences or death, the agency said in the recall notice. It said the company has received more than 26,000 complaints regarding this problem and is aware of 2,175 injuries and 1 death so far. In all, 322,005 devices have been recalled.

If the pumps in question – Model 630G (distributed September 2016 to October 2019) and 670G (June 2017 to August 2019) – have broken or missing retainer rings, the insulin cartridge can end up loose in the reservoir compartment, which can lead to incorrect dosing and therefore potentially to hyperglycemia or hypoglycemia, according to the statement.

Model 630G was approved by the FDA in August 2016, and the 670G in September that same year.

On Nov. 21, 2019, Medtronic advised patients with type 1 diabetes who use the pumps to:

• Examine the retainer ring to see if it is loose, broken, or missing.
• Stop using the pump if the reservoir does not lock correctly or if the retainer ring is loose, damaged, or missing. Patients should contact Medtronic for a replacement pump and follow their doctor’s recommendations and perform manual insulin injections.
• Continue using the pump if the reservoir locks in place correctly.
• Check pump and retainer ring if the pump is dropped by accident, and stop use if it is damaged.
• Check the pump and retainer ring every set change to verify the reservoir is locked correctly.

More information regarding this recall, including how to contact Medtronic Technical Support, can be found on the FDA website.

[email protected]

Medtronic is recalling certain MiniMed600 insulin pumps as part of a class I recall, the most serious kind of recall, because of a potentially fatal risk of incorrect dosing, according to a Food and Drug Administration MedWatch release.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

A class I recall such as this indicates that there is reasonable probability that using a defective pump will cause serious adverse health consequences or death, the agency said in the recall notice. It said the company has received more than 26,000 complaints regarding this problem and is aware of 2,175 injuries and 1 death so far. In all, 322,005 devices have been recalled.

If the pumps in question – Model 630G (distributed September 2016 to October 2019) and 670G (June 2017 to August 2019) – have broken or missing retainer rings, the insulin cartridge can end up loose in the reservoir compartment, which can lead to incorrect dosing and therefore potentially to hyperglycemia or hypoglycemia, according to the statement.

Model 630G was approved by the FDA in August 2016, and the 670G in September that same year.

On Nov. 21, 2019, Medtronic advised patients with type 1 diabetes who use the pumps to:

• Examine the retainer ring to see if it is loose, broken, or missing.
• Stop using the pump if the reservoir does not lock correctly or if the retainer ring is loose, damaged, or missing. Patients should contact Medtronic for a replacement pump and follow their doctor’s recommendations and perform manual insulin injections.
• Continue using the pump if the reservoir locks in place correctly.
• Check pump and retainer ring if the pump is dropped by accident, and stop use if it is damaged.
• Check the pump and retainer ring every set change to verify the reservoir is locked correctly.

More information regarding this recall, including how to contact Medtronic Technical Support, can be found on the FDA website.

[email protected]

Medtronic is recalling certain MiniMed600 insulin pumps as part of a class I recall, the most serious kind of recall, because of a potentially fatal risk of incorrect dosing, according to a Food and Drug Administration MedWatch release.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

A class I recall such as this indicates that there is reasonable probability that using a defective pump will cause serious adverse health consequences or death, the agency said in the recall notice. It said the company has received more than 26,000 complaints regarding this problem and is aware of 2,175 injuries and 1 death so far. In all, 322,005 devices have been recalled.

If the pumps in question – Model 630G (distributed September 2016 to October 2019) and 670G (June 2017 to August 2019) – have broken or missing retainer rings, the insulin cartridge can end up loose in the reservoir compartment, which can lead to incorrect dosing and therefore potentially to hyperglycemia or hypoglycemia, according to the statement.

Model 630G was approved by the FDA in August 2016, and the 670G in September that same year.

On Nov. 21, 2019, Medtronic advised patients with type 1 diabetes who use the pumps to:

• Examine the retainer ring to see if it is loose, broken, or missing.
• Stop using the pump if the reservoir does not lock correctly or if the retainer ring is loose, damaged, or missing. Patients should contact Medtronic for a replacement pump and follow their doctor’s recommendations and perform manual insulin injections.
• Continue using the pump if the reservoir locks in place correctly.
• Check pump and retainer ring if the pump is dropped by accident, and stop use if it is damaged.
• Check the pump and retainer ring every set change to verify the reservoir is locked correctly.

More information regarding this recall, including how to contact Medtronic Technical Support, can be found on the FDA website.

[email protected]

In 2017, roughly 3 years after evidence from several studies made endovascular thrombectomy first-line treatment for selected acute ischemic stroke patients, the treatment was available at barely more than one-third of all U.S. stroke centers, available within 30-minute access to just over 30% of Americans, and available within 15-minute access to one-fifth of U.S. residents, based on information in a comprehensive U.S. database.

Heba Sarraj

These numbers showed that “current direct EVT [endovascular thrombectomy] access in the United States is suboptimal under predominate EMS routing protocols,” Amrou Sarraj, MD, and his associates wrote in an article published online in Stroke on Feb. 12. “Only in eight states did the coverage exceed 25% of the population, and nine states had coverage for less than 10% of the population. These results reflect limited access to an effective treatment modality that would improve clinical outcomes in patients with large strokes and prevent potentially devastating disability,” wrote Dr. Sarraj, chief of the general neurology service at Memorial-Hermann Hospital in Houston and coauthors.

Their analysis of data collected in 2017 by the Medicare Provider Analysis and Review (MEDPAR) database, maintained by the Centers for Medicare & Medicaid Services, identified two apparently effective ways to improve EVT access for acute ischemic stroke patients: First, systematically divert patients to a nearby center that offers EVT even when it means bypassing a closer stroke center that does not perform EVT when the added travel time is less than 15 minutes. Second, convert selected stroke centers that currently do not perform EVT into centers that do. Between these two approaches, the strategy of having ambulances bypass stroke centers that do not perform EVT and continuing to ones that do generally has the greater potential to boost access, the authors found. They based their analysis exclusively on their calculations of expected consequences rather than actual experience.

The calculations showed that bypassing non-EVT centers when the added bypass time computed to less than 15 minutes linked with an anticipated overall U.S. gain in access of about 17%, or 52 million people, extending the ability of acute ischemic stroke patients able to quickly reach an EVT center to about 37% of the American public. The second approach to boost access, converting the top 10% of stroke centers based on case volume that currently do not provide EVT to centers that do offer it, would result in expanded access for about 23 million additional Americans, raising the total with access to about 27% of the public, the new report said.

As part of this analysis, the MEDPAR data identified 1,941 U.S. centers providing stroke services during 2017, of which 713 (37%) had performed at least one EVT procedure. By comparison, 2015 MEDPAR data showed 577 U.S. stroke centers performing EVT, indicating that during the 2-3 years following several reports in early 2015 on the net benefits of EVT for acute ischemic stroke patients, the number of U.S. stroke centers offering this treatment had grown by a relative 24%. Based on the locations of the stroke centers that made EVT available in 2017, Dr. Sarraj and coauthors calculated that the 713 EVT-capable stroke centers provided emergency access within a 15-minute ground-ambulance trip for 61 million Americans (20% of the U.S. population), and within a 30-minute ground-transport trip to 95 million residents (31%).

Boosting these numbers by implementing a systematic bypass of stroke patients past non-EVT stroke centers to nearby centers that are EVT capable “has the benefit of ease of implementation and requires less time and resources,” the authors said. However, they also noted the heterogeneity of circumstances based on variables like population density and stroke center distribution, which means that in some locations the most effective way to boost access would be by increasing the number of stroke centers that provide EVT.

In 2018, Dr. Sarraj and associates reported results from a similar analysis of MEDPAR data that used 30-minute and 60-minute ground-transport times as the criteria for their calculations.

The study received no commercial funding. Dr. Sarraj reported receiving research funding from Stryker Neurovascular outside of this work. One coauthor reported serving in roles for the University of Texas Health System for which the institution has been funded via various industry and government grants, and another coauthor reported receiving research funding from the Patient-Centered Outcomes Research Institute, the National Institutes of Health, Genentech, and CSL Behring, as well as consulting fees from Frazer Ltd.

[email protected]

SOURCE: Sarraj A et al. Stroke. 2020 Feb 12. doi: 10.1161/STROKEAHA.120.028850.

In 2017, roughly 3 years after evidence from several studies made endovascular thrombectomy first-line treatment for selected acute ischemic stroke patients, the treatment was available at barely more than one-third of all U.S. stroke centers, available within 30-minute access to just over 30% of Americans, and available within 15-minute access to one-fifth of U.S. residents, based on information in a comprehensive U.S. database.

Heba Sarraj

These numbers showed that “current direct EVT [endovascular thrombectomy] access in the United States is suboptimal under predominate EMS routing protocols,” Amrou Sarraj, MD, and his associates wrote in an article published online in Stroke on Feb. 12. “Only in eight states did the coverage exceed 25% of the population, and nine states had coverage for less than 10% of the population. These results reflect limited access to an effective treatment modality that would improve clinical outcomes in patients with large strokes and prevent potentially devastating disability,” wrote Dr. Sarraj, chief of the general neurology service at Memorial-Hermann Hospital in Houston and coauthors.

Their analysis of data collected in 2017 by the Medicare Provider Analysis and Review (MEDPAR) database, maintained by the Centers for Medicare & Medicaid Services, identified two apparently effective ways to improve EVT access for acute ischemic stroke patients: First, systematically divert patients to a nearby center that offers EVT even when it means bypassing a closer stroke center that does not perform EVT when the added travel time is less than 15 minutes. Second, convert selected stroke centers that currently do not perform EVT into centers that do. Between these two approaches, the strategy of having ambulances bypass stroke centers that do not perform EVT and continuing to ones that do generally has the greater potential to boost access, the authors found. They based their analysis exclusively on their calculations of expected consequences rather than actual experience.

The calculations showed that bypassing non-EVT centers when the added bypass time computed to less than 15 minutes linked with an anticipated overall U.S. gain in access of about 17%, or 52 million people, extending the ability of acute ischemic stroke patients able to quickly reach an EVT center to about 37% of the American public. The second approach to boost access, converting the top 10% of stroke centers based on case volume that currently do not provide EVT to centers that do offer it, would result in expanded access for about 23 million additional Americans, raising the total with access to about 27% of the public, the new report said.

As part of this analysis, the MEDPAR data identified 1,941 U.S. centers providing stroke services during 2017, of which 713 (37%) had performed at least one EVT procedure. By comparison, 2015 MEDPAR data showed 577 U.S. stroke centers performing EVT, indicating that during the 2-3 years following several reports in early 2015 on the net benefits of EVT for acute ischemic stroke patients, the number of U.S. stroke centers offering this treatment had grown by a relative 24%. Based on the locations of the stroke centers that made EVT available in 2017, Dr. Sarraj and coauthors calculated that the 713 EVT-capable stroke centers provided emergency access within a 15-minute ground-ambulance trip for 61 million Americans (20% of the U.S. population), and within a 30-minute ground-transport trip to 95 million residents (31%).

Boosting these numbers by implementing a systematic bypass of stroke patients past non-EVT stroke centers to nearby centers that are EVT capable “has the benefit of ease of implementation and requires less time and resources,” the authors said. However, they also noted the heterogeneity of circumstances based on variables like population density and stroke center distribution, which means that in some locations the most effective way to boost access would be by increasing the number of stroke centers that provide EVT.

In 2018, Dr. Sarraj and associates reported results from a similar analysis of MEDPAR data that used 30-minute and 60-minute ground-transport times as the criteria for their calculations.

The study received no commercial funding. Dr. Sarraj reported receiving research funding from Stryker Neurovascular outside of this work. One coauthor reported serving in roles for the University of Texas Health System for which the institution has been funded via various industry and government grants, and another coauthor reported receiving research funding from the Patient-Centered Outcomes Research Institute, the National Institutes of Health, Genentech, and CSL Behring, as well as consulting fees from Frazer Ltd.

[email protected]

SOURCE: Sarraj A et al. Stroke. 2020 Feb 12. doi: 10.1161/STROKEAHA.120.028850.

In 2017, roughly 3 years after evidence from several studies made endovascular thrombectomy first-line treatment for selected acute ischemic stroke patients, the treatment was available at barely more than one-third of all U.S. stroke centers, available within 30-minute access to just over 30% of Americans, and available within 15-minute access to one-fifth of U.S. residents, based on information in a comprehensive U.S. database.

Heba Sarraj

These numbers showed that “current direct EVT [endovascular thrombectomy] access in the United States is suboptimal under predominate EMS routing protocols,” Amrou Sarraj, MD, and his associates wrote in an article published online in Stroke on Feb. 12. “Only in eight states did the coverage exceed 25% of the population, and nine states had coverage for less than 10% of the population. These results reflect limited access to an effective treatment modality that would improve clinical outcomes in patients with large strokes and prevent potentially devastating disability,” wrote Dr. Sarraj, chief of the general neurology service at Memorial-Hermann Hospital in Houston and coauthors.

Their analysis of data collected in 2017 by the Medicare Provider Analysis and Review (MEDPAR) database, maintained by the Centers for Medicare & Medicaid Services, identified two apparently effective ways to improve EVT access for acute ischemic stroke patients: First, systematically divert patients to a nearby center that offers EVT even when it means bypassing a closer stroke center that does not perform EVT when the added travel time is less than 15 minutes. Second, convert selected stroke centers that currently do not perform EVT into centers that do. Between these two approaches, the strategy of having ambulances bypass stroke centers that do not perform EVT and continuing to ones that do generally has the greater potential to boost access, the authors found. They based their analysis exclusively on their calculations of expected consequences rather than actual experience.

The calculations showed that bypassing non-EVT centers when the added bypass time computed to less than 15 minutes linked with an anticipated overall U.S. gain in access of about 17%, or 52 million people, extending the ability of acute ischemic stroke patients able to quickly reach an EVT center to about 37% of the American public. The second approach to boost access, converting the top 10% of stroke centers based on case volume that currently do not provide EVT to centers that do offer it, would result in expanded access for about 23 million additional Americans, raising the total with access to about 27% of the public, the new report said.

As part of this analysis, the MEDPAR data identified 1,941 U.S. centers providing stroke services during 2017, of which 713 (37%) had performed at least one EVT procedure. By comparison, 2015 MEDPAR data showed 577 U.S. stroke centers performing EVT, indicating that during the 2-3 years following several reports in early 2015 on the net benefits of EVT for acute ischemic stroke patients, the number of U.S. stroke centers offering this treatment had grown by a relative 24%. Based on the locations of the stroke centers that made EVT available in 2017, Dr. Sarraj and coauthors calculated that the 713 EVT-capable stroke centers provided emergency access within a 15-minute ground-ambulance trip for 61 million Americans (20% of the U.S. population), and within a 30-minute ground-transport trip to 95 million residents (31%).

Boosting these numbers by implementing a systematic bypass of stroke patients past non-EVT stroke centers to nearby centers that are EVT capable “has the benefit of ease of implementation and requires less time and resources,” the authors said. However, they also noted the heterogeneity of circumstances based on variables like population density and stroke center distribution, which means that in some locations the most effective way to boost access would be by increasing the number of stroke centers that provide EVT.

In 2018, Dr. Sarraj and associates reported results from a similar analysis of MEDPAR data that used 30-minute and 60-minute ground-transport times as the criteria for their calculations.

The study received no commercial funding. Dr. Sarraj reported receiving research funding from Stryker Neurovascular outside of this work. One coauthor reported serving in roles for the University of Texas Health System for which the institution has been funded via various industry and government grants, and another coauthor reported receiving research funding from the Patient-Centered Outcomes Research Institute, the National Institutes of Health, Genentech, and CSL Behring, as well as consulting fees from Frazer Ltd.

[email protected]

SOURCE: Sarraj A et al. Stroke. 2020 Feb 12. doi: 10.1161/STROKEAHA.120.028850.

The American Academy of Neurology (AAN) has issued a new guideline for the treatment of sleep problems in children and teenagers with autism spectrum disorders (ASD). The guideline was published online ahead of print Feb. 12 in Neurology.

“While up to 40% of children and teens in the general population will have sleep problems at some point during their childhood, such problems usually lessen with age,” lead author Ashura Williams Buckley, MD, director of the Sleep and Neurodevelopment Service at the National Institute of Mental Health in Bethesda, Md., said in a press release. “For children and teens with autism, sleep problems are more common and more likely to persist, resulting in poor health and poor quality of life. Some sleep problems may be directly related to autism, but others are not. Regardless, autism symptoms may make sleep problems worse.”
 

Few evidence-based treatments are available

Dr. Williams Buckley and colleagues developed the current guideline to evaluate which pharmacologic, behavioral, and complementary and alternative medicine (CAM) interventions improve bedtime resistance, sleep onset latency, sleep continuity, total sleep time, and daytime behavior in children and adolescents with ASD. The panel evaluated 900 abstracts of articles that had been included in systematic reviews, as well as 1,087 additional abstracts. One hundred thirty-nine articles were potentially relevant, 12 met criteria for data extraction, and eight were rated class III or higher and were included in the panel’s review.

The authors observed what they called a dearth of evidence-based treatments for sleep dysregulation in ASD. Evidence indicates that melatonin, with or without cognitive–behavioral therapy (CBT), improves several sleep outcomes, compared with placebo. “Evidence for other interventions is largely lacking,” wrote Dr. Williams Buckley and colleagues. They observed a lack of long-term safety data for melatonin in children, which they considered concerning, because melatonin affects the hypothalamic–gonadal axis and can potentially influence pubertal development.
 

Screening for comorbid conditions and concomitant medications

The guideline recommends that clinicians assess children with ASD and sleep disturbances for coexisting conditions and concomitant medications that could be contributing to these sleep disturbances. They should ensure that children receive appropriate treatment for coexisting conditions and adjust or discontinue potentially problematic medications appropriately, according to the guideline.

Furthermore, clinicians should counsel parents or guardians about behavioral strategies as a first-line treatment for improving sleep function. These strategies could be administered alone or with pharmacologic or neutraceutical approaches as needed, according to the authors. Suggested behavioral approaches include unmodified extinction (i.e., imposing a bedtime and ignoring a child’s protests), graduated extinction (i.e., ignoring protests for a specified period before responding), positive routines (i.e., establishing pre-bedtime calming rituals), and bedtime fading (i.e., putting a child to bed close to the time he or she begins to fall asleep).

If a child’s contributing coexisting conditions and medications have been addressed and behavioral strategies have not been helpful, clinicians should offer melatonin, according to the guideline. Because over-the-counter formulations contain variable concentrations of melatonin, clinicians should write a prescription for it or recommend high-purity pharmaceutical grade melatonin. The initial dose should be 1-3 mg/day at 60-30 minutes before bedtime. The dose can be titrated to 10 mg/day. Clinicians also should counsel children and their parents about potential adverse events of melatonin and the lack of long-term safety data, according to the guideline.

In addition, clinicians should advise children and parents that no evidence supports the routine use of weighted blankets or specialized mattress technology for improving sleep. Parents who ask about weighted blankets should be told that the reviewed trial reported no serious adverse events with this intervention, and that blankets could be a reasonable nonpharmacologic approach for some patients, according to the guideline.
 

Optimal outcome measures are undefined

Dr. Williams Buckley and colleagues also suggested areas for future research. Investigators have not yet defined optimal outcome measures (e.g., questionnaires, polysomnography, and actigraphy) that balance tolerability and accuracy, they wrote. Clinically important differences for most measures also have yet to be determined. Researchers should investigate whether long-term adverse events are associated with chronic melatonin use and study patients with ASD and comorbid mood disorders, wrote the authors. “Research tying the underlying neurobiology in early-life sleep disruption to behavior might help clinicians and researchers understand which treatments might work for which people with ASD,” they concluded.

The AAN supported the development of the guideline. Dr. Williams Buckley had no conflicts of interest. Six authors had conflicts of interest that the AAN deemed not significant enough to prevent their participation in the development of the guideline.

[email protected]

SOURCE: Williams Buckley A et al. Neurology. 2020;94:393-405. doi: 10.1212/WNL0000000000009033.

The American Academy of Neurology (AAN) has issued a new guideline for the treatment of sleep problems in children and teenagers with autism spectrum disorders (ASD). The guideline was published online ahead of print Feb. 12 in Neurology.

“While up to 40% of children and teens in the general population will have sleep problems at some point during their childhood, such problems usually lessen with age,” lead author Ashura Williams Buckley, MD, director of the Sleep and Neurodevelopment Service at the National Institute of Mental Health in Bethesda, Md., said in a press release. “For children and teens with autism, sleep problems are more common and more likely to persist, resulting in poor health and poor quality of life. Some sleep problems may be directly related to autism, but others are not. Regardless, autism symptoms may make sleep problems worse.”
 

Few evidence-based treatments are available

Dr. Williams Buckley and colleagues developed the current guideline to evaluate which pharmacologic, behavioral, and complementary and alternative medicine (CAM) interventions improve bedtime resistance, sleep onset latency, sleep continuity, total sleep time, and daytime behavior in children and adolescents with ASD. The panel evaluated 900 abstracts of articles that had been included in systematic reviews, as well as 1,087 additional abstracts. One hundred thirty-nine articles were potentially relevant, 12 met criteria for data extraction, and eight were rated class III or higher and were included in the panel’s review.

The authors observed what they called a dearth of evidence-based treatments for sleep dysregulation in ASD. Evidence indicates that melatonin, with or without cognitive–behavioral therapy (CBT), improves several sleep outcomes, compared with placebo. “Evidence for other interventions is largely lacking,” wrote Dr. Williams Buckley and colleagues. They observed a lack of long-term safety data for melatonin in children, which they considered concerning, because melatonin affects the hypothalamic–gonadal axis and can potentially influence pubertal development.
 

Screening for comorbid conditions and concomitant medications

The guideline recommends that clinicians assess children with ASD and sleep disturbances for coexisting conditions and concomitant medications that could be contributing to these sleep disturbances. They should ensure that children receive appropriate treatment for coexisting conditions and adjust or discontinue potentially problematic medications appropriately, according to the guideline.

Furthermore, clinicians should counsel parents or guardians about behavioral strategies as a first-line treatment for improving sleep function. These strategies could be administered alone or with pharmacologic or neutraceutical approaches as needed, according to the authors. Suggested behavioral approaches include unmodified extinction (i.e., imposing a bedtime and ignoring a child’s protests), graduated extinction (i.e., ignoring protests for a specified period before responding), positive routines (i.e., establishing pre-bedtime calming rituals), and bedtime fading (i.e., putting a child to bed close to the time he or she begins to fall asleep).

If a child’s contributing coexisting conditions and medications have been addressed and behavioral strategies have not been helpful, clinicians should offer melatonin, according to the guideline. Because over-the-counter formulations contain variable concentrations of melatonin, clinicians should write a prescription for it or recommend high-purity pharmaceutical grade melatonin. The initial dose should be 1-3 mg/day at 60-30 minutes before bedtime. The dose can be titrated to 10 mg/day. Clinicians also should counsel children and their parents about potential adverse events of melatonin and the lack of long-term safety data, according to the guideline.

In addition, clinicians should advise children and parents that no evidence supports the routine use of weighted blankets or specialized mattress technology for improving sleep. Parents who ask about weighted blankets should be told that the reviewed trial reported no serious adverse events with this intervention, and that blankets could be a reasonable nonpharmacologic approach for some patients, according to the guideline.
 

Optimal outcome measures are undefined

Dr. Williams Buckley and colleagues also suggested areas for future research. Investigators have not yet defined optimal outcome measures (e.g., questionnaires, polysomnography, and actigraphy) that balance tolerability and accuracy, they wrote. Clinically important differences for most measures also have yet to be determined. Researchers should investigate whether long-term adverse events are associated with chronic melatonin use and study patients with ASD and comorbid mood disorders, wrote the authors. “Research tying the underlying neurobiology in early-life sleep disruption to behavior might help clinicians and researchers understand which treatments might work for which people with ASD,” they concluded.

The AAN supported the development of the guideline. Dr. Williams Buckley had no conflicts of interest. Six authors had conflicts of interest that the AAN deemed not significant enough to prevent their participation in the development of the guideline.

[email protected]

SOURCE: Williams Buckley A et al. Neurology. 2020;94:393-405. doi: 10.1212/WNL0000000000009033.

The American Academy of Neurology (AAN) has issued a new guideline for the treatment of sleep problems in children and teenagers with autism spectrum disorders (ASD). The guideline was published online ahead of print Feb. 12 in Neurology.

“While up to 40% of children and teens in the general population will have sleep problems at some point during their childhood, such problems usually lessen with age,” lead author Ashura Williams Buckley, MD, director of the Sleep and Neurodevelopment Service at the National Institute of Mental Health in Bethesda, Md., said in a press release. “For children and teens with autism, sleep problems are more common and more likely to persist, resulting in poor health and poor quality of life. Some sleep problems may be directly related to autism, but others are not. Regardless, autism symptoms may make sleep problems worse.”
 

Few evidence-based treatments are available

Dr. Williams Buckley and colleagues developed the current guideline to evaluate which pharmacologic, behavioral, and complementary and alternative medicine (CAM) interventions improve bedtime resistance, sleep onset latency, sleep continuity, total sleep time, and daytime behavior in children and adolescents with ASD. The panel evaluated 900 abstracts of articles that had been included in systematic reviews, as well as 1,087 additional abstracts. One hundred thirty-nine articles were potentially relevant, 12 met criteria for data extraction, and eight were rated class III or higher and were included in the panel’s review.

The authors observed what they called a dearth of evidence-based treatments for sleep dysregulation in ASD. Evidence indicates that melatonin, with or without cognitive–behavioral therapy (CBT), improves several sleep outcomes, compared with placebo. “Evidence for other interventions is largely lacking,” wrote Dr. Williams Buckley and colleagues. They observed a lack of long-term safety data for melatonin in children, which they considered concerning, because melatonin affects the hypothalamic–gonadal axis and can potentially influence pubertal development.
 

Screening for comorbid conditions and concomitant medications

The guideline recommends that clinicians assess children with ASD and sleep disturbances for coexisting conditions and concomitant medications that could be contributing to these sleep disturbances. They should ensure that children receive appropriate treatment for coexisting conditions and adjust or discontinue potentially problematic medications appropriately, according to the guideline.

Furthermore, clinicians should counsel parents or guardians about behavioral strategies as a first-line treatment for improving sleep function. These strategies could be administered alone or with pharmacologic or neutraceutical approaches as needed, according to the authors. Suggested behavioral approaches include unmodified extinction (i.e., imposing a bedtime and ignoring a child’s protests), graduated extinction (i.e., ignoring protests for a specified period before responding), positive routines (i.e., establishing pre-bedtime calming rituals), and bedtime fading (i.e., putting a child to bed close to the time he or she begins to fall asleep).

If a child’s contributing coexisting conditions and medications have been addressed and behavioral strategies have not been helpful, clinicians should offer melatonin, according to the guideline. Because over-the-counter formulations contain variable concentrations of melatonin, clinicians should write a prescription for it or recommend high-purity pharmaceutical grade melatonin. The initial dose should be 1-3 mg/day at 60-30 minutes before bedtime. The dose can be titrated to 10 mg/day. Clinicians also should counsel children and their parents about potential adverse events of melatonin and the lack of long-term safety data, according to the guideline.

In addition, clinicians should advise children and parents that no evidence supports the routine use of weighted blankets or specialized mattress technology for improving sleep. Parents who ask about weighted blankets should be told that the reviewed trial reported no serious adverse events with this intervention, and that blankets could be a reasonable nonpharmacologic approach for some patients, according to the guideline.
 

Optimal outcome measures are undefined

Dr. Williams Buckley and colleagues also suggested areas for future research. Investigators have not yet defined optimal outcome measures (e.g., questionnaires, polysomnography, and actigraphy) that balance tolerability and accuracy, they wrote. Clinically important differences for most measures also have yet to be determined. Researchers should investigate whether long-term adverse events are associated with chronic melatonin use and study patients with ASD and comorbid mood disorders, wrote the authors. “Research tying the underlying neurobiology in early-life sleep disruption to behavior might help clinicians and researchers understand which treatments might work for which people with ASD,” they concluded.

The AAN supported the development of the guideline. Dr. Williams Buckley had no conflicts of interest. Six authors had conflicts of interest that the AAN deemed not significant enough to prevent their participation in the development of the guideline.

[email protected]

SOURCE: Williams Buckley A et al. Neurology. 2020;94:393-405. doi: 10.1212/WNL0000000000009033.

The controversy regarding the safety of treating peripheral artery disease (PAD) with paclitaxel-coated devices has only deepened in the new year, with two recent studies suggesting opposite safety findings.
 

The debate began with a 2018 meta-analysis showing a late mortality signal associated with paclitaxel drug-coated balloons (DCBs) that sent reverberations through the interventional cardiology community (J Am Heart Assoc. 2018 Dec 18;7[24]:e011245).

Now, in a new meta-analysis involving eight randomized controlled trials (RCTs) and more than 1,400 patients with critical limb ischemia (CLI), the same researchers found significantly more early amputations and deaths in those treated with DCB below the knee, compared with conventional balloon angioplasty.

“The findings of our latest report add to previous evidence underpinning major safety concerns around use of paclitaxel in lower limb angioplasties – increased long-term patient mortality in cases of intermittent claudication,” lead author Konstantinos Katsanos MD, MSc, PhD, Patras University Hospital, Greece, said in an interview.

By contrast, a retrospective study of insurance claims in Germany showed no heightened mortality with paclitaxel-coated balloons and stents, compared with uncoated devices, in close to 38,000 patients with PAD.

On the contrary, use of paclitaxel-coated devices was associated with higher long-term survival, better amputation-free survival (AFS), and lower rates of major cardiovascular events in the treatment of chronic limb-threatening ischemia (CLTI).

These findings “emphasize the difference between population-based evidence and randomized trials,” lead author Christian-Alexander Behrendt, MD, University Medical Center Hamburg-Eppendorf, Germany, said in an interview.

Downstream “showers”

In the new meta-analysis led by Dr. Katsanos, published online Jan. 15, the 1,420 patients were treated with five different DCBs and 97% had CLI (J Vasc Intervent Radiol 2020 Feb;31[2]:202-12).

In up to 1-year follow-up, the paclitaxel DCB group had fewer target lesion revascularizations (TLR) than those of the uncoated device group (11.8% vs. 25.6%; risk ratio, 0.53; 95% confidence interval, 0.35-0.81) but worse AFS (13.7% vs. 9.4%; hazard ratio [HR], 1.52; 95% CI, 1.12-2.07).

The latter finding was driven by nonsignificant increased risks for all-cause death (odds ratio [OR], 1.39; 95% CI, 0.94-2.07) and major amputations (OR, 1.63; 95% CI, 0.92-2.90).

In dose-subgroup analyses, AFS was significantly worse in cases with high-dose (3.0-3.5 mcg/mm²) devices, but not in the single trial with a low-dose DCB (2.0 mcg/mm²).

“Considering the well-described downstream ‘showers’ of paclitaxel particles with current drug-coated balloons, we hypothesize that nontarget paclitaxel embolization is a plausible mechanism for distal foot and systemic toxicity,” Dr. Katsanos said.

Short time frame

Eric Secemsky, MD, of Harvard Medical School, and director of vascular intervention at Beth Israel Deaconess Medical Center, Boston, suggested in an interview that this theorized mechanism of harm in below-the-knee procedures could potentially shed light on a similar mechanism at play in above-the-knee procedures.

“We didn’t understand why people could potentially be dying in above-the-knee [procedures], and the suggestion here is that these devices might perhaps be causing particular embolization or maybe delayed wound healing,” Dr. Secemsky speculated.

However, “I don’t know that this is true, so I am cautious to say this is true,” he emphasized.

Dr. Secemsky said a strength of the Katsanos analysis is that the RCTs included more than 1,000 patients, but noted that it is hard to vet the quality and rigor of the data, as some of the studies have not yet been published. He also noted that paclitaxel-coated devices are not approved by the Food and Drug Administration in the United States for below-the-knee procedures.

Moreover, he continued, “two studies were driving the signal of harm: the IN.PACT DEEP, which included an iteration of their DCB that is no longer being tested; and the unpublished SINGA-PACLI trial. Those studies contributed most of the adverse events seen in this meta-analysis.”

In addition, the trials had different lengths of follow-up (6-12 months), he said. “Thus, the five trials with data available to 12 months are driving the 1-year findings, whereas three RCTs, including the primary RCT showing safety [Lutonix-BTK trial], only contribute data to 6 months.”

For this reason, “we are not too excited about this meta-analysis as of now, [because] all it tells us is that we need more data to support the safety of drug-coated devices in this population,” Dr. Secemsky said.

Dr. Katsanos explained that, “to address the differences in follow-up period and number of cases lost to follow-up, the primary endpoint was calculated on the log-hazard scale and expressed as a hazard ratio, as recommended for time-to-event outcomes.”

He highlighted that a short-term time frame of 6 months to 1 year was chosen “because it is clinically relevant to limb-threatening CLI.”

Sensitivity tests also “showed consistent direction and magnitude of the summary treatment effects in case of both AFS and freedom from TLR,” Dr. Katsanos emphasized.

Lower mortality, fewer amputations

The second study, published online Jan. 8, drew on health insurance claims in the German BARMER database to analyze 37,914 patients (mean age, 73.3 years, 49% female) and 21,546 propensity-score-matched patients with symptomatic CLTI or intermittent claudication (IC) with an index revascularization during 2010-2018 (Eur J Vasc Endovasc Surg. 2020 Jan 8. doi: 10.1016/j.ejvs.2019.12.034).

Patients were first stratified by CLTI or IC, and then by balloon vs. stent use. Paclitaxel-coated devices were then compared with uncoated devices within each stratum. The primary outcome was all-cause mortality at the end of follow-up.

From 2010 to 2018, the annual use of paclitaxel-coated devices increased dramatically from 3% to 39% in the CLTI group and from 4% to 48% in the IC group (P less than .001 for both).

A total of 2,454 deaths occurred within 5 years of follow-up (median, 2.7 years; longest, 8 years).

A Cox proportional hazards model (based on propensity-score-matched cohorts at 5 years) showed that, compared with uncoated devices, use of paclitaxel-coated devices in the CLTI group was associated with several improvements:

• Overall survival: HR, 0.83; 95% CI, 0.77-0.90.
• Amputation-free survival: HR, 0.85; 95% CI, 0.78-0.91.
• Major cardiovascular events: HR, 0.82; 95% CI, 0.77-0.88.

In the IC group, mortality was significantly better with DCB (HR, 0.87; 95% CI, 0.76-0.99) or a combination of DCB and drug-eluting stents (HR, 0.88; 95% CI, 0.80-0.98) than with uncoated devices, but similar for DES alone (HR, 0.91; 95% CI, 0.77-1.08).

No benefit was found for paclitaxel-coated devices in the IC group for AFS (HR, 0.91; 95% CI, 0.82-1.00) or major cardiovascular events (HR, 0.93; 95% CI, 0.87-1.00).

The authors acknowledge that “unmeasured confounding” may partly explain the results. It may be that patients revascularized with DCB or DES “are more likely to be treated in highly specialized trial centers with clear follow-up protocol.”

Moreover, these patients may have received “the best treatment,” including statin therapy, added Dr. Behrendt.

More evidence needed

Dr. Secemsky, who was not involved with either study, said the German investigators “did a wonderful job with this analysis in a large population of several thousand patients, showing nicely that after accounting for differences in comorbidities, the patients had no evidence of harm with [paclitaxel-coated] devices through 5 years.”

However, he cautioned, median follow-up time was just over 2 years. “Although the investigators had data all the way out to 5 years, over time, the number of patients contributing data became smaller, which results in more uncertainty with these longer-term findings,” he said. “As such, we still need to look at additional long-term data in this patient population to confirm the safety of these devices.”

At present, the “major consideration we want to address is whether it’s safe to use these devices, and we’re undertaking these analyses to examine safety, not to see if they improve mortality,” although the present study “has a suggestion of mortality benefit,” Dr. Secemsky said.

Dr. Katsanos added that paclitaxel-coated balloons “remain under investigation for below-knee arteries and critical limb ischemia,” with “a few randomized controlled trials on the way.”

“We need definitive evidence from high-quality multicenter controlled trials that these devices may improve wound healing and limb salvage without any systemic mortality risk,” he said.

Dr. Katsanos receives personal fees from Boston Scientific and Philips Healthcare. The study by Dr. Behrendt was part of the IDOMENEO project funded by the German Joint Federal Committee. Dr. Behrendt reports no relevant financial relationships. Dr. Secemsky reports institutional grants from Cook Medical, BD Bard, Medtronic, Beth Israel Deaconess Medical Center, and Boston Scientific, and reports consultancy for Cook Medical, BD Bard, and Medtronic.
 

This article first appeared on Medscape.com.

The controversy regarding the safety of treating peripheral artery disease (PAD) with paclitaxel-coated devices has only deepened in the new year, with two recent studies suggesting opposite safety findings.
 

The debate began with a 2018 meta-analysis showing a late mortality signal associated with paclitaxel drug-coated balloons (DCBs) that sent reverberations through the interventional cardiology community (J Am Heart Assoc. 2018 Dec 18;7[24]:e011245).

Now, in a new meta-analysis involving eight randomized controlled trials (RCTs) and more than 1,400 patients with critical limb ischemia (CLI), the same researchers found significantly more early amputations and deaths in those treated with DCB below the knee, compared with conventional balloon angioplasty.

“The findings of our latest report add to previous evidence underpinning major safety concerns around use of paclitaxel in lower limb angioplasties – increased long-term patient mortality in cases of intermittent claudication,” lead author Konstantinos Katsanos MD, MSc, PhD, Patras University Hospital, Greece, said in an interview.

By contrast, a retrospective study of insurance claims in Germany showed no heightened mortality with paclitaxel-coated balloons and stents, compared with uncoated devices, in close to 38,000 patients with PAD.

On the contrary, use of paclitaxel-coated devices was associated with higher long-term survival, better amputation-free survival (AFS), and lower rates of major cardiovascular events in the treatment of chronic limb-threatening ischemia (CLTI).

These findings “emphasize the difference between population-based evidence and randomized trials,” lead author Christian-Alexander Behrendt, MD, University Medical Center Hamburg-Eppendorf, Germany, said in an interview.

Downstream “showers”

In the new meta-analysis led by Dr. Katsanos, published online Jan. 15, the 1,420 patients were treated with five different DCBs and 97% had CLI (J Vasc Intervent Radiol 2020 Feb;31[2]:202-12).

In up to 1-year follow-up, the paclitaxel DCB group had fewer target lesion revascularizations (TLR) than those of the uncoated device group (11.8% vs. 25.6%; risk ratio, 0.53; 95% confidence interval, 0.35-0.81) but worse AFS (13.7% vs. 9.4%; hazard ratio [HR], 1.52; 95% CI, 1.12-2.07).

The latter finding was driven by nonsignificant increased risks for all-cause death (odds ratio [OR], 1.39; 95% CI, 0.94-2.07) and major amputations (OR, 1.63; 95% CI, 0.92-2.90).

In dose-subgroup analyses, AFS was significantly worse in cases with high-dose (3.0-3.5 mcg/mm²) devices, but not in the single trial with a low-dose DCB (2.0 mcg/mm²).

“Considering the well-described downstream ‘showers’ of paclitaxel particles with current drug-coated balloons, we hypothesize that nontarget paclitaxel embolization is a plausible mechanism for distal foot and systemic toxicity,” Dr. Katsanos said.

Short time frame

Eric Secemsky, MD, of Harvard Medical School, and director of vascular intervention at Beth Israel Deaconess Medical Center, Boston, suggested in an interview that this theorized mechanism of harm in below-the-knee procedures could potentially shed light on a similar mechanism at play in above-the-knee procedures.

“We didn’t understand why people could potentially be dying in above-the-knee [procedures], and the suggestion here is that these devices might perhaps be causing particular embolization or maybe delayed wound healing,” Dr. Secemsky speculated.

However, “I don’t know that this is true, so I am cautious to say this is true,” he emphasized.

Dr. Secemsky said a strength of the Katsanos analysis is that the RCTs included more than 1,000 patients, but noted that it is hard to vet the quality and rigor of the data, as some of the studies have not yet been published. He also noted that paclitaxel-coated devices are not approved by the Food and Drug Administration in the United States for below-the-knee procedures.

Moreover, he continued, “two studies were driving the signal of harm: the IN.PACT DEEP, which included an iteration of their DCB that is no longer being tested; and the unpublished SINGA-PACLI trial. Those studies contributed most of the adverse events seen in this meta-analysis.”

In addition, the trials had different lengths of follow-up (6-12 months), he said. “Thus, the five trials with data available to 12 months are driving the 1-year findings, whereas three RCTs, including the primary RCT showing safety [Lutonix-BTK trial], only contribute data to 6 months.”

For this reason, “we are not too excited about this meta-analysis as of now, [because] all it tells us is that we need more data to support the safety of drug-coated devices in this population,” Dr. Secemsky said.

Dr. Katsanos explained that, “to address the differences in follow-up period and number of cases lost to follow-up, the primary endpoint was calculated on the log-hazard scale and expressed as a hazard ratio, as recommended for time-to-event outcomes.”

He highlighted that a short-term time frame of 6 months to 1 year was chosen “because it is clinically relevant to limb-threatening CLI.”

Sensitivity tests also “showed consistent direction and magnitude of the summary treatment effects in case of both AFS and freedom from TLR,” Dr. Katsanos emphasized.

Lower mortality, fewer amputations

The second study, published online Jan. 8, drew on health insurance claims in the German BARMER database to analyze 37,914 patients (mean age, 73.3 years, 49% female) and 21,546 propensity-score-matched patients with symptomatic CLTI or intermittent claudication (IC) with an index revascularization during 2010-2018 (Eur J Vasc Endovasc Surg. 2020 Jan 8. doi: 10.1016/j.ejvs.2019.12.034).

Patients were first stratified by CLTI or IC, and then by balloon vs. stent use. Paclitaxel-coated devices were then compared with uncoated devices within each stratum. The primary outcome was all-cause mortality at the end of follow-up.

From 2010 to 2018, the annual use of paclitaxel-coated devices increased dramatically from 3% to 39% in the CLTI group and from 4% to 48% in the IC group (P less than .001 for both).

A total of 2,454 deaths occurred within 5 years of follow-up (median, 2.7 years; longest, 8 years).

A Cox proportional hazards model (based on propensity-score-matched cohorts at 5 years) showed that, compared with uncoated devices, use of paclitaxel-coated devices in the CLTI group was associated with several improvements:

• Overall survival: HR, 0.83; 95% CI, 0.77-0.90.
• Amputation-free survival: HR, 0.85; 95% CI, 0.78-0.91.
• Major cardiovascular events: HR, 0.82; 95% CI, 0.77-0.88.

In the IC group, mortality was significantly better with DCB (HR, 0.87; 95% CI, 0.76-0.99) or a combination of DCB and drug-eluting stents (HR, 0.88; 95% CI, 0.80-0.98) than with uncoated devices, but similar for DES alone (HR, 0.91; 95% CI, 0.77-1.08).

No benefit was found for paclitaxel-coated devices in the IC group for AFS (HR, 0.91; 95% CI, 0.82-1.00) or major cardiovascular events (HR, 0.93; 95% CI, 0.87-1.00).

The authors acknowledge that “unmeasured confounding” may partly explain the results. It may be that patients revascularized with DCB or DES “are more likely to be treated in highly specialized trial centers with clear follow-up protocol.”

Moreover, these patients may have received “the best treatment,” including statin therapy, added Dr. Behrendt.

More evidence needed

Dr. Secemsky, who was not involved with either study, said the German investigators “did a wonderful job with this analysis in a large population of several thousand patients, showing nicely that after accounting for differences in comorbidities, the patients had no evidence of harm with [paclitaxel-coated] devices through 5 years.”

However, he cautioned, median follow-up time was just over 2 years. “Although the investigators had data all the way out to 5 years, over time, the number of patients contributing data became smaller, which results in more uncertainty with these longer-term findings,” he said. “As such, we still need to look at additional long-term data in this patient population to confirm the safety of these devices.”

At present, the “major consideration we want to address is whether it’s safe to use these devices, and we’re undertaking these analyses to examine safety, not to see if they improve mortality,” although the present study “has a suggestion of mortality benefit,” Dr. Secemsky said.

Dr. Katsanos added that paclitaxel-coated balloons “remain under investigation for below-knee arteries and critical limb ischemia,” with “a few randomized controlled trials on the way.”

“We need definitive evidence from high-quality multicenter controlled trials that these devices may improve wound healing and limb salvage without any systemic mortality risk,” he said.

Dr. Katsanos receives personal fees from Boston Scientific and Philips Healthcare. The study by Dr. Behrendt was part of the IDOMENEO project funded by the German Joint Federal Committee. Dr. Behrendt reports no relevant financial relationships. Dr. Secemsky reports institutional grants from Cook Medical, BD Bard, Medtronic, Beth Israel Deaconess Medical Center, and Boston Scientific, and reports consultancy for Cook Medical, BD Bard, and Medtronic.
 

This article first appeared on Medscape.com.

The controversy regarding the safety of treating peripheral artery disease (PAD) with paclitaxel-coated devices has only deepened in the new year, with two recent studies suggesting opposite safety findings.
 

The debate began with a 2018 meta-analysis showing a late mortality signal associated with paclitaxel drug-coated balloons (DCBs) that sent reverberations through the interventional cardiology community (J Am Heart Assoc. 2018 Dec 18;7[24]:e011245).

Now, in a new meta-analysis involving eight randomized controlled trials (RCTs) and more than 1,400 patients with critical limb ischemia (CLI), the same researchers found significantly more early amputations and deaths in those treated with DCB below the knee, compared with conventional balloon angioplasty.

“The findings of our latest report add to previous evidence underpinning major safety concerns around use of paclitaxel in lower limb angioplasties – increased long-term patient mortality in cases of intermittent claudication,” lead author Konstantinos Katsanos MD, MSc, PhD, Patras University Hospital, Greece, said in an interview.

By contrast, a retrospective study of insurance claims in Germany showed no heightened mortality with paclitaxel-coated balloons and stents, compared with uncoated devices, in close to 38,000 patients with PAD.

On the contrary, use of paclitaxel-coated devices was associated with higher long-term survival, better amputation-free survival (AFS), and lower rates of major cardiovascular events in the treatment of chronic limb-threatening ischemia (CLTI).

These findings “emphasize the difference between population-based evidence and randomized trials,” lead author Christian-Alexander Behrendt, MD, University Medical Center Hamburg-Eppendorf, Germany, said in an interview.

Downstream “showers”

In the new meta-analysis led by Dr. Katsanos, published online Jan. 15, the 1,420 patients were treated with five different DCBs and 97% had CLI (J Vasc Intervent Radiol 2020 Feb;31[2]:202-12).

In up to 1-year follow-up, the paclitaxel DCB group had fewer target lesion revascularizations (TLR) than those of the uncoated device group (11.8% vs. 25.6%; risk ratio, 0.53; 95% confidence interval, 0.35-0.81) but worse AFS (13.7% vs. 9.4%; hazard ratio [HR], 1.52; 95% CI, 1.12-2.07).

The latter finding was driven by nonsignificant increased risks for all-cause death (odds ratio [OR], 1.39; 95% CI, 0.94-2.07) and major amputations (OR, 1.63; 95% CI, 0.92-2.90).

In dose-subgroup analyses, AFS was significantly worse in cases with high-dose (3.0-3.5 mcg/mm²) devices, but not in the single trial with a low-dose DCB (2.0 mcg/mm²).

“Considering the well-described downstream ‘showers’ of paclitaxel particles with current drug-coated balloons, we hypothesize that nontarget paclitaxel embolization is a plausible mechanism for distal foot and systemic toxicity,” Dr. Katsanos said.

Short time frame

Eric Secemsky, MD, of Harvard Medical School, and director of vascular intervention at Beth Israel Deaconess Medical Center, Boston, suggested in an interview that this theorized mechanism of harm in below-the-knee procedures could potentially shed light on a similar mechanism at play in above-the-knee procedures.

“We didn’t understand why people could potentially be dying in above-the-knee [procedures], and the suggestion here is that these devices might perhaps be causing particular embolization or maybe delayed wound healing,” Dr. Secemsky speculated.

However, “I don’t know that this is true, so I am cautious to say this is true,” he emphasized.

Dr. Secemsky said a strength of the Katsanos analysis is that the RCTs included more than 1,000 patients, but noted that it is hard to vet the quality and rigor of the data, as some of the studies have not yet been published. He also noted that paclitaxel-coated devices are not approved by the Food and Drug Administration in the United States for below-the-knee procedures.

Moreover, he continued, “two studies were driving the signal of harm: the IN.PACT DEEP, which included an iteration of their DCB that is no longer being tested; and the unpublished SINGA-PACLI trial. Those studies contributed most of the adverse events seen in this meta-analysis.”

In addition, the trials had different lengths of follow-up (6-12 months), he said. “Thus, the five trials with data available to 12 months are driving the 1-year findings, whereas three RCTs, including the primary RCT showing safety [Lutonix-BTK trial], only contribute data to 6 months.”

For this reason, “we are not too excited about this meta-analysis as of now, [because] all it tells us is that we need more data to support the safety of drug-coated devices in this population,” Dr. Secemsky said.

Dr. Katsanos explained that, “to address the differences in follow-up period and number of cases lost to follow-up, the primary endpoint was calculated on the log-hazard scale and expressed as a hazard ratio, as recommended for time-to-event outcomes.”

He highlighted that a short-term time frame of 6 months to 1 year was chosen “because it is clinically relevant to limb-threatening CLI.”

Sensitivity tests also “showed consistent direction and magnitude of the summary treatment effects in case of both AFS and freedom from TLR,” Dr. Katsanos emphasized.

Lower mortality, fewer amputations

The second study, published online Jan. 8, drew on health insurance claims in the German BARMER database to analyze 37,914 patients (mean age, 73.3 years, 49% female) and 21,546 propensity-score-matched patients with symptomatic CLTI or intermittent claudication (IC) with an index revascularization during 2010-2018 (Eur J Vasc Endovasc Surg. 2020 Jan 8. doi: 10.1016/j.ejvs.2019.12.034).

Patients were first stratified by CLTI or IC, and then by balloon vs. stent use. Paclitaxel-coated devices were then compared with uncoated devices within each stratum. The primary outcome was all-cause mortality at the end of follow-up.

From 2010 to 2018, the annual use of paclitaxel-coated devices increased dramatically from 3% to 39% in the CLTI group and from 4% to 48% in the IC group (P less than .001 for both).

A total of 2,454 deaths occurred within 5 years of follow-up (median, 2.7 years; longest, 8 years).

A Cox proportional hazards model (based on propensity-score-matched cohorts at 5 years) showed that, compared with uncoated devices, use of paclitaxel-coated devices in the CLTI group was associated with several improvements:

• Overall survival: HR, 0.83; 95% CI, 0.77-0.90.
• Amputation-free survival: HR, 0.85; 95% CI, 0.78-0.91.
• Major cardiovascular events: HR, 0.82; 95% CI, 0.77-0.88.

In the IC group, mortality was significantly better with DCB (HR, 0.87; 95% CI, 0.76-0.99) or a combination of DCB and drug-eluting stents (HR, 0.88; 95% CI, 0.80-0.98) than with uncoated devices, but similar for DES alone (HR, 0.91; 95% CI, 0.77-1.08).

No benefit was found for paclitaxel-coated devices in the IC group for AFS (HR, 0.91; 95% CI, 0.82-1.00) or major cardiovascular events (HR, 0.93; 95% CI, 0.87-1.00).

The authors acknowledge that “unmeasured confounding” may partly explain the results. It may be that patients revascularized with DCB or DES “are more likely to be treated in highly specialized trial centers with clear follow-up protocol.”

Moreover, these patients may have received “the best treatment,” including statin therapy, added Dr. Behrendt.

More evidence needed

Dr. Secemsky, who was not involved with either study, said the German investigators “did a wonderful job with this analysis in a large population of several thousand patients, showing nicely that after accounting for differences in comorbidities, the patients had no evidence of harm with [paclitaxel-coated] devices through 5 years.”

However, he cautioned, median follow-up time was just over 2 years. “Although the investigators had data all the way out to 5 years, over time, the number of patients contributing data became smaller, which results in more uncertainty with these longer-term findings,” he said. “As such, we still need to look at additional long-term data in this patient population to confirm the safety of these devices.”

At present, the “major consideration we want to address is whether it’s safe to use these devices, and we’re undertaking these analyses to examine safety, not to see if they improve mortality,” although the present study “has a suggestion of mortality benefit,” Dr. Secemsky said.

Dr. Katsanos added that paclitaxel-coated balloons “remain under investigation for below-knee arteries and critical limb ischemia,” with “a few randomized controlled trials on the way.”

“We need definitive evidence from high-quality multicenter controlled trials that these devices may improve wound healing and limb salvage without any systemic mortality risk,” he said.

Dr. Katsanos receives personal fees from Boston Scientific and Philips Healthcare. The study by Dr. Behrendt was part of the IDOMENEO project funded by the German Joint Federal Committee. Dr. Behrendt reports no relevant financial relationships. Dr. Secemsky reports institutional grants from Cook Medical, BD Bard, Medtronic, Beth Israel Deaconess Medical Center, and Boston Scientific, and reports consultancy for Cook Medical, BD Bard, and Medtronic.
 

This article first appeared on Medscape.com.

The Trump administration on Feb. 10 argued for cutting spending for a federal agency at the forefront of the efforts to combat the coronavirus, while also seeking to slow spending in certain parts of the Medicare and Medicaid programs.

President Donald Trump presented his fiscal 2021 request to Congress for refilling the coffers of federal agencies. In any administration, an annual budget serves only as a political blueprint, as the White House document itself makes no changes in federal spending.

In Mr. Trump’s case, several of his requests for agencies within the Department of Health & Human Services run counter to recent budget trends. Republicans and Democrats in Congress have worked together in recent years to increase budgets for major federal health agencies.

But Mr. Trump asked Congress to cut annual budget authority for the National Institute of Allergy and Infectious Diseases by $430 million to $5.446 billion for fiscal 2021. In contrast, Congress has raised the annual budget for NIAID, a key agency in combating the coronavirus, from $5.545 billion in fiscal 2019 to $5.876 billion in fiscal 2020, which began in October, according to an HHS summary of Mr. Trump’s request.

For the Centers for Disease Control and Prevention, which is central to the battle against the coronavirus, Mr. Trump proposed a drop in discretionary funding to $5.627 billion. In contrast, Congress raised the CDC budget from $6.544 billion in fiscal 2019 to $6.917 in fiscal 2020.

Mr. Trump also wants to cut $559 million from the budget of the National Cancer Institute, dropping it to $5.881 billion in fiscal 2021. In contrast, Congress raised NCI’s budget from $6.121 billion in fiscal 2019 to $6.440 billion in fiscal 2020.

Mr. Trump requested a $2.6 billion reduction in the National Institutes of Health’s total discretionary budget, seeking to drop it to $37.70 billion. In contrast, Congress raised NIH’s budget from $37.887 in fiscal 2019 to $40.304 billion in fiscal 2020.

Mr. Trump’s budget proposal also includes an estimate of $152 billion in savings over a decade for Medicaid through the implementation of what the administration calls “community engagement” requirements.

The Trump administration has been at odds with Democrats for years about whether work requirements should be attached to Medicaid. “Well-designed community engagement incentives have great potential to improve health and well-being while empowering beneficiaries to rise out of poverty,” HHS said in a budget document.

Yet researchers last year reported that Arkansas’ attempt to attach work requirements to Medicaid caused almost 17,000 adults to lose this health care coverage within the first 6 months, and there was no significant difference in employment.

The researchers say this loss of coverage was partly a result of bureaucratic obstacles and confusion about the new rules. In June 2018, Arkansas became the first state to implement work requirements for Medicaid, Benjamin D. Sommers, MD, PhD, of the Harvard T.H. Chan School of Public Health, Boston, and colleagues wrote in the New England Journal of Medicine (2019 Sep 12;381[11]:1073-82). 

Budget ‘would thwart’ progress

A few medical groups on Monday quickly criticized Mr. Trump’s proposals.

“In a time where our nation continues to face significant public health challenges — including 2019 novel coronavirus, climate change, gun violence, and costly chronic diseases such as heart disease and cancer – the administration should be investing more resources in better health, not cutting federal health budgets,” said Georges C. Benjamin, MD, executive director of the American Public Health Association, in a statement.

David J. Skorton, MD, chief executive and president of the Association of American Medical Colleges (AAMC) also urged increased investment in fighting disease.

“We must continue the bipartisan budget trajectory set forth by Congress over the last several years, not reverse course,” Dr. Skorton said in a statement.

Mr. Trump’s proposed cuts in medical research “would thwart scientific progress on strategies to prevent, diagnose, treat, and cure medical conditions that affect countless patients nationwide,” he said.

In total, the new 2021 appropriations for HHS would fall by $9.46 billion to $85.667 billion under Mr. Trump’s proposal. Appropriations, also called discretionary budget authority, represents the operating budgets for federal agencies. These are decided through annual spending bills.

Congress has separate sets of laws for handling payments the federal government makes through Medicare and Medicaid. These are known as mandatory spending.

‘Untenable cuts’

AAMC’s Dr. Skorton also objected to what he termed Mr. Trump’s bid “to reduce and consolidate Medicare, Medicaid, and children’s hospital graduate medical education into a single grant program.”

This would force teaching hospitals to absorb $52 billion in “untenable cuts,” he said.

“The proposal ignores the intent of the Medicare GME program, which is to ensure an adequate physician workforce to care for Medicare beneficiaries and support the critical patient care missions of America’s teaching hospitals,” Dr. Skorton said.

The budget also seeks cuts to Medicaid, which come in addition to the administration’s “recent proposals to scale back Medicaid coverage,” Dr. Skorton said.

“More than 26% of all Medicaid hospitalizations occur at AAMC-member teaching hospitals, even though these institutions represent only 5% of all hospitals,” Dr. Skorton said. “Each of the administration’s proposals on their own would be devastating for patients – and combined, they would be disastrous.”

Rick Pollack, the chief executive and president of the American Hospital Association, described Mr. Trump’s fiscal 2021 proposal as another bid to undermine medical care in the United States.

“Every year, we adapt to a constantly changing environment, but every year, the administration aims to gut our nation’s health care infrastructure,” Mr. Pollack said in a statement.

In it, he noted that about one in five people in America depend on Medicaid, with children accounting for a large proportion of those covered by the state-federal program.

“The budget’s proposal on Medicaid financing and service delivery would cut hundreds of billions of dollars from the Medicaid program annually,” Mr. Pollack said.

He also objected to “hundreds of billions of proposed reductions to Medicare” endorsed by Mr. Trump.

Medical malpractice overhaul

The Trump administration also offered many suggestions for changing federal laws to reduce health care spending. Among these was a proposed overhaul of the approach to medical malpractice cases.

The president’s budget proposal estimates $40 billion in savings over a decade from steps to limit medical liability, according to a report from the Office of Management and Budget (OMB).

“The current medical liability system does not work for patients or providers, nor does it promote high-quality, evidence-based care,” OMB said. “Providers practice with a threat of potentially frivolous lawsuits, and injured patients often do not receive just compensation for their injuries.”

Mr. Trump’s fiscal 2021 budget calls for a cap on noneconomic damage awards of $250,000, which would increase with inflation over time, and a 3-year statute of limitations. Under this plan, courts could also modify attorney’s fee arrangements. HHS could provide guidance to states on how to create expert panels and administrative health care tribunals to review medical liability.

These steps would lead to lower health care spending, with clinicians dropping “defensive medicine practices,” OMB said. That would benefit the Medicare and Medicaid programs as well as lowering costs of health insurance in general.

Mr. Trump’s fiscal 2021 budget also includes a series of proposals for Medicare that it estimates would, in aggregate, save $755.5 billion over a decade.

Site-neutral policy

A large chunk of the estimated Medicare savings in Mr. Trump’s fiscal 2021 health budget would come from lowering payments to hospitals for services provided in their outpatient and physician offices.

In the fiscal 2021 proposal, HHS noted that “Medicare generally pays on-campus hospital outpatient departments substantially more than physician offices for the same services.”

Mr. Trump’s budget proposal seeks a more expansive shift to what’s called a “site-neutral” payment for services delivered in hospital outpatient programs or physician offices. This would bring these payments more in line with those made to independent physician practices.

“This proposal would eliminate the often significant disparity between what Medicare pays in these different settings for the same services,” HHS said in the budget summary.

HHS estimated this change in policy would generate $117.2 billion in savings over a decade. Combined with saving from medical malpractice reforms, the Trump administration estimates these two moves combined could save about $164 billion over a decade.

The site-neutral policy has been a legal battleground, with hospital and physician groups winning a round last year. 

Another Medicare proposal included in Mr. Trump’s fiscal 2021 budget homes in on this issue for cases where a hospital owns a physician office. Medicare now pays most off-campus hospital outpatient departments higher rates than the program’s physician fee schedule dictates for the same services.

Switching to a site-neutral policy for these hospital-owned physician offices would result in $47.2 billion in savings over a decade, HHS said in the budget document.
 

This article first appeared on Medscape.com.

The Trump administration on Feb. 10 argued for cutting spending for a federal agency at the forefront of the efforts to combat the coronavirus, while also seeking to slow spending in certain parts of the Medicare and Medicaid programs.

President Donald Trump presented his fiscal 2021 request to Congress for refilling the coffers of federal agencies. In any administration, an annual budget serves only as a political blueprint, as the White House document itself makes no changes in federal spending.

In Mr. Trump’s case, several of his requests for agencies within the Department of Health & Human Services run counter to recent budget trends. Republicans and Democrats in Congress have worked together in recent years to increase budgets for major federal health agencies.

But Mr. Trump asked Congress to cut annual budget authority for the National Institute of Allergy and Infectious Diseases by $430 million to $5.446 billion for fiscal 2021. In contrast, Congress has raised the annual budget for NIAID, a key agency in combating the coronavirus, from $5.545 billion in fiscal 2019 to $5.876 billion in fiscal 2020, which began in October, according to an HHS summary of Mr. Trump’s request.

For the Centers for Disease Control and Prevention, which is central to the battle against the coronavirus, Mr. Trump proposed a drop in discretionary funding to $5.627 billion. In contrast, Congress raised the CDC budget from $6.544 billion in fiscal 2019 to $6.917 in fiscal 2020.

Mr. Trump also wants to cut $559 million from the budget of the National Cancer Institute, dropping it to $5.881 billion in fiscal 2021. In contrast, Congress raised NCI’s budget from $6.121 billion in fiscal 2019 to $6.440 billion in fiscal 2020.

Mr. Trump requested a $2.6 billion reduction in the National Institutes of Health’s total discretionary budget, seeking to drop it to $37.70 billion. In contrast, Congress raised NIH’s budget from $37.887 in fiscal 2019 to $40.304 billion in fiscal 2020.

Mr. Trump’s budget proposal also includes an estimate of $152 billion in savings over a decade for Medicaid through the implementation of what the administration calls “community engagement” requirements.

The Trump administration has been at odds with Democrats for years about whether work requirements should be attached to Medicaid. “Well-designed community engagement incentives have great potential to improve health and well-being while empowering beneficiaries to rise out of poverty,” HHS said in a budget document.

Yet researchers last year reported that Arkansas’ attempt to attach work requirements to Medicaid caused almost 17,000 adults to lose this health care coverage within the first 6 months, and there was no significant difference in employment.

The researchers say this loss of coverage was partly a result of bureaucratic obstacles and confusion about the new rules. In June 2018, Arkansas became the first state to implement work requirements for Medicaid, Benjamin D. Sommers, MD, PhD, of the Harvard T.H. Chan School of Public Health, Boston, and colleagues wrote in the New England Journal of Medicine (2019 Sep 12;381[11]:1073-82). 

Budget ‘would thwart’ progress

A few medical groups on Monday quickly criticized Mr. Trump’s proposals.

“In a time where our nation continues to face significant public health challenges — including 2019 novel coronavirus, climate change, gun violence, and costly chronic diseases such as heart disease and cancer – the administration should be investing more resources in better health, not cutting federal health budgets,” said Georges C. Benjamin, MD, executive director of the American Public Health Association, in a statement.

David J. Skorton, MD, chief executive and president of the Association of American Medical Colleges (AAMC) also urged increased investment in fighting disease.

“We must continue the bipartisan budget trajectory set forth by Congress over the last several years, not reverse course,” Dr. Skorton said in a statement.

Mr. Trump’s proposed cuts in medical research “would thwart scientific progress on strategies to prevent, diagnose, treat, and cure medical conditions that affect countless patients nationwide,” he said.

In total, the new 2021 appropriations for HHS would fall by $9.46 billion to $85.667 billion under Mr. Trump’s proposal. Appropriations, also called discretionary budget authority, represents the operating budgets for federal agencies. These are decided through annual spending bills.

Congress has separate sets of laws for handling payments the federal government makes through Medicare and Medicaid. These are known as mandatory spending.

‘Untenable cuts’

AAMC’s Dr. Skorton also objected to what he termed Mr. Trump’s bid “to reduce and consolidate Medicare, Medicaid, and children’s hospital graduate medical education into a single grant program.”

This would force teaching hospitals to absorb $52 billion in “untenable cuts,” he said.

“The proposal ignores the intent of the Medicare GME program, which is to ensure an adequate physician workforce to care for Medicare beneficiaries and support the critical patient care missions of America’s teaching hospitals,” Dr. Skorton said.

The budget also seeks cuts to Medicaid, which come in addition to the administration’s “recent proposals to scale back Medicaid coverage,” Dr. Skorton said.

“More than 26% of all Medicaid hospitalizations occur at AAMC-member teaching hospitals, even though these institutions represent only 5% of all hospitals,” Dr. Skorton said. “Each of the administration’s proposals on their own would be devastating for patients – and combined, they would be disastrous.”

Rick Pollack, the chief executive and president of the American Hospital Association, described Mr. Trump’s fiscal 2021 proposal as another bid to undermine medical care in the United States.

“Every year, we adapt to a constantly changing environment, but every year, the administration aims to gut our nation’s health care infrastructure,” Mr. Pollack said in a statement.

In it, he noted that about one in five people in America depend on Medicaid, with children accounting for a large proportion of those covered by the state-federal program.

“The budget’s proposal on Medicaid financing and service delivery would cut hundreds of billions of dollars from the Medicaid program annually,” Mr. Pollack said.

He also objected to “hundreds of billions of proposed reductions to Medicare” endorsed by Mr. Trump.

Medical malpractice overhaul

The Trump administration also offered many suggestions for changing federal laws to reduce health care spending. Among these was a proposed overhaul of the approach to medical malpractice cases.

The president’s budget proposal estimates $40 billion in savings over a decade from steps to limit medical liability, according to a report from the Office of Management and Budget (OMB).

“The current medical liability system does not work for patients or providers, nor does it promote high-quality, evidence-based care,” OMB said. “Providers practice with a threat of potentially frivolous lawsuits, and injured patients often do not receive just compensation for their injuries.”

Mr. Trump’s fiscal 2021 budget calls for a cap on noneconomic damage awards of $250,000, which would increase with inflation over time, and a 3-year statute of limitations. Under this plan, courts could also modify attorney’s fee arrangements. HHS could provide guidance to states on how to create expert panels and administrative health care tribunals to review medical liability.

These steps would lead to lower health care spending, with clinicians dropping “defensive medicine practices,” OMB said. That would benefit the Medicare and Medicaid programs as well as lowering costs of health insurance in general.

Mr. Trump’s fiscal 2021 budget also includes a series of proposals for Medicare that it estimates would, in aggregate, save $755.5 billion over a decade.

Site-neutral policy

A large chunk of the estimated Medicare savings in Mr. Trump’s fiscal 2021 health budget would come from lowering payments to hospitals for services provided in their outpatient and physician offices.

In the fiscal 2021 proposal, HHS noted that “Medicare generally pays on-campus hospital outpatient departments substantially more than physician offices for the same services.”

Mr. Trump’s budget proposal seeks a more expansive shift to what’s called a “site-neutral” payment for services delivered in hospital outpatient programs or physician offices. This would bring these payments more in line with those made to independent physician practices.

“This proposal would eliminate the often significant disparity between what Medicare pays in these different settings for the same services,” HHS said in the budget summary.

HHS estimated this change in policy would generate $117.2 billion in savings over a decade. Combined with saving from medical malpractice reforms, the Trump administration estimates these two moves combined could save about $164 billion over a decade.

The site-neutral policy has been a legal battleground, with hospital and physician groups winning a round last year. 

Another Medicare proposal included in Mr. Trump’s fiscal 2021 budget homes in on this issue for cases where a hospital owns a physician office. Medicare now pays most off-campus hospital outpatient departments higher rates than the program’s physician fee schedule dictates for the same services.

Switching to a site-neutral policy for these hospital-owned physician offices would result in $47.2 billion in savings over a decade, HHS said in the budget document.
 

This article first appeared on Medscape.com.

The Trump administration on Feb. 10 argued for cutting spending for a federal agency at the forefront of the efforts to combat the coronavirus, while also seeking to slow spending in certain parts of the Medicare and Medicaid programs.

President Donald Trump presented his fiscal 2021 request to Congress for refilling the coffers of federal agencies. In any administration, an annual budget serves only as a political blueprint, as the White House document itself makes no changes in federal spending.

In Mr. Trump’s case, several of his requests for agencies within the Department of Health & Human Services run counter to recent budget trends. Republicans and Democrats in Congress have worked together in recent years to increase budgets for major federal health agencies.

But Mr. Trump asked Congress to cut annual budget authority for the National Institute of Allergy and Infectious Diseases by $430 million to $5.446 billion for fiscal 2021. In contrast, Congress has raised the annual budget for NIAID, a key agency in combating the coronavirus, from $5.545 billion in fiscal 2019 to $5.876 billion in fiscal 2020, which began in October, according to an HHS summary of Mr. Trump’s request.

For the Centers for Disease Control and Prevention, which is central to the battle against the coronavirus, Mr. Trump proposed a drop in discretionary funding to $5.627 billion. In contrast, Congress raised the CDC budget from $6.544 billion in fiscal 2019 to $6.917 in fiscal 2020.

Mr. Trump also wants to cut $559 million from the budget of the National Cancer Institute, dropping it to $5.881 billion in fiscal 2021. In contrast, Congress raised NCI’s budget from $6.121 billion in fiscal 2019 to $6.440 billion in fiscal 2020.

Mr. Trump requested a $2.6 billion reduction in the National Institutes of Health’s total discretionary budget, seeking to drop it to $37.70 billion. In contrast, Congress raised NIH’s budget from $37.887 in fiscal 2019 to $40.304 billion in fiscal 2020.

Mr. Trump’s budget proposal also includes an estimate of $152 billion in savings over a decade for Medicaid through the implementation of what the administration calls “community engagement” requirements.

The Trump administration has been at odds with Democrats for years about whether work requirements should be attached to Medicaid. “Well-designed community engagement incentives have great potential to improve health and well-being while empowering beneficiaries to rise out of poverty,” HHS said in a budget document.

Yet researchers last year reported that Arkansas’ attempt to attach work requirements to Medicaid caused almost 17,000 adults to lose this health care coverage within the first 6 months, and there was no significant difference in employment.

The researchers say this loss of coverage was partly a result of bureaucratic obstacles and confusion about the new rules. In June 2018, Arkansas became the first state to implement work requirements for Medicaid, Benjamin D. Sommers, MD, PhD, of the Harvard T.H. Chan School of Public Health, Boston, and colleagues wrote in the New England Journal of Medicine (2019 Sep 12;381[11]:1073-82). 

Budget ‘would thwart’ progress

A few medical groups on Monday quickly criticized Mr. Trump’s proposals.

“In a time where our nation continues to face significant public health challenges — including 2019 novel coronavirus, climate change, gun violence, and costly chronic diseases such as heart disease and cancer – the administration should be investing more resources in better health, not cutting federal health budgets,” said Georges C. Benjamin, MD, executive director of the American Public Health Association, in a statement.

David J. Skorton, MD, chief executive and president of the Association of American Medical Colleges (AAMC) also urged increased investment in fighting disease.

“We must continue the bipartisan budget trajectory set forth by Congress over the last several years, not reverse course,” Dr. Skorton said in a statement.

Mr. Trump’s proposed cuts in medical research “would thwart scientific progress on strategies to prevent, diagnose, treat, and cure medical conditions that affect countless patients nationwide,” he said.

In total, the new 2021 appropriations for HHS would fall by $9.46 billion to $85.667 billion under Mr. Trump’s proposal. Appropriations, also called discretionary budget authority, represents the operating budgets for federal agencies. These are decided through annual spending bills.

Congress has separate sets of laws for handling payments the federal government makes through Medicare and Medicaid. These are known as mandatory spending.

‘Untenable cuts’

AAMC’s Dr. Skorton also objected to what he termed Mr. Trump’s bid “to reduce and consolidate Medicare, Medicaid, and children’s hospital graduate medical education into a single grant program.”

This would force teaching hospitals to absorb $52 billion in “untenable cuts,” he said.

“The proposal ignores the intent of the Medicare GME program, which is to ensure an adequate physician workforce to care for Medicare beneficiaries and support the critical patient care missions of America’s teaching hospitals,” Dr. Skorton said.

The budget also seeks cuts to Medicaid, which come in addition to the administration’s “recent proposals to scale back Medicaid coverage,” Dr. Skorton said.

“More than 26% of all Medicaid hospitalizations occur at AAMC-member teaching hospitals, even though these institutions represent only 5% of all hospitals,” Dr. Skorton said. “Each of the administration’s proposals on their own would be devastating for patients – and combined, they would be disastrous.”

Rick Pollack, the chief executive and president of the American Hospital Association, described Mr. Trump’s fiscal 2021 proposal as another bid to undermine medical care in the United States.

“Every year, we adapt to a constantly changing environment, but every year, the administration aims to gut our nation’s health care infrastructure,” Mr. Pollack said in a statement.

In it, he noted that about one in five people in America depend on Medicaid, with children accounting for a large proportion of those covered by the state-federal program.

“The budget’s proposal on Medicaid financing and service delivery would cut hundreds of billions of dollars from the Medicaid program annually,” Mr. Pollack said.

He also objected to “hundreds of billions of proposed reductions to Medicare” endorsed by Mr. Trump.

Medical malpractice overhaul

The Trump administration also offered many suggestions for changing federal laws to reduce health care spending. Among these was a proposed overhaul of the approach to medical malpractice cases.

The president’s budget proposal estimates $40 billion in savings over a decade from steps to limit medical liability, according to a report from the Office of Management and Budget (OMB).

“The current medical liability system does not work for patients or providers, nor does it promote high-quality, evidence-based care,” OMB said. “Providers practice with a threat of potentially frivolous lawsuits, and injured patients often do not receive just compensation for their injuries.”

Mr. Trump’s fiscal 2021 budget calls for a cap on noneconomic damage awards of $250,000, which would increase with inflation over time, and a 3-year statute of limitations. Under this plan, courts could also modify attorney’s fee arrangements. HHS could provide guidance to states on how to create expert panels and administrative health care tribunals to review medical liability.

These steps would lead to lower health care spending, with clinicians dropping “defensive medicine practices,” OMB said. That would benefit the Medicare and Medicaid programs as well as lowering costs of health insurance in general.

Mr. Trump’s fiscal 2021 budget also includes a series of proposals for Medicare that it estimates would, in aggregate, save $755.5 billion over a decade.

Site-neutral policy

A large chunk of the estimated Medicare savings in Mr. Trump’s fiscal 2021 health budget would come from lowering payments to hospitals for services provided in their outpatient and physician offices.

In the fiscal 2021 proposal, HHS noted that “Medicare generally pays on-campus hospital outpatient departments substantially more than physician offices for the same services.”

Mr. Trump’s budget proposal seeks a more expansive shift to what’s called a “site-neutral” payment for services delivered in hospital outpatient programs or physician offices. This would bring these payments more in line with those made to independent physician practices.

“This proposal would eliminate the often significant disparity between what Medicare pays in these different settings for the same services,” HHS said in the budget summary.

HHS estimated this change in policy would generate $117.2 billion in savings over a decade. Combined with saving from medical malpractice reforms, the Trump administration estimates these two moves combined could save about $164 billion over a decade.

The site-neutral policy has been a legal battleground, with hospital and physician groups winning a round last year. 

Another Medicare proposal included in Mr. Trump’s fiscal 2021 budget homes in on this issue for cases where a hospital owns a physician office. Medicare now pays most off-campus hospital outpatient departments higher rates than the program’s physician fee schedule dictates for the same services.

Switching to a site-neutral policy for these hospital-owned physician offices would result in $47.2 billion in savings over a decade, HHS said in the budget document.
 

This article first appeared on Medscape.com.

Soylent stitches are people!

Michael Burrell/iStock/Getty Images Plus

Ask anyone in advertising and they’ll tell you that branding is everything. Now, there may be a bit of self-promotion involved there. But you can’t deny that naming your product appropriately is important, and we’re going to say with some degree of confidence that “human textile” is not the greatest name in the world.

Now, we don’t want to question the team of French researchers too much. After all, according to their research published in Acta Biomaterialia, they’ve come up with quite the nifty and potentially lifesaving innovation: stitches made from human skin.

By taking sheets of human skin cells (eww) and cutting them into strips, the researchers were able to weave the strips into a sort of yarn, the advantages of which should be obvious. Patients can say goodbye to pesky issues of compatibility and adverse immune response when doctors and surgeons can stitch wounds, sew pouches, and create tubes and valves with yarn crafted from themselves.

We just can’t get past the name they chose. Human textile. The process of making them is gruesome enough already. No need to call to mind some horrific dystopian future in which cotton can no longer grow and we have to recycle humans (alive or dead, depending on how grim you’re feeling) in big industrial textile mills to craft clothing for ourselves.

It’s just too bad Charlton Heston is dead; he’d have made a great spokesperson.
 

Towering over dementia

McIninch/iStock/Getty Images Plus

Let us take a moment to pity the plight of the shorter brother. Always losing the battle of the boards in fraternal driveway basketball games. Never reaching the Pop-Tarts cruelly stashed high in the pantry by one’s taller, greedier sibling. Always being addressed during family dinners as “Frodo.”

And new research findings add to the burden borne by altitude-impaired brothers everywhere: Being the short one may boost your risk of dementia.

Danish researchers at the University of Copenhagen examined the potential role that height in young adulthood plays later in dementia risk. The planet’s taller-brother Danes (the world’s third-tallest nation) analyzed data from more than 666,000 Danish men, including more than 70,000 brothers.

They found that, for every 6 cm of height in those above average height, the risk of dementia dropped 10%. And that inverse relationship between height and dementia risk held even in the shared environments of families: Being the taller brother delivered relatively more dementia protection. Even being smarter, better educated, and savvier at playing point guard didn’t erase shorter brothers’ dementia/height disadvantage.

Before you take solace in a Coors stubby, littler brothers, let’s remember the advantages shorter siblings still enjoy: Never being called “Ichabod.” Walking tall in low-ceilinged parking garages. Fitting comfortably into 911s and F-18s alike. Draining threes from anywhere in the driveway.

Oh, and clearly being Mom’s favorite.
 

Swinging for longevity

Kraig Scarbinsky/Photodisc

They say that laughter is the best medicine, but we always assumed that it applied to the people doing the laughing.

That may not be the case, according to a report presented at the American Stroke Association International Stroke Conference in Dallas.

It may be even better to get laughed at, and Adnan Qureshi, MD, of the University of Missouri, Columbia, and associates have data from the Cardiovascular Health Study of adults aged 65 years and older to prove it.

It’s all about the golf. The 384 golfers among the almost 5,900 participants had a death rate of 15.1% over the 10-year follow-up.

As for the nongolfers – the ones who make fun of golfers’ clothes and say that golf is boring, who joke about riding around in carts and hanging around with old people, who laugh because the lowest score wins, who say it’s easy to hit a little white ball that’s not even moving, who think an albatross is just a bird ... um, we seem to have gotten a bit off topic here.

Anyway, the death rate for the nongolfers in the study was a significantly higher 24.6%. So, suck on that, nongolfers, because it looks like the golfers will be having the last laugh. In plaid pants.

Soylent stitches are people!

Michael Burrell/iStock/Getty Images Plus

Ask anyone in advertising and they’ll tell you that branding is everything. Now, there may be a bit of self-promotion involved there. But you can’t deny that naming your product appropriately is important, and we’re going to say with some degree of confidence that “human textile” is not the greatest name in the world.

Now, we don’t want to question the team of French researchers too much. After all, according to their research published in Acta Biomaterialia, they’ve come up with quite the nifty and potentially lifesaving innovation: stitches made from human skin.

By taking sheets of human skin cells (eww) and cutting them into strips, the researchers were able to weave the strips into a sort of yarn, the advantages of which should be obvious. Patients can say goodbye to pesky issues of compatibility and adverse immune response when doctors and surgeons can stitch wounds, sew pouches, and create tubes and valves with yarn crafted from themselves.

We just can’t get past the name they chose. Human textile. The process of making them is gruesome enough already. No need to call to mind some horrific dystopian future in which cotton can no longer grow and we have to recycle humans (alive or dead, depending on how grim you’re feeling) in big industrial textile mills to craft clothing for ourselves.

It’s just too bad Charlton Heston is dead; he’d have made a great spokesperson.
 

Towering over dementia

McIninch/iStock/Getty Images Plus

Let us take a moment to pity the plight of the shorter brother. Always losing the battle of the boards in fraternal driveway basketball games. Never reaching the Pop-Tarts cruelly stashed high in the pantry by one’s taller, greedier sibling. Always being addressed during family dinners as “Frodo.”

And new research findings add to the burden borne by altitude-impaired brothers everywhere: Being the short one may boost your risk of dementia.

Danish researchers at the University of Copenhagen examined the potential role that height in young adulthood plays later in dementia risk. The planet’s taller-brother Danes (the world’s third-tallest nation) analyzed data from more than 666,000 Danish men, including more than 70,000 brothers.

They found that, for every 6 cm of height in those above average height, the risk of dementia dropped 10%. And that inverse relationship between height and dementia risk held even in the shared environments of families: Being the taller brother delivered relatively more dementia protection. Even being smarter, better educated, and savvier at playing point guard didn’t erase shorter brothers’ dementia/height disadvantage.

Before you take solace in a Coors stubby, littler brothers, let’s remember the advantages shorter siblings still enjoy: Never being called “Ichabod.” Walking tall in low-ceilinged parking garages. Fitting comfortably into 911s and F-18s alike. Draining threes from anywhere in the driveway.

Oh, and clearly being Mom’s favorite.
 

Swinging for longevity

Kraig Scarbinsky/Photodisc

They say that laughter is the best medicine, but we always assumed that it applied to the people doing the laughing.

That may not be the case, according to a report presented at the American Stroke Association International Stroke Conference in Dallas.

It may be even better to get laughed at, and Adnan Qureshi, MD, of the University of Missouri, Columbia, and associates have data from the Cardiovascular Health Study of adults aged 65 years and older to prove it.

It’s all about the golf. The 384 golfers among the almost 5,900 participants had a death rate of 15.1% over the 10-year follow-up.

As for the nongolfers – the ones who make fun of golfers’ clothes and say that golf is boring, who joke about riding around in carts and hanging around with old people, who laugh because the lowest score wins, who say it’s easy to hit a little white ball that’s not even moving, who think an albatross is just a bird ... um, we seem to have gotten a bit off topic here.

Anyway, the death rate for the nongolfers in the study was a significantly higher 24.6%. So, suck on that, nongolfers, because it looks like the golfers will be having the last laugh. In plaid pants.

Soylent stitches are people!

Michael Burrell/iStock/Getty Images Plus

Ask anyone in advertising and they’ll tell you that branding is everything. Now, there may be a bit of self-promotion involved there. But you can’t deny that naming your product appropriately is important, and we’re going to say with some degree of confidence that “human textile” is not the greatest name in the world.

Now, we don’t want to question the team of French researchers too much. After all, according to their research published in Acta Biomaterialia, they’ve come up with quite the nifty and potentially lifesaving innovation: stitches made from human skin.

By taking sheets of human skin cells (eww) and cutting them into strips, the researchers were able to weave the strips into a sort of yarn, the advantages of which should be obvious. Patients can say goodbye to pesky issues of compatibility and adverse immune response when doctors and surgeons can stitch wounds, sew pouches, and create tubes and valves with yarn crafted from themselves.

We just can’t get past the name they chose. Human textile. The process of making them is gruesome enough already. No need to call to mind some horrific dystopian future in which cotton can no longer grow and we have to recycle humans (alive or dead, depending on how grim you’re feeling) in big industrial textile mills to craft clothing for ourselves.

It’s just too bad Charlton Heston is dead; he’d have made a great spokesperson.
 

Towering over dementia

McIninch/iStock/Getty Images Plus

Let us take a moment to pity the plight of the shorter brother. Always losing the battle of the boards in fraternal driveway basketball games. Never reaching the Pop-Tarts cruelly stashed high in the pantry by one’s taller, greedier sibling. Always being addressed during family dinners as “Frodo.”

And new research findings add to the burden borne by altitude-impaired brothers everywhere: Being the short one may boost your risk of dementia.

Danish researchers at the University of Copenhagen examined the potential role that height in young adulthood plays later in dementia risk. The planet’s taller-brother Danes (the world’s third-tallest nation) analyzed data from more than 666,000 Danish men, including more than 70,000 brothers.

They found that, for every 6 cm of height in those above average height, the risk of dementia dropped 10%. And that inverse relationship between height and dementia risk held even in the shared environments of families: Being the taller brother delivered relatively more dementia protection. Even being smarter, better educated, and savvier at playing point guard didn’t erase shorter brothers’ dementia/height disadvantage.

Before you take solace in a Coors stubby, littler brothers, let’s remember the advantages shorter siblings still enjoy: Never being called “Ichabod.” Walking tall in low-ceilinged parking garages. Fitting comfortably into 911s and F-18s alike. Draining threes from anywhere in the driveway.

Oh, and clearly being Mom’s favorite.
 

Swinging for longevity

Kraig Scarbinsky/Photodisc

They say that laughter is the best medicine, but we always assumed that it applied to the people doing the laughing.

That may not be the case, according to a report presented at the American Stroke Association International Stroke Conference in Dallas.

It may be even better to get laughed at, and Adnan Qureshi, MD, of the University of Missouri, Columbia, and associates have data from the Cardiovascular Health Study of adults aged 65 years and older to prove it.

It’s all about the golf. The 384 golfers among the almost 5,900 participants had a death rate of 15.1% over the 10-year follow-up.

As for the nongolfers – the ones who make fun of golfers’ clothes and say that golf is boring, who joke about riding around in carts and hanging around with old people, who laugh because the lowest score wins, who say it’s easy to hit a little white ball that’s not even moving, who think an albatross is just a bird ... um, we seem to have gotten a bit off topic here.

Anyway, the death rate for the nongolfers in the study was a significantly higher 24.6%. So, suck on that, nongolfers, because it looks like the golfers will be having the last laugh. In plaid pants.

Top-line results from the seminal phase 2/3 Dominantly Inherited Alzheimer’s Network–Trials Unit (DIAN-TU) study show that the novel drugs gantenerumab (Roche) and solanezumab (Lilly) did not meet the primary endpoint in patients with early-stage, dominantly inherited Alzheimer’s disease (AD), investigators have announced.

In the international trial, which included almost 200 participants, the two experimental agents were evaluated separately. However, initial analyses showed that neither significantly slowed cognitive decline, the primary outcome measure, nor memory loss.

Still, the researchers noted that they will continue exploring data from DIAN-TU’s cognitive and clinical outcomes and are awaiting analyses of various biomarkers.

“Although the drugs we evaluated were not successful, the trial will move us forward in understanding Alzheimer’s,” principal investigator Randall J. Bateman, MD, of Washington University, St. Louis, said in a news release.

Funders for the trial included the National Institute on Aging and the Alzheimer’s Association.

“While the top-line data fell short, the Alzheimer’s Association looks forward to a more complete report at upcoming scientific conferences. We learn from every trial,” Maria Carrillo, PhD, chief scientific officer at the Alzheimer’s Association, noted in the organization’s own release.

Rebecca M. Edelmayer, PhD, director of scientific engagement for the Alzheimer’s Association, agreed with Dr. Carrillo that, although the results were disappointing, the data will be beneficial for the field.

“It’s always a difficult day when we get news like this,” Dr. Edelmayer said in an interview. However, “this research is going to absolutely provide valuable information once we can really pick through all of the data.”

Rare condition

Dominantly inherited AD, also known as familial AD or autosomal dominant AD, is rare but can affect memory and cognitive skills in individuals as young as age 30. It is caused by mutations on chromosomes 21, 14, and/or 1 that play a part in the breakdown of amyloid proteins and formation of amyloid plaques.

Both gantenerumab and solanezumab were created to target and neutralize amyloid-beta, albeit through different mechanisms. Both are also being assessed in other trials as treatment for more common forms of AD.

As reported by Medscape Medical News, results of the phase 3 EXPEDITION3 trial of solanezumab in patients with mild AD were negative, as were two other phase 3 trials. The drug is now being evaluated in the ongoing solanezumab Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) study.

Although the phase 3 SCARLET ROAD trial of gantenerumab for mild AD was stopped early for futility in 2014, it was continued as an open-label extension at the high dose for 2 years. During that period, follow-up analyses showed a dramatic decline in amyloid-beta deposition in the participants – leading to the launch of the phase 3 GRADUATE 1 and GRADUATE 2 trials.

Starting in 2012, DIAN-TU was conducted at 24 sites in the United States, the United Kingdom, Canada, Europe, and Australia. It followed 194 adult patients for up to 7 years (average duration, 5 years). Its original estimated completion date was December 2020, as stated on clinicaltrials.gov.

All participants had family members with a genetic mutation that causes early-onset Alzheimer’s disease. They already had very mild symptoms of cognitive decline and memory loss at the start of the trial or were expected to develop symptoms within 15 years of enrollment.

“People who inherit the mutation are all but guaranteed to develop symptoms at about the same age their parents did,” the release noted.

“While devastating for families, such mutations allow researchers to identify people in the early stages of the disease before their behavior and memory begin to change,” it added.

The Alzheimer’s Association noted in its release that a child of a parent with the mutation has a 50/50 chance of inheriting the disease. “This form affects less than 1% of the individuals living with Alzheimer’s disease today,” Dr. Edelmayer noted.

Detailed data coming soon

Trial participants were randomly assigned to receive either solanezumab, gantenerumab, or matching placebo. To act as a comparator group, family members without the AD mutation were also included.

The primary measure was change from baseline in the DIAN-TU cognitive composite score. Secondary measures included changes on the Mini-Mental State Examination, the Functional Assessment Scale, the Neuropsychiatric Inventory Questionnaire, the 12-item International Shopping List Test, the Memory Complaint Questionnaire, and the Wechsler Memory Scale Logical Memory/Paragraph Memory test.

The researchers also conducted imaging scans and collected samples of blood and cerebrospinal fluid.

Along with announcing the negative top-line results for the trial, the investigators noted that “a more detailed analysis of the trial’s data” will be presented at the Advances in Alzheimer’s and Parkinson’s Therapies in Vienna on April 2, 2020, and at the Alzheimer’s Association International Conference in Amsterdam in July.

The researchers will continue to explore all data gathered – but already new insights have been discovered into the development and progression of AD, Dr. Bateman noted.

Included among these discoveries is that brain changes that occur as the disease progresses are similar among those with the inherited, early-onset form of AD and the late-onset form.

“The trial’s innovative design ... will make advances for future Alzheimer’s trials. Ongoing and continued research and trials will bring us closer to our goal to stop Alzheimer’s,” Dr. Bateman said. “We will continue until we are successful.”

“These results reflect the difficult nature of treating [AD] and the great need for continued research,” said Daniel Skovronsky, MD, PhD, chief scientific officer and president of Lilly Research Labs.

“If we have learned one thing after more than 30 years of Alzheimer’s research, it is that even negative results propel the science forward,” he added.

Lilly noted in a statement that the DIAN-TU top-line results will not affect its ongoing A4 study of solanezumab. Roche noted in its own statement that the findings also will not affect the company’s ongoing GRADUATE studies of gantenerumab.

“The work doesn’t stop here”

Richard J. Hodes, MD, director of the National Institute on Aging, said that DIAN-TU will advance the field’s knowledge about a complex disease.

“We look forward to learning more through the published, peer-reviewed data, which will provide a broad range of scientists with crucial information and guidance for future research,” he said.

Howard Fillit, MD, founding executive director and chief science officer at the Alzheimer’s Drug Discovery Foundation (ADDF), agreed.

“While we are disappointed that patients in this study did not see a benefit, we need to keep in mind that Alzheimer’s is a complicated disease due to complex, multifactorial causes,” he said in a statement.

“ADDF has long supported a broader approach that moves past targeting beta-amyloid and advances a diverse pipeline of drugs addressing multiple targets” in AD, Dr. Fillit added. “We need multiple ‘shots on goals’ to discover effective drugs.”

Dr. Edelmayer said the results emphasize that “this story isn’t yet completely told” and that there is still a lot to learn from the data, especially regarding the biomarkers that were tested.

“With that information, we will gain valuable insight into the outcomes that have been released but will also probably better understand where we should be putting our energies and focus moving forward,” she said.

Going forward, “we will continue this fight until we have an effective treatment for all individuals living with Alzheimer’s, whether it’s dominantly inherited [AD] or the more common version, which is the late-onset or sporadic form of the disease,” said Dr. Edelmayer.

“We have to stay optimistic. The work doesn’t stop here.”

The trial was funded by Eli Lilly, Roche, the Alzheimer’s Association, the National Institute on Aging, the GHR Foundation, and FBRI.

This article first appeared on Medscape.com.

Top-line results from the seminal phase 2/3 Dominantly Inherited Alzheimer’s Network–Trials Unit (DIAN-TU) study show that the novel drugs gantenerumab (Roche) and solanezumab (Lilly) did not meet the primary endpoint in patients with early-stage, dominantly inherited Alzheimer’s disease (AD), investigators have announced.

In the international trial, which included almost 200 participants, the two experimental agents were evaluated separately. However, initial analyses showed that neither significantly slowed cognitive decline, the primary outcome measure, nor memory loss.

Still, the researchers noted that they will continue exploring data from DIAN-TU’s cognitive and clinical outcomes and are awaiting analyses of various biomarkers.

“Although the drugs we evaluated were not successful, the trial will move us forward in understanding Alzheimer’s,” principal investigator Randall J. Bateman, MD, of Washington University, St. Louis, said in a news release.

Funders for the trial included the National Institute on Aging and the Alzheimer’s Association.

“While the top-line data fell short, the Alzheimer’s Association looks forward to a more complete report at upcoming scientific conferences. We learn from every trial,” Maria Carrillo, PhD, chief scientific officer at the Alzheimer’s Association, noted in the organization’s own release.

Rebecca M. Edelmayer, PhD, director of scientific engagement for the Alzheimer’s Association, agreed with Dr. Carrillo that, although the results were disappointing, the data will be beneficial for the field.

“It’s always a difficult day when we get news like this,” Dr. Edelmayer said in an interview. However, “this research is going to absolutely provide valuable information once we can really pick through all of the data.”

Rare condition

Dominantly inherited AD, also known as familial AD or autosomal dominant AD, is rare but can affect memory and cognitive skills in individuals as young as age 30. It is caused by mutations on chromosomes 21, 14, and/or 1 that play a part in the breakdown of amyloid proteins and formation of amyloid plaques.

Both gantenerumab and solanezumab were created to target and neutralize amyloid-beta, albeit through different mechanisms. Both are also being assessed in other trials as treatment for more common forms of AD.

As reported by Medscape Medical News, results of the phase 3 EXPEDITION3 trial of solanezumab in patients with mild AD were negative, as were two other phase 3 trials. The drug is now being evaluated in the ongoing solanezumab Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) study.

Although the phase 3 SCARLET ROAD trial of gantenerumab for mild AD was stopped early for futility in 2014, it was continued as an open-label extension at the high dose for 2 years. During that period, follow-up analyses showed a dramatic decline in amyloid-beta deposition in the participants – leading to the launch of the phase 3 GRADUATE 1 and GRADUATE 2 trials.

Starting in 2012, DIAN-TU was conducted at 24 sites in the United States, the United Kingdom, Canada, Europe, and Australia. It followed 194 adult patients for up to 7 years (average duration, 5 years). Its original estimated completion date was December 2020, as stated on clinicaltrials.gov.

All participants had family members with a genetic mutation that causes early-onset Alzheimer’s disease. They already had very mild symptoms of cognitive decline and memory loss at the start of the trial or were expected to develop symptoms within 15 years of enrollment.

“People who inherit the mutation are all but guaranteed to develop symptoms at about the same age their parents did,” the release noted.

“While devastating for families, such mutations allow researchers to identify people in the early stages of the disease before their behavior and memory begin to change,” it added.

The Alzheimer’s Association noted in its release that a child of a parent with the mutation has a 50/50 chance of inheriting the disease. “This form affects less than 1% of the individuals living with Alzheimer’s disease today,” Dr. Edelmayer noted.

Detailed data coming soon

Trial participants were randomly assigned to receive either solanezumab, gantenerumab, or matching placebo. To act as a comparator group, family members without the AD mutation were also included.

The primary measure was change from baseline in the DIAN-TU cognitive composite score. Secondary measures included changes on the Mini-Mental State Examination, the Functional Assessment Scale, the Neuropsychiatric Inventory Questionnaire, the 12-item International Shopping List Test, the Memory Complaint Questionnaire, and the Wechsler Memory Scale Logical Memory/Paragraph Memory test.

The researchers also conducted imaging scans and collected samples of blood and cerebrospinal fluid.

Along with announcing the negative top-line results for the trial, the investigators noted that “a more detailed analysis of the trial’s data” will be presented at the Advances in Alzheimer’s and Parkinson’s Therapies in Vienna on April 2, 2020, and at the Alzheimer’s Association International Conference in Amsterdam in July.

The researchers will continue to explore all data gathered – but already new insights have been discovered into the development and progression of AD, Dr. Bateman noted.

Included among these discoveries is that brain changes that occur as the disease progresses are similar among those with the inherited, early-onset form of AD and the late-onset form.

“The trial’s innovative design ... will make advances for future Alzheimer’s trials. Ongoing and continued research and trials will bring us closer to our goal to stop Alzheimer’s,” Dr. Bateman said. “We will continue until we are successful.”

“These results reflect the difficult nature of treating [AD] and the great need for continued research,” said Daniel Skovronsky, MD, PhD, chief scientific officer and president of Lilly Research Labs.

“If we have learned one thing after more than 30 years of Alzheimer’s research, it is that even negative results propel the science forward,” he added.

Lilly noted in a statement that the DIAN-TU top-line results will not affect its ongoing A4 study of solanezumab. Roche noted in its own statement that the findings also will not affect the company’s ongoing GRADUATE studies of gantenerumab.

“The work doesn’t stop here”

Richard J. Hodes, MD, director of the National Institute on Aging, said that DIAN-TU will advance the field’s knowledge about a complex disease.

“We look forward to learning more through the published, peer-reviewed data, which will provide a broad range of scientists with crucial information and guidance for future research,” he said.

Howard Fillit, MD, founding executive director and chief science officer at the Alzheimer’s Drug Discovery Foundation (ADDF), agreed.

“While we are disappointed that patients in this study did not see a benefit, we need to keep in mind that Alzheimer’s is a complicated disease due to complex, multifactorial causes,” he said in a statement.

“ADDF has long supported a broader approach that moves past targeting beta-amyloid and advances a diverse pipeline of drugs addressing multiple targets” in AD, Dr. Fillit added. “We need multiple ‘shots on goals’ to discover effective drugs.”

Dr. Edelmayer said the results emphasize that “this story isn’t yet completely told” and that there is still a lot to learn from the data, especially regarding the biomarkers that were tested.

“With that information, we will gain valuable insight into the outcomes that have been released but will also probably better understand where we should be putting our energies and focus moving forward,” she said.

Going forward, “we will continue this fight until we have an effective treatment for all individuals living with Alzheimer’s, whether it’s dominantly inherited [AD] or the more common version, which is the late-onset or sporadic form of the disease,” said Dr. Edelmayer.

“We have to stay optimistic. The work doesn’t stop here.”

The trial was funded by Eli Lilly, Roche, the Alzheimer’s Association, the National Institute on Aging, the GHR Foundation, and FBRI.

This article first appeared on Medscape.com.

Top-line results from the seminal phase 2/3 Dominantly Inherited Alzheimer’s Network–Trials Unit (DIAN-TU) study show that the novel drugs gantenerumab (Roche) and solanezumab (Lilly) did not meet the primary endpoint in patients with early-stage, dominantly inherited Alzheimer’s disease (AD), investigators have announced.

In the international trial, which included almost 200 participants, the two experimental agents were evaluated separately. However, initial analyses showed that neither significantly slowed cognitive decline, the primary outcome measure, nor memory loss.

Still, the researchers noted that they will continue exploring data from DIAN-TU’s cognitive and clinical outcomes and are awaiting analyses of various biomarkers.

“Although the drugs we evaluated were not successful, the trial will move us forward in understanding Alzheimer’s,” principal investigator Randall J. Bateman, MD, of Washington University, St. Louis, said in a news release.

Funders for the trial included the National Institute on Aging and the Alzheimer’s Association.

“While the top-line data fell short, the Alzheimer’s Association looks forward to a more complete report at upcoming scientific conferences. We learn from every trial,” Maria Carrillo, PhD, chief scientific officer at the Alzheimer’s Association, noted in the organization’s own release.

Rebecca M. Edelmayer, PhD, director of scientific engagement for the Alzheimer’s Association, agreed with Dr. Carrillo that, although the results were disappointing, the data will be beneficial for the field.

“It’s always a difficult day when we get news like this,” Dr. Edelmayer said in an interview. However, “this research is going to absolutely provide valuable information once we can really pick through all of the data.”

Rare condition

Dominantly inherited AD, also known as familial AD or autosomal dominant AD, is rare but can affect memory and cognitive skills in individuals as young as age 30. It is caused by mutations on chromosomes 21, 14, and/or 1 that play a part in the breakdown of amyloid proteins and formation of amyloid plaques.

Both gantenerumab and solanezumab were created to target and neutralize amyloid-beta, albeit through different mechanisms. Both are also being assessed in other trials as treatment for more common forms of AD.

As reported by Medscape Medical News, results of the phase 3 EXPEDITION3 trial of solanezumab in patients with mild AD were negative, as were two other phase 3 trials. The drug is now being evaluated in the ongoing solanezumab Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) study.

Although the phase 3 SCARLET ROAD trial of gantenerumab for mild AD was stopped early for futility in 2014, it was continued as an open-label extension at the high dose for 2 years. During that period, follow-up analyses showed a dramatic decline in amyloid-beta deposition in the participants – leading to the launch of the phase 3 GRADUATE 1 and GRADUATE 2 trials.

Starting in 2012, DIAN-TU was conducted at 24 sites in the United States, the United Kingdom, Canada, Europe, and Australia. It followed 194 adult patients for up to 7 years (average duration, 5 years). Its original estimated completion date was December 2020, as stated on clinicaltrials.gov.

All participants had family members with a genetic mutation that causes early-onset Alzheimer’s disease. They already had very mild symptoms of cognitive decline and memory loss at the start of the trial or were expected to develop symptoms within 15 years of enrollment.

“People who inherit the mutation are all but guaranteed to develop symptoms at about the same age their parents did,” the release noted.

“While devastating for families, such mutations allow researchers to identify people in the early stages of the disease before their behavior and memory begin to change,” it added.

The Alzheimer’s Association noted in its release that a child of a parent with the mutation has a 50/50 chance of inheriting the disease. “This form affects less than 1% of the individuals living with Alzheimer’s disease today,” Dr. Edelmayer noted.

Detailed data coming soon

Trial participants were randomly assigned to receive either solanezumab, gantenerumab, or matching placebo. To act as a comparator group, family members without the AD mutation were also included.

The primary measure was change from baseline in the DIAN-TU cognitive composite score. Secondary measures included changes on the Mini-Mental State Examination, the Functional Assessment Scale, the Neuropsychiatric Inventory Questionnaire, the 12-item International Shopping List Test, the Memory Complaint Questionnaire, and the Wechsler Memory Scale Logical Memory/Paragraph Memory test.

The researchers also conducted imaging scans and collected samples of blood and cerebrospinal fluid.

Along with announcing the negative top-line results for the trial, the investigators noted that “a more detailed analysis of the trial’s data” will be presented at the Advances in Alzheimer’s and Parkinson’s Therapies in Vienna on April 2, 2020, and at the Alzheimer’s Association International Conference in Amsterdam in July.

The researchers will continue to explore all data gathered – but already new insights have been discovered into the development and progression of AD, Dr. Bateman noted.

Included among these discoveries is that brain changes that occur as the disease progresses are similar among those with the inherited, early-onset form of AD and the late-onset form.

“The trial’s innovative design ... will make advances for future Alzheimer’s trials. Ongoing and continued research and trials will bring us closer to our goal to stop Alzheimer’s,” Dr. Bateman said. “We will continue until we are successful.”

“These results reflect the difficult nature of treating [AD] and the great need for continued research,” said Daniel Skovronsky, MD, PhD, chief scientific officer and president of Lilly Research Labs.

“If we have learned one thing after more than 30 years of Alzheimer’s research, it is that even negative results propel the science forward,” he added.

Lilly noted in a statement that the DIAN-TU top-line results will not affect its ongoing A4 study of solanezumab. Roche noted in its own statement that the findings also will not affect the company’s ongoing GRADUATE studies of gantenerumab.

“The work doesn’t stop here”

Richard J. Hodes, MD, director of the National Institute on Aging, said that DIAN-TU will advance the field’s knowledge about a complex disease.

“We look forward to learning more through the published, peer-reviewed data, which will provide a broad range of scientists with crucial information and guidance for future research,” he said.

Howard Fillit, MD, founding executive director and chief science officer at the Alzheimer’s Drug Discovery Foundation (ADDF), agreed.

“While we are disappointed that patients in this study did not see a benefit, we need to keep in mind that Alzheimer’s is a complicated disease due to complex, multifactorial causes,” he said in a statement.

“ADDF has long supported a broader approach that moves past targeting beta-amyloid and advances a diverse pipeline of drugs addressing multiple targets” in AD, Dr. Fillit added. “We need multiple ‘shots on goals’ to discover effective drugs.”

Dr. Edelmayer said the results emphasize that “this story isn’t yet completely told” and that there is still a lot to learn from the data, especially regarding the biomarkers that were tested.

“With that information, we will gain valuable insight into the outcomes that have been released but will also probably better understand where we should be putting our energies and focus moving forward,” she said.

Going forward, “we will continue this fight until we have an effective treatment for all individuals living with Alzheimer’s, whether it’s dominantly inherited [AD] or the more common version, which is the late-onset or sporadic form of the disease,” said Dr. Edelmayer.

“We have to stay optimistic. The work doesn’t stop here.”

The trial was funded by Eli Lilly, Roche, the Alzheimer’s Association, the National Institute on Aging, the GHR Foundation, and FBRI.

This article first appeared on Medscape.com.

AUSTIN, TEX. – Patients with inflammatory bowel disease (IBD) who want to have children can benefit from better education about recent findings that disease control, laparoscopic surgery, and in vitro fertilization (IVF) have improved their chances of conceiving, according to a review of published reports presented here at the Crohn’s & Colitis Congress, a partnership of the Crohn’s & Colitis Congress Foundation and the American Gastroenterological Association.

Richard Mark Kirkner/MDedge News

“Decreased fertility in IBD is due to voluntary childlessness, which we can change with education; surgery for IBD, which we can improve with laparoscopic surgery; and increased disease activity, which we can also make a difference in,” Sonia Friedman, MD, of Harvard Medical School, Boston, said in an interview.

Dr. Friedman and coauthors last year published an analysis of the Danish National Birth Cohort, which showed women with IBD had an 28% greater relative risk of taking a year or more to get pregnant than controls without IBD, and that the relative risk was even higher in women with Crohn’s disease — 54% (Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2019.08.031). “We found that women with Crohn’s surgery had decreased fertility by 2.54 times greater relative risk,” she said.

“Fertility, pregnancy is the most important thing to patients,” Dr. Friedman said in an interview. “That’s what people ask me about the most. In the population of IBD patients, the onset is age 15-35, and these people are in the prime of their reproductive years.” Sexual function, known to be decreased in men and women with IBD, is also an overriding concern in these patients, she said. “There needs to be a lot more information out there about it.”

She said gastroenterologists should keep in mind that much of the evidence documenting reduced fertility after ileo-pouch anal anastomosis is dated and focused on open surgery, which caused profound scarring of the pelvis and fallopian tubes, thus hindering conception. Laparoscopic ileoanal J-pouch surgery (IPAA) has yielded much improved outcomes in women of child-bearing age, she said, citing a study late last year that reported women who had laparoscopic IPAA had a median time to pregnancy of 3.5 months versus 9 months for women who had open IPAA (Surgery. 2019;166:670-7).

“It’s really important to discuss the issues of fertility, especially for patients contemplating surgery,” Dr. Friedman said. “Emphasize that there are good outcomes with laparoscopic surgery, and they can have assisted reproductive technology [ART], or in vitro fertilization, if needed. Never withhold surgery based on fear of infertility.”

Her practice is to refer women with IBD in remission for IVF if they’ve tried to get pregnant every month for a year or more and to refer women with IBD surgery for IVF after trying to get pregnant for 6 months. Dr. Friedman coauthored two studies of the Danish National Birth Cohort of ART in women with Crohn’s disease and ulcerative colitis (UC) along with controls (Gut. 2016;65:767-76; Gut. 2017;66:556-58). “We found that women with Crohn’s and UC had a decreased chance of having a clinical pregnancy, but they had no problem carrying the pregnancy to term,” she said.

Those findings raised questions about the etiology of decreased fertility in IBD patients, which could include factors such as IVF technique, reproductive hormone and microbiome changes, or IBD medications. “How can we carry that forward to all women with IBD?” she said. Women with IBD have less chance of conceiving with each IVF treatment cycle than do women without IBD, she said. “The most interesting thing is that the reduced chance of live birth after IVF treatment in Crohn’s and UC is related to the stages of implantation and not to the ability to maintain the fetus throughout pregnancy,” she said.

Dr. Friedman has no financial relationships to disclose.

The AGA IBD Parenthood Project can help guide your patients with IBD throughout their pregnancy, from trying to conceive through postpartum care. Learn more at IBDParenthoodProject.org.

SOURCE: Friedman S. Crohn’s & Colitis Congress, Session Sp86.

AUSTIN, TEX. – Patients with inflammatory bowel disease (IBD) who want to have children can benefit from better education about recent findings that disease control, laparoscopic surgery, and in vitro fertilization (IVF) have improved their chances of conceiving, according to a review of published reports presented here at the Crohn’s & Colitis Congress, a partnership of the Crohn’s & Colitis Congress Foundation and the American Gastroenterological Association.

Richard Mark Kirkner/MDedge News

“Decreased fertility in IBD is due to voluntary childlessness, which we can change with education; surgery for IBD, which we can improve with laparoscopic surgery; and increased disease activity, which we can also make a difference in,” Sonia Friedman, MD, of Harvard Medical School, Boston, said in an interview.

Dr. Friedman and coauthors last year published an analysis of the Danish National Birth Cohort, which showed women with IBD had an 28% greater relative risk of taking a year or more to get pregnant than controls without IBD, and that the relative risk was even higher in women with Crohn’s disease — 54% (Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2019.08.031). “We found that women with Crohn’s surgery had decreased fertility by 2.54 times greater relative risk,” she said.

“Fertility, pregnancy is the most important thing to patients,” Dr. Friedman said in an interview. “That’s what people ask me about the most. In the population of IBD patients, the onset is age 15-35, and these people are in the prime of their reproductive years.” Sexual function, known to be decreased in men and women with IBD, is also an overriding concern in these patients, she said. “There needs to be a lot more information out there about it.”

She said gastroenterologists should keep in mind that much of the evidence documenting reduced fertility after ileo-pouch anal anastomosis is dated and focused on open surgery, which caused profound scarring of the pelvis and fallopian tubes, thus hindering conception. Laparoscopic ileoanal J-pouch surgery (IPAA) has yielded much improved outcomes in women of child-bearing age, she said, citing a study late last year that reported women who had laparoscopic IPAA had a median time to pregnancy of 3.5 months versus 9 months for women who had open IPAA (Surgery. 2019;166:670-7).

“It’s really important to discuss the issues of fertility, especially for patients contemplating surgery,” Dr. Friedman said. “Emphasize that there are good outcomes with laparoscopic surgery, and they can have assisted reproductive technology [ART], or in vitro fertilization, if needed. Never withhold surgery based on fear of infertility.”

Her practice is to refer women with IBD in remission for IVF if they’ve tried to get pregnant every month for a year or more and to refer women with IBD surgery for IVF after trying to get pregnant for 6 months. Dr. Friedman coauthored two studies of the Danish National Birth Cohort of ART in women with Crohn’s disease and ulcerative colitis (UC) along with controls (Gut. 2016;65:767-76; Gut. 2017;66:556-58). “We found that women with Crohn’s and UC had a decreased chance of having a clinical pregnancy, but they had no problem carrying the pregnancy to term,” she said.

Those findings raised questions about the etiology of decreased fertility in IBD patients, which could include factors such as IVF technique, reproductive hormone and microbiome changes, or IBD medications. “How can we carry that forward to all women with IBD?” she said. Women with IBD have less chance of conceiving with each IVF treatment cycle than do women without IBD, she said. “The most interesting thing is that the reduced chance of live birth after IVF treatment in Crohn’s and UC is related to the stages of implantation and not to the ability to maintain the fetus throughout pregnancy,” she said.

Dr. Friedman has no financial relationships to disclose.

The AGA IBD Parenthood Project can help guide your patients with IBD throughout their pregnancy, from trying to conceive through postpartum care. Learn more at IBDParenthoodProject.org.

SOURCE: Friedman S. Crohn’s & Colitis Congress, Session Sp86.

AUSTIN, TEX. – Patients with inflammatory bowel disease (IBD) who want to have children can benefit from better education about recent findings that disease control, laparoscopic surgery, and in vitro fertilization (IVF) have improved their chances of conceiving, according to a review of published reports presented here at the Crohn’s & Colitis Congress, a partnership of the Crohn’s & Colitis Congress Foundation and the American Gastroenterological Association.

Richard Mark Kirkner/MDedge News

“Decreased fertility in IBD is due to voluntary childlessness, which we can change with education; surgery for IBD, which we can improve with laparoscopic surgery; and increased disease activity, which we can also make a difference in,” Sonia Friedman, MD, of Harvard Medical School, Boston, said in an interview.

Dr. Friedman and coauthors last year published an analysis of the Danish National Birth Cohort, which showed women with IBD had an 28% greater relative risk of taking a year or more to get pregnant than controls without IBD, and that the relative risk was even higher in women with Crohn’s disease — 54% (Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2019.08.031). “We found that women with Crohn’s surgery had decreased fertility by 2.54 times greater relative risk,” she said.

“Fertility, pregnancy is the most important thing to patients,” Dr. Friedman said in an interview. “That’s what people ask me about the most. In the population of IBD patients, the onset is age 15-35, and these people are in the prime of their reproductive years.” Sexual function, known to be decreased in men and women with IBD, is also an overriding concern in these patients, she said. “There needs to be a lot more information out there about it.”

She said gastroenterologists should keep in mind that much of the evidence documenting reduced fertility after ileo-pouch anal anastomosis is dated and focused on open surgery, which caused profound scarring of the pelvis and fallopian tubes, thus hindering conception. Laparoscopic ileoanal J-pouch surgery (IPAA) has yielded much improved outcomes in women of child-bearing age, she said, citing a study late last year that reported women who had laparoscopic IPAA had a median time to pregnancy of 3.5 months versus 9 months for women who had open IPAA (Surgery. 2019;166:670-7).

“It’s really important to discuss the issues of fertility, especially for patients contemplating surgery,” Dr. Friedman said. “Emphasize that there are good outcomes with laparoscopic surgery, and they can have assisted reproductive technology [ART], or in vitro fertilization, if needed. Never withhold surgery based on fear of infertility.”

Her practice is to refer women with IBD in remission for IVF if they’ve tried to get pregnant every month for a year or more and to refer women with IBD surgery for IVF after trying to get pregnant for 6 months. Dr. Friedman coauthored two studies of the Danish National Birth Cohort of ART in women with Crohn’s disease and ulcerative colitis (UC) along with controls (Gut. 2016;65:767-76; Gut. 2017;66:556-58). “We found that women with Crohn’s and UC had a decreased chance of having a clinical pregnancy, but they had no problem carrying the pregnancy to term,” she said.

Those findings raised questions about the etiology of decreased fertility in IBD patients, which could include factors such as IVF technique, reproductive hormone and microbiome changes, or IBD medications. “How can we carry that forward to all women with IBD?” she said. Women with IBD have less chance of conceiving with each IVF treatment cycle than do women without IBD, she said. “The most interesting thing is that the reduced chance of live birth after IVF treatment in Crohn’s and UC is related to the stages of implantation and not to the ability to maintain the fetus throughout pregnancy,” she said.

Dr. Friedman has no financial relationships to disclose.

The AGA IBD Parenthood Project can help guide your patients with IBD throughout their pregnancy, from trying to conceive through postpartum care. Learn more at IBDParenthoodProject.org.

SOURCE: Friedman S. Crohn’s & Colitis Congress, Session Sp86.

Clinical trials supporting Food and Drug Adminstration approval of contemporary cancer therapies frequently failed to capture major adverse cardiovascular events (MACE) and, when they did, reported rates 2.6-fold lower than noncancer trials, new research shows.

Overall, 51.3% of trials did not report MACE, with that number reaching 57.6% in trials enrolling patients with baseline cardiovascular disease (CVD).

Nearly 40% of trials did not report any CVD events in follow-up, the authors reported online Feb. 10, 2020, in the Journal of the American College of Cardiology (2020;75:620-8).

“Even in drug classes where there were established or emerging associations with cardiotoxic events, often there were no reported heart events or cardiovascular events across years of follow-up in trials that examined hundreds or even thousands of patients. That was actually pretty surprising,” senior author Daniel Addison, MD, codirector of the cardio-oncology program at the Ohio State University Medical Center, Columbus, said in an interview.

The study was prompted by a series of events that crescendoed when his team was called to the ICU to determine whether a novel targeted agent played a role in the heart decline of a patient with acute myeloid leukemia. “I had a resident ask me a very important question: ‘How do we really know for sure that the trial actually reflects the true risk of heart events?’ to which I told him, ‘it’s difficult to know,’ ” he said.

“I think many of us rely heavily on what we see in the trials, particularly when they make it to the top journals, and quite frankly, we generally take it at face value,” Dr. Addison observed.
 

Lower Rate of Reported Events

The investigators reviewed CV events reported in 97,365 patients (median age, 61 years; 46% female) enrolled in 189 phase 2 and 3 trials supporting FDA approval of 123 anticancer drugs from 1998 to 2018. Biologic, targeted, or immune-based therapies accounted for 72.5% of drug approvals.

Over 148,138 person-years of follow-up (median trial duration, 30 months), there were 1,148 incidents of MACE (375 heart failure, 253 MIs, 180 strokes, 65 atrial fibrillation, 29 coronary revascularizations, and 246 CVD deaths). MACE rates were higher in the intervention group than in the control group (792 vs. 356; P less than .01). Among the 64 trials that excluded patients with baseline CVD, there were 269 incidents of MACE.

To put this finding in context, the researchers examined the reported incidence of MACE among some 6,000 similarly aged participants in the Multi-Ethnic Study of Atherosclerosis (MESA). The overall weighted-average incidence rate was 1,408 per 100,000 person-years among MESA participants, compared with 542 events per 100,000 person-years among oncology trial participants (716 per 100,000 in the intervention arm). This represents a reported-to-expected ratio of 0.38 – a 2.6-fold lower rate of reported events (P less than .001) – and a risk difference of 866.

Further, MACE reporting was lower by a factor of 1.7 among all cancer trial participants irrespective of baseline CVD status (reported-to-expected ratio, 0.56; risk difference, 613; P less than .001).

There was no significant difference in MACE reporting between independent or industry-sponsored trials, the authors report.
 

No malicious intent

“There are likely some that might lean toward not wanting to attribute blame to a new drug when the drug is in a study, but I really think that the leading factor is lack of awareness,” Dr. Addison said. “I’ve talked with several cancer collaborators around the country who run large clinical trials, and I think often, when an event may be brought to someone’s attention, there is a tendency to just write it off as kind of a generic expected event due to age, or just something that’s not really pertinent to the study. So they don’t really focus on it as much.”

“Closer collaboration between cardiologists and cancer physicians is needed to better determine true cardiac risks among patients treated with these drugs.”

Breast cancer oncologist Marc E. Lippman, MD, of Georgetown University Medical Center and Georgetown Lombardi Comprehensive Cancer Center, Washington, D.C., isn’t convinced a lack of awareness is the culprit.

“I don’t agree with that at all,” he said in an interview. “I think there are very, very clear rules and guidelines these days for adverse-event reporting. I think that’s not a very likely explanation – that it’s not on the radar.”

Part of the problem may be that some of the toxicities, particularly cardiovascular, may not emerge for years, he said. Participant screening for the trials also likely removed patients with high cardiovascular risk. “It’s very understandable to me – I’m not saying it’s good particularly – but I think it’s very understandable that, if you’re trying to develop a drug, the last thing you’d want to have is a lot of toxicity that you might have avoided by just being restrictive in who you let into the study,” Dr. Lippman said.

The underreported CVD events may also reflect the rapidly changing profile of cardiovascular toxicities associated with novel anticancer therapies.

“Providers, both cancer and noncancer, generally put cardiotoxicity in the box of anthracyclines and radiation, but particularly over the last decade, we’ve begun to understand it’s well beyond any one class of drugs,” Dr. Addison said.

“I agree completely,” Dr. Lippman said. For example, “the checkpoint inhibitors are so unbelievably different in terms of their toxicities that many people simply didn’t even know what they were getting into at first.”
 

One size does not fit all

Javid Moslehi, MD, director of the cardio-oncology program at Vanderbilt University, Nashville, Tenn., said echocardiography – recommended to detect changes in left ventricular function in patients exposed to anthracyclines or targeted agents like trastuzumab (Herceptin) – isn’t enough to address today’s cancer therapy–related CVD events.

Courtesy Joe Howell

“Initial drugs like anthracyclines or Herceptin in cardio-oncology were associated with systolic cardiac dysfunction, whereas the majority of issues we see in the cardio-oncology clinics today are vascular, metabolic, arrhythmogenic, and inflammatory,” he said in an interview. “Echocardiography misses the big and increasingly complex picture.”

His group, for example, has been studying myocarditis associated with immunotherapies, but none of the clinical trials require screening or surveillance for myocarditis with a cardiac biomarker like troponin.

The group also recently identified 303 deaths in patients exposed to ibrutinib, a drug that revolutionized the treatment of several B-cell malignancies but is associated with higher rates of atrial fibrillation, which is also associated with increased bleeding risk. “So there’s a little bit of a double whammy there, given that we often treat atrial fibrillation with anticoagulation and where we can cause complications in patients,” Dr. Moslehi noted.

Although there needs to be closer collaboration between cardiologists and oncologists on individual trials, cardiologists also have to realize that oncology care has become very personalized, he suggested.

“What’s probably relevant for the breast cancer patient may not be relevant for the prostate cancer patient and their respective treatments,” Dr. Moslehi said. “So if we were to say, ‘every person should get an echo,’ that may be less relevant to the prostate cancer patient where treatments can cause vascular and metabolic perturbations or to the patient treated with immunotherapy who may have myocarditis, where many of the echos can be normal. There’s no one-size-fits-all for these things.”

Wearable technologies like smartwatches could play a role in improving the reporting of CVD events with novel therapies but a lot more research needs to be done to validate these tools, Dr. Addison said. “But as we continue on into the 21st century, this is going to expand and may potentially help us,” he added.

In the interim, better standardization is needed of the cardiovascular events reported in oncology trials, particularly the Common Terminology Criteria for Adverse Events (CTCAE), said Dr. Moslehi, who also serves as chair of the American Heart Association’s subcommittee on cardio-oncology.

“Cardiovascular definitions are not exactly uniform and are not consistent with what we in cardiology consider to be important or relevant,” he said. “So I think there needs to be better standardization of these definitions, specifically within the CTCAE, which is what the oncologists use to identify adverse events.”

In a linked editorial (J Am Coll Cardiol. 2020;75:629-31), Dr. Lippman and cardiologist Nanette Bishopric, MD, of the Medstar Heart and Vascular Institute in Washington, D.C., suggested it may also be time to organize a consortium that can carry out “rigorous multicenter clinical investigations to evaluate the cardiotoxicity of emerging cancer treatments,” similar to the Thrombosis in Myocardial Infarction Study Group.

“The success of this consortium in pioneering and targeting multiple generations of drugs for the treatment of MI, involving tens of thousands of patients and thousands of collaborations across multiple national borders, is a model for how to move forward in providing the new hope of cancer cure without the trade-off of years lost to heart disease,” the editorialists concluded.

The study was supported in part by National Institutes of Health grants, including a K12-CA133250 grant to Dr. Addison. Dr. Bishopric reported being on the scientific board of C&C Biopharma. Dr. Lippman reports being on the board of directors of and holding stock in Seattle Genetics. Dr. Moslehi reported having served on advisory boards for Pfizer, Novartis, Bristol-Myers Squibb, Deciphera, Audentes Pharmaceuticals, Nektar, Takeda, Ipsen, Myokardia, AstraZeneca, GlaxoSmithKline, Intrexon, and Regeneron.

This article first appeared on Medscape.com.

Clinical trials supporting Food and Drug Adminstration approval of contemporary cancer therapies frequently failed to capture major adverse cardiovascular events (MACE) and, when they did, reported rates 2.6-fold lower than noncancer trials, new research shows.

Overall, 51.3% of trials did not report MACE, with that number reaching 57.6% in trials enrolling patients with baseline cardiovascular disease (CVD).

Nearly 40% of trials did not report any CVD events in follow-up, the authors reported online Feb. 10, 2020, in the Journal of the American College of Cardiology (2020;75:620-8).

“Even in drug classes where there were established or emerging associations with cardiotoxic events, often there were no reported heart events or cardiovascular events across years of follow-up in trials that examined hundreds or even thousands of patients. That was actually pretty surprising,” senior author Daniel Addison, MD, codirector of the cardio-oncology program at the Ohio State University Medical Center, Columbus, said in an interview.

The study was prompted by a series of events that crescendoed when his team was called to the ICU to determine whether a novel targeted agent played a role in the heart decline of a patient with acute myeloid leukemia. “I had a resident ask me a very important question: ‘How do we really know for sure that the trial actually reflects the true risk of heart events?’ to which I told him, ‘it’s difficult to know,’ ” he said.

“I think many of us rely heavily on what we see in the trials, particularly when they make it to the top journals, and quite frankly, we generally take it at face value,” Dr. Addison observed.
 

Lower Rate of Reported Events

The investigators reviewed CV events reported in 97,365 patients (median age, 61 years; 46% female) enrolled in 189 phase 2 and 3 trials supporting FDA approval of 123 anticancer drugs from 1998 to 2018. Biologic, targeted, or immune-based therapies accounted for 72.5% of drug approvals.

Over 148,138 person-years of follow-up (median trial duration, 30 months), there were 1,148 incidents of MACE (375 heart failure, 253 MIs, 180 strokes, 65 atrial fibrillation, 29 coronary revascularizations, and 246 CVD deaths). MACE rates were higher in the intervention group than in the control group (792 vs. 356; P less than .01). Among the 64 trials that excluded patients with baseline CVD, there were 269 incidents of MACE.

To put this finding in context, the researchers examined the reported incidence of MACE among some 6,000 similarly aged participants in the Multi-Ethnic Study of Atherosclerosis (MESA). The overall weighted-average incidence rate was 1,408 per 100,000 person-years among MESA participants, compared with 542 events per 100,000 person-years among oncology trial participants (716 per 100,000 in the intervention arm). This represents a reported-to-expected ratio of 0.38 – a 2.6-fold lower rate of reported events (P less than .001) – and a risk difference of 866.

Further, MACE reporting was lower by a factor of 1.7 among all cancer trial participants irrespective of baseline CVD status (reported-to-expected ratio, 0.56; risk difference, 613; P less than .001).

There was no significant difference in MACE reporting between independent or industry-sponsored trials, the authors report.
 

No malicious intent

“There are likely some that might lean toward not wanting to attribute blame to a new drug when the drug is in a study, but I really think that the leading factor is lack of awareness,” Dr. Addison said. “I’ve talked with several cancer collaborators around the country who run large clinical trials, and I think often, when an event may be brought to someone’s attention, there is a tendency to just write it off as kind of a generic expected event due to age, or just something that’s not really pertinent to the study. So they don’t really focus on it as much.”

“Closer collaboration between cardiologists and cancer physicians is needed to better determine true cardiac risks among patients treated with these drugs.”

Breast cancer oncologist Marc E. Lippman, MD, of Georgetown University Medical Center and Georgetown Lombardi Comprehensive Cancer Center, Washington, D.C., isn’t convinced a lack of awareness is the culprit.

“I don’t agree with that at all,” he said in an interview. “I think there are very, very clear rules and guidelines these days for adverse-event reporting. I think that’s not a very likely explanation – that it’s not on the radar.”

Part of the problem may be that some of the toxicities, particularly cardiovascular, may not emerge for years, he said. Participant screening for the trials also likely removed patients with high cardiovascular risk. “It’s very understandable to me – I’m not saying it’s good particularly – but I think it’s very understandable that, if you’re trying to develop a drug, the last thing you’d want to have is a lot of toxicity that you might have avoided by just being restrictive in who you let into the study,” Dr. Lippman said.

The underreported CVD events may also reflect the rapidly changing profile of cardiovascular toxicities associated with novel anticancer therapies.

“Providers, both cancer and noncancer, generally put cardiotoxicity in the box of anthracyclines and radiation, but particularly over the last decade, we’ve begun to understand it’s well beyond any one class of drugs,” Dr. Addison said.

“I agree completely,” Dr. Lippman said. For example, “the checkpoint inhibitors are so unbelievably different in terms of their toxicities that many people simply didn’t even know what they were getting into at first.”
 

One size does not fit all

Javid Moslehi, MD, director of the cardio-oncology program at Vanderbilt University, Nashville, Tenn., said echocardiography – recommended to detect changes in left ventricular function in patients exposed to anthracyclines or targeted agents like trastuzumab (Herceptin) – isn’t enough to address today’s cancer therapy–related CVD events.

Courtesy Joe Howell

“Initial drugs like anthracyclines or Herceptin in cardio-oncology were associated with systolic cardiac dysfunction, whereas the majority of issues we see in the cardio-oncology clinics today are vascular, metabolic, arrhythmogenic, and inflammatory,” he said in an interview. “Echocardiography misses the big and increasingly complex picture.”

His group, for example, has been studying myocarditis associated with immunotherapies, but none of the clinical trials require screening or surveillance for myocarditis with a cardiac biomarker like troponin.

The group also recently identified 303 deaths in patients exposed to ibrutinib, a drug that revolutionized the treatment of several B-cell malignancies but is associated with higher rates of atrial fibrillation, which is also associated with increased bleeding risk. “So there’s a little bit of a double whammy there, given that we often treat atrial fibrillation with anticoagulation and where we can cause complications in patients,” Dr. Moslehi noted.

Although there needs to be closer collaboration between cardiologists and oncologists on individual trials, cardiologists also have to realize that oncology care has become very personalized, he suggested.

“What’s probably relevant for the breast cancer patient may not be relevant for the prostate cancer patient and their respective treatments,” Dr. Moslehi said. “So if we were to say, ‘every person should get an echo,’ that may be less relevant to the prostate cancer patient where treatments can cause vascular and metabolic perturbations or to the patient treated with immunotherapy who may have myocarditis, where many of the echos can be normal. There’s no one-size-fits-all for these things.”

Wearable technologies like smartwatches could play a role in improving the reporting of CVD events with novel therapies but a lot more research needs to be done to validate these tools, Dr. Addison said. “But as we continue on into the 21st century, this is going to expand and may potentially help us,” he added.

In the interim, better standardization is needed of the cardiovascular events reported in oncology trials, particularly the Common Terminology Criteria for Adverse Events (CTCAE), said Dr. Moslehi, who also serves as chair of the American Heart Association’s subcommittee on cardio-oncology.

“Cardiovascular definitions are not exactly uniform and are not consistent with what we in cardiology consider to be important or relevant,” he said. “So I think there needs to be better standardization of these definitions, specifically within the CTCAE, which is what the oncologists use to identify adverse events.”

In a linked editorial (J Am Coll Cardiol. 2020;75:629-31), Dr. Lippman and cardiologist Nanette Bishopric, MD, of the Medstar Heart and Vascular Institute in Washington, D.C., suggested it may also be time to organize a consortium that can carry out “rigorous multicenter clinical investigations to evaluate the cardiotoxicity of emerging cancer treatments,” similar to the Thrombosis in Myocardial Infarction Study Group.

“The success of this consortium in pioneering and targeting multiple generations of drugs for the treatment of MI, involving tens of thousands of patients and thousands of collaborations across multiple national borders, is a model for how to move forward in providing the new hope of cancer cure without the trade-off of years lost to heart disease,” the editorialists concluded.

The study was supported in part by National Institutes of Health grants, including a K12-CA133250 grant to Dr. Addison. Dr. Bishopric reported being on the scientific board of C&C Biopharma. Dr. Lippman reports being on the board of directors of and holding stock in Seattle Genetics. Dr. Moslehi reported having served on advisory boards for Pfizer, Novartis, Bristol-Myers Squibb, Deciphera, Audentes Pharmaceuticals, Nektar, Takeda, Ipsen, Myokardia, AstraZeneca, GlaxoSmithKline, Intrexon, and Regeneron.

This article first appeared on Medscape.com.

Clinical trials supporting Food and Drug Adminstration approval of contemporary cancer therapies frequently failed to capture major adverse cardiovascular events (MACE) and, when they did, reported rates 2.6-fold lower than noncancer trials, new research shows.

Overall, 51.3% of trials did not report MACE, with that number reaching 57.6% in trials enrolling patients with baseline cardiovascular disease (CVD).

Nearly 40% of trials did not report any CVD events in follow-up, the authors reported online Feb. 10, 2020, in the Journal of the American College of Cardiology (2020;75:620-8).

“Even in drug classes where there were established or emerging associations with cardiotoxic events, often there were no reported heart events or cardiovascular events across years of follow-up in trials that examined hundreds or even thousands of patients. That was actually pretty surprising,” senior author Daniel Addison, MD, codirector of the cardio-oncology program at the Ohio State University Medical Center, Columbus, said in an interview.

The study was prompted by a series of events that crescendoed when his team was called to the ICU to determine whether a novel targeted agent played a role in the heart decline of a patient with acute myeloid leukemia. “I had a resident ask me a very important question: ‘How do we really know for sure that the trial actually reflects the true risk of heart events?’ to which I told him, ‘it’s difficult to know,’ ” he said.

“I think many of us rely heavily on what we see in the trials, particularly when they make it to the top journals, and quite frankly, we generally take it at face value,” Dr. Addison observed.
 

Lower Rate of Reported Events

The investigators reviewed CV events reported in 97,365 patients (median age, 61 years; 46% female) enrolled in 189 phase 2 and 3 trials supporting FDA approval of 123 anticancer drugs from 1998 to 2018. Biologic, targeted, or immune-based therapies accounted for 72.5% of drug approvals.

Over 148,138 person-years of follow-up (median trial duration, 30 months), there were 1,148 incidents of MACE (375 heart failure, 253 MIs, 180 strokes, 65 atrial fibrillation, 29 coronary revascularizations, and 246 CVD deaths). MACE rates were higher in the intervention group than in the control group (792 vs. 356; P less than .01). Among the 64 trials that excluded patients with baseline CVD, there were 269 incidents of MACE.

To put this finding in context, the researchers examined the reported incidence of MACE among some 6,000 similarly aged participants in the Multi-Ethnic Study of Atherosclerosis (MESA). The overall weighted-average incidence rate was 1,408 per 100,000 person-years among MESA participants, compared with 542 events per 100,000 person-years among oncology trial participants (716 per 100,000 in the intervention arm). This represents a reported-to-expected ratio of 0.38 – a 2.6-fold lower rate of reported events (P less than .001) – and a risk difference of 866.

Further, MACE reporting was lower by a factor of 1.7 among all cancer trial participants irrespective of baseline CVD status (reported-to-expected ratio, 0.56; risk difference, 613; P less than .001).

There was no significant difference in MACE reporting between independent or industry-sponsored trials, the authors report.
 

No malicious intent

“There are likely some that might lean toward not wanting to attribute blame to a new drug when the drug is in a study, but I really think that the leading factor is lack of awareness,” Dr. Addison said. “I’ve talked with several cancer collaborators around the country who run large clinical trials, and I think often, when an event may be brought to someone’s attention, there is a tendency to just write it off as kind of a generic expected event due to age, or just something that’s not really pertinent to the study. So they don’t really focus on it as much.”

“Closer collaboration between cardiologists and cancer physicians is needed to better determine true cardiac risks among patients treated with these drugs.”

Breast cancer oncologist Marc E. Lippman, MD, of Georgetown University Medical Center and Georgetown Lombardi Comprehensive Cancer Center, Washington, D.C., isn’t convinced a lack of awareness is the culprit.

“I don’t agree with that at all,” he said in an interview. “I think there are very, very clear rules and guidelines these days for adverse-event reporting. I think that’s not a very likely explanation – that it’s not on the radar.”

Part of the problem may be that some of the toxicities, particularly cardiovascular, may not emerge for years, he said. Participant screening for the trials also likely removed patients with high cardiovascular risk. “It’s very understandable to me – I’m not saying it’s good particularly – but I think it’s very understandable that, if you’re trying to develop a drug, the last thing you’d want to have is a lot of toxicity that you might have avoided by just being restrictive in who you let into the study,” Dr. Lippman said.

The underreported CVD events may also reflect the rapidly changing profile of cardiovascular toxicities associated with novel anticancer therapies.

“Providers, both cancer and noncancer, generally put cardiotoxicity in the box of anthracyclines and radiation, but particularly over the last decade, we’ve begun to understand it’s well beyond any one class of drugs,” Dr. Addison said.

“I agree completely,” Dr. Lippman said. For example, “the checkpoint inhibitors are so unbelievably different in terms of their toxicities that many people simply didn’t even know what they were getting into at first.”
 

One size does not fit all

Javid Moslehi, MD, director of the cardio-oncology program at Vanderbilt University, Nashville, Tenn., said echocardiography – recommended to detect changes in left ventricular function in patients exposed to anthracyclines or targeted agents like trastuzumab (Herceptin) – isn’t enough to address today’s cancer therapy–related CVD events.

Courtesy Joe Howell

“Initial drugs like anthracyclines or Herceptin in cardio-oncology were associated with systolic cardiac dysfunction, whereas the majority of issues we see in the cardio-oncology clinics today are vascular, metabolic, arrhythmogenic, and inflammatory,” he said in an interview. “Echocardiography misses the big and increasingly complex picture.”

His group, for example, has been studying myocarditis associated with immunotherapies, but none of the clinical trials require screening or surveillance for myocarditis with a cardiac biomarker like troponin.

The group also recently identified 303 deaths in patients exposed to ibrutinib, a drug that revolutionized the treatment of several B-cell malignancies but is associated with higher rates of atrial fibrillation, which is also associated with increased bleeding risk. “So there’s a little bit of a double whammy there, given that we often treat atrial fibrillation with anticoagulation and where we can cause complications in patients,” Dr. Moslehi noted.

Although there needs to be closer collaboration between cardiologists and oncologists on individual trials, cardiologists also have to realize that oncology care has become very personalized, he suggested.

“What’s probably relevant for the breast cancer patient may not be relevant for the prostate cancer patient and their respective treatments,” Dr. Moslehi said. “So if we were to say, ‘every person should get an echo,’ that may be less relevant to the prostate cancer patient where treatments can cause vascular and metabolic perturbations or to the patient treated with immunotherapy who may have myocarditis, where many of the echos can be normal. There’s no one-size-fits-all for these things.”

Wearable technologies like smartwatches could play a role in improving the reporting of CVD events with novel therapies but a lot more research needs to be done to validate these tools, Dr. Addison said. “But as we continue on into the 21st century, this is going to expand and may potentially help us,” he added.

In the interim, better standardization is needed of the cardiovascular events reported in oncology trials, particularly the Common Terminology Criteria for Adverse Events (CTCAE), said Dr. Moslehi, who also serves as chair of the American Heart Association’s subcommittee on cardio-oncology.

“Cardiovascular definitions are not exactly uniform and are not consistent with what we in cardiology consider to be important or relevant,” he said. “So I think there needs to be better standardization of these definitions, specifically within the CTCAE, which is what the oncologists use to identify adverse events.”

In a linked editorial (J Am Coll Cardiol. 2020;75:629-31), Dr. Lippman and cardiologist Nanette Bishopric, MD, of the Medstar Heart and Vascular Institute in Washington, D.C., suggested it may also be time to organize a consortium that can carry out “rigorous multicenter clinical investigations to evaluate the cardiotoxicity of emerging cancer treatments,” similar to the Thrombosis in Myocardial Infarction Study Group.

“The success of this consortium in pioneering and targeting multiple generations of drugs for the treatment of MI, involving tens of thousands of patients and thousands of collaborations across multiple national borders, is a model for how to move forward in providing the new hope of cancer cure without the trade-off of years lost to heart disease,” the editorialists concluded.

The study was supported in part by National Institutes of Health grants, including a K12-CA133250 grant to Dr. Addison. Dr. Bishopric reported being on the scientific board of C&C Biopharma. Dr. Lippman reports being on the board of directors of and holding stock in Seattle Genetics. Dr. Moslehi reported having served on advisory boards for Pfizer, Novartis, Bristol-Myers Squibb, Deciphera, Audentes Pharmaceuticals, Nektar, Takeda, Ipsen, Myokardia, AstraZeneca, GlaxoSmithKline, Intrexon, and Regeneron.

This article first appeared on Medscape.com.

U.S. rates of heroin use, heroin use disorder, and heroin injections all increased overall among adults during a recent 17-year period, but rates have plateaued, new research shows.
 

Although on the face of it this may seem like good news, investigators at the Substance Abuse and Mental Health Services Administration (SAMHSA) note that the plateau in heroin use may simply reflect a switch to fentanyl.

“The recent leveling off of heroin use might reflect shifts from heroin to illicit fentanyl-related compounds,” wrote the investigators, led by Beth Han, MD, PhD, MPH.

The study was published online Feb. 11 as a research letter in JAMA (2020;323[6]:568-71).

National data

For the study, researchers collected data from a nationally representative group of adults aged 18 years or older who participated in the 2002-2018 National Survey on Drug Use and Health (NSDUH).

The analysis included 800,500 respondents during the study period. The mean age of respondents was 34.5 years, and 53.2% were women.

Results showed that the reported past-year prevalence of heroin use increased from 0.17% in 2002 to 0.32% in 2018 (average annual percentage change [AAPC], 5.6; 95% confidence interval [CI], 1.0-10.5; P = .02). During 2002-2016, the APC was 7.6 (95% CI, 6.3-9.0; P less than .001) but then plateaued during 2016-2018 (APC, –7.1; 95% CI, –36.9 to 36.7; P = .69).

The prevalence of heroin use disorder increased from 0.10% in 2002 to 0.21% in 2018 (AAPC, 6.0; 95% CI, 3.2-8.8; P less than .001). The rate remained stable during 2002-2008, increased during 2008-2015, then plateaued during 2015-2018.

The prevalence of heroin injections increased from 0.09% in 2002 to 0.17% in 2018 (AAPC, 6.9; 95% CI, 5.7-8.0; P less than .001), although there was a dip from the previous year. This rate increased during the study period among both men and women, those aged 35-49 years, non-Hispanic whites, and those residing in the Northeast or West regions.

For individuals up to age 25 years and those living in the Midwest, the heroin injection rate stopped increasing and plateaued, but there was an overall increase during the study period.

In 2018, the rate of past-year heroin injection was highest in those in the Northeast, those up to age 49 years, men, and non-Hispanic whites.

More infectious disease testing

Prevalence of heroin injection did not increase among adults who used heroin or who had heroin use disorder. This, the researchers note, “suggests that increases in heroin injection are related to overall increases in heroin use rather than increases in the propensity to inject.”

Future research should examine differences in heroin injection trends across subgroups, the authors wrote.

The researchers advocate for expanding HIV and hepatitis testing and treatment, the provision of sterile syringes, and use of Food and Drug Administration–approved medications for opioid use disorders, particularly among populations at greatest risk – adults in the Northeast, those aged 18-49 years, men, and non-Hispanic whites.

“In parallel, interventions to prevent opioid misuse and opioid use disorder are needed to avert further increases in injection drug use,” they noted.

A limitation of the study was that the NSDUH excludes jail and prison populations and homeless people not in living shelters. In addition, the NSDUH is subject to recall bias.

The study was jointly sponsored by SAMHSA and the National Institute on Drug Abuse of the National Institutes of Health. One author reports owning stock in General Electric Co, 3M Co, and Pfizer Inc.

A version of this article first appeared on Medscape.com.

U.S. rates of heroin use, heroin use disorder, and heroin injections all increased overall among adults during a recent 17-year period, but rates have plateaued, new research shows.
 

Although on the face of it this may seem like good news, investigators at the Substance Abuse and Mental Health Services Administration (SAMHSA) note that the plateau in heroin use may simply reflect a switch to fentanyl.

“The recent leveling off of heroin use might reflect shifts from heroin to illicit fentanyl-related compounds,” wrote the investigators, led by Beth Han, MD, PhD, MPH.

The study was published online Feb. 11 as a research letter in JAMA (2020;323[6]:568-71).

National data

For the study, researchers collected data from a nationally representative group of adults aged 18 years or older who participated in the 2002-2018 National Survey on Drug Use and Health (NSDUH).

The analysis included 800,500 respondents during the study period. The mean age of respondents was 34.5 years, and 53.2% were women.

Results showed that the reported past-year prevalence of heroin use increased from 0.17% in 2002 to 0.32% in 2018 (average annual percentage change [AAPC], 5.6; 95% confidence interval [CI], 1.0-10.5; P = .02). During 2002-2016, the APC was 7.6 (95% CI, 6.3-9.0; P less than .001) but then plateaued during 2016-2018 (APC, –7.1; 95% CI, –36.9 to 36.7; P = .69).

The prevalence of heroin use disorder increased from 0.10% in 2002 to 0.21% in 2018 (AAPC, 6.0; 95% CI, 3.2-8.8; P less than .001). The rate remained stable during 2002-2008, increased during 2008-2015, then plateaued during 2015-2018.

The prevalence of heroin injections increased from 0.09% in 2002 to 0.17% in 2018 (AAPC, 6.9; 95% CI, 5.7-8.0; P less than .001), although there was a dip from the previous year. This rate increased during the study period among both men and women, those aged 35-49 years, non-Hispanic whites, and those residing in the Northeast or West regions.

For individuals up to age 25 years and those living in the Midwest, the heroin injection rate stopped increasing and plateaued, but there was an overall increase during the study period.

In 2018, the rate of past-year heroin injection was highest in those in the Northeast, those up to age 49 years, men, and non-Hispanic whites.

More infectious disease testing

Prevalence of heroin injection did not increase among adults who used heroin or who had heroin use disorder. This, the researchers note, “suggests that increases in heroin injection are related to overall increases in heroin use rather than increases in the propensity to inject.”

Future research should examine differences in heroin injection trends across subgroups, the authors wrote.

The researchers advocate for expanding HIV and hepatitis testing and treatment, the provision of sterile syringes, and use of Food and Drug Administration–approved medications for opioid use disorders, particularly among populations at greatest risk – adults in the Northeast, those aged 18-49 years, men, and non-Hispanic whites.

“In parallel, interventions to prevent opioid misuse and opioid use disorder are needed to avert further increases in injection drug use,” they noted.

A limitation of the study was that the NSDUH excludes jail and prison populations and homeless people not in living shelters. In addition, the NSDUH is subject to recall bias.

The study was jointly sponsored by SAMHSA and the National Institute on Drug Abuse of the National Institutes of Health. One author reports owning stock in General Electric Co, 3M Co, and Pfizer Inc.

A version of this article first appeared on Medscape.com.

U.S. rates of heroin use, heroin use disorder, and heroin injections all increased overall among adults during a recent 17-year period, but rates have plateaued, new research shows.
 

Although on the face of it this may seem like good news, investigators at the Substance Abuse and Mental Health Services Administration (SAMHSA) note that the plateau in heroin use may simply reflect a switch to fentanyl.

“The recent leveling off of heroin use might reflect shifts from heroin to illicit fentanyl-related compounds,” wrote the investigators, led by Beth Han, MD, PhD, MPH.

The study was published online Feb. 11 as a research letter in JAMA (2020;323[6]:568-71).

National data

For the study, researchers collected data from a nationally representative group of adults aged 18 years or older who participated in the 2002-2018 National Survey on Drug Use and Health (NSDUH).

The analysis included 800,500 respondents during the study period. The mean age of respondents was 34.5 years, and 53.2% were women.

Results showed that the reported past-year prevalence of heroin use increased from 0.17% in 2002 to 0.32% in 2018 (average annual percentage change [AAPC], 5.6; 95% confidence interval [CI], 1.0-10.5; P = .02). During 2002-2016, the APC was 7.6 (95% CI, 6.3-9.0; P less than .001) but then plateaued during 2016-2018 (APC, –7.1; 95% CI, –36.9 to 36.7; P = .69).

The prevalence of heroin use disorder increased from 0.10% in 2002 to 0.21% in 2018 (AAPC, 6.0; 95% CI, 3.2-8.8; P less than .001). The rate remained stable during 2002-2008, increased during 2008-2015, then plateaued during 2015-2018.

The prevalence of heroin injections increased from 0.09% in 2002 to 0.17% in 2018 (AAPC, 6.9; 95% CI, 5.7-8.0; P less than .001), although there was a dip from the previous year. This rate increased during the study period among both men and women, those aged 35-49 years, non-Hispanic whites, and those residing in the Northeast or West regions.

For individuals up to age 25 years and those living in the Midwest, the heroin injection rate stopped increasing and plateaued, but there was an overall increase during the study period.

In 2018, the rate of past-year heroin injection was highest in those in the Northeast, those up to age 49 years, men, and non-Hispanic whites.

More infectious disease testing

Prevalence of heroin injection did not increase among adults who used heroin or who had heroin use disorder. This, the researchers note, “suggests that increases in heroin injection are related to overall increases in heroin use rather than increases in the propensity to inject.”

Future research should examine differences in heroin injection trends across subgroups, the authors wrote.

The researchers advocate for expanding HIV and hepatitis testing and treatment, the provision of sterile syringes, and use of Food and Drug Administration–approved medications for opioid use disorders, particularly among populations at greatest risk – adults in the Northeast, those aged 18-49 years, men, and non-Hispanic whites.

“In parallel, interventions to prevent opioid misuse and opioid use disorder are needed to avert further increases in injection drug use,” they noted.

A limitation of the study was that the NSDUH excludes jail and prison populations and homeless people not in living shelters. In addition, the NSDUH is subject to recall bias.

The study was jointly sponsored by SAMHSA and the National Institute on Drug Abuse of the National Institutes of Health. One author reports owning stock in General Electric Co, 3M Co, and Pfizer Inc.

A version of this article first appeared on Medscape.com.