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.

The U.S. Multi-Society Task Force on Colorectal Cancer (CRC) recently updated recommendations for patient follow-up after colonoscopy and polypectomy.

The new guidance was based on advancements in both research and technology since the last recommendations were published in 2012, reported lead author Samir Gupta, MD, AGAF, of the University of California, San Diego, and colleagues.

“[Since 2012,] a number of articles have been published on risk of CRC based on colonoscopy findings and patient characteristics, as well as the potential impact of screening and surveillance colonoscopy on outcomes, such as incident CRC and polyps,” the investigators wrote in Gastroenterology. “Further, recent studies increasingly reflect the modern era of colonoscopy with more awareness of the importance of quality factors (e.g., adequate bowel preparation, cecal intubation, adequate adenoma detection, and complete polyp resection), and utilization of state of the art technologies (e.g., high-definition colonoscopes).”

The task force, which comprised the American College of Gastroenterology, the American Gastroenterological Association, and the American Society of Gastrointestinal Endoscopy, identified key topics using PICO (patient, intervention, comparison, and outcome) questions before conducting a comprehensive literature review that included 136 articles. Based on these findings, two task force members generated recommendations that were further refined through consensus discussion. The recommendations were copublished in the March issues of the American Journal of Gastroenterology, Gastroenterology, and Gastrointestinal Endoscopy.

According to Dr. Gupta and colleagues, some of the new recommendations, particularly those that advise less stringent follow-up, may encounter resistance from various stakeholders.

“Patients, primary care physicians, and colonoscopists may have concerns about lengthening a previously recommended interval, and will need to engage in shared decision making regarding whether to lengthen the follow-up interval based upon the guidance here or utilize the recommendation made at the time of the prior colonoscopy,” the task force wrote.

The most prominent recommendations of this kind concern patients who undergo removal of tubular adenomas less than 10 mm in size. For patients who have 1-2 of these adenomas removed, the task force now recommends follow-up after 7-10 years, instead of the previously recommended interval of 5-10 years.

“[This decision was] based on the growing body of evidence to support low risk for metachronous advanced neoplasia,” the task force wrote. “In this population, the risk for metachronous advanced neoplasia is similar to that for individuals with no adenoma. Importantly, the observed risk for fatal CRC among individuals with 1-10 adenomas less than 10 mm is lower than average for the general population.”

Along similar lines, patients who undergo removal of 3-4 small adenomas now have a recommended 3-5 year follow-up window, instead of the previously strict recommendation for follow-up at 3 years.

But not all of the new guidance is less stringent. While the task force previously recommended a follow-up period of less than 3 years after removal of more than 10 adenomas, they now recommend follow-up at 1 year. This change was made to simplify guidance, the investigators wrote, noting that the evidence base in this area “has not been markedly strengthened” since 2012.

Compared with the old guidance, the updated publication offers more detailed recommendations for follow-up after removal of serrated polyps. On this topic, 10 clinical scenarios are presented, with follow-up ranging from 6 months after piecemeal resection of a sessile serrated polyp greater than 20 mm to 10 years after removal of 20 or fewer hyperplastic polyps less than 10 mm that were located in the rectum or sigmoid colon. Incidentally, these two recommendations are strong and based on moderate evidence, whereas the remaining recommendations for serrated polyps are weak and based on very-low-quality evidence.

Because of such knowledge gaps, the investigators emphasized the need for more data. The publication includes extensive discussion of pressing research topics and appropriate methods of investigation.

“Our review highlights several opportunities for research to clarify risk stratification and management of patients post-polypectomy,” the task force wrote. “In order to optimize risk-reduction strategies, the mechanisms driving metachronous advanced neoplasia after baseline polypectomy and their relative frequency need to be better understood through studies that include large numbers of patients with interval cancers and/or advanced neoplasia after baseline polypectomy. Mechanisms may include new/incident growth, incomplete baseline resection, and missed neoplasia; each of these potential causes may require different interventions for improvement.”

The task force also suggested that some basic questions beyond risk stratification remain unanswered, such as the impact of surveillance on CRC incidence and mortality.

“Such evidence is needed given the increasing proportion of patients who are having adenomas detected as part of increased participation in CRC screening,” the task force wrote.

Other suggested topics of investigation include age-related analyses that incorporate procedural risk, cost-effectiveness studies, and comparisons of nonendoscopic methods of surveillance, such as fecal immunochemical testing.

The study was funded by the National Institutes of Health and the Department of Veterans Affairs. The investigators reported relationships with Covidien, Ironwood, Medtronic, and others.

SOURCE: Gupta S et al. Gastroenterology. 2020 Feb 7. doi: 10.1053/j.gastro.2019.10.026.

The U.S. Multi-Society Task Force on Colorectal Cancer (CRC) recently updated recommendations for patient follow-up after colonoscopy and polypectomy.

The new guidance was based on advancements in both research and technology since the last recommendations were published in 2012, reported lead author Samir Gupta, MD, AGAF, of the University of California, San Diego, and colleagues.

“[Since 2012,] a number of articles have been published on risk of CRC based on colonoscopy findings and patient characteristics, as well as the potential impact of screening and surveillance colonoscopy on outcomes, such as incident CRC and polyps,” the investigators wrote in Gastroenterology. “Further, recent studies increasingly reflect the modern era of colonoscopy with more awareness of the importance of quality factors (e.g., adequate bowel preparation, cecal intubation, adequate adenoma detection, and complete polyp resection), and utilization of state of the art technologies (e.g., high-definition colonoscopes).”

The task force, which comprised the American College of Gastroenterology, the American Gastroenterological Association, and the American Society of Gastrointestinal Endoscopy, identified key topics using PICO (patient, intervention, comparison, and outcome) questions before conducting a comprehensive literature review that included 136 articles. Based on these findings, two task force members generated recommendations that were further refined through consensus discussion. The recommendations were copublished in the March issues of the American Journal of Gastroenterology, Gastroenterology, and Gastrointestinal Endoscopy.

According to Dr. Gupta and colleagues, some of the new recommendations, particularly those that advise less stringent follow-up, may encounter resistance from various stakeholders.

“Patients, primary care physicians, and colonoscopists may have concerns about lengthening a previously recommended interval, and will need to engage in shared decision making regarding whether to lengthen the follow-up interval based upon the guidance here or utilize the recommendation made at the time of the prior colonoscopy,” the task force wrote.

The most prominent recommendations of this kind concern patients who undergo removal of tubular adenomas less than 10 mm in size. For patients who have 1-2 of these adenomas removed, the task force now recommends follow-up after 7-10 years, instead of the previously recommended interval of 5-10 years.

“[This decision was] based on the growing body of evidence to support low risk for metachronous advanced neoplasia,” the task force wrote. “In this population, the risk for metachronous advanced neoplasia is similar to that for individuals with no adenoma. Importantly, the observed risk for fatal CRC among individuals with 1-10 adenomas less than 10 mm is lower than average for the general population.”

Along similar lines, patients who undergo removal of 3-4 small adenomas now have a recommended 3-5 year follow-up window, instead of the previously strict recommendation for follow-up at 3 years.

But not all of the new guidance is less stringent. While the task force previously recommended a follow-up period of less than 3 years after removal of more than 10 adenomas, they now recommend follow-up at 1 year. This change was made to simplify guidance, the investigators wrote, noting that the evidence base in this area “has not been markedly strengthened” since 2012.

Compared with the old guidance, the updated publication offers more detailed recommendations for follow-up after removal of serrated polyps. On this topic, 10 clinical scenarios are presented, with follow-up ranging from 6 months after piecemeal resection of a sessile serrated polyp greater than 20 mm to 10 years after removal of 20 or fewer hyperplastic polyps less than 10 mm that were located in the rectum or sigmoid colon. Incidentally, these two recommendations are strong and based on moderate evidence, whereas the remaining recommendations for serrated polyps are weak and based on very-low-quality evidence.

Because of such knowledge gaps, the investigators emphasized the need for more data. The publication includes extensive discussion of pressing research topics and appropriate methods of investigation.

“Our review highlights several opportunities for research to clarify risk stratification and management of patients post-polypectomy,” the task force wrote. “In order to optimize risk-reduction strategies, the mechanisms driving metachronous advanced neoplasia after baseline polypectomy and their relative frequency need to be better understood through studies that include large numbers of patients with interval cancers and/or advanced neoplasia after baseline polypectomy. Mechanisms may include new/incident growth, incomplete baseline resection, and missed neoplasia; each of these potential causes may require different interventions for improvement.”

The task force also suggested that some basic questions beyond risk stratification remain unanswered, such as the impact of surveillance on CRC incidence and mortality.

“Such evidence is needed given the increasing proportion of patients who are having adenomas detected as part of increased participation in CRC screening,” the task force wrote.

Other suggested topics of investigation include age-related analyses that incorporate procedural risk, cost-effectiveness studies, and comparisons of nonendoscopic methods of surveillance, such as fecal immunochemical testing.

The study was funded by the National Institutes of Health and the Department of Veterans Affairs. The investigators reported relationships with Covidien, Ironwood, Medtronic, and others.

SOURCE: Gupta S et al. Gastroenterology. 2020 Feb 7. doi: 10.1053/j.gastro.2019.10.026.

The U.S. Multi-Society Task Force on Colorectal Cancer (CRC) recently updated recommendations for patient follow-up after colonoscopy and polypectomy.

The new guidance was based on advancements in both research and technology since the last recommendations were published in 2012, reported lead author Samir Gupta, MD, AGAF, of the University of California, San Diego, and colleagues.

“[Since 2012,] a number of articles have been published on risk of CRC based on colonoscopy findings and patient characteristics, as well as the potential impact of screening and surveillance colonoscopy on outcomes, such as incident CRC and polyps,” the investigators wrote in Gastroenterology. “Further, recent studies increasingly reflect the modern era of colonoscopy with more awareness of the importance of quality factors (e.g., adequate bowel preparation, cecal intubation, adequate adenoma detection, and complete polyp resection), and utilization of state of the art technologies (e.g., high-definition colonoscopes).”

The task force, which comprised the American College of Gastroenterology, the American Gastroenterological Association, and the American Society of Gastrointestinal Endoscopy, identified key topics using PICO (patient, intervention, comparison, and outcome) questions before conducting a comprehensive literature review that included 136 articles. Based on these findings, two task force members generated recommendations that were further refined through consensus discussion. The recommendations were copublished in the March issues of the American Journal of Gastroenterology, Gastroenterology, and Gastrointestinal Endoscopy.

According to Dr. Gupta and colleagues, some of the new recommendations, particularly those that advise less stringent follow-up, may encounter resistance from various stakeholders.

“Patients, primary care physicians, and colonoscopists may have concerns about lengthening a previously recommended interval, and will need to engage in shared decision making regarding whether to lengthen the follow-up interval based upon the guidance here or utilize the recommendation made at the time of the prior colonoscopy,” the task force wrote.

The most prominent recommendations of this kind concern patients who undergo removal of tubular adenomas less than 10 mm in size. For patients who have 1-2 of these adenomas removed, the task force now recommends follow-up after 7-10 years, instead of the previously recommended interval of 5-10 years.

“[This decision was] based on the growing body of evidence to support low risk for metachronous advanced neoplasia,” the task force wrote. “In this population, the risk for metachronous advanced neoplasia is similar to that for individuals with no adenoma. Importantly, the observed risk for fatal CRC among individuals with 1-10 adenomas less than 10 mm is lower than average for the general population.”

Along similar lines, patients who undergo removal of 3-4 small adenomas now have a recommended 3-5 year follow-up window, instead of the previously strict recommendation for follow-up at 3 years.

But not all of the new guidance is less stringent. While the task force previously recommended a follow-up period of less than 3 years after removal of more than 10 adenomas, they now recommend follow-up at 1 year. This change was made to simplify guidance, the investigators wrote, noting that the evidence base in this area “has not been markedly strengthened” since 2012.

Compared with the old guidance, the updated publication offers more detailed recommendations for follow-up after removal of serrated polyps. On this topic, 10 clinical scenarios are presented, with follow-up ranging from 6 months after piecemeal resection of a sessile serrated polyp greater than 20 mm to 10 years after removal of 20 or fewer hyperplastic polyps less than 10 mm that were located in the rectum or sigmoid colon. Incidentally, these two recommendations are strong and based on moderate evidence, whereas the remaining recommendations for serrated polyps are weak and based on very-low-quality evidence.

Because of such knowledge gaps, the investigators emphasized the need for more data. The publication includes extensive discussion of pressing research topics and appropriate methods of investigation.

“Our review highlights several opportunities for research to clarify risk stratification and management of patients post-polypectomy,” the task force wrote. “In order to optimize risk-reduction strategies, the mechanisms driving metachronous advanced neoplasia after baseline polypectomy and their relative frequency need to be better understood through studies that include large numbers of patients with interval cancers and/or advanced neoplasia after baseline polypectomy. Mechanisms may include new/incident growth, incomplete baseline resection, and missed neoplasia; each of these potential causes may require different interventions for improvement.”

The task force also suggested that some basic questions beyond risk stratification remain unanswered, such as the impact of surveillance on CRC incidence and mortality.

“Such evidence is needed given the increasing proportion of patients who are having adenomas detected as part of increased participation in CRC screening,” the task force wrote.

Other suggested topics of investigation include age-related analyses that incorporate procedural risk, cost-effectiveness studies, and comparisons of nonendoscopic methods of surveillance, such as fecal immunochemical testing.

The study was funded by the National Institutes of Health and the Department of Veterans Affairs. The investigators reported relationships with Covidien, Ironwood, Medtronic, and others.

SOURCE: Gupta S et al. Gastroenterology. 2020 Feb 7. doi: 10.1053/j.gastro.2019.10.026.

Candida auris (C. auris) infection was first detected in New York, in July 2016. As of June 2019, 801 patients have been identified in New York as having C auris—and of those, 3 had pan-resistant infection.

CDC researchers say C auris is “a globally emerging yeast.” Cases with resistance to all 3 classes of commonly prescribed antifungal drugs have been reported in multiple countries.

In New York, of the first 277 available clinical isolates, 276 were resistant to fluconazole and 170 were resistant to amphotericin B. None were resistant to echinocandins. Subsequent testing found 99.7% of 331 isolates from infected patients with susceptibilities were resistant to fluconazole, 63% were resistant to amphotericin B, and 4% were resistant to echinocandins. Three of the subsequent isolates were pan-resistant.

The first 2 of those 3 patients were > 50 years old and residents of long-term care facilities. Each had multiple medical conditions, including ventilator dependence and colonization with multidrug-resistant bacteria. Neither patient was known to have received antifungal medications before the diagnosis of C. auris infection, but both were treated with prolonged courses of echinocandins after the diagnosis. Cultures taken after echinocandin therapy showed resistance to fluconazole, amphotericin B, and echinocandins. Both patients died, but the role of C. auris in their deaths is unclear.

The researchers found no epidemiologic links between the 2 patients. They were residents at different health care facilities, neither had any known domestic or foreign travel. No pan-resistant isolates were identified among contacts or on environmental surfaces from their rooms or common equipment at the 3 facilities where they had been patients. Although C. auris was isolated from other patients, none was pan-resistant.

A retrospective review of all New York C. auris isolates turned up a third pan-resistant patient. The patient also was aged > 50 years old , had multiple comorbidities, and a prolonged hospital and long-term care stay. However, the patient received care at a third unique facility. This third patient, who died from underlying medical conditions, was also not known to have traveled recently, and had no known contact with the other 2 patients.

Isolates from all 3 patients were initially sensitive to echinocandins. Resistance was detected after treatment, indicating it emerged during treatment with the drugs. The researchers found no evidence of transmission.

Approximately 3 years after the beginning of the New York outbreak, the pan-resistant isolates still appear to be rare, the researchers say, but “their emergence is concerning.” They urge close monitoring for patients on antifungal treatment for C. auris, along with follow-up cultures and repeat susceptibility testing, especially in patients previously treated with echinocandins.

Candida auris (C. auris) infection was first detected in New York, in July 2016. As of June 2019, 801 patients have been identified in New York as having C auris—and of those, 3 had pan-resistant infection.

CDC researchers say C auris is “a globally emerging yeast.” Cases with resistance to all 3 classes of commonly prescribed antifungal drugs have been reported in multiple countries.

In New York, of the first 277 available clinical isolates, 276 were resistant to fluconazole and 170 were resistant to amphotericin B. None were resistant to echinocandins. Subsequent testing found 99.7% of 331 isolates from infected patients with susceptibilities were resistant to fluconazole, 63% were resistant to amphotericin B, and 4% were resistant to echinocandins. Three of the subsequent isolates were pan-resistant.

The first 2 of those 3 patients were > 50 years old and residents of long-term care facilities. Each had multiple medical conditions, including ventilator dependence and colonization with multidrug-resistant bacteria. Neither patient was known to have received antifungal medications before the diagnosis of C. auris infection, but both were treated with prolonged courses of echinocandins after the diagnosis. Cultures taken after echinocandin therapy showed resistance to fluconazole, amphotericin B, and echinocandins. Both patients died, but the role of C. auris in their deaths is unclear.

The researchers found no epidemiologic links between the 2 patients. They were residents at different health care facilities, neither had any known domestic or foreign travel. No pan-resistant isolates were identified among contacts or on environmental surfaces from their rooms or common equipment at the 3 facilities where they had been patients. Although C. auris was isolated from other patients, none was pan-resistant.

A retrospective review of all New York C. auris isolates turned up a third pan-resistant patient. The patient also was aged > 50 years old , had multiple comorbidities, and a prolonged hospital and long-term care stay. However, the patient received care at a third unique facility. This third patient, who died from underlying medical conditions, was also not known to have traveled recently, and had no known contact with the other 2 patients.

Isolates from all 3 patients were initially sensitive to echinocandins. Resistance was detected after treatment, indicating it emerged during treatment with the drugs. The researchers found no evidence of transmission.

Approximately 3 years after the beginning of the New York outbreak, the pan-resistant isolates still appear to be rare, the researchers say, but “their emergence is concerning.” They urge close monitoring for patients on antifungal treatment for C. auris, along with follow-up cultures and repeat susceptibility testing, especially in patients previously treated with echinocandins.

Candida auris (C. auris) infection was first detected in New York, in July 2016. As of June 2019, 801 patients have been identified in New York as having C auris—and of those, 3 had pan-resistant infection.

CDC researchers say C auris is “a globally emerging yeast.” Cases with resistance to all 3 classes of commonly prescribed antifungal drugs have been reported in multiple countries.

In New York, of the first 277 available clinical isolates, 276 were resistant to fluconazole and 170 were resistant to amphotericin B. None were resistant to echinocandins. Subsequent testing found 99.7% of 331 isolates from infected patients with susceptibilities were resistant to fluconazole, 63% were resistant to amphotericin B, and 4% were resistant to echinocandins. Three of the subsequent isolates were pan-resistant.

The first 2 of those 3 patients were > 50 years old and residents of long-term care facilities. Each had multiple medical conditions, including ventilator dependence and colonization with multidrug-resistant bacteria. Neither patient was known to have received antifungal medications before the diagnosis of C. auris infection, but both were treated with prolonged courses of echinocandins after the diagnosis. Cultures taken after echinocandin therapy showed resistance to fluconazole, amphotericin B, and echinocandins. Both patients died, but the role of C. auris in their deaths is unclear.

The researchers found no epidemiologic links between the 2 patients. They were residents at different health care facilities, neither had any known domestic or foreign travel. No pan-resistant isolates were identified among contacts or on environmental surfaces from their rooms or common equipment at the 3 facilities where they had been patients. Although C. auris was isolated from other patients, none was pan-resistant.

A retrospective review of all New York C. auris isolates turned up a third pan-resistant patient. The patient also was aged > 50 years old , had multiple comorbidities, and a prolonged hospital and long-term care stay. However, the patient received care at a third unique facility. This third patient, who died from underlying medical conditions, was also not known to have traveled recently, and had no known contact with the other 2 patients.

Isolates from all 3 patients were initially sensitive to echinocandins. Resistance was detected after treatment, indicating it emerged during treatment with the drugs. The researchers found no evidence of transmission.

Approximately 3 years after the beginning of the New York outbreak, the pan-resistant isolates still appear to be rare, the researchers say, but “their emergence is concerning.” They urge close monitoring for patients on antifungal treatment for C. auris, along with follow-up cultures and repeat susceptibility testing, especially in patients previously treated with echinocandins.

Carbon monoxide (CO)—colorless, odorless, tasteless and highly toxic—is one of the most common causes of unintentional poisoning deaths in the US. Researchers who described their analysis of CO-related incidents in the military for the Medical Surveillance Monthly Report say military activities, materials, and settings pose “unique and potentially lethal sources of significant CO exposure.”

They reported on episodes of CO poisoning among members of the US Armed Forces between 2009 and 2019 and expanded on reports that dated back to 2001. Their analysis included reserve members and nonservice member beneficiaries.

Over the 10 years, there were 1,288 confirmed/probable cases of CO poisoning among active component service members, 366 among reserve component service members, and 4,754 among nonservice member beneficiaries. The highest number of active-duty members with CO confirmed/probable poisoning were reported at Fort Carson, Colorado (60) and NMC San Diego, California (52).

Of the confirmed/probable cases among active-duty members, 613 were classified as having unintentional intent, 538 undetermined intent, and 136 self-harm intent. One was due to assault. Most of the cases were related to work in repair/engineering occupations. Although the majority of sources were “other or unspecified,” motor vehicle exhaust accounted for 17% of the confirmed cases and all of the probable cases. Similarly, in the reserve component and among nonservice member beneficiaries, vehicle exhaust was the second-most common source.

The researchers found that CO poisoning-related injuries/diagnoses in the military often involved a single exposure that affected multiple personnel. For example, 21 soldiers showed symptoms during a multi-day exercise at the Yukon Training Center.

Excessive CO exposure is “entirely preventable,” the researchers say. Primary medical care providers—including unit medics and emergency medical technicians—should be knowledgeable about and sensitive to the “diverse and nonspecific” early clinical manifestations of CO intoxication, such as dizziness, headache, malaise, fatigue, disorientation, nausea, and vomiting. High CO exposure can cause more pronounced and severe symptoms, including syncope, seizures, acute stroke-like syndromes, and coma.

 It’s important to remember, the researchers add, that increased oxygen demand from muscular activity exacerbates the symptoms of CO exposure, but individuals at rest may experience no other symptoms before losing consciousness.

An editorial comment notes that the full impact of morbidity and mortality from CO poisoning is difficult to estimate. For one thing, because the symptoms can be so nonspecific, clinicians may not consider CO poisoning when patients present for care.

This study differs from previous ones in that it uses code data from both the Ninth and Tenth Revisions of the International Classification of Diseases. Such data, the editorial comment says, can be used at national and Military Health System–wide levels with relatively few resources, providing useful information on trends and risk factors that can be used in designing interventions

Carbon monoxide (CO)—colorless, odorless, tasteless and highly toxic—is one of the most common causes of unintentional poisoning deaths in the US. Researchers who described their analysis of CO-related incidents in the military for the Medical Surveillance Monthly Report say military activities, materials, and settings pose “unique and potentially lethal sources of significant CO exposure.”

They reported on episodes of CO poisoning among members of the US Armed Forces between 2009 and 2019 and expanded on reports that dated back to 2001. Their analysis included reserve members and nonservice member beneficiaries.

Over the 10 years, there were 1,288 confirmed/probable cases of CO poisoning among active component service members, 366 among reserve component service members, and 4,754 among nonservice member beneficiaries. The highest number of active-duty members with CO confirmed/probable poisoning were reported at Fort Carson, Colorado (60) and NMC San Diego, California (52).

Of the confirmed/probable cases among active-duty members, 613 were classified as having unintentional intent, 538 undetermined intent, and 136 self-harm intent. One was due to assault. Most of the cases were related to work in repair/engineering occupations. Although the majority of sources were “other or unspecified,” motor vehicle exhaust accounted for 17% of the confirmed cases and all of the probable cases. Similarly, in the reserve component and among nonservice member beneficiaries, vehicle exhaust was the second-most common source.

The researchers found that CO poisoning-related injuries/diagnoses in the military often involved a single exposure that affected multiple personnel. For example, 21 soldiers showed symptoms during a multi-day exercise at the Yukon Training Center.

Excessive CO exposure is “entirely preventable,” the researchers say. Primary medical care providers—including unit medics and emergency medical technicians—should be knowledgeable about and sensitive to the “diverse and nonspecific” early clinical manifestations of CO intoxication, such as dizziness, headache, malaise, fatigue, disorientation, nausea, and vomiting. High CO exposure can cause more pronounced and severe symptoms, including syncope, seizures, acute stroke-like syndromes, and coma.

 It’s important to remember, the researchers add, that increased oxygen demand from muscular activity exacerbates the symptoms of CO exposure, but individuals at rest may experience no other symptoms before losing consciousness.

An editorial comment notes that the full impact of morbidity and mortality from CO poisoning is difficult to estimate. For one thing, because the symptoms can be so nonspecific, clinicians may not consider CO poisoning when patients present for care.

This study differs from previous ones in that it uses code data from both the Ninth and Tenth Revisions of the International Classification of Diseases. Such data, the editorial comment says, can be used at national and Military Health System–wide levels with relatively few resources, providing useful information on trends and risk factors that can be used in designing interventions

Carbon monoxide (CO)—colorless, odorless, tasteless and highly toxic—is one of the most common causes of unintentional poisoning deaths in the US. Researchers who described their analysis of CO-related incidents in the military for the Medical Surveillance Monthly Report say military activities, materials, and settings pose “unique and potentially lethal sources of significant CO exposure.”

They reported on episodes of CO poisoning among members of the US Armed Forces between 2009 and 2019 and expanded on reports that dated back to 2001. Their analysis included reserve members and nonservice member beneficiaries.

Over the 10 years, there were 1,288 confirmed/probable cases of CO poisoning among active component service members, 366 among reserve component service members, and 4,754 among nonservice member beneficiaries. The highest number of active-duty members with CO confirmed/probable poisoning were reported at Fort Carson, Colorado (60) and NMC San Diego, California (52).

Of the confirmed/probable cases among active-duty members, 613 were classified as having unintentional intent, 538 undetermined intent, and 136 self-harm intent. One was due to assault. Most of the cases were related to work in repair/engineering occupations. Although the majority of sources were “other or unspecified,” motor vehicle exhaust accounted for 17% of the confirmed cases and all of the probable cases. Similarly, in the reserve component and among nonservice member beneficiaries, vehicle exhaust was the second-most common source.

The researchers found that CO poisoning-related injuries/diagnoses in the military often involved a single exposure that affected multiple personnel. For example, 21 soldiers showed symptoms during a multi-day exercise at the Yukon Training Center.

Excessive CO exposure is “entirely preventable,” the researchers say. Primary medical care providers—including unit medics and emergency medical technicians—should be knowledgeable about and sensitive to the “diverse and nonspecific” early clinical manifestations of CO intoxication, such as dizziness, headache, malaise, fatigue, disorientation, nausea, and vomiting. High CO exposure can cause more pronounced and severe symptoms, including syncope, seizures, acute stroke-like syndromes, and coma.

 It’s important to remember, the researchers add, that increased oxygen demand from muscular activity exacerbates the symptoms of CO exposure, but individuals at rest may experience no other symptoms before losing consciousness.

An editorial comment notes that the full impact of morbidity and mortality from CO poisoning is difficult to estimate. For one thing, because the symptoms can be so nonspecific, clinicians may not consider CO poisoning when patients present for care.

This study differs from previous ones in that it uses code data from both the Ninth and Tenth Revisions of the International Classification of Diseases. Such data, the editorial comment says, can be used at national and Military Health System–wide levels with relatively few resources, providing useful information on trends and risk factors that can be used in designing interventions

BALTIMORE – Among patients with medial temporal lobe epilepsy, functional outcomes of stereotactic laser amygdalohippocampotomy (SLAH) are superior to those of open resection, according to data presented at the annual meeting of the American Epilepsy Society. In addition, improvements in functional status are strongly associated with improvements in global cognitive performance.

Previous data have indicated that SLAH results in superior cognitive outcomes, compared with selective and standard open resection, in the treatment of medial temporal lobe epilepsy. The rates of seizure freedom following these procedures are equivalent. Daniel Drane, PhD, associate professor of neurology at Emory University in Atlanta, and colleagues hypothesized that the preservation of cognitive skills following SLAH would be apparent in real-world settings. To test this hypothesis, they investigated changes in functional status following SLAH.
 

Functional status correlated with neurocognitive change

Dr. Drane and colleagues compared functional outcomes in 53 patients who underwent SLAH at the Emory University Epilepsy Center and 20 patients who underwent open resection at the same center. The investigators created a hierarchical classification of functional status using the following criteria (from best to worst): employed and independent with all activities of daily living (ADLs), unemployed and independent with all ADLs, unemployed and independent with lower ADLs only (i.e., independent with self-care, but not with management of finances, medications, etc.), and unemployed and unable to manage any ADLs without assistance. Dr. Drane and colleagues rated all patients on these criteria at baseline and at 1 year after surgery. They classified patients as improving, declining, or remaining stable in functional status. Finally, the investigators used Fisher’s exact test to compare the proportional ratings of change between surgical procedures.

At baseline, the proportions of patients in each functional group were similar between patients who later underwent SLAH and those who later underwent open resection. Significantly more patients who underwent SLAH, however, had functional improvement, compared with patients who underwent open resection (13.2% vs. 0%). Furthermore, fewer patients who underwent SLAH had functional decline, compared with those who underwent open resection (3.7% vs. 35%).

Dr. Drane and colleagues found a strong correlation between functional status and global ratings of neurocognitive change, but no correlation between functional status and seizure-freedom status. Patients who underwent SLAH were less likely to have a decline in employment status than were patients who underwent open resection were (4.2% vs. 45.4%).
 

Weighing surgical options for a given patient

“This study provides a real-world metric of meaningful change following surgery, which is, critically, independent of seizure freedom outcome,” said Dr. Drane. “If a patient becomes seizure free but declines in functional status, presumably due to compromised cognitive function, this outcome is likely not going to lead to a better quality of life. Overall, our data suggest that functional status is driven more by cognitive outcome than by seizure freedom, and that it is an equally important metric for determining whether or not surgery has been successful. We would hope that the epilepsy surgical team would try to balance the desire to achieve seizure freedom against the potential risks and benefits of surgery on cognitive performance and functional status.”

Neurologists must consider various factors when deciding whether open resection or SLAH is the better option for a given patient. “Our prior work has shown that SLAH will not cause naming or object recognition deficits, while such deficits will result in a substantial proportion of patients undergoing open resection procedures,” said Dr. Drane. “Declarative memory can seemingly be hurt by either procedure, although it would appear that rates of decline are substantially less following SLAH. As functional status appears to be related to cognitive outcome, SLAH would always be the better choice from the standpoint of risk analysis, particularly since one can almost always go back an complete an open resection at a later date.

“Seizure freedom rates appear to be slightly higher with open resection than with SLAH,” Dr. Drane continued. “This [result] would be the one factor that would represent the one reason to opt for an open resection rather than SLAH. Factors that might push one in this direction could be risk for SUDEP (i.e., someone at very high risk may want to just be done with the seizures) and impaired baseline cognitive functioning (i.e., someone with severely impaired cognitive functioning might be viewed as having less to lose). In the latter case, however, we would caution that low-functioning individuals can sometimes lose their remaining functional abilities even if we cannot do a very good job of measuring cognitive change in such cases due to their poor baseline performance.”

The hemisphere to undergo operation also may influence the choice of procedure. “Some epileptologists will suggest that the choice of using SLAH is more important for patients having surgery involving their language-dominant cerebral hemisphere,” said Dr. Drane. “While postsurgical deficits in these patients are clearly more easy to identify, I would argue that a case can be made for starting with SLAH in the nondominant temporal lobe cases as well. Many of the functions that can be potentially harmed by surgical procedures involving the nondominant (typically right) hemisphere have more subtle effects, but their cumulative impact can yet be harmful.”

The study was partially supported by funding from the National Institutes of Health and Medtronic. The investigators did not report any conflicts of interest.

egreb@mdedge.com

SOURCE: Drane DL et al. AES 2019. Abstract 1.34.

BALTIMORE – Among patients with medial temporal lobe epilepsy, functional outcomes of stereotactic laser amygdalohippocampotomy (SLAH) are superior to those of open resection, according to data presented at the annual meeting of the American Epilepsy Society. In addition, improvements in functional status are strongly associated with improvements in global cognitive performance.

Previous data have indicated that SLAH results in superior cognitive outcomes, compared with selective and standard open resection, in the treatment of medial temporal lobe epilepsy. The rates of seizure freedom following these procedures are equivalent. Daniel Drane, PhD, associate professor of neurology at Emory University in Atlanta, and colleagues hypothesized that the preservation of cognitive skills following SLAH would be apparent in real-world settings. To test this hypothesis, they investigated changes in functional status following SLAH.
 

Functional status correlated with neurocognitive change

Dr. Drane and colleagues compared functional outcomes in 53 patients who underwent SLAH at the Emory University Epilepsy Center and 20 patients who underwent open resection at the same center. The investigators created a hierarchical classification of functional status using the following criteria (from best to worst): employed and independent with all activities of daily living (ADLs), unemployed and independent with all ADLs, unemployed and independent with lower ADLs only (i.e., independent with self-care, but not with management of finances, medications, etc.), and unemployed and unable to manage any ADLs without assistance. Dr. Drane and colleagues rated all patients on these criteria at baseline and at 1 year after surgery. They classified patients as improving, declining, or remaining stable in functional status. Finally, the investigators used Fisher’s exact test to compare the proportional ratings of change between surgical procedures.

At baseline, the proportions of patients in each functional group were similar between patients who later underwent SLAH and those who later underwent open resection. Significantly more patients who underwent SLAH, however, had functional improvement, compared with patients who underwent open resection (13.2% vs. 0%). Furthermore, fewer patients who underwent SLAH had functional decline, compared with those who underwent open resection (3.7% vs. 35%).

Dr. Drane and colleagues found a strong correlation between functional status and global ratings of neurocognitive change, but no correlation between functional status and seizure-freedom status. Patients who underwent SLAH were less likely to have a decline in employment status than were patients who underwent open resection were (4.2% vs. 45.4%).
 

Weighing surgical options for a given patient

“This study provides a real-world metric of meaningful change following surgery, which is, critically, independent of seizure freedom outcome,” said Dr. Drane. “If a patient becomes seizure free but declines in functional status, presumably due to compromised cognitive function, this outcome is likely not going to lead to a better quality of life. Overall, our data suggest that functional status is driven more by cognitive outcome than by seizure freedom, and that it is an equally important metric for determining whether or not surgery has been successful. We would hope that the epilepsy surgical team would try to balance the desire to achieve seizure freedom against the potential risks and benefits of surgery on cognitive performance and functional status.”

Neurologists must consider various factors when deciding whether open resection or SLAH is the better option for a given patient. “Our prior work has shown that SLAH will not cause naming or object recognition deficits, while such deficits will result in a substantial proportion of patients undergoing open resection procedures,” said Dr. Drane. “Declarative memory can seemingly be hurt by either procedure, although it would appear that rates of decline are substantially less following SLAH. As functional status appears to be related to cognitive outcome, SLAH would always be the better choice from the standpoint of risk analysis, particularly since one can almost always go back an complete an open resection at a later date.

“Seizure freedom rates appear to be slightly higher with open resection than with SLAH,” Dr. Drane continued. “This [result] would be the one factor that would represent the one reason to opt for an open resection rather than SLAH. Factors that might push one in this direction could be risk for SUDEP (i.e., someone at very high risk may want to just be done with the seizures) and impaired baseline cognitive functioning (i.e., someone with severely impaired cognitive functioning might be viewed as having less to lose). In the latter case, however, we would caution that low-functioning individuals can sometimes lose their remaining functional abilities even if we cannot do a very good job of measuring cognitive change in such cases due to their poor baseline performance.”

The hemisphere to undergo operation also may influence the choice of procedure. “Some epileptologists will suggest that the choice of using SLAH is more important for patients having surgery involving their language-dominant cerebral hemisphere,” said Dr. Drane. “While postsurgical deficits in these patients are clearly more easy to identify, I would argue that a case can be made for starting with SLAH in the nondominant temporal lobe cases as well. Many of the functions that can be potentially harmed by surgical procedures involving the nondominant (typically right) hemisphere have more subtle effects, but their cumulative impact can yet be harmful.”

The study was partially supported by funding from the National Institutes of Health and Medtronic. The investigators did not report any conflicts of interest.

egreb@mdedge.com

SOURCE: Drane DL et al. AES 2019. Abstract 1.34.

BALTIMORE – Among patients with medial temporal lobe epilepsy, functional outcomes of stereotactic laser amygdalohippocampotomy (SLAH) are superior to those of open resection, according to data presented at the annual meeting of the American Epilepsy Society. In addition, improvements in functional status are strongly associated with improvements in global cognitive performance.

Previous data have indicated that SLAH results in superior cognitive outcomes, compared with selective and standard open resection, in the treatment of medial temporal lobe epilepsy. The rates of seizure freedom following these procedures are equivalent. Daniel Drane, PhD, associate professor of neurology at Emory University in Atlanta, and colleagues hypothesized that the preservation of cognitive skills following SLAH would be apparent in real-world settings. To test this hypothesis, they investigated changes in functional status following SLAH.
 

Functional status correlated with neurocognitive change

Dr. Drane and colleagues compared functional outcomes in 53 patients who underwent SLAH at the Emory University Epilepsy Center and 20 patients who underwent open resection at the same center. The investigators created a hierarchical classification of functional status using the following criteria (from best to worst): employed and independent with all activities of daily living (ADLs), unemployed and independent with all ADLs, unemployed and independent with lower ADLs only (i.e., independent with self-care, but not with management of finances, medications, etc.), and unemployed and unable to manage any ADLs without assistance. Dr. Drane and colleagues rated all patients on these criteria at baseline and at 1 year after surgery. They classified patients as improving, declining, or remaining stable in functional status. Finally, the investigators used Fisher’s exact test to compare the proportional ratings of change between surgical procedures.

At baseline, the proportions of patients in each functional group were similar between patients who later underwent SLAH and those who later underwent open resection. Significantly more patients who underwent SLAH, however, had functional improvement, compared with patients who underwent open resection (13.2% vs. 0%). Furthermore, fewer patients who underwent SLAH had functional decline, compared with those who underwent open resection (3.7% vs. 35%).

Dr. Drane and colleagues found a strong correlation between functional status and global ratings of neurocognitive change, but no correlation between functional status and seizure-freedom status. Patients who underwent SLAH were less likely to have a decline in employment status than were patients who underwent open resection were (4.2% vs. 45.4%).
 

Weighing surgical options for a given patient

“This study provides a real-world metric of meaningful change following surgery, which is, critically, independent of seizure freedom outcome,” said Dr. Drane. “If a patient becomes seizure free but declines in functional status, presumably due to compromised cognitive function, this outcome is likely not going to lead to a better quality of life. Overall, our data suggest that functional status is driven more by cognitive outcome than by seizure freedom, and that it is an equally important metric for determining whether or not surgery has been successful. We would hope that the epilepsy surgical team would try to balance the desire to achieve seizure freedom against the potential risks and benefits of surgery on cognitive performance and functional status.”

Neurologists must consider various factors when deciding whether open resection or SLAH is the better option for a given patient. “Our prior work has shown that SLAH will not cause naming or object recognition deficits, while such deficits will result in a substantial proportion of patients undergoing open resection procedures,” said Dr. Drane. “Declarative memory can seemingly be hurt by either procedure, although it would appear that rates of decline are substantially less following SLAH. As functional status appears to be related to cognitive outcome, SLAH would always be the better choice from the standpoint of risk analysis, particularly since one can almost always go back an complete an open resection at a later date.

“Seizure freedom rates appear to be slightly higher with open resection than with SLAH,” Dr. Drane continued. “This [result] would be the one factor that would represent the one reason to opt for an open resection rather than SLAH. Factors that might push one in this direction could be risk for SUDEP (i.e., someone at very high risk may want to just be done with the seizures) and impaired baseline cognitive functioning (i.e., someone with severely impaired cognitive functioning might be viewed as having less to lose). In the latter case, however, we would caution that low-functioning individuals can sometimes lose their remaining functional abilities even if we cannot do a very good job of measuring cognitive change in such cases due to their poor baseline performance.”

The hemisphere to undergo operation also may influence the choice of procedure. “Some epileptologists will suggest that the choice of using SLAH is more important for patients having surgery involving their language-dominant cerebral hemisphere,” said Dr. Drane. “While postsurgical deficits in these patients are clearly more easy to identify, I would argue that a case can be made for starting with SLAH in the nondominant temporal lobe cases as well. Many of the functions that can be potentially harmed by surgical procedures involving the nondominant (typically right) hemisphere have more subtle effects, but their cumulative impact can yet be harmful.”

The study was partially supported by funding from the National Institutes of Health and Medtronic. The investigators did not report any conflicts of interest.

egreb@mdedge.com

SOURCE: Drane DL et al. AES 2019. Abstract 1.34.