MDedge Neurology

If you’ve knocked yourself out to earn a Merit-Based Incentive Payment System (MIPS) bonus payment, it’s pretty safe to say that getting a 1.68% payment boost probably didn’t feel like a “win” that was worth the effort.

And although it saved you from having a negative 5% payment adjustment, many physicians don’t feel that it was worth the effort.

On Jan. 6, the Centers for Medicare & Medicaid Services announced the 2020 payouts for MIPS.

Based on 2018 participation, the bonus for those who scored a perfect 100 is only a 1.68% boost in Medicare reimbursement, slightly lower than last year’s 1.88%. This decline comes as no surprise as the agency leader admits: “As the program matures, we expect that the increases in the performance thresholds in future program years will create a smaller distribution of positive payment adjustments.” Overall, more than 97% of participants avoided having a negative 5% payment adjustment.

Indeed, these bonus monies are based on a short-term appropriation of extra funds from Congress. After these temporary funds are no longer available, there will be little, if any, monies to distribute as the program is based on a “losers-feed-the-winners” construct.

It may be very tempting for many physicians to decide to ignore MIPS, with the rationale that 1.68% is not worth the effort. But don’t let your foot off the gas pedal yet, since the penalty for not participating in 2020 is a substantial 9%. Physicians should make sure that they, at minimum, achieve the 45 points necessary to avoid that pitfall this reporting year.

However, it is certainly time to reconsider efforts to participate at the highest level.
 

Should you or shouldn’t you bother with MIPS?

Let’s say you have $75,000 in revenue from Medicare Part B per year. Depending on the services you offer in your practice, that equates to 500-750 encounters with Medicare beneficiaries per year. (A reminder that MIPS affects only Part B; Medicare Advantage plans do not partake in the program.)

The recent announcement reveals that perfection would equate to an additional $1,260 per year. That’s only if you received the full 100 points; if you were simply an “exceptional performer,” the government will allot an additional $157. That’s less than you get paid for a single office visit.

The difference between perfection and compliance is approximately $1,000. Failure to participate, however, knocks $6,750 off your bottom line. Clearly, that’s a substantial financial loss that would affect most practices. Obviously, the numbers change if you have higher – or lower – Medicare revenue, but it’s important to do the math.

Why? Physicians are spending a significant amount of money to comply with the program requirements. This includes substantial payments to registries – typically $200 to >$1,000 per year – to report the quality measures for the program; electronic health record (EHR) systems, many of which require additional funding for the “upgrade” to a MIPS-compatible system, are also a sizable investment.

These hard costs pale in comparison with the time spent on understanding the ever-changing requirements of the program and the process by which your practice will implement them. Take, for example, something as innocuous as the required “Support Electronic Referral Loops by Receiving and Incorporating Health Information.”

You first must understand the elements of the measure: What is a “referral loop?” When do we need to generate one? To whom shall it be sent? What needs to be included in “health information?” What is the electronic address to which we should route the information? How do we obtain that address? Then you must determine how your EHR system captures and reports it.

Only then comes the hard part: How are we going to implement this? That’s only one of more than a dozen required elements: six quality measures, two (to four) improvement activities, and four promoting interoperability requirements. Each one of these elements has a host of requirements, all listed on multipage specification sheets.

The government does not seem to be listening. John Cullen, MD, president of the American Academy of Family Physicians, testified at the Senate Finance Committee in May 2019 that MIPS “has created a burdensome and extremely complex program that has increased practice costs ... ” Yet, later that year, CMS issued another hefty ruling that outlines significant changes to the program, despite the fact that it’s in its fourth performance year.
 

Turning frustration into action

Frustration or even anger may be one reaction, but now is an opportune time to determine your investment in the program. At a minimum, it’s vital to understand and meet the threshold to avoid the penalty. It’s been shifting to date, but it’s now set at 9% for perpetuity.

First, it’s crucial to check on your participation status. CMS revealed that the participation database was recently corrected for so-called inconsistencies, so it pays to double-check. It only takes seconds: Insert your NPI in the QPP Participation Status Tool to determine your eligibility for 2020.

In 2020, the threshold to avoid the penalty is 45 points. To get the 45 points, practices must participate in two improvement activities, which is not difficult as there are 118 options. That will garner 15 points. Then there are 45 points available from the quality category; you need at least 30 to reach the 45-point threshold for penalty avoidance.
 

Smart MIPS hacks that can help you

To obtain the additional 30 points, turn your attention to the quality category. There are 268 quality measures; choose at least six to measure. If you report directly from your EHR system, you’ll get a bonus point for each reported measure, plus one just for trying. (There are a few other opportunities for bonus points, such as improving your scores over last year.) Those bonus points give you a base with which to work, but getting to 45 will require effort to report successfully on at least a couple of the measures.

The quality category has a total of 100 points available, which are converted to 45 toward your composite score. Since you need 30 to reach that magical 45 (if 15 were attained from improvement activities), that means you must come up with 75 points in the quality category. Between the bonus points and measuring a handful of measures successfully through the year, you’ll achieve this threshold.

There are two other categories in the program: promoting interoperability (PI) and cost. The PI category mirrors the old “meaningful use” program; however, it has become increasingly difficult over the years. If you think that you can meet the required elements, you can pick up 25 more points toward your composite score.

Cost is a bit of an unknown, as the scoring is based on a retrospective review of your claims. You’ll likely pick up a few more points on this 15-point category, but there’s no method to determine performance until after the reporting period. Therefore, be cautious about relying on this category.

The best MIPS hack, however, is if you are a small practice. CMS – remarkably – defines a “small practice” as 15 or fewer eligible professionals. If you qualify under this paradigm, you have multiple options to ease compliance:

Apply for a “hardship exemption” simply on the basis of being small; the exemption relates to the promoting operability category, shifting those points to the quality category.

Gain three points per quality measure, regardless of data completeness; this compares to just one point for other physicians.

Capture all of the points available from the Improvement Activities category by confirming participation with just a single activity. (This also applies to all physicians in rural or Health Professional Shortage Areas.)

In the event that you don’t qualify as a “small practice” or you’re still falling short of the requirements, CMS allows for the ultimate “out”: You can apply for exemption on the basis of an “extreme and uncontrollable circumstance.” The applications for these exceptions open this summer.

Unless you qualify for the program exemption, it’s important to keep pace with the program to ensure that you reach the 45-point threshold. It may not, however, be worthwhile to gear up for all 100 points unless your estimate of the potential return – and what it costs you to get there – reveals otherwise. MIPS is not going anywhere; the program is written into the law.

But that doesn’t mean that CMS can’t make tweaks and updates. Hopefully, the revisions won’t create even more administrative burden as the program is quickly turning into a big stick with only a small carrot at the end.

Elizabeth Woodcock is president of Woodcock & Associates in Atlanta. She has disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

If you’ve knocked yourself out to earn a Merit-Based Incentive Payment System (MIPS) bonus payment, it’s pretty safe to say that getting a 1.68% payment boost probably didn’t feel like a “win” that was worth the effort.

And although it saved you from having a negative 5% payment adjustment, many physicians don’t feel that it was worth the effort.

On Jan. 6, the Centers for Medicare & Medicaid Services announced the 2020 payouts for MIPS.

Based on 2018 participation, the bonus for those who scored a perfect 100 is only a 1.68% boost in Medicare reimbursement, slightly lower than last year’s 1.88%. This decline comes as no surprise as the agency leader admits: “As the program matures, we expect that the increases in the performance thresholds in future program years will create a smaller distribution of positive payment adjustments.” Overall, more than 97% of participants avoided having a negative 5% payment adjustment.

Indeed, these bonus monies are based on a short-term appropriation of extra funds from Congress. After these temporary funds are no longer available, there will be little, if any, monies to distribute as the program is based on a “losers-feed-the-winners” construct.

It may be very tempting for many physicians to decide to ignore MIPS, with the rationale that 1.68% is not worth the effort. But don’t let your foot off the gas pedal yet, since the penalty for not participating in 2020 is a substantial 9%. Physicians should make sure that they, at minimum, achieve the 45 points necessary to avoid that pitfall this reporting year.

However, it is certainly time to reconsider efforts to participate at the highest level.
 

Should you or shouldn’t you bother with MIPS?

Let’s say you have $75,000 in revenue from Medicare Part B per year. Depending on the services you offer in your practice, that equates to 500-750 encounters with Medicare beneficiaries per year. (A reminder that MIPS affects only Part B; Medicare Advantage plans do not partake in the program.)

The recent announcement reveals that perfection would equate to an additional $1,260 per year. That’s only if you received the full 100 points; if you were simply an “exceptional performer,” the government will allot an additional $157. That’s less than you get paid for a single office visit.

The difference between perfection and compliance is approximately $1,000. Failure to participate, however, knocks $6,750 off your bottom line. Clearly, that’s a substantial financial loss that would affect most practices. Obviously, the numbers change if you have higher – or lower – Medicare revenue, but it’s important to do the math.

Why? Physicians are spending a significant amount of money to comply with the program requirements. This includes substantial payments to registries – typically $200 to >$1,000 per year – to report the quality measures for the program; electronic health record (EHR) systems, many of which require additional funding for the “upgrade” to a MIPS-compatible system, are also a sizable investment.

These hard costs pale in comparison with the time spent on understanding the ever-changing requirements of the program and the process by which your practice will implement them. Take, for example, something as innocuous as the required “Support Electronic Referral Loops by Receiving and Incorporating Health Information.”

You first must understand the elements of the measure: What is a “referral loop?” When do we need to generate one? To whom shall it be sent? What needs to be included in “health information?” What is the electronic address to which we should route the information? How do we obtain that address? Then you must determine how your EHR system captures and reports it.

Only then comes the hard part: How are we going to implement this? That’s only one of more than a dozen required elements: six quality measures, two (to four) improvement activities, and four promoting interoperability requirements. Each one of these elements has a host of requirements, all listed on multipage specification sheets.

The government does not seem to be listening. John Cullen, MD, president of the American Academy of Family Physicians, testified at the Senate Finance Committee in May 2019 that MIPS “has created a burdensome and extremely complex program that has increased practice costs ... ” Yet, later that year, CMS issued another hefty ruling that outlines significant changes to the program, despite the fact that it’s in its fourth performance year.
 

Turning frustration into action

Frustration or even anger may be one reaction, but now is an opportune time to determine your investment in the program. At a minimum, it’s vital to understand and meet the threshold to avoid the penalty. It’s been shifting to date, but it’s now set at 9% for perpetuity.

First, it’s crucial to check on your participation status. CMS revealed that the participation database was recently corrected for so-called inconsistencies, so it pays to double-check. It only takes seconds: Insert your NPI in the QPP Participation Status Tool to determine your eligibility for 2020.

In 2020, the threshold to avoid the penalty is 45 points. To get the 45 points, practices must participate in two improvement activities, which is not difficult as there are 118 options. That will garner 15 points. Then there are 45 points available from the quality category; you need at least 30 to reach the 45-point threshold for penalty avoidance.
 

Smart MIPS hacks that can help you

To obtain the additional 30 points, turn your attention to the quality category. There are 268 quality measures; choose at least six to measure. If you report directly from your EHR system, you’ll get a bonus point for each reported measure, plus one just for trying. (There are a few other opportunities for bonus points, such as improving your scores over last year.) Those bonus points give you a base with which to work, but getting to 45 will require effort to report successfully on at least a couple of the measures.

The quality category has a total of 100 points available, which are converted to 45 toward your composite score. Since you need 30 to reach that magical 45 (if 15 were attained from improvement activities), that means you must come up with 75 points in the quality category. Between the bonus points and measuring a handful of measures successfully through the year, you’ll achieve this threshold.

There are two other categories in the program: promoting interoperability (PI) and cost. The PI category mirrors the old “meaningful use” program; however, it has become increasingly difficult over the years. If you think that you can meet the required elements, you can pick up 25 more points toward your composite score.

Cost is a bit of an unknown, as the scoring is based on a retrospective review of your claims. You’ll likely pick up a few more points on this 15-point category, but there’s no method to determine performance until after the reporting period. Therefore, be cautious about relying on this category.

The best MIPS hack, however, is if you are a small practice. CMS – remarkably – defines a “small practice” as 15 or fewer eligible professionals. If you qualify under this paradigm, you have multiple options to ease compliance:

Apply for a “hardship exemption” simply on the basis of being small; the exemption relates to the promoting operability category, shifting those points to the quality category.

Gain three points per quality measure, regardless of data completeness; this compares to just one point for other physicians.

Capture all of the points available from the Improvement Activities category by confirming participation with just a single activity. (This also applies to all physicians in rural or Health Professional Shortage Areas.)

In the event that you don’t qualify as a “small practice” or you’re still falling short of the requirements, CMS allows for the ultimate “out”: You can apply for exemption on the basis of an “extreme and uncontrollable circumstance.” The applications for these exceptions open this summer.

Unless you qualify for the program exemption, it’s important to keep pace with the program to ensure that you reach the 45-point threshold. It may not, however, be worthwhile to gear up for all 100 points unless your estimate of the potential return – and what it costs you to get there – reveals otherwise. MIPS is not going anywhere; the program is written into the law.

But that doesn’t mean that CMS can’t make tweaks and updates. Hopefully, the revisions won’t create even more administrative burden as the program is quickly turning into a big stick with only a small carrot at the end.

Elizabeth Woodcock is president of Woodcock & Associates in Atlanta. She has disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

If you’ve knocked yourself out to earn a Merit-Based Incentive Payment System (MIPS) bonus payment, it’s pretty safe to say that getting a 1.68% payment boost probably didn’t feel like a “win” that was worth the effort.

And although it saved you from having a negative 5% payment adjustment, many physicians don’t feel that it was worth the effort.

On Jan. 6, the Centers for Medicare & Medicaid Services announced the 2020 payouts for MIPS.

Based on 2018 participation, the bonus for those who scored a perfect 100 is only a 1.68% boost in Medicare reimbursement, slightly lower than last year’s 1.88%. This decline comes as no surprise as the agency leader admits: “As the program matures, we expect that the increases in the performance thresholds in future program years will create a smaller distribution of positive payment adjustments.” Overall, more than 97% of participants avoided having a negative 5% payment adjustment.

Indeed, these bonus monies are based on a short-term appropriation of extra funds from Congress. After these temporary funds are no longer available, there will be little, if any, monies to distribute as the program is based on a “losers-feed-the-winners” construct.

It may be very tempting for many physicians to decide to ignore MIPS, with the rationale that 1.68% is not worth the effort. But don’t let your foot off the gas pedal yet, since the penalty for not participating in 2020 is a substantial 9%. Physicians should make sure that they, at minimum, achieve the 45 points necessary to avoid that pitfall this reporting year.

However, it is certainly time to reconsider efforts to participate at the highest level.
 

Should you or shouldn’t you bother with MIPS?

Let’s say you have $75,000 in revenue from Medicare Part B per year. Depending on the services you offer in your practice, that equates to 500-750 encounters with Medicare beneficiaries per year. (A reminder that MIPS affects only Part B; Medicare Advantage plans do not partake in the program.)

The recent announcement reveals that perfection would equate to an additional $1,260 per year. That’s only if you received the full 100 points; if you were simply an “exceptional performer,” the government will allot an additional $157. That’s less than you get paid for a single office visit.

The difference between perfection and compliance is approximately $1,000. Failure to participate, however, knocks $6,750 off your bottom line. Clearly, that’s a substantial financial loss that would affect most practices. Obviously, the numbers change if you have higher – or lower – Medicare revenue, but it’s important to do the math.

Why? Physicians are spending a significant amount of money to comply with the program requirements. This includes substantial payments to registries – typically $200 to >$1,000 per year – to report the quality measures for the program; electronic health record (EHR) systems, many of which require additional funding for the “upgrade” to a MIPS-compatible system, are also a sizable investment.

These hard costs pale in comparison with the time spent on understanding the ever-changing requirements of the program and the process by which your practice will implement them. Take, for example, something as innocuous as the required “Support Electronic Referral Loops by Receiving and Incorporating Health Information.”

You first must understand the elements of the measure: What is a “referral loop?” When do we need to generate one? To whom shall it be sent? What needs to be included in “health information?” What is the electronic address to which we should route the information? How do we obtain that address? Then you must determine how your EHR system captures and reports it.

Only then comes the hard part: How are we going to implement this? That’s only one of more than a dozen required elements: six quality measures, two (to four) improvement activities, and four promoting interoperability requirements. Each one of these elements has a host of requirements, all listed on multipage specification sheets.

The government does not seem to be listening. John Cullen, MD, president of the American Academy of Family Physicians, testified at the Senate Finance Committee in May 2019 that MIPS “has created a burdensome and extremely complex program that has increased practice costs ... ” Yet, later that year, CMS issued another hefty ruling that outlines significant changes to the program, despite the fact that it’s in its fourth performance year.
 

Turning frustration into action

Frustration or even anger may be one reaction, but now is an opportune time to determine your investment in the program. At a minimum, it’s vital to understand and meet the threshold to avoid the penalty. It’s been shifting to date, but it’s now set at 9% for perpetuity.

First, it’s crucial to check on your participation status. CMS revealed that the participation database was recently corrected for so-called inconsistencies, so it pays to double-check. It only takes seconds: Insert your NPI in the QPP Participation Status Tool to determine your eligibility for 2020.

In 2020, the threshold to avoid the penalty is 45 points. To get the 45 points, practices must participate in two improvement activities, which is not difficult as there are 118 options. That will garner 15 points. Then there are 45 points available from the quality category; you need at least 30 to reach the 45-point threshold for penalty avoidance.
 

Smart MIPS hacks that can help you

To obtain the additional 30 points, turn your attention to the quality category. There are 268 quality measures; choose at least six to measure. If you report directly from your EHR system, you’ll get a bonus point for each reported measure, plus one just for trying. (There are a few other opportunities for bonus points, such as improving your scores over last year.) Those bonus points give you a base with which to work, but getting to 45 will require effort to report successfully on at least a couple of the measures.

The quality category has a total of 100 points available, which are converted to 45 toward your composite score. Since you need 30 to reach that magical 45 (if 15 were attained from improvement activities), that means you must come up with 75 points in the quality category. Between the bonus points and measuring a handful of measures successfully through the year, you’ll achieve this threshold.

There are two other categories in the program: promoting interoperability (PI) and cost. The PI category mirrors the old “meaningful use” program; however, it has become increasingly difficult over the years. If you think that you can meet the required elements, you can pick up 25 more points toward your composite score.

Cost is a bit of an unknown, as the scoring is based on a retrospective review of your claims. You’ll likely pick up a few more points on this 15-point category, but there’s no method to determine performance until after the reporting period. Therefore, be cautious about relying on this category.

The best MIPS hack, however, is if you are a small practice. CMS – remarkably – defines a “small practice” as 15 or fewer eligible professionals. If you qualify under this paradigm, you have multiple options to ease compliance:

Apply for a “hardship exemption” simply on the basis of being small; the exemption relates to the promoting operability category, shifting those points to the quality category.

Gain three points per quality measure, regardless of data completeness; this compares to just one point for other physicians.

Capture all of the points available from the Improvement Activities category by confirming participation with just a single activity. (This also applies to all physicians in rural or Health Professional Shortage Areas.)

In the event that you don’t qualify as a “small practice” or you’re still falling short of the requirements, CMS allows for the ultimate “out”: You can apply for exemption on the basis of an “extreme and uncontrollable circumstance.” The applications for these exceptions open this summer.

Unless you qualify for the program exemption, it’s important to keep pace with the program to ensure that you reach the 45-point threshold. It may not, however, be worthwhile to gear up for all 100 points unless your estimate of the potential return – and what it costs you to get there – reveals otherwise. MIPS is not going anywhere; the program is written into the law.

But that doesn’t mean that CMS can’t make tweaks and updates. Hopefully, the revisions won’t create even more administrative burden as the program is quickly turning into a big stick with only a small carrot at the end.

Elizabeth Woodcock is president of Woodcock & Associates in Atlanta. She has disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

The cost of health care is keeping more Americans from seeing a doctor, even as the number of individuals with insurance coverage increases, according to a new study.

“Despite short-term gains owing to the [Affordable Care Act], over the past 20 years the portion of adults aged 18-64 years unable to see a physician owing to the cost increased, mostly because of an increase among persons with insurance,” Laura Hawks, MD, of Cambridge (Mass.) Health Alliance and Harvard Medical School in Boston and colleagues wrote in a new research report published in JAMA Internal Medicine.

“In 2017, nearly one-fifth of individuals with any chronic condition (diabetes, obesity, or cardiovascular disease) said they were unable to see a physician owing to cost,” they continued.

Researchers examined 20 years of data (January 1998 through December 2017) from the Centers for Disease Control and Prevention’s Behavioral Risk Factor Surveillance System to identify trends in unmet need for physician and preventive services.

Among adults aged 18-64 years who responded to the survey in 1998 and 2017, uninsurance decreased by 2.1 percentage points, falling from 16.9% to 14.8%. But at the same time, the portion of adults who were unable to see a physician because of cost rose by 2.7 percentage points, from 11.4% to 15.7%. Looking specifically at adults who had insurance coverage, the researchers found that cost was a barrier for 11.5% of them in 2017, up from 7.1% in 1998.

These results come against a backdrop of growing medical costs, increasing deductibles and copayments, an increasing use of cost containment measures like prior authorization, and narrow provider networks in the wake of the transition to value-based payment structures, the authors noted.

“Our finding that financial access to physician care worsened is concerning,” Dr. Hawks and her colleagues wrote. “Persons with conditions such as diabetes, hypertension, cardiovascular disease, and poor health status risk substantial harms if they forgo physician care. Financial barriers to care have been associated with increased hospitalizations and worse health outcomes in patients with cardiovascular disease and hypertension and increased morbidity among patients with diabetes.”

One of the trends highlighted by the study authors is the growing number of employers offering plans with a high deductible.

“Enrollment in a high-deductible health plan, which has become increasingly common in the last decade, a trend uninterrupted by the ACA, is associated with forgoing needed care, especially among those of lower socioeconomic status,” the authors wrote. “Other changes in insurance benefit design, such as imposing tiered copayments and coinsurance obligations, eliminating coverage for some services (e.g., eyeglasses) and narrowing provider networks (which can force some patients to go out-of-network for care) may also have undermined the affordability of care.”

There was some positive news among the findings, however.

“The main encouraging finding from our analysis is the increase in the proportion of persons – both insured and uninsured – receiving cholesterol checks and flu shots,” Dr. Hawk and her colleagues wrote, adding that this increase “may be attributable to the increasing implementation of quality metrics, financial incentives, and improved systems for the delivery of these services.”

However, not all preventive services that had cost barriers eliminated under the ACA saw improvement, such as cancer screening. They note that the proportion of women who did not receive mammography increased during the study period and then plateaued, but did not improve following the implementation of the ACA. The authors described the reasons for this as “unclear.”

Dr. Hawks received funding support from an Institutional National Research Service award and from Cambridge Health Alliance, her employer. Other authors reported membership in Physicians for a National Health Program.

gtwachtman@mdedge.com

SOURCE: Hawks L et al. JAMA Intern Med. 2020 Jan 27. doi: 10.1001/jamainternmed.2019.6538.

The cost of health care is keeping more Americans from seeing a doctor, even as the number of individuals with insurance coverage increases, according to a new study.

“Despite short-term gains owing to the [Affordable Care Act], over the past 20 years the portion of adults aged 18-64 years unable to see a physician owing to the cost increased, mostly because of an increase among persons with insurance,” Laura Hawks, MD, of Cambridge (Mass.) Health Alliance and Harvard Medical School in Boston and colleagues wrote in a new research report published in JAMA Internal Medicine.

“In 2017, nearly one-fifth of individuals with any chronic condition (diabetes, obesity, or cardiovascular disease) said they were unable to see a physician owing to cost,” they continued.

Researchers examined 20 years of data (January 1998 through December 2017) from the Centers for Disease Control and Prevention’s Behavioral Risk Factor Surveillance System to identify trends in unmet need for physician and preventive services.

Among adults aged 18-64 years who responded to the survey in 1998 and 2017, uninsurance decreased by 2.1 percentage points, falling from 16.9% to 14.8%. But at the same time, the portion of adults who were unable to see a physician because of cost rose by 2.7 percentage points, from 11.4% to 15.7%. Looking specifically at adults who had insurance coverage, the researchers found that cost was a barrier for 11.5% of them in 2017, up from 7.1% in 1998.

These results come against a backdrop of growing medical costs, increasing deductibles and copayments, an increasing use of cost containment measures like prior authorization, and narrow provider networks in the wake of the transition to value-based payment structures, the authors noted.

“Our finding that financial access to physician care worsened is concerning,” Dr. Hawks and her colleagues wrote. “Persons with conditions such as diabetes, hypertension, cardiovascular disease, and poor health status risk substantial harms if they forgo physician care. Financial barriers to care have been associated with increased hospitalizations and worse health outcomes in patients with cardiovascular disease and hypertension and increased morbidity among patients with diabetes.”

One of the trends highlighted by the study authors is the growing number of employers offering plans with a high deductible.

“Enrollment in a high-deductible health plan, which has become increasingly common in the last decade, a trend uninterrupted by the ACA, is associated with forgoing needed care, especially among those of lower socioeconomic status,” the authors wrote. “Other changes in insurance benefit design, such as imposing tiered copayments and coinsurance obligations, eliminating coverage for some services (e.g., eyeglasses) and narrowing provider networks (which can force some patients to go out-of-network for care) may also have undermined the affordability of care.”

There was some positive news among the findings, however.

“The main encouraging finding from our analysis is the increase in the proportion of persons – both insured and uninsured – receiving cholesterol checks and flu shots,” Dr. Hawk and her colleagues wrote, adding that this increase “may be attributable to the increasing implementation of quality metrics, financial incentives, and improved systems for the delivery of these services.”

However, not all preventive services that had cost barriers eliminated under the ACA saw improvement, such as cancer screening. They note that the proportion of women who did not receive mammography increased during the study period and then plateaued, but did not improve following the implementation of the ACA. The authors described the reasons for this as “unclear.”

Dr. Hawks received funding support from an Institutional National Research Service award and from Cambridge Health Alliance, her employer. Other authors reported membership in Physicians for a National Health Program.

gtwachtman@mdedge.com

SOURCE: Hawks L et al. JAMA Intern Med. 2020 Jan 27. doi: 10.1001/jamainternmed.2019.6538.

The cost of health care is keeping more Americans from seeing a doctor, even as the number of individuals with insurance coverage increases, according to a new study.

“Despite short-term gains owing to the [Affordable Care Act], over the past 20 years the portion of adults aged 18-64 years unable to see a physician owing to the cost increased, mostly because of an increase among persons with insurance,” Laura Hawks, MD, of Cambridge (Mass.) Health Alliance and Harvard Medical School in Boston and colleagues wrote in a new research report published in JAMA Internal Medicine.

“In 2017, nearly one-fifth of individuals with any chronic condition (diabetes, obesity, or cardiovascular disease) said they were unable to see a physician owing to cost,” they continued.

Researchers examined 20 years of data (January 1998 through December 2017) from the Centers for Disease Control and Prevention’s Behavioral Risk Factor Surveillance System to identify trends in unmet need for physician and preventive services.

Among adults aged 18-64 years who responded to the survey in 1998 and 2017, uninsurance decreased by 2.1 percentage points, falling from 16.9% to 14.8%. But at the same time, the portion of adults who were unable to see a physician because of cost rose by 2.7 percentage points, from 11.4% to 15.7%. Looking specifically at adults who had insurance coverage, the researchers found that cost was a barrier for 11.5% of them in 2017, up from 7.1% in 1998.

These results come against a backdrop of growing medical costs, increasing deductibles and copayments, an increasing use of cost containment measures like prior authorization, and narrow provider networks in the wake of the transition to value-based payment structures, the authors noted.

“Our finding that financial access to physician care worsened is concerning,” Dr. Hawks and her colleagues wrote. “Persons with conditions such as diabetes, hypertension, cardiovascular disease, and poor health status risk substantial harms if they forgo physician care. Financial barriers to care have been associated with increased hospitalizations and worse health outcomes in patients with cardiovascular disease and hypertension and increased morbidity among patients with diabetes.”

One of the trends highlighted by the study authors is the growing number of employers offering plans with a high deductible.

“Enrollment in a high-deductible health plan, which has become increasingly common in the last decade, a trend uninterrupted by the ACA, is associated with forgoing needed care, especially among those of lower socioeconomic status,” the authors wrote. “Other changes in insurance benefit design, such as imposing tiered copayments and coinsurance obligations, eliminating coverage for some services (e.g., eyeglasses) and narrowing provider networks (which can force some patients to go out-of-network for care) may also have undermined the affordability of care.”

There was some positive news among the findings, however.

“The main encouraging finding from our analysis is the increase in the proportion of persons – both insured and uninsured – receiving cholesterol checks and flu shots,” Dr. Hawk and her colleagues wrote, adding that this increase “may be attributable to the increasing implementation of quality metrics, financial incentives, and improved systems for the delivery of these services.”

However, not all preventive services that had cost barriers eliminated under the ACA saw improvement, such as cancer screening. They note that the proportion of women who did not receive mammography increased during the study period and then plateaued, but did not improve following the implementation of the ACA. The authors described the reasons for this as “unclear.”

Dr. Hawks received funding support from an Institutional National Research Service award and from Cambridge Health Alliance, her employer. Other authors reported membership in Physicians for a National Health Program.

gtwachtman@mdedge.com

SOURCE: Hawks L et al. JAMA Intern Med. 2020 Jan 27. doi: 10.1001/jamainternmed.2019.6538.

An oral solution of celecoxib is more effective than placebo for the acute treatment of migraine, according to trial results published in the January issue of Headache.

Two hours after treatment, a significantly greater proportion of patients who received the liquid solution, known as DFN-15, had freedom from pain and freedom from their most bothersome accompanying symptom – nausea, photophobia, or phonophobia – compared with patients who received placebo. The pain freedom rates were 35.6% with celecoxib oral solution and 21.7% with placebo. The rates of freedom from the most bothersome symptom were 57.8% with celecoxib oral solution and 44.8% with placebo.

About 9% of patients who received celecoxib oral solution had treatment-emergent adverse events related to the study drug, the most common of which were dysgeusia (4.2%) and nausea (3.2%). In comparison, about 6% of patients who received placebo had treatment-emergent adverse events. There were no serious treatment-emergent adverse events.

“DFN‐15 has the potential to become a reliable and convenient acute therapeutic option for patients with migraine,” said lead author Richard B. Lipton, MD, and colleagues. Dr. Lipton is affiliated with the Albert Einstein College of Medicine in New York.
 

Assessing celecoxib in migraineurs

Evidence-based guidelines recommend nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, diclofenac, ibuprofen, and naproxen, as effective acute migraine treatments, but these medications may increase the risk of adverse gastrointestinal events, the authors said. Celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, is indicated for the treatment of acute pain in patients with ankylosing spondylitis, osteoarthritis, primary dysmenorrhea, and rheumatoid arthritis. Although it produces analgesia similar to other NSAIDs, among patients with osteoarthritis and rheumatoid arthritis, celecoxib is associated with significantly lower risk of gastrointestinal events, compared with naproxen and ibuprofen, and significantly lower risk of renal events, compared with ibuprofen.

Researchers have studied an oral capsule form of celecoxib (Celebrex, Pfizer) as an acute treatment for migraine in an open-label study that compared celecoxib with naproxen sodium. “While preliminary results suggest comparable efficacy but better tolerability than widely used and guideline-recommended NSAIDs, celecoxib is not currently approved for migraine,” the authors said.

Compared with the oral capsule formulation, the oral liquid solution DFN-15 has a faster median time to peak concentration under fasting conditions (within 1 hour vs. 2.5 hours), which “could translate into more rapid onset of pain relief,” the authors said. In addition, DFN-15 may have greater bioavailability, which could lower dose requirements and improve safety and tolerability. To compare the efficacy, tolerability, and safety of 120-mg DFN-15 with placebo for the acute treatment of migraine, researchers conducted a randomized, double-blind, placebo-controlled study.
 

Participants used single-dose bottles

Researchers randomized 622 patients 1:1 to DFN-15 or placebo, and 567 treated a migraine during the trial. Patients had a mean age of 40 years, and 87% were female. Patients had episodic migraine with or without aura, no signs of medication overuse, and two-eight migraine attacks per month. For the trial, patients treated a single migraine attack of moderate to severe intensity within 1 hour of onset. “Each subject was given a single‐dose bottle of DFN‐15 120 mg or matching placebo containing 4.8 mL liquid,” Dr. Lipton and colleagues said. “They were instructed to drink the entire contents of the bottle to ensure complete consumption of study medication.”

Freedom from pain and freedom from the most bothersome symptom at 2 hours were the coprimary endpoints. “DFN‐15 was also significantly superior to placebo on multiple secondary 2‐hour endpoints, including freedom from photophobia, pain relief, change in functional disability from baseline, overall and 24‐hour satisfaction with treatment, and use of rescue medication,” they reported.

“A new COX‐2 inhibitor that is effective and rapidly absorbed could provide an important new option for a wide range of patients,” the authors said. “Though cross‐study comparisons are problematic, the current results for DFN‐15 indicate that its efficacy is similar to that of NSAIDs and small‐molecule calcitonin gene‐related peptide receptor antagonists (gepants), based on placebo‐subtracted rates pain freedom in acute treatment trials (14%‐21%). DFN‐15 may also be useful among triptan users, who are at elevated risk of medication‐overuse headache and for whom TEAEs within 24 hours postdose are common. ... The form and delivery system of DFN‐15 – a ready‐to‐use solution in a 4.8‐mL single‐use bottle – may support patient adherence.”

The trial had robust placebo response rates, which may have been influenced by “the novelty of a ready‐made oral solution, which has not been previously tested for the acute treatment of migraine,” the authors noted. In addition, the trial does not address the treatment of mild pain or treatment across multiple attacks.

The trial was supported by Dr. Reddy’s Laboratories, manufacturer of DFN-15. Two authors are employed by and own stock in Dr. Reddy’s. Dr. Lipton and a coauthor disclosed research support from and consulting for Dr. Reddy’s.
 

jremaly@mdedge.com

SOURCE: Lipton RB et al. Headache. 2020;60(1):58-70. doi: 10.1111/head.13663.

An oral solution of celecoxib is more effective than placebo for the acute treatment of migraine, according to trial results published in the January issue of Headache.

Two hours after treatment, a significantly greater proportion of patients who received the liquid solution, known as DFN-15, had freedom from pain and freedom from their most bothersome accompanying symptom – nausea, photophobia, or phonophobia – compared with patients who received placebo. The pain freedom rates were 35.6% with celecoxib oral solution and 21.7% with placebo. The rates of freedom from the most bothersome symptom were 57.8% with celecoxib oral solution and 44.8% with placebo.

About 9% of patients who received celecoxib oral solution had treatment-emergent adverse events related to the study drug, the most common of which were dysgeusia (4.2%) and nausea (3.2%). In comparison, about 6% of patients who received placebo had treatment-emergent adverse events. There were no serious treatment-emergent adverse events.

“DFN‐15 has the potential to become a reliable and convenient acute therapeutic option for patients with migraine,” said lead author Richard B. Lipton, MD, and colleagues. Dr. Lipton is affiliated with the Albert Einstein College of Medicine in New York.
 

Assessing celecoxib in migraineurs

Evidence-based guidelines recommend nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, diclofenac, ibuprofen, and naproxen, as effective acute migraine treatments, but these medications may increase the risk of adverse gastrointestinal events, the authors said. Celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, is indicated for the treatment of acute pain in patients with ankylosing spondylitis, osteoarthritis, primary dysmenorrhea, and rheumatoid arthritis. Although it produces analgesia similar to other NSAIDs, among patients with osteoarthritis and rheumatoid arthritis, celecoxib is associated with significantly lower risk of gastrointestinal events, compared with naproxen and ibuprofen, and significantly lower risk of renal events, compared with ibuprofen.

Researchers have studied an oral capsule form of celecoxib (Celebrex, Pfizer) as an acute treatment for migraine in an open-label study that compared celecoxib with naproxen sodium. “While preliminary results suggest comparable efficacy but better tolerability than widely used and guideline-recommended NSAIDs, celecoxib is not currently approved for migraine,” the authors said.

Compared with the oral capsule formulation, the oral liquid solution DFN-15 has a faster median time to peak concentration under fasting conditions (within 1 hour vs. 2.5 hours), which “could translate into more rapid onset of pain relief,” the authors said. In addition, DFN-15 may have greater bioavailability, which could lower dose requirements and improve safety and tolerability. To compare the efficacy, tolerability, and safety of 120-mg DFN-15 with placebo for the acute treatment of migraine, researchers conducted a randomized, double-blind, placebo-controlled study.
 

Participants used single-dose bottles

Researchers randomized 622 patients 1:1 to DFN-15 or placebo, and 567 treated a migraine during the trial. Patients had a mean age of 40 years, and 87% were female. Patients had episodic migraine with or without aura, no signs of medication overuse, and two-eight migraine attacks per month. For the trial, patients treated a single migraine attack of moderate to severe intensity within 1 hour of onset. “Each subject was given a single‐dose bottle of DFN‐15 120 mg or matching placebo containing 4.8 mL liquid,” Dr. Lipton and colleagues said. “They were instructed to drink the entire contents of the bottle to ensure complete consumption of study medication.”

Freedom from pain and freedom from the most bothersome symptom at 2 hours were the coprimary endpoints. “DFN‐15 was also significantly superior to placebo on multiple secondary 2‐hour endpoints, including freedom from photophobia, pain relief, change in functional disability from baseline, overall and 24‐hour satisfaction with treatment, and use of rescue medication,” they reported.

“A new COX‐2 inhibitor that is effective and rapidly absorbed could provide an important new option for a wide range of patients,” the authors said. “Though cross‐study comparisons are problematic, the current results for DFN‐15 indicate that its efficacy is similar to that of NSAIDs and small‐molecule calcitonin gene‐related peptide receptor antagonists (gepants), based on placebo‐subtracted rates pain freedom in acute treatment trials (14%‐21%). DFN‐15 may also be useful among triptan users, who are at elevated risk of medication‐overuse headache and for whom TEAEs within 24 hours postdose are common. ... The form and delivery system of DFN‐15 – a ready‐to‐use solution in a 4.8‐mL single‐use bottle – may support patient adherence.”

The trial had robust placebo response rates, which may have been influenced by “the novelty of a ready‐made oral solution, which has not been previously tested for the acute treatment of migraine,” the authors noted. In addition, the trial does not address the treatment of mild pain or treatment across multiple attacks.

The trial was supported by Dr. Reddy’s Laboratories, manufacturer of DFN-15. Two authors are employed by and own stock in Dr. Reddy’s. Dr. Lipton and a coauthor disclosed research support from and consulting for Dr. Reddy’s.
 

jremaly@mdedge.com

SOURCE: Lipton RB et al. Headache. 2020;60(1):58-70. doi: 10.1111/head.13663.

An oral solution of celecoxib is more effective than placebo for the acute treatment of migraine, according to trial results published in the January issue of Headache.

Two hours after treatment, a significantly greater proportion of patients who received the liquid solution, known as DFN-15, had freedom from pain and freedom from their most bothersome accompanying symptom – nausea, photophobia, or phonophobia – compared with patients who received placebo. The pain freedom rates were 35.6% with celecoxib oral solution and 21.7% with placebo. The rates of freedom from the most bothersome symptom were 57.8% with celecoxib oral solution and 44.8% with placebo.

About 9% of patients who received celecoxib oral solution had treatment-emergent adverse events related to the study drug, the most common of which were dysgeusia (4.2%) and nausea (3.2%). In comparison, about 6% of patients who received placebo had treatment-emergent adverse events. There were no serious treatment-emergent adverse events.

“DFN‐15 has the potential to become a reliable and convenient acute therapeutic option for patients with migraine,” said lead author Richard B. Lipton, MD, and colleagues. Dr. Lipton is affiliated with the Albert Einstein College of Medicine in New York.
 

Assessing celecoxib in migraineurs

Evidence-based guidelines recommend nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, diclofenac, ibuprofen, and naproxen, as effective acute migraine treatments, but these medications may increase the risk of adverse gastrointestinal events, the authors said. Celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, is indicated for the treatment of acute pain in patients with ankylosing spondylitis, osteoarthritis, primary dysmenorrhea, and rheumatoid arthritis. Although it produces analgesia similar to other NSAIDs, among patients with osteoarthritis and rheumatoid arthritis, celecoxib is associated with significantly lower risk of gastrointestinal events, compared with naproxen and ibuprofen, and significantly lower risk of renal events, compared with ibuprofen.

Researchers have studied an oral capsule form of celecoxib (Celebrex, Pfizer) as an acute treatment for migraine in an open-label study that compared celecoxib with naproxen sodium. “While preliminary results suggest comparable efficacy but better tolerability than widely used and guideline-recommended NSAIDs, celecoxib is not currently approved for migraine,” the authors said.

Compared with the oral capsule formulation, the oral liquid solution DFN-15 has a faster median time to peak concentration under fasting conditions (within 1 hour vs. 2.5 hours), which “could translate into more rapid onset of pain relief,” the authors said. In addition, DFN-15 may have greater bioavailability, which could lower dose requirements and improve safety and tolerability. To compare the efficacy, tolerability, and safety of 120-mg DFN-15 with placebo for the acute treatment of migraine, researchers conducted a randomized, double-blind, placebo-controlled study.
 

Participants used single-dose bottles

Researchers randomized 622 patients 1:1 to DFN-15 or placebo, and 567 treated a migraine during the trial. Patients had a mean age of 40 years, and 87% were female. Patients had episodic migraine with or without aura, no signs of medication overuse, and two-eight migraine attacks per month. For the trial, patients treated a single migraine attack of moderate to severe intensity within 1 hour of onset. “Each subject was given a single‐dose bottle of DFN‐15 120 mg or matching placebo containing 4.8 mL liquid,” Dr. Lipton and colleagues said. “They were instructed to drink the entire contents of the bottle to ensure complete consumption of study medication.”

Freedom from pain and freedom from the most bothersome symptom at 2 hours were the coprimary endpoints. “DFN‐15 was also significantly superior to placebo on multiple secondary 2‐hour endpoints, including freedom from photophobia, pain relief, change in functional disability from baseline, overall and 24‐hour satisfaction with treatment, and use of rescue medication,” they reported.

“A new COX‐2 inhibitor that is effective and rapidly absorbed could provide an important new option for a wide range of patients,” the authors said. “Though cross‐study comparisons are problematic, the current results for DFN‐15 indicate that its efficacy is similar to that of NSAIDs and small‐molecule calcitonin gene‐related peptide receptor antagonists (gepants), based on placebo‐subtracted rates pain freedom in acute treatment trials (14%‐21%). DFN‐15 may also be useful among triptan users, who are at elevated risk of medication‐overuse headache and for whom TEAEs within 24 hours postdose are common. ... The form and delivery system of DFN‐15 – a ready‐to‐use solution in a 4.8‐mL single‐use bottle – may support patient adherence.”

The trial had robust placebo response rates, which may have been influenced by “the novelty of a ready‐made oral solution, which has not been previously tested for the acute treatment of migraine,” the authors noted. In addition, the trial does not address the treatment of mild pain or treatment across multiple attacks.

The trial was supported by Dr. Reddy’s Laboratories, manufacturer of DFN-15. Two authors are employed by and own stock in Dr. Reddy’s. Dr. Lipton and a coauthor disclosed research support from and consulting for Dr. Reddy’s.
 

jremaly@mdedge.com

SOURCE: Lipton RB et al. Headache. 2020;60(1):58-70. doi: 10.1111/head.13663.

Adult soccer players who frequently head the ball may have a heightened risk of memory impairment if they are carriers of the APOE e4 allele, according to authors of a recent longitudinal study. Worse verbal memory was linked to high levels of ball heading among those players who were APOE e4–positive, compared with those who were APOE e4–negative, according to the authors, led by Liane E. Hunter, PhD, of the Gruss Magnetic Resonance Imaging Center at Albert Einstein College of Medicine, New York.

These findings, while preliminary, do raise the possibility that “safe levels for soccer heading” could be proposed to protect players from harm or that APOE e4-positive players might be advised to limit their exposure to head impacts, Dr. Hunter and coauthors wrote in a report in JAMA Neurology.

However, the findings should “in no way” be used to justify APOE testing to make clinical decisions regarding the safety of playing soccer, said Sarah J. Banks, PhD, of the University of California, San Diego, and Jesse Mez, MD, of Boston University in a related editorial (doi: 10.1001/jamaneurol.2019.4451). “Like most good science, the study provides an important, but incremental, step to understanding gene-environment interactions in sports,” Dr. Banks and Dr. Mez wrote in their editorial.

While there are some studies tying APOE e4 to poorer neuropsychiatric performance in boxers and U.S. football players, there are no such studies looking at the role of APOE e4 in soccer players exposed to repetitive “subconcussive” ball heading, according to Dr. Hunter and coresearchers. Accordingly, they sought to analyze APOE e4 and neuropsychological performance in relation to ball heading in 352 adult amateur soccer players enrolled in the Einstein Soccer Study between November 2013 and January 2018. About three-quarters of the players were male, and the median age at enrollment was 23 years.

The players completed a computer-based questionnaire designed to estimate their exposure to soccer heading at enrollment and at follow-up visits every 3-6 months. To test verbal memory at each visit, players were asked to memorize a 12-item grocery list, and then asked to recall the items 20 minutes later.

High levels of heading were linked to poorer performance on the verbal memory task, similar to one previously reported study, investigators said.

There was no association overall of APOE e4 and heading with performance on the shopping list task, according to investigators. By contrast, there was a 4.1-fold increased deficit in verbal memory for APOE e4–positive players with high heading exposure, compared with those with low exposure, investigators reported. Likewise, there was an 8.5-fold increased deficit in verbal memory for APOE e4–positive players with high versus moderate heading exposure.

That said, the absolute difference in performance was “subtle” and difficult to interpret in the context of a cross-sectional study, Dr. Banks and Dr. Mez said in their editorial.

In absolute terms, the mean decrease in scores on the 13-point shopping list task between the high and low heading exposure was 1.13 points greater for the APOE e4–positive group, compared with the APOE e4–negative group, and the decrease between the high and moderate heading exposure groups was 0.98 points greater, according to the report.

“The effect size of our interaction is relatively small,” Dr. Hunter and colleagues acknowledged in their report. “However, similar to the widely cited model of disease evolution in Alzheimer disease, our findings may be evidence of early subclinical effects, which could accumulate in APOE e4–positive players over a protracted time frame and ultimately be associated with overt clinical dysfunction.”

Several study authors said they had received grants from the National Institutes of Health and affiliated institutes, the Migraine Research Foundation, and the National Headache Foundation. They reported disclosures related to Amgen, Avanir, Biohaven Holdings, Biovision, Boston Scientific, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Merck, and Pfizer, among others.

SOURCE: Hunter LE et al. JAMA Neurol. 2020 Jan 27. doi: 10.1001/jamaneurol.2019.4828.

Adult soccer players who frequently head the ball may have a heightened risk of memory impairment if they are carriers of the APOE e4 allele, according to authors of a recent longitudinal study. Worse verbal memory was linked to high levels of ball heading among those players who were APOE e4–positive, compared with those who were APOE e4–negative, according to the authors, led by Liane E. Hunter, PhD, of the Gruss Magnetic Resonance Imaging Center at Albert Einstein College of Medicine, New York.

These findings, while preliminary, do raise the possibility that “safe levels for soccer heading” could be proposed to protect players from harm or that APOE e4-positive players might be advised to limit their exposure to head impacts, Dr. Hunter and coauthors wrote in a report in JAMA Neurology.

However, the findings should “in no way” be used to justify APOE testing to make clinical decisions regarding the safety of playing soccer, said Sarah J. Banks, PhD, of the University of California, San Diego, and Jesse Mez, MD, of Boston University in a related editorial (doi: 10.1001/jamaneurol.2019.4451). “Like most good science, the study provides an important, but incremental, step to understanding gene-environment interactions in sports,” Dr. Banks and Dr. Mez wrote in their editorial.

While there are some studies tying APOE e4 to poorer neuropsychiatric performance in boxers and U.S. football players, there are no such studies looking at the role of APOE e4 in soccer players exposed to repetitive “subconcussive” ball heading, according to Dr. Hunter and coresearchers. Accordingly, they sought to analyze APOE e4 and neuropsychological performance in relation to ball heading in 352 adult amateur soccer players enrolled in the Einstein Soccer Study between November 2013 and January 2018. About three-quarters of the players were male, and the median age at enrollment was 23 years.

The players completed a computer-based questionnaire designed to estimate their exposure to soccer heading at enrollment and at follow-up visits every 3-6 months. To test verbal memory at each visit, players were asked to memorize a 12-item grocery list, and then asked to recall the items 20 minutes later.

High levels of heading were linked to poorer performance on the verbal memory task, similar to one previously reported study, investigators said.

There was no association overall of APOE e4 and heading with performance on the shopping list task, according to investigators. By contrast, there was a 4.1-fold increased deficit in verbal memory for APOE e4–positive players with high heading exposure, compared with those with low exposure, investigators reported. Likewise, there was an 8.5-fold increased deficit in verbal memory for APOE e4–positive players with high versus moderate heading exposure.

That said, the absolute difference in performance was “subtle” and difficult to interpret in the context of a cross-sectional study, Dr. Banks and Dr. Mez said in their editorial.

In absolute terms, the mean decrease in scores on the 13-point shopping list task between the high and low heading exposure was 1.13 points greater for the APOE e4–positive group, compared with the APOE e4–negative group, and the decrease between the high and moderate heading exposure groups was 0.98 points greater, according to the report.

“The effect size of our interaction is relatively small,” Dr. Hunter and colleagues acknowledged in their report. “However, similar to the widely cited model of disease evolution in Alzheimer disease, our findings may be evidence of early subclinical effects, which could accumulate in APOE e4–positive players over a protracted time frame and ultimately be associated with overt clinical dysfunction.”

Several study authors said they had received grants from the National Institutes of Health and affiliated institutes, the Migraine Research Foundation, and the National Headache Foundation. They reported disclosures related to Amgen, Avanir, Biohaven Holdings, Biovision, Boston Scientific, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Merck, and Pfizer, among others.

SOURCE: Hunter LE et al. JAMA Neurol. 2020 Jan 27. doi: 10.1001/jamaneurol.2019.4828.

Adult soccer players who frequently head the ball may have a heightened risk of memory impairment if they are carriers of the APOE e4 allele, according to authors of a recent longitudinal study. Worse verbal memory was linked to high levels of ball heading among those players who were APOE e4–positive, compared with those who were APOE e4–negative, according to the authors, led by Liane E. Hunter, PhD, of the Gruss Magnetic Resonance Imaging Center at Albert Einstein College of Medicine, New York.

These findings, while preliminary, do raise the possibility that “safe levels for soccer heading” could be proposed to protect players from harm or that APOE e4-positive players might be advised to limit their exposure to head impacts, Dr. Hunter and coauthors wrote in a report in JAMA Neurology.

However, the findings should “in no way” be used to justify APOE testing to make clinical decisions regarding the safety of playing soccer, said Sarah J. Banks, PhD, of the University of California, San Diego, and Jesse Mez, MD, of Boston University in a related editorial (doi: 10.1001/jamaneurol.2019.4451). “Like most good science, the study provides an important, but incremental, step to understanding gene-environment interactions in sports,” Dr. Banks and Dr. Mez wrote in their editorial.

While there are some studies tying APOE e4 to poorer neuropsychiatric performance in boxers and U.S. football players, there are no such studies looking at the role of APOE e4 in soccer players exposed to repetitive “subconcussive” ball heading, according to Dr. Hunter and coresearchers. Accordingly, they sought to analyze APOE e4 and neuropsychological performance in relation to ball heading in 352 adult amateur soccer players enrolled in the Einstein Soccer Study between November 2013 and January 2018. About three-quarters of the players were male, and the median age at enrollment was 23 years.

The players completed a computer-based questionnaire designed to estimate their exposure to soccer heading at enrollment and at follow-up visits every 3-6 months. To test verbal memory at each visit, players were asked to memorize a 12-item grocery list, and then asked to recall the items 20 minutes later.

High levels of heading were linked to poorer performance on the verbal memory task, similar to one previously reported study, investigators said.

There was no association overall of APOE e4 and heading with performance on the shopping list task, according to investigators. By contrast, there was a 4.1-fold increased deficit in verbal memory for APOE e4–positive players with high heading exposure, compared with those with low exposure, investigators reported. Likewise, there was an 8.5-fold increased deficit in verbal memory for APOE e4–positive players with high versus moderate heading exposure.

That said, the absolute difference in performance was “subtle” and difficult to interpret in the context of a cross-sectional study, Dr. Banks and Dr. Mez said in their editorial.

In absolute terms, the mean decrease in scores on the 13-point shopping list task between the high and low heading exposure was 1.13 points greater for the APOE e4–positive group, compared with the APOE e4–negative group, and the decrease between the high and moderate heading exposure groups was 0.98 points greater, according to the report.

“The effect size of our interaction is relatively small,” Dr. Hunter and colleagues acknowledged in their report. “However, similar to the widely cited model of disease evolution in Alzheimer disease, our findings may be evidence of early subclinical effects, which could accumulate in APOE e4–positive players over a protracted time frame and ultimately be associated with overt clinical dysfunction.”

Several study authors said they had received grants from the National Institutes of Health and affiliated institutes, the Migraine Research Foundation, and the National Headache Foundation. They reported disclosures related to Amgen, Avanir, Biohaven Holdings, Biovision, Boston Scientific, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Merck, and Pfizer, among others.

SOURCE: Hunter LE et al. JAMA Neurol. 2020 Jan 27. doi: 10.1001/jamaneurol.2019.4828.

A group of leading medical journal editors is seeking to improve the completeness and transparency of financial disclosure reporting with a proposed new disclosure form that puts more onus on readers to decide whether relationships and activities should influence how they view published papers.

The proposed changes are described in an editorial published simultaneously today in the Annals of Internal Medicine, British Medical Journal, Journal of the American Medical Association, The Lancet, New England Journal of Medicine, and several other journals whose editors are members of the International Committee of Medical Journal Editors (ICMJE).

“While no approach to disclosure will be perfect or foolproof, we hope the changes we propose will help promote transparency and trust,” the editorial stated (Ann Intern Med. 2020 Jan 27. doi: 10.7326/M19-3933).

The ICMJE adopted its currently used electronic form – the “ICMJE Form for the Disclosure of Potential Conflicts of Interest” – 10 years ago in an effort to create some uniformity amidst a patchwork of differing disclosure requirements for authors.

It’s not known how many journals outside of the ICMJE’s member journals routinely use the disclosure form, but the organization’s website houses an extensive list of journals whose editors or publishers have requested to be listed as following the ICMJE’s recommendations for editing, reporting, and publishing, including those concerning disclosures. The ICMJE does not “certify” journals. The full set of recommendations was updated in December 2019.

Most authors are committed to transparent reporting, but “opinions differ over which relationships or activities to report,” the editorial stated.

An author might choose to omit an item that others deem important because of a difference in opinion regarding “relevance,” confusion over definitions, or a simple oversight. Some authors may be “concerned that readers will interpret the listing of any item as a ‘potential conflict of interest’ as indicative of problematic influence and wrongdoing,” the editorial stated.

The revised form, like the current one, asks authors to disclose relationships and activities that are directly related to the reported work, as well as those that are topically related (within the broadly defined field addressed in the work). But unlike the current form, the new version provides a checklist of relationships and activities and asks authors to check ‘yes’ or ‘no’ for each one (and to name them when the answer is ‘yes’).

Items in the checklist include grants, payments/honoraria for lectures, patents issued or planned, stock/stock options, and leadership or fiduciary roles in committees, boards, or societies.

The proposed new form makes no mention of “potential conflicts of interest” or “relevancy,” per say. Authors aren’t asked to determine what might be interpreted as a potential conflict of interest, but instead are asked for a “complete listing” of what readers may find “pertinent” to their work.

“We’re trying to move away from calling everything a [potential] ‘conflict,’ ” Darren B. Taichman, MD, PhD, secretary of ICMJE and executive editor of the Annals of Internal Medicine, said in an interview. “We want to remove for authors the concern or stigma, if you will, that anything listed on a form implies that there is something wrong, because that’s just not true. … We want readers to decide what relationships are important as they interpret the work.”

Dr. Taichman said in the interview that the ICMJE’s updating of the form was more a function of “good housekeeping” and continuous appreciation of disclosure as an important issue, rather than any one specific issue, such as concern over a “relevancy” approach to disclosures.

The ICMJE is seeking feedback about its proposed form, which is available with a link for providing comments, at www.icmje.org.

Broader national efforts

Editors and others have been increasingly moving, however, toward asking for more complete disclosures where authors aren’t asked to judge “relevancy” and where readers can make decisions on their own. The American Society of Clinical Oncology, which produces the Journal of Clinical Oncology (JCO) as well as practice guidelines and continuing medical education programs, moved about 5 years ago to a system of general disclosure that asks physicians and others to disclose all financial interests and industry relationships, with no qualifiers.

Earlier in January 2020, the Accreditation Council for Continuing Medical Education issued proposed revisions to its Standards for Integrity and Independence in Accredited Continuing Education. These revisions, which are open for comment, require CME providers to collect disclosure information about all financial relationships of speakers and presenters. It’s up to the CME provider to then determine which relationships are relevant, according to the proposed document.

More change is on the way, as disclosure issues are being deliberated nationally in the wake of a highly publicized disclosure failure at Memorial Sloan Kettering Cancer Center in 2018. Chief medical officer José Baselga, MD, PhD, failed to report millions of dollars of industry payments and ownership interests in journal articles he wrote or cowrote over several years.

In February 2019, leaders from journals, academia, medical societies, and other institutions gathered in Washington for a closed-door meeting to hash out various disclosure related issues.

Hosted by the Association of American Medical Colleges and cosponsored by Memorial Sloan Kettering Cancer Center, ASCO, JAMA, and the Council of Medical Specialty Societies, the meeting led to a series of working groups that are creating additional recommendations “due out soon in 2020,” Heather Pierce, senior director of science policy and regulatory counsel for the AAMC, said in an interview.

Among the questions being discussed: What disclosures should be verified and who should do so? How can disclosures be made more complete and easier for researchers? And, “most importantly,” said Ms. Pierce, how can policy requirements across each of these sectors be aligned so that there’s more coordination and oversight – and with it, public trust?

Some critics of current disclosure policies have called for more reporting of compensation amounts, and Ms. Pierce said that this has been part of cross-sector discussions.

The ICMJE’s proposed form invites, but does not require, authors to indicate what payments were made to them or their institutions. “Part of this is due to the fact that it’s hard to define, let alone agree on, what’s an important amount,” Dr. Taichman said.

A push for registries

The ICMJE is also aiming to make the disclosure process more efficient for authors – and to eliminate inconsistent and incomplete disclosures – by accepting disclosures from web-based repositories, according to the editorial. Repositories allow authors to maintain an inventory of their relationships and activities and then create electronic disclosures that are tailored to the requirements of the ICMJE, medical societies, and other entities.

The AAMC-run repository, called Convey, is consistent with ICMJE reporting requirements and other criteria (e.g., there are no fees for individuals to enter, store, or export their data), but the development of other repositories may be helpful “for meeting regional, linguistic, and regulatory needs” of authors across the world, the editorial stated.

The Annals of Internal Medicine and the New England Journal of Medicine are both currently collecting disclosures through Convey. The platform was born from discussions that followed a 2009 Institute of Medicine report on conflicts of interest.

Signers of the ICMJE editorial include representatives of the National Library of Medicine and the World Association of Medical Editors, in addition to editors in chief and other leaders of the ICMJE member journals.

A group of leading medical journal editors is seeking to improve the completeness and transparency of financial disclosure reporting with a proposed new disclosure form that puts more onus on readers to decide whether relationships and activities should influence how they view published papers.

The proposed changes are described in an editorial published simultaneously today in the Annals of Internal Medicine, British Medical Journal, Journal of the American Medical Association, The Lancet, New England Journal of Medicine, and several other journals whose editors are members of the International Committee of Medical Journal Editors (ICMJE).

“While no approach to disclosure will be perfect or foolproof, we hope the changes we propose will help promote transparency and trust,” the editorial stated (Ann Intern Med. 2020 Jan 27. doi: 10.7326/M19-3933).

The ICMJE adopted its currently used electronic form – the “ICMJE Form for the Disclosure of Potential Conflicts of Interest” – 10 years ago in an effort to create some uniformity amidst a patchwork of differing disclosure requirements for authors.

It’s not known how many journals outside of the ICMJE’s member journals routinely use the disclosure form, but the organization’s website houses an extensive list of journals whose editors or publishers have requested to be listed as following the ICMJE’s recommendations for editing, reporting, and publishing, including those concerning disclosures. The ICMJE does not “certify” journals. The full set of recommendations was updated in December 2019.

Most authors are committed to transparent reporting, but “opinions differ over which relationships or activities to report,” the editorial stated.

An author might choose to omit an item that others deem important because of a difference in opinion regarding “relevance,” confusion over definitions, or a simple oversight. Some authors may be “concerned that readers will interpret the listing of any item as a ‘potential conflict of interest’ as indicative of problematic influence and wrongdoing,” the editorial stated.

The revised form, like the current one, asks authors to disclose relationships and activities that are directly related to the reported work, as well as those that are topically related (within the broadly defined field addressed in the work). But unlike the current form, the new version provides a checklist of relationships and activities and asks authors to check ‘yes’ or ‘no’ for each one (and to name them when the answer is ‘yes’).

Items in the checklist include grants, payments/honoraria for lectures, patents issued or planned, stock/stock options, and leadership or fiduciary roles in committees, boards, or societies.

The proposed new form makes no mention of “potential conflicts of interest” or “relevancy,” per say. Authors aren’t asked to determine what might be interpreted as a potential conflict of interest, but instead are asked for a “complete listing” of what readers may find “pertinent” to their work.

“We’re trying to move away from calling everything a [potential] ‘conflict,’ ” Darren B. Taichman, MD, PhD, secretary of ICMJE and executive editor of the Annals of Internal Medicine, said in an interview. “We want to remove for authors the concern or stigma, if you will, that anything listed on a form implies that there is something wrong, because that’s just not true. … We want readers to decide what relationships are important as they interpret the work.”

Dr. Taichman said in the interview that the ICMJE’s updating of the form was more a function of “good housekeeping” and continuous appreciation of disclosure as an important issue, rather than any one specific issue, such as concern over a “relevancy” approach to disclosures.

The ICMJE is seeking feedback about its proposed form, which is available with a link for providing comments, at www.icmje.org.

Broader national efforts

Editors and others have been increasingly moving, however, toward asking for more complete disclosures where authors aren’t asked to judge “relevancy” and where readers can make decisions on their own. The American Society of Clinical Oncology, which produces the Journal of Clinical Oncology (JCO) as well as practice guidelines and continuing medical education programs, moved about 5 years ago to a system of general disclosure that asks physicians and others to disclose all financial interests and industry relationships, with no qualifiers.

Earlier in January 2020, the Accreditation Council for Continuing Medical Education issued proposed revisions to its Standards for Integrity and Independence in Accredited Continuing Education. These revisions, which are open for comment, require CME providers to collect disclosure information about all financial relationships of speakers and presenters. It’s up to the CME provider to then determine which relationships are relevant, according to the proposed document.

More change is on the way, as disclosure issues are being deliberated nationally in the wake of a highly publicized disclosure failure at Memorial Sloan Kettering Cancer Center in 2018. Chief medical officer José Baselga, MD, PhD, failed to report millions of dollars of industry payments and ownership interests in journal articles he wrote or cowrote over several years.

In February 2019, leaders from journals, academia, medical societies, and other institutions gathered in Washington for a closed-door meeting to hash out various disclosure related issues.

Hosted by the Association of American Medical Colleges and cosponsored by Memorial Sloan Kettering Cancer Center, ASCO, JAMA, and the Council of Medical Specialty Societies, the meeting led to a series of working groups that are creating additional recommendations “due out soon in 2020,” Heather Pierce, senior director of science policy and regulatory counsel for the AAMC, said in an interview.

Among the questions being discussed: What disclosures should be verified and who should do so? How can disclosures be made more complete and easier for researchers? And, “most importantly,” said Ms. Pierce, how can policy requirements across each of these sectors be aligned so that there’s more coordination and oversight – and with it, public trust?

Some critics of current disclosure policies have called for more reporting of compensation amounts, and Ms. Pierce said that this has been part of cross-sector discussions.

The ICMJE’s proposed form invites, but does not require, authors to indicate what payments were made to them or their institutions. “Part of this is due to the fact that it’s hard to define, let alone agree on, what’s an important amount,” Dr. Taichman said.

A push for registries

The ICMJE is also aiming to make the disclosure process more efficient for authors – and to eliminate inconsistent and incomplete disclosures – by accepting disclosures from web-based repositories, according to the editorial. Repositories allow authors to maintain an inventory of their relationships and activities and then create electronic disclosures that are tailored to the requirements of the ICMJE, medical societies, and other entities.

The AAMC-run repository, called Convey, is consistent with ICMJE reporting requirements and other criteria (e.g., there are no fees for individuals to enter, store, or export their data), but the development of other repositories may be helpful “for meeting regional, linguistic, and regulatory needs” of authors across the world, the editorial stated.

The Annals of Internal Medicine and the New England Journal of Medicine are both currently collecting disclosures through Convey. The platform was born from discussions that followed a 2009 Institute of Medicine report on conflicts of interest.

Signers of the ICMJE editorial include representatives of the National Library of Medicine and the World Association of Medical Editors, in addition to editors in chief and other leaders of the ICMJE member journals.

A group of leading medical journal editors is seeking to improve the completeness and transparency of financial disclosure reporting with a proposed new disclosure form that puts more onus on readers to decide whether relationships and activities should influence how they view published papers.

The proposed changes are described in an editorial published simultaneously today in the Annals of Internal Medicine, British Medical Journal, Journal of the American Medical Association, The Lancet, New England Journal of Medicine, and several other journals whose editors are members of the International Committee of Medical Journal Editors (ICMJE).

“While no approach to disclosure will be perfect or foolproof, we hope the changes we propose will help promote transparency and trust,” the editorial stated (Ann Intern Med. 2020 Jan 27. doi: 10.7326/M19-3933).

The ICMJE adopted its currently used electronic form – the “ICMJE Form for the Disclosure of Potential Conflicts of Interest” – 10 years ago in an effort to create some uniformity amidst a patchwork of differing disclosure requirements for authors.

It’s not known how many journals outside of the ICMJE’s member journals routinely use the disclosure form, but the organization’s website houses an extensive list of journals whose editors or publishers have requested to be listed as following the ICMJE’s recommendations for editing, reporting, and publishing, including those concerning disclosures. The ICMJE does not “certify” journals. The full set of recommendations was updated in December 2019.

Most authors are committed to transparent reporting, but “opinions differ over which relationships or activities to report,” the editorial stated.

An author might choose to omit an item that others deem important because of a difference in opinion regarding “relevance,” confusion over definitions, or a simple oversight. Some authors may be “concerned that readers will interpret the listing of any item as a ‘potential conflict of interest’ as indicative of problematic influence and wrongdoing,” the editorial stated.

The revised form, like the current one, asks authors to disclose relationships and activities that are directly related to the reported work, as well as those that are topically related (within the broadly defined field addressed in the work). But unlike the current form, the new version provides a checklist of relationships and activities and asks authors to check ‘yes’ or ‘no’ for each one (and to name them when the answer is ‘yes’).

Items in the checklist include grants, payments/honoraria for lectures, patents issued or planned, stock/stock options, and leadership or fiduciary roles in committees, boards, or societies.

The proposed new form makes no mention of “potential conflicts of interest” or “relevancy,” per say. Authors aren’t asked to determine what might be interpreted as a potential conflict of interest, but instead are asked for a “complete listing” of what readers may find “pertinent” to their work.

“We’re trying to move away from calling everything a [potential] ‘conflict,’ ” Darren B. Taichman, MD, PhD, secretary of ICMJE and executive editor of the Annals of Internal Medicine, said in an interview. “We want to remove for authors the concern or stigma, if you will, that anything listed on a form implies that there is something wrong, because that’s just not true. … We want readers to decide what relationships are important as they interpret the work.”

Dr. Taichman said in the interview that the ICMJE’s updating of the form was more a function of “good housekeeping” and continuous appreciation of disclosure as an important issue, rather than any one specific issue, such as concern over a “relevancy” approach to disclosures.

The ICMJE is seeking feedback about its proposed form, which is available with a link for providing comments, at www.icmje.org.

Broader national efforts

Editors and others have been increasingly moving, however, toward asking for more complete disclosures where authors aren’t asked to judge “relevancy” and where readers can make decisions on their own. The American Society of Clinical Oncology, which produces the Journal of Clinical Oncology (JCO) as well as practice guidelines and continuing medical education programs, moved about 5 years ago to a system of general disclosure that asks physicians and others to disclose all financial interests and industry relationships, with no qualifiers.

Earlier in January 2020, the Accreditation Council for Continuing Medical Education issued proposed revisions to its Standards for Integrity and Independence in Accredited Continuing Education. These revisions, which are open for comment, require CME providers to collect disclosure information about all financial relationships of speakers and presenters. It’s up to the CME provider to then determine which relationships are relevant, according to the proposed document.

More change is on the way, as disclosure issues are being deliberated nationally in the wake of a highly publicized disclosure failure at Memorial Sloan Kettering Cancer Center in 2018. Chief medical officer José Baselga, MD, PhD, failed to report millions of dollars of industry payments and ownership interests in journal articles he wrote or cowrote over several years.

In February 2019, leaders from journals, academia, medical societies, and other institutions gathered in Washington for a closed-door meeting to hash out various disclosure related issues.

Hosted by the Association of American Medical Colleges and cosponsored by Memorial Sloan Kettering Cancer Center, ASCO, JAMA, and the Council of Medical Specialty Societies, the meeting led to a series of working groups that are creating additional recommendations “due out soon in 2020,” Heather Pierce, senior director of science policy and regulatory counsel for the AAMC, said in an interview.

Among the questions being discussed: What disclosures should be verified and who should do so? How can disclosures be made more complete and easier for researchers? And, “most importantly,” said Ms. Pierce, how can policy requirements across each of these sectors be aligned so that there’s more coordination and oversight – and with it, public trust?

Some critics of current disclosure policies have called for more reporting of compensation amounts, and Ms. Pierce said that this has been part of cross-sector discussions.

The ICMJE’s proposed form invites, but does not require, authors to indicate what payments were made to them or their institutions. “Part of this is due to the fact that it’s hard to define, let alone agree on, what’s an important amount,” Dr. Taichman said.

A push for registries

The ICMJE is also aiming to make the disclosure process more efficient for authors – and to eliminate inconsistent and incomplete disclosures – by accepting disclosures from web-based repositories, according to the editorial. Repositories allow authors to maintain an inventory of their relationships and activities and then create electronic disclosures that are tailored to the requirements of the ICMJE, medical societies, and other entities.

The AAMC-run repository, called Convey, is consistent with ICMJE reporting requirements and other criteria (e.g., there are no fees for individuals to enter, store, or export their data), but the development of other repositories may be helpful “for meeting regional, linguistic, and regulatory needs” of authors across the world, the editorial stated.

The Annals of Internal Medicine and the New England Journal of Medicine are both currently collecting disclosures through Convey. The platform was born from discussions that followed a 2009 Institute of Medicine report on conflicts of interest.

Signers of the ICMJE editorial include representatives of the National Library of Medicine and the World Association of Medical Editors, in addition to editors in chief and other leaders of the ICMJE member journals.

Modafinil exposure during pregnancy was associated with an approximately tripled risk of congenital malformations in a large Danish registry-based study.

Modafinil (Provigil) is commonly prescribed to address daytime sleepiness in narcolepsy and multiple sclerosis. An interim postmarketing safety analysis showed increased rates of major malformation in modafinil-exposed pregnancies, so the manufacturer issued an alert advising health care professionals of this safety signal in June 2019, wrote Per Damkier, MD, PhD, corresponding author of a JAMA research letter reporting the Danish study results. The postmarketing study had shown a major malformation rate of about 15% in modafinil-exposed pregnancies, much higher than the 3% background rate.

Dr. Damkier and Anne Broe, MD, PhD, both of the department of clinical biochemistry and pharmacology at Odense (Denmark) University Hospital, compared outcomes for pregnant women who were prescribed modafinil at any point during the first trimester of pregnancy with those who were prescribed an active comparator, methylphenidate, as well as with those who had neither exposure. Methylphenidate is not associated with congenital malformations and is used for indications similar to modafinil.

Looking at all pregnancies for whom complete records existed in Danish health registries between 2004 and 2017, the investigators found 49 modafinil-exposed pregnancies, 963 methylphenidate-exposed pregnancies, and 828,644 pregnancies with neither exposure.

Six major congenital malformations occurred in the modafinil-exposed group for an absolute risk of 12%. Major malformations occurred in 43 (4.5%) of the methylphenidate-exposed group and 32,466 (3.9%) of the unexposed group.

Using the extensive data available in public registries, the authors were able to perform logistic regression to adjust for concomitant use of other psychotropic medication; comorbidities such as diabetes and hypertension; and demographic and anthropometric measures such as maternal age, smoking status, and body mass index.

After this statistical adjustment, the researchers found that modafinil exposure during the first trimester of pregnancy was associated with an odds ratio of 3.4 (95% confidence interval, 1.2-9.7) for major congenital malformation, compared with first-trimester methylphenidate exposure. Compared with the unexposed cohort, modafinil-exposed pregnancies had an adjusted odds ratio of 2.7 (95% CI, 1.1-6.9) for major congenital malformation.

A total of 13 (27%) women who took modafinil had multiple sclerosis, but the authors excluded women who’d received a prescription for the multiple sclerosis drug teriflunomide (Aubagio), a known teratogen. Sleep disorders were reported for 39% of modafinil users, compared with 4.5% of methylphenidate users. Rates of psychoactive drug use were 41% for the modafinil group and 30% for the methylphenidate group.

The authors acknowledged the possibility of residual confounders affecting their results, and of the statistical problems with the very small sample size of modafinil-exposed pregnancies. Also, actual medication use – rather than prescription redemption – wasn’t captured in the study.

The study was partially funded by the Novo Nordisk Foundation. The authors reported no conflicts of interest.

koakes@mdedge.com

SOURCE: Damkier P, Broe A. JAMA. 2020;323(4):374-6.

Modafinil exposure during pregnancy was associated with an approximately tripled risk of congenital malformations in a large Danish registry-based study.

Modafinil (Provigil) is commonly prescribed to address daytime sleepiness in narcolepsy and multiple sclerosis. An interim postmarketing safety analysis showed increased rates of major malformation in modafinil-exposed pregnancies, so the manufacturer issued an alert advising health care professionals of this safety signal in June 2019, wrote Per Damkier, MD, PhD, corresponding author of a JAMA research letter reporting the Danish study results. The postmarketing study had shown a major malformation rate of about 15% in modafinil-exposed pregnancies, much higher than the 3% background rate.

Dr. Damkier and Anne Broe, MD, PhD, both of the department of clinical biochemistry and pharmacology at Odense (Denmark) University Hospital, compared outcomes for pregnant women who were prescribed modafinil at any point during the first trimester of pregnancy with those who were prescribed an active comparator, methylphenidate, as well as with those who had neither exposure. Methylphenidate is not associated with congenital malformations and is used for indications similar to modafinil.

Looking at all pregnancies for whom complete records existed in Danish health registries between 2004 and 2017, the investigators found 49 modafinil-exposed pregnancies, 963 methylphenidate-exposed pregnancies, and 828,644 pregnancies with neither exposure.

Six major congenital malformations occurred in the modafinil-exposed group for an absolute risk of 12%. Major malformations occurred in 43 (4.5%) of the methylphenidate-exposed group and 32,466 (3.9%) of the unexposed group.

Using the extensive data available in public registries, the authors were able to perform logistic regression to adjust for concomitant use of other psychotropic medication; comorbidities such as diabetes and hypertension; and demographic and anthropometric measures such as maternal age, smoking status, and body mass index.

After this statistical adjustment, the researchers found that modafinil exposure during the first trimester of pregnancy was associated with an odds ratio of 3.4 (95% confidence interval, 1.2-9.7) for major congenital malformation, compared with first-trimester methylphenidate exposure. Compared with the unexposed cohort, modafinil-exposed pregnancies had an adjusted odds ratio of 2.7 (95% CI, 1.1-6.9) for major congenital malformation.

A total of 13 (27%) women who took modafinil had multiple sclerosis, but the authors excluded women who’d received a prescription for the multiple sclerosis drug teriflunomide (Aubagio), a known teratogen. Sleep disorders were reported for 39% of modafinil users, compared with 4.5% of methylphenidate users. Rates of psychoactive drug use were 41% for the modafinil group and 30% for the methylphenidate group.

The authors acknowledged the possibility of residual confounders affecting their results, and of the statistical problems with the very small sample size of modafinil-exposed pregnancies. Also, actual medication use – rather than prescription redemption – wasn’t captured in the study.

The study was partially funded by the Novo Nordisk Foundation. The authors reported no conflicts of interest.

koakes@mdedge.com

SOURCE: Damkier P, Broe A. JAMA. 2020;323(4):374-6.

Modafinil exposure during pregnancy was associated with an approximately tripled risk of congenital malformations in a large Danish registry-based study.

Modafinil (Provigil) is commonly prescribed to address daytime sleepiness in narcolepsy and multiple sclerosis. An interim postmarketing safety analysis showed increased rates of major malformation in modafinil-exposed pregnancies, so the manufacturer issued an alert advising health care professionals of this safety signal in June 2019, wrote Per Damkier, MD, PhD, corresponding author of a JAMA research letter reporting the Danish study results. The postmarketing study had shown a major malformation rate of about 15% in modafinil-exposed pregnancies, much higher than the 3% background rate.

Dr. Damkier and Anne Broe, MD, PhD, both of the department of clinical biochemistry and pharmacology at Odense (Denmark) University Hospital, compared outcomes for pregnant women who were prescribed modafinil at any point during the first trimester of pregnancy with those who were prescribed an active comparator, methylphenidate, as well as with those who had neither exposure. Methylphenidate is not associated with congenital malformations and is used for indications similar to modafinil.

Looking at all pregnancies for whom complete records existed in Danish health registries between 2004 and 2017, the investigators found 49 modafinil-exposed pregnancies, 963 methylphenidate-exposed pregnancies, and 828,644 pregnancies with neither exposure.

Six major congenital malformations occurred in the modafinil-exposed group for an absolute risk of 12%. Major malformations occurred in 43 (4.5%) of the methylphenidate-exposed group and 32,466 (3.9%) of the unexposed group.

Using the extensive data available in public registries, the authors were able to perform logistic regression to adjust for concomitant use of other psychotropic medication; comorbidities such as diabetes and hypertension; and demographic and anthropometric measures such as maternal age, smoking status, and body mass index.

After this statistical adjustment, the researchers found that modafinil exposure during the first trimester of pregnancy was associated with an odds ratio of 3.4 (95% confidence interval, 1.2-9.7) for major congenital malformation, compared with first-trimester methylphenidate exposure. Compared with the unexposed cohort, modafinil-exposed pregnancies had an adjusted odds ratio of 2.7 (95% CI, 1.1-6.9) for major congenital malformation.

A total of 13 (27%) women who took modafinil had multiple sclerosis, but the authors excluded women who’d received a prescription for the multiple sclerosis drug teriflunomide (Aubagio), a known teratogen. Sleep disorders were reported for 39% of modafinil users, compared with 4.5% of methylphenidate users. Rates of psychoactive drug use were 41% for the modafinil group and 30% for the methylphenidate group.

The authors acknowledged the possibility of residual confounders affecting their results, and of the statistical problems with the very small sample size of modafinil-exposed pregnancies. Also, actual medication use – rather than prescription redemption – wasn’t captured in the study.

The study was partially funded by the Novo Nordisk Foundation. The authors reported no conflicts of interest.

koakes@mdedge.com

SOURCE: Damkier P, Broe A. JAMA. 2020;323(4):374-6.

For patients with acute ischemic stroke, prolonged durations of blood pressure above or below certain thresholds during endovascular therapy may be linked to poor functional outcome, results of a retrospective study suggest.

Copyright American Stroke Association

Mean arterial blood pressure (MABP) lower than 70 mm Hg for 10 minutes or more, or higher than 90 mm Hg for 45 minutes or more, represented “critical thresholds” associated with worse neurologic outcomes, the study authors wrote in JAMA Neurology.

“These results suggest MABP may be a modifiable therapeutic target to prevent or reduce poor functional outcome in patients undergoing endovascular therapy for acute ischemic stroke, and that MABP should possibly be maintained within such narrow limits, wrote the authors, led by Mads Rasmussen, MD, PhD, of the department of anesthesia at Aarhus (Denmark) University Hospital.

The findings come from an analysis of BP data from 365 patients with acute ischemic stroke enrolled in three randomized trials evaluating different strategies for anesthesia. Among those patients, the mean age was approximately 71 years, and about 45% were women.

The investigators looked at a variety of BP-related variables during endovascular therapy to assess their impact on functional outcome, based on modified Rankin Scale (mRS) scores at 90 days.

Having an MABP below 70 mm Hg for a cumulative time of at least 10 minutes substantially increased odds of higher 90-day mRS scores (odds ratio, 1.51; 95% confidence interval, 1.02-2.22), according to Dr. Rasmussen and colleagues. The number needed to harm (NNH) at this threshold was 10; in other words, to harm 1 patient, 10 patients are needed with procedural MABP below 70 mm Hg for at least 10 minutes.

Likewise, having an MABP above 90 mm Hg for a cumulated time of at least 45 minutes significantly increased odds of higher 90-day mRS scores, with an OR of 1.49 (95% CI, 1.11-2.02) and a number needed to harm of 10.

Odds of shifting toward a worse neurologic outcome increased by 62% for every continuous 10 minutes of MABP below 70 mm Hg, and by 8% for every continuous 10 minutes above 90 mm Hg.

The maximum MABP during the procedure was significantly associated with neurologic outcomes in the study, while by contrast, maximum procedural systolic BP was not, according to the investigators.

In general, the study findings suggest that MABP is “more sensitive” than systolic BP when assessing hypotension and hypertension in these patients. However, these findings are subject to a number of limitations, the investigators wrote, including the retrospective nature of the analysis and the selected group of patients enrolled in studies designed to evaluate anesthesia strategies, not hemodynamic management.

“Randomized studies are needed to determine the optimal blood pressure management strategy during endovascular therapy,” the investigators wrote.

Dr. Rasmussen reported grant support from the Health Research Foundation of Central Denmark Region and the National Helicopter Emergency Medical Service Foundation. Coauthors reported receiving grant support from the Novo Nordisk Foundation; a research award from the Patient-Centered Outcomes Research Institute; and personal fees from Abbott Medical Sweden, I4L Innovation for Life, Boehringer Ingelheim, Medtronic, and Zoll.

SOURCE: Rasmussen M et al. JAMA Neurol. 2020 Jan 27. doi: 10.1001/jamaneurol.2019.4838.

For patients with acute ischemic stroke, prolonged durations of blood pressure above or below certain thresholds during endovascular therapy may be linked to poor functional outcome, results of a retrospective study suggest.

Copyright American Stroke Association

Mean arterial blood pressure (MABP) lower than 70 mm Hg for 10 minutes or more, or higher than 90 mm Hg for 45 minutes or more, represented “critical thresholds” associated with worse neurologic outcomes, the study authors wrote in JAMA Neurology.

“These results suggest MABP may be a modifiable therapeutic target to prevent or reduce poor functional outcome in patients undergoing endovascular therapy for acute ischemic stroke, and that MABP should possibly be maintained within such narrow limits, wrote the authors, led by Mads Rasmussen, MD, PhD, of the department of anesthesia at Aarhus (Denmark) University Hospital.

The findings come from an analysis of BP data from 365 patients with acute ischemic stroke enrolled in three randomized trials evaluating different strategies for anesthesia. Among those patients, the mean age was approximately 71 years, and about 45% were women.

The investigators looked at a variety of BP-related variables during endovascular therapy to assess their impact on functional outcome, based on modified Rankin Scale (mRS) scores at 90 days.

Having an MABP below 70 mm Hg for a cumulative time of at least 10 minutes substantially increased odds of higher 90-day mRS scores (odds ratio, 1.51; 95% confidence interval, 1.02-2.22), according to Dr. Rasmussen and colleagues. The number needed to harm (NNH) at this threshold was 10; in other words, to harm 1 patient, 10 patients are needed with procedural MABP below 70 mm Hg for at least 10 minutes.

Likewise, having an MABP above 90 mm Hg for a cumulated time of at least 45 minutes significantly increased odds of higher 90-day mRS scores, with an OR of 1.49 (95% CI, 1.11-2.02) and a number needed to harm of 10.

Odds of shifting toward a worse neurologic outcome increased by 62% for every continuous 10 minutes of MABP below 70 mm Hg, and by 8% for every continuous 10 minutes above 90 mm Hg.

The maximum MABP during the procedure was significantly associated with neurologic outcomes in the study, while by contrast, maximum procedural systolic BP was not, according to the investigators.

In general, the study findings suggest that MABP is “more sensitive” than systolic BP when assessing hypotension and hypertension in these patients. However, these findings are subject to a number of limitations, the investigators wrote, including the retrospective nature of the analysis and the selected group of patients enrolled in studies designed to evaluate anesthesia strategies, not hemodynamic management.

“Randomized studies are needed to determine the optimal blood pressure management strategy during endovascular therapy,” the investigators wrote.

Dr. Rasmussen reported grant support from the Health Research Foundation of Central Denmark Region and the National Helicopter Emergency Medical Service Foundation. Coauthors reported receiving grant support from the Novo Nordisk Foundation; a research award from the Patient-Centered Outcomes Research Institute; and personal fees from Abbott Medical Sweden, I4L Innovation for Life, Boehringer Ingelheim, Medtronic, and Zoll.

SOURCE: Rasmussen M et al. JAMA Neurol. 2020 Jan 27. doi: 10.1001/jamaneurol.2019.4838.

For patients with acute ischemic stroke, prolonged durations of blood pressure above or below certain thresholds during endovascular therapy may be linked to poor functional outcome, results of a retrospective study suggest.

Copyright American Stroke Association

Mean arterial blood pressure (MABP) lower than 70 mm Hg for 10 minutes or more, or higher than 90 mm Hg for 45 minutes or more, represented “critical thresholds” associated with worse neurologic outcomes, the study authors wrote in JAMA Neurology.

“These results suggest MABP may be a modifiable therapeutic target to prevent or reduce poor functional outcome in patients undergoing endovascular therapy for acute ischemic stroke, and that MABP should possibly be maintained within such narrow limits, wrote the authors, led by Mads Rasmussen, MD, PhD, of the department of anesthesia at Aarhus (Denmark) University Hospital.

The findings come from an analysis of BP data from 365 patients with acute ischemic stroke enrolled in three randomized trials evaluating different strategies for anesthesia. Among those patients, the mean age was approximately 71 years, and about 45% were women.

The investigators looked at a variety of BP-related variables during endovascular therapy to assess their impact on functional outcome, based on modified Rankin Scale (mRS) scores at 90 days.

Having an MABP below 70 mm Hg for a cumulative time of at least 10 minutes substantially increased odds of higher 90-day mRS scores (odds ratio, 1.51; 95% confidence interval, 1.02-2.22), according to Dr. Rasmussen and colleagues. The number needed to harm (NNH) at this threshold was 10; in other words, to harm 1 patient, 10 patients are needed with procedural MABP below 70 mm Hg for at least 10 minutes.

Likewise, having an MABP above 90 mm Hg for a cumulated time of at least 45 minutes significantly increased odds of higher 90-day mRS scores, with an OR of 1.49 (95% CI, 1.11-2.02) and a number needed to harm of 10.

Odds of shifting toward a worse neurologic outcome increased by 62% for every continuous 10 minutes of MABP below 70 mm Hg, and by 8% for every continuous 10 minutes above 90 mm Hg.

The maximum MABP during the procedure was significantly associated with neurologic outcomes in the study, while by contrast, maximum procedural systolic BP was not, according to the investigators.

In general, the study findings suggest that MABP is “more sensitive” than systolic BP when assessing hypotension and hypertension in these patients. However, these findings are subject to a number of limitations, the investigators wrote, including the retrospective nature of the analysis and the selected group of patients enrolled in studies designed to evaluate anesthesia strategies, not hemodynamic management.

“Randomized studies are needed to determine the optimal blood pressure management strategy during endovascular therapy,” the investigators wrote.

Dr. Rasmussen reported grant support from the Health Research Foundation of Central Denmark Region and the National Helicopter Emergency Medical Service Foundation. Coauthors reported receiving grant support from the Novo Nordisk Foundation; a research award from the Patient-Centered Outcomes Research Institute; and personal fees from Abbott Medical Sweden, I4L Innovation for Life, Boehringer Ingelheim, Medtronic, and Zoll.

SOURCE: Rasmussen M et al. JAMA Neurol. 2020 Jan 27. doi: 10.1001/jamaneurol.2019.4838.

SNOWMASS, COLO. – The tragic opioid epidemic has “one small bright spot”: an expanding pool of eligible donor hearts for transplantation, Akshay S. Desai, MD, said at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

Bruce Jancin/MDedge News

For decades, the annual volume of heart transplantations performed in the U.S. was static because of the huge mismatch between donor organ supply and demand. But heart transplant volume has increased steadily in the last few years – a result of the opioid epidemic.

Data from the U.S. Organ Procurement and Transplantation Network show that the proportion of donor hearts obtained from individuals who died from drug intoxication climbed from a mere 1.5% in 1999 to 17.6% in 2017, the most recent year for which data are available. Meanwhile, the size of the heart transplant waiting list, which rose year after year in 2009-2015, has since declined (N Engl J Med. 2019 Feb 7;380[6]:597-9).

“What’s amazing is that, even though these patients might have historically been considered high risk in general, the organs recovered from these patients – and particularly the hearts – don’t seem to be any worse in terms of allograft survival than the organs recovered from patients who died from other causes, which are the traditional sources, like blunt head trauma, gunshot wounds, or stroke, that lead to brain death. In general, these organs are useful and do quite well,” according to Dr. Desai, medical director of the cardiomyopathy and heart failure program at Brigham and Women’s Hospital, Boston.

He highlighted several other recent developments in the field of cardiac transplantation that promise to further expand the donor heart pool, including acceptance of hepatitis C–infected donors and organ donation after circulatory rather than brain death. Dr. Desai also drew attention to the unintended perverse consequences of a recent redesign of the U.S. donor heart allocation system and discussed the impressive improvement in clinical outcomes with mechanical circulatory support. He noted that, while relatively few cardiologists practice in the highly specialized centers where heart transplants take place, virtually all cardiologists are affected by advances in heart transplantation since hundreds of thousands of the estimated 7 million Americans with heart failure have advanced disease.

Heart transplantation, he emphasized, is becoming increasingly complex. Recipients are on average older, sicker, and have more comorbidities than in times past. As a result, there is greater need for dual organ transplants: heart/lung, heart/liver, or heart/kidney. Plus, more patients come to transplantation after prior cardiac surgery for implantation of a ventricular assist device, so sensitization to blood products is a growing issue. And, of course, the pool of transplant candidates has expanded.

“We’re now forced to take patients previously considered to have contraindications to transplant; for example, diabetes was a contraindication to transplant in the early years, but now it’s the rule in 35%-40% of our patients who present with advanced heart failure,” the cardiologist noted.
 

Transplants from HCV-infected donors to uninfected recipients

Hearts and lungs from donors with hepatitis C viremia were traditionally deemed unsuitable for transplant. That’s all changed in the current era of highly effective direct-acting antiviral agents for the treatment of HCV infection.

In the DONATE HCV trial, Dr. Desai’s colleagues at Brigham and Women’s Hospital showed that giving HCV-uninfected recipients of hearts or lungs from HCV-viremic donors a shortened 4-week course of treatment with sofosbuvir-velpatasvir (Epclusa) beginning within a few hours after transplantation uniformly blocked viral replication. Six months after transplantation, none of the study participants had a detectable HCV viral load, and all had excellent graft function (N Engl J Med. 2019 Apr 25;380[17]:1606-17).

“This is effective prevention of HCV infection by aggressive upfront therapy,” Dr. Desai explained. “We can now take organs from HCV-viremic patients and use them in solid organ transplantation. This has led to a skyrocketing increase in donors with HCV infection, and those donations have helped us clear the waiting list.”
 

Donation after circulatory death

Australian transplant physicians have pioneered the use of donor hearts obtained after circulatory death in individuals with devastating neurologic injury who didn’t quite meet the criteria for brain death, which is the traditional prerequisite. In the new scenario, withdrawal of life-supporting therapy is followed by circulatory death, then the donor heart is procured and preserved via extracorporeal perfusion until transplantation.

The Australians report excellent outcomes, with rates of overall survival and rejection episodes similar to outcomes from brain-dead donors (J Am Coll Cardiol. 2019 Apr 2;73[12]:1447-59). The first U.S. heart transplant involving donation after circulatory death took place at Duke University in Durham, North Carolina. A multicenter U.S. clinical trial of this practice is underway.

If the results are positive and the practice of donation after circulatory death becomes widely implemented, the U.S. heart donor pool could increase by 30%.
 

Recent overhaul of donor heart allocation system may have backfired

The U.S. donor heart allocation system was redesigned in the fall of 2018 in an effort to reduce waiting times. One of the biggest changes involved breaking down the category with the highest urgency status into three new subcategories based upon sickness. Now, the highest-urgency category is for patients in cardiogenic shock who are supported by extracorporeal membrane oxygenation (ECMO) or other temporary mechanical circulatory support devices.

But an analysis of United Network for Organ Sharing (UNOS) data suggests this change has unintended adverse consequences for clinical outcomes.

Indeed, the investigators reported that the use of ECMO support is fourfold greater in the new system, the use of durable left ventricular assist devices (LVADs) as a bridge to transplant is down, and outcomes are worse. The 180-day rate of freedom from death or retransplantation was 77.9%, down significantly from 93.4% in the former system. In a multivariate analysis, patients transplanted in the new system had an adjusted 2.1-fold increased risk of death or retransplantation (J Heart Lung Transplant. 2020 Jan;39[1]:1-4).

“When you create a new listing system, you create new incentives, and people start to manage patients differently,” Dr. Desai observed. “Increasingly now, the path direct to transplant is through temporary mechanical circulatory support rather than durable mechanical circulatory support. Is that a good idea? We don’t know, but if you look at the best data, those on ECMO or percutaneous VADs have the worst outcomes. So the question of whether we should take the sickest of sick patients directly to transplant as a standard strategy has come under scrutiny.”
 

Improved durable LVAD technology brings impressive clinical outcomes

Results of the landmark MOMENTUM 3 randomized trial showed that 2-year clinical outcomes with the magnetically levitated centrifugal-flow HeartMate 3 LVAD now rival those of percutaneous mitral valve repair using the MitraClip device. Two-year all-cause mortality in the LVAD recipients was 22% versus 29.1% with the MitraClip in the COAPT trial and 34.9% in the MITRA-FR trial. The HeartMate 3 reduces the hemocompatibility issues that plagued earlier-generation durable LVADs, with resultant lower rates of pump thrombosis, stroke, and GI bleeding. Indeed, the outcomes in MOMENTUM 3 were so good – and so similar – with the HeartMate 3, regardless of whether the intended treatment goal was as a bridge to transplant or as lifelong destination therapy, that the investigators have recently proposed doing away with those distinctions.

“It is possible that use of arbitrary categorizations based on current or future transplant eligibility should be clinically abandoned in favor of a single preimplant strategy: to extend the survival and improve the quality of life of patients with medically refractory heart failure,” according to the investigators (JAMA Cardiol. 2020 Jan 15. doi: 10.1001/jamacardio.2019.5323).

The next step forward in LVAD technology is already on the horizon: a fully implantable device that eliminates the transcutaneous drive-line for the power supply, which is prone to infection and diminishes overall quality of life. This investigational device utilizes wireless coplanar energy transfer, with a coil ring placed around the lung and fixed to the chest wall. The implanted battery provides more than 6 hours of power without a recharge (J Heart Lung Transplant. 2019 Apr;38[4]:339-43).

“The first LVAD patient has gone swimming in Kazakhstan,” according to Dr. Desai.

Myocardial recovery in LVAD recipients remains elusive

The initial hope for LVADs was that they would not only be able to serve as a bridge to transplantation or as lifetime therapy, but that the prolonged unloading of the ventricle would enable potent medical therapy to rescue myocardial function so that the device could eventually be explanted. That does happen, but only rarely. In a large registry study, myocardial recovery occurred in only about 1% of patients on mechanical circulatory support. Attempts to enhance the process by add-on stem cell therapy have thus far been ineffective.

“For the moment, recovery is still a hope, not a reality,” the cardiologist said.

He reported serving as a consultant to more than a dozen pharmaceutical or medical device companies and receiving research grants from Alnylam, AstraZeneca, Bayer Healthcare, MyoKardia, and Novartis.

bjancin@mdedge.com
 

SNOWMASS, COLO. – The tragic opioid epidemic has “one small bright spot”: an expanding pool of eligible donor hearts for transplantation, Akshay S. Desai, MD, said at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

Bruce Jancin/MDedge News

For decades, the annual volume of heart transplantations performed in the U.S. was static because of the huge mismatch between donor organ supply and demand. But heart transplant volume has increased steadily in the last few years – a result of the opioid epidemic.

Data from the U.S. Organ Procurement and Transplantation Network show that the proportion of donor hearts obtained from individuals who died from drug intoxication climbed from a mere 1.5% in 1999 to 17.6% in 2017, the most recent year for which data are available. Meanwhile, the size of the heart transplant waiting list, which rose year after year in 2009-2015, has since declined (N Engl J Med. 2019 Feb 7;380[6]:597-9).

“What’s amazing is that, even though these patients might have historically been considered high risk in general, the organs recovered from these patients – and particularly the hearts – don’t seem to be any worse in terms of allograft survival than the organs recovered from patients who died from other causes, which are the traditional sources, like blunt head trauma, gunshot wounds, or stroke, that lead to brain death. In general, these organs are useful and do quite well,” according to Dr. Desai, medical director of the cardiomyopathy and heart failure program at Brigham and Women’s Hospital, Boston.

He highlighted several other recent developments in the field of cardiac transplantation that promise to further expand the donor heart pool, including acceptance of hepatitis C–infected donors and organ donation after circulatory rather than brain death. Dr. Desai also drew attention to the unintended perverse consequences of a recent redesign of the U.S. donor heart allocation system and discussed the impressive improvement in clinical outcomes with mechanical circulatory support. He noted that, while relatively few cardiologists practice in the highly specialized centers where heart transplants take place, virtually all cardiologists are affected by advances in heart transplantation since hundreds of thousands of the estimated 7 million Americans with heart failure have advanced disease.

Heart transplantation, he emphasized, is becoming increasingly complex. Recipients are on average older, sicker, and have more comorbidities than in times past. As a result, there is greater need for dual organ transplants: heart/lung, heart/liver, or heart/kidney. Plus, more patients come to transplantation after prior cardiac surgery for implantation of a ventricular assist device, so sensitization to blood products is a growing issue. And, of course, the pool of transplant candidates has expanded.

“We’re now forced to take patients previously considered to have contraindications to transplant; for example, diabetes was a contraindication to transplant in the early years, but now it’s the rule in 35%-40% of our patients who present with advanced heart failure,” the cardiologist noted.
 

Transplants from HCV-infected donors to uninfected recipients

Hearts and lungs from donors with hepatitis C viremia were traditionally deemed unsuitable for transplant. That’s all changed in the current era of highly effective direct-acting antiviral agents for the treatment of HCV infection.

In the DONATE HCV trial, Dr. Desai’s colleagues at Brigham and Women’s Hospital showed that giving HCV-uninfected recipients of hearts or lungs from HCV-viremic donors a shortened 4-week course of treatment with sofosbuvir-velpatasvir (Epclusa) beginning within a few hours after transplantation uniformly blocked viral replication. Six months after transplantation, none of the study participants had a detectable HCV viral load, and all had excellent graft function (N Engl J Med. 2019 Apr 25;380[17]:1606-17).

“This is effective prevention of HCV infection by aggressive upfront therapy,” Dr. Desai explained. “We can now take organs from HCV-viremic patients and use them in solid organ transplantation. This has led to a skyrocketing increase in donors with HCV infection, and those donations have helped us clear the waiting list.”
 

Donation after circulatory death

Australian transplant physicians have pioneered the use of donor hearts obtained after circulatory death in individuals with devastating neurologic injury who didn’t quite meet the criteria for brain death, which is the traditional prerequisite. In the new scenario, withdrawal of life-supporting therapy is followed by circulatory death, then the donor heart is procured and preserved via extracorporeal perfusion until transplantation.

The Australians report excellent outcomes, with rates of overall survival and rejection episodes similar to outcomes from brain-dead donors (J Am Coll Cardiol. 2019 Apr 2;73[12]:1447-59). The first U.S. heart transplant involving donation after circulatory death took place at Duke University in Durham, North Carolina. A multicenter U.S. clinical trial of this practice is underway.

If the results are positive and the practice of donation after circulatory death becomes widely implemented, the U.S. heart donor pool could increase by 30%.
 

Recent overhaul of donor heart allocation system may have backfired

The U.S. donor heart allocation system was redesigned in the fall of 2018 in an effort to reduce waiting times. One of the biggest changes involved breaking down the category with the highest urgency status into three new subcategories based upon sickness. Now, the highest-urgency category is for patients in cardiogenic shock who are supported by extracorporeal membrane oxygenation (ECMO) or other temporary mechanical circulatory support devices.

But an analysis of United Network for Organ Sharing (UNOS) data suggests this change has unintended adverse consequences for clinical outcomes.

Indeed, the investigators reported that the use of ECMO support is fourfold greater in the new system, the use of durable left ventricular assist devices (LVADs) as a bridge to transplant is down, and outcomes are worse. The 180-day rate of freedom from death or retransplantation was 77.9%, down significantly from 93.4% in the former system. In a multivariate analysis, patients transplanted in the new system had an adjusted 2.1-fold increased risk of death or retransplantation (J Heart Lung Transplant. 2020 Jan;39[1]:1-4).

“When you create a new listing system, you create new incentives, and people start to manage patients differently,” Dr. Desai observed. “Increasingly now, the path direct to transplant is through temporary mechanical circulatory support rather than durable mechanical circulatory support. Is that a good idea? We don’t know, but if you look at the best data, those on ECMO or percutaneous VADs have the worst outcomes. So the question of whether we should take the sickest of sick patients directly to transplant as a standard strategy has come under scrutiny.”
 

Improved durable LVAD technology brings impressive clinical outcomes

Results of the landmark MOMENTUM 3 randomized trial showed that 2-year clinical outcomes with the magnetically levitated centrifugal-flow HeartMate 3 LVAD now rival those of percutaneous mitral valve repair using the MitraClip device. Two-year all-cause mortality in the LVAD recipients was 22% versus 29.1% with the MitraClip in the COAPT trial and 34.9% in the MITRA-FR trial. The HeartMate 3 reduces the hemocompatibility issues that plagued earlier-generation durable LVADs, with resultant lower rates of pump thrombosis, stroke, and GI bleeding. Indeed, the outcomes in MOMENTUM 3 were so good – and so similar – with the HeartMate 3, regardless of whether the intended treatment goal was as a bridge to transplant or as lifelong destination therapy, that the investigators have recently proposed doing away with those distinctions.

“It is possible that use of arbitrary categorizations based on current or future transplant eligibility should be clinically abandoned in favor of a single preimplant strategy: to extend the survival and improve the quality of life of patients with medically refractory heart failure,” according to the investigators (JAMA Cardiol. 2020 Jan 15. doi: 10.1001/jamacardio.2019.5323).

The next step forward in LVAD technology is already on the horizon: a fully implantable device that eliminates the transcutaneous drive-line for the power supply, which is prone to infection and diminishes overall quality of life. This investigational device utilizes wireless coplanar energy transfer, with a coil ring placed around the lung and fixed to the chest wall. The implanted battery provides more than 6 hours of power without a recharge (J Heart Lung Transplant. 2019 Apr;38[4]:339-43).

“The first LVAD patient has gone swimming in Kazakhstan,” according to Dr. Desai.

Myocardial recovery in LVAD recipients remains elusive

The initial hope for LVADs was that they would not only be able to serve as a bridge to transplantation or as lifetime therapy, but that the prolonged unloading of the ventricle would enable potent medical therapy to rescue myocardial function so that the device could eventually be explanted. That does happen, but only rarely. In a large registry study, myocardial recovery occurred in only about 1% of patients on mechanical circulatory support. Attempts to enhance the process by add-on stem cell therapy have thus far been ineffective.

“For the moment, recovery is still a hope, not a reality,” the cardiologist said.

He reported serving as a consultant to more than a dozen pharmaceutical or medical device companies and receiving research grants from Alnylam, AstraZeneca, Bayer Healthcare, MyoKardia, and Novartis.

bjancin@mdedge.com
 

SNOWMASS, COLO. – The tragic opioid epidemic has “one small bright spot”: an expanding pool of eligible donor hearts for transplantation, Akshay S. Desai, MD, said at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

Bruce Jancin/MDedge News

For decades, the annual volume of heart transplantations performed in the U.S. was static because of the huge mismatch between donor organ supply and demand. But heart transplant volume has increased steadily in the last few years – a result of the opioid epidemic.

Data from the U.S. Organ Procurement and Transplantation Network show that the proportion of donor hearts obtained from individuals who died from drug intoxication climbed from a mere 1.5% in 1999 to 17.6% in 2017, the most recent year for which data are available. Meanwhile, the size of the heart transplant waiting list, which rose year after year in 2009-2015, has since declined (N Engl J Med. 2019 Feb 7;380[6]:597-9).

“What’s amazing is that, even though these patients might have historically been considered high risk in general, the organs recovered from these patients – and particularly the hearts – don’t seem to be any worse in terms of allograft survival than the organs recovered from patients who died from other causes, which are the traditional sources, like blunt head trauma, gunshot wounds, or stroke, that lead to brain death. In general, these organs are useful and do quite well,” according to Dr. Desai, medical director of the cardiomyopathy and heart failure program at Brigham and Women’s Hospital, Boston.

He highlighted several other recent developments in the field of cardiac transplantation that promise to further expand the donor heart pool, including acceptance of hepatitis C–infected donors and organ donation after circulatory rather than brain death. Dr. Desai also drew attention to the unintended perverse consequences of a recent redesign of the U.S. donor heart allocation system and discussed the impressive improvement in clinical outcomes with mechanical circulatory support. He noted that, while relatively few cardiologists practice in the highly specialized centers where heart transplants take place, virtually all cardiologists are affected by advances in heart transplantation since hundreds of thousands of the estimated 7 million Americans with heart failure have advanced disease.

Heart transplantation, he emphasized, is becoming increasingly complex. Recipients are on average older, sicker, and have more comorbidities than in times past. As a result, there is greater need for dual organ transplants: heart/lung, heart/liver, or heart/kidney. Plus, more patients come to transplantation after prior cardiac surgery for implantation of a ventricular assist device, so sensitization to blood products is a growing issue. And, of course, the pool of transplant candidates has expanded.

“We’re now forced to take patients previously considered to have contraindications to transplant; for example, diabetes was a contraindication to transplant in the early years, but now it’s the rule in 35%-40% of our patients who present with advanced heart failure,” the cardiologist noted.
 

Transplants from HCV-infected donors to uninfected recipients

Hearts and lungs from donors with hepatitis C viremia were traditionally deemed unsuitable for transplant. That’s all changed in the current era of highly effective direct-acting antiviral agents for the treatment of HCV infection.

In the DONATE HCV trial, Dr. Desai’s colleagues at Brigham and Women’s Hospital showed that giving HCV-uninfected recipients of hearts or lungs from HCV-viremic donors a shortened 4-week course of treatment with sofosbuvir-velpatasvir (Epclusa) beginning within a few hours after transplantation uniformly blocked viral replication. Six months after transplantation, none of the study participants had a detectable HCV viral load, and all had excellent graft function (N Engl J Med. 2019 Apr 25;380[17]:1606-17).

“This is effective prevention of HCV infection by aggressive upfront therapy,” Dr. Desai explained. “We can now take organs from HCV-viremic patients and use them in solid organ transplantation. This has led to a skyrocketing increase in donors with HCV infection, and those donations have helped us clear the waiting list.”
 

Donation after circulatory death

Australian transplant physicians have pioneered the use of donor hearts obtained after circulatory death in individuals with devastating neurologic injury who didn’t quite meet the criteria for brain death, which is the traditional prerequisite. In the new scenario, withdrawal of life-supporting therapy is followed by circulatory death, then the donor heart is procured and preserved via extracorporeal perfusion until transplantation.

The Australians report excellent outcomes, with rates of overall survival and rejection episodes similar to outcomes from brain-dead donors (J Am Coll Cardiol. 2019 Apr 2;73[12]:1447-59). The first U.S. heart transplant involving donation after circulatory death took place at Duke University in Durham, North Carolina. A multicenter U.S. clinical trial of this practice is underway.

If the results are positive and the practice of donation after circulatory death becomes widely implemented, the U.S. heart donor pool could increase by 30%.
 

Recent overhaul of donor heart allocation system may have backfired

The U.S. donor heart allocation system was redesigned in the fall of 2018 in an effort to reduce waiting times. One of the biggest changes involved breaking down the category with the highest urgency status into three new subcategories based upon sickness. Now, the highest-urgency category is for patients in cardiogenic shock who are supported by extracorporeal membrane oxygenation (ECMO) or other temporary mechanical circulatory support devices.

But an analysis of United Network for Organ Sharing (UNOS) data suggests this change has unintended adverse consequences for clinical outcomes.

Indeed, the investigators reported that the use of ECMO support is fourfold greater in the new system, the use of durable left ventricular assist devices (LVADs) as a bridge to transplant is down, and outcomes are worse. The 180-day rate of freedom from death or retransplantation was 77.9%, down significantly from 93.4% in the former system. In a multivariate analysis, patients transplanted in the new system had an adjusted 2.1-fold increased risk of death or retransplantation (J Heart Lung Transplant. 2020 Jan;39[1]:1-4).

“When you create a new listing system, you create new incentives, and people start to manage patients differently,” Dr. Desai observed. “Increasingly now, the path direct to transplant is through temporary mechanical circulatory support rather than durable mechanical circulatory support. Is that a good idea? We don’t know, but if you look at the best data, those on ECMO or percutaneous VADs have the worst outcomes. So the question of whether we should take the sickest of sick patients directly to transplant as a standard strategy has come under scrutiny.”
 

Improved durable LVAD technology brings impressive clinical outcomes

Results of the landmark MOMENTUM 3 randomized trial showed that 2-year clinical outcomes with the magnetically levitated centrifugal-flow HeartMate 3 LVAD now rival those of percutaneous mitral valve repair using the MitraClip device. Two-year all-cause mortality in the LVAD recipients was 22% versus 29.1% with the MitraClip in the COAPT trial and 34.9% in the MITRA-FR trial. The HeartMate 3 reduces the hemocompatibility issues that plagued earlier-generation durable LVADs, with resultant lower rates of pump thrombosis, stroke, and GI bleeding. Indeed, the outcomes in MOMENTUM 3 were so good – and so similar – with the HeartMate 3, regardless of whether the intended treatment goal was as a bridge to transplant or as lifelong destination therapy, that the investigators have recently proposed doing away with those distinctions.

“It is possible that use of arbitrary categorizations based on current or future transplant eligibility should be clinically abandoned in favor of a single preimplant strategy: to extend the survival and improve the quality of life of patients with medically refractory heart failure,” according to the investigators (JAMA Cardiol. 2020 Jan 15. doi: 10.1001/jamacardio.2019.5323).

The next step forward in LVAD technology is already on the horizon: a fully implantable device that eliminates the transcutaneous drive-line for the power supply, which is prone to infection and diminishes overall quality of life. This investigational device utilizes wireless coplanar energy transfer, with a coil ring placed around the lung and fixed to the chest wall. The implanted battery provides more than 6 hours of power without a recharge (J Heart Lung Transplant. 2019 Apr;38[4]:339-43).

“The first LVAD patient has gone swimming in Kazakhstan,” according to Dr. Desai.

Myocardial recovery in LVAD recipients remains elusive

The initial hope for LVADs was that they would not only be able to serve as a bridge to transplantation or as lifetime therapy, but that the prolonged unloading of the ventricle would enable potent medical therapy to rescue myocardial function so that the device could eventually be explanted. That does happen, but only rarely. In a large registry study, myocardial recovery occurred in only about 1% of patients on mechanical circulatory support. Attempts to enhance the process by add-on stem cell therapy have thus far been ineffective.

“For the moment, recovery is still a hope, not a reality,” the cardiologist said.

He reported serving as a consultant to more than a dozen pharmaceutical or medical device companies and receiving research grants from Alnylam, AstraZeneca, Bayer Healthcare, MyoKardia, and Novartis.

bjancin@mdedge.com
 

NATIONAL HARBOR, MD. – A pilot program of daily arrhythmia self-vigilance has allowed selected patients with no atrial fibrillation following a catheter ablation procedure to safely come off a regimen of daily oral anticoagulation despite having residual risk factors for ischemic stroke.

Mitchel L. Zoler/MDedge News

This program, which started several years ago at the University of Pennsylvania in Philadelphia, has now managed 190 patients and followed them for a median of just over 3 years, and during 576 patient-years of follow-up, just a single patient had an ischemic cerebrovascular event that occurred with no atrial fibrillation (AFib) recurrence and appeared to be caused by an atherosclerotic embolism, Francis E. Marchlinski, MD, said at the annual International AF Symposium.

Although this strategy has not yet been tested in a prospective, randomized trial, this anecdotal, single-center experience suggests that the approach is “safe and effective” for selected patients who are eager to come off of their anticoagulation regimen when they remain arrhythmia free following catheter ablation of their AFib, said Dr. Marchlinski, professor of medicine and director of electrophysiology at the University of Pennsylvania. He and his associates developed this strategy as a way to more safely allow these patients to stop taking a daily oral anticoagulant because he found that many patients were stopping on their own, with no safety strategy in place.

“Patients tell me they don’t want to be on an oral anticoagulant because a parent had a hemorrhagic stroke, and they say they’re willing to accept the risk” of having an ischemic stroke by coming off anticoagulation. “This is a way for them to do it safely,” Dr. Marchlinski said in an interview. He stressed that he only allows his patients to go this route if they understand the risk and accept their shared responsibility for vigilant, twice-daily pulse monitoring to detect resumption of an irregular heart beat.

Since 2011, Dr. Marchlinski’s program ablated 1,216 patients with AFib who then remained arrhythmia free during 3 weeks of continuous ECG monitoring following their procedure. Among these patients, 443 had a CHA2DS2-VAScscore of either 0 (men) or 1 (women) that indicated no ongoing need for oral anticoagulation according to current guidelines. Of the remaining 773 patients with a CHA2DS2-VASc score of at least 1 in men and 2 in women, the clinicians determined 583 to be ineligible for the program because of their unwillingness to accept the risk, unwillingness to comply with daily pulse checks, a history of asymptomatic AFib, a CHA2DS2-VASc score greater than 4, or a resting pulse above 90 beats per minute, leaving 190 patients eligible to participate. Among these patients, 105 (55%) had a CHA2DS2-VASc score of 2-4, which should prompt anticoagulation according to current guidelines.Participating patients committed to check their resting pulse by palpation at least twice daily and to contacting the program immediately if their resting rate spiked by more than 20 beats per minutes or in another way seemed irregular. Patients were also instructed to restart their oral anticoagulation immediately if they experienced AFib symptoms that persisted for more than 5 minutes. Many patients in the program also use a wearable device (usually a watch) to monitor their resting pulse and to generate a 30-second ECG recording that they can send as an electronic file to the University of Pennsylvania staff. “We embrace wearables,” Dr. Marchlinski said. Those without a wearable can undergo transtelephonic EEG monitoring to document a suspected arrhythmia recurrence, and all patients undergo annual monitoring by continuous ECG for at least 2 weeks.During follow-up, in addition to the 1 patient free from recurrent AFib who had an atherosclerotic embolism, 34 patients resumed anticoagulant treatment because of AFib recurrence; 12 withdrew from the program because of noncompliance or preference, or because an exclusion appeared; 29 resumed oral anticoagulation transiently but then discontinued the drug a second time when their AFib recurrence resolved; and 114 patients (60% of the starting cohort of 190) remained completely off anticoagulation during a median of 37 months. These data updated a published report from Dr. Marchlinski and his associates on their first 99 patients followed for a median of 30 months (J Cardiovasc Electrophysiol. 2019 May;30[5]:631-8).

This experience underscored the need for ongoing rhythm monitoring even in the absence of AFib symptoms, as six patients developed asymptomatic AFib detected by monitoring, including one patient whose recurrence occurred 30 months after the ablation procedure.

Dr. Marchlinski stressed the stringent selection process he applies to limit this approach to patients who are willing to faithfully monitor their pulse and symptoms daily, and who accept the risk that this approach may pose and their responsibility to stay in contact with the clinical team. The program calls patients at the 6-month mark between annual monitoring to remind them of their need for daily attention.

“Being off anticoagulants is very important to these patients,” he explained, and he highlighted the added workload this strategy places on his staff. “I think this has legs” for adoption by other cardiac arrhythmia programs, “but it depends on the time the staff is willing to spend” monitoring and following these patients, some of whom regularly send in ECG traces from their wearable devices for assessment. “It takes a village” to make this program work, he said.

Dr. Marchlinski has been a consultant to or has received honoraria from Abbott EP/St. Jude, Biosense Webster, Biotronik, Boston Scientific, and Medtronic.

mzoler@mdedge.com

NATIONAL HARBOR, MD. – A pilot program of daily arrhythmia self-vigilance has allowed selected patients with no atrial fibrillation following a catheter ablation procedure to safely come off a regimen of daily oral anticoagulation despite having residual risk factors for ischemic stroke.

Mitchel L. Zoler/MDedge News

This program, which started several years ago at the University of Pennsylvania in Philadelphia, has now managed 190 patients and followed them for a median of just over 3 years, and during 576 patient-years of follow-up, just a single patient had an ischemic cerebrovascular event that occurred with no atrial fibrillation (AFib) recurrence and appeared to be caused by an atherosclerotic embolism, Francis E. Marchlinski, MD, said at the annual International AF Symposium.

Although this strategy has not yet been tested in a prospective, randomized trial, this anecdotal, single-center experience suggests that the approach is “safe and effective” for selected patients who are eager to come off of their anticoagulation regimen when they remain arrhythmia free following catheter ablation of their AFib, said Dr. Marchlinski, professor of medicine and director of electrophysiology at the University of Pennsylvania. He and his associates developed this strategy as a way to more safely allow these patients to stop taking a daily oral anticoagulant because he found that many patients were stopping on their own, with no safety strategy in place.

“Patients tell me they don’t want to be on an oral anticoagulant because a parent had a hemorrhagic stroke, and they say they’re willing to accept the risk” of having an ischemic stroke by coming off anticoagulation. “This is a way for them to do it safely,” Dr. Marchlinski said in an interview. He stressed that he only allows his patients to go this route if they understand the risk and accept their shared responsibility for vigilant, twice-daily pulse monitoring to detect resumption of an irregular heart beat.

Since 2011, Dr. Marchlinski’s program ablated 1,216 patients with AFib who then remained arrhythmia free during 3 weeks of continuous ECG monitoring following their procedure. Among these patients, 443 had a CHA2DS2-VAScscore of either 0 (men) or 1 (women) that indicated no ongoing need for oral anticoagulation according to current guidelines. Of the remaining 773 patients with a CHA2DS2-VASc score of at least 1 in men and 2 in women, the clinicians determined 583 to be ineligible for the program because of their unwillingness to accept the risk, unwillingness to comply with daily pulse checks, a history of asymptomatic AFib, a CHA2DS2-VASc score greater than 4, or a resting pulse above 90 beats per minute, leaving 190 patients eligible to participate. Among these patients, 105 (55%) had a CHA2DS2-VASc score of 2-4, which should prompt anticoagulation according to current guidelines.Participating patients committed to check their resting pulse by palpation at least twice daily and to contacting the program immediately if their resting rate spiked by more than 20 beats per minutes or in another way seemed irregular. Patients were also instructed to restart their oral anticoagulation immediately if they experienced AFib symptoms that persisted for more than 5 minutes. Many patients in the program also use a wearable device (usually a watch) to monitor their resting pulse and to generate a 30-second ECG recording that they can send as an electronic file to the University of Pennsylvania staff. “We embrace wearables,” Dr. Marchlinski said. Those without a wearable can undergo transtelephonic EEG monitoring to document a suspected arrhythmia recurrence, and all patients undergo annual monitoring by continuous ECG for at least 2 weeks.During follow-up, in addition to the 1 patient free from recurrent AFib who had an atherosclerotic embolism, 34 patients resumed anticoagulant treatment because of AFib recurrence; 12 withdrew from the program because of noncompliance or preference, or because an exclusion appeared; 29 resumed oral anticoagulation transiently but then discontinued the drug a second time when their AFib recurrence resolved; and 114 patients (60% of the starting cohort of 190) remained completely off anticoagulation during a median of 37 months. These data updated a published report from Dr. Marchlinski and his associates on their first 99 patients followed for a median of 30 months (J Cardiovasc Electrophysiol. 2019 May;30[5]:631-8).

This experience underscored the need for ongoing rhythm monitoring even in the absence of AFib symptoms, as six patients developed asymptomatic AFib detected by monitoring, including one patient whose recurrence occurred 30 months after the ablation procedure.

Dr. Marchlinski stressed the stringent selection process he applies to limit this approach to patients who are willing to faithfully monitor their pulse and symptoms daily, and who accept the risk that this approach may pose and their responsibility to stay in contact with the clinical team. The program calls patients at the 6-month mark between annual monitoring to remind them of their need for daily attention.

“Being off anticoagulants is very important to these patients,” he explained, and he highlighted the added workload this strategy places on his staff. “I think this has legs” for adoption by other cardiac arrhythmia programs, “but it depends on the time the staff is willing to spend” monitoring and following these patients, some of whom regularly send in ECG traces from their wearable devices for assessment. “It takes a village” to make this program work, he said.

Dr. Marchlinski has been a consultant to or has received honoraria from Abbott EP/St. Jude, Biosense Webster, Biotronik, Boston Scientific, and Medtronic.

mzoler@mdedge.com

NATIONAL HARBOR, MD. – A pilot program of daily arrhythmia self-vigilance has allowed selected patients with no atrial fibrillation following a catheter ablation procedure to safely come off a regimen of daily oral anticoagulation despite having residual risk factors for ischemic stroke.

Mitchel L. Zoler/MDedge News

This program, which started several years ago at the University of Pennsylvania in Philadelphia, has now managed 190 patients and followed them for a median of just over 3 years, and during 576 patient-years of follow-up, just a single patient had an ischemic cerebrovascular event that occurred with no atrial fibrillation (AFib) recurrence and appeared to be caused by an atherosclerotic embolism, Francis E. Marchlinski, MD, said at the annual International AF Symposium.

Although this strategy has not yet been tested in a prospective, randomized trial, this anecdotal, single-center experience suggests that the approach is “safe and effective” for selected patients who are eager to come off of their anticoagulation regimen when they remain arrhythmia free following catheter ablation of their AFib, said Dr. Marchlinski, professor of medicine and director of electrophysiology at the University of Pennsylvania. He and his associates developed this strategy as a way to more safely allow these patients to stop taking a daily oral anticoagulant because he found that many patients were stopping on their own, with no safety strategy in place.

“Patients tell me they don’t want to be on an oral anticoagulant because a parent had a hemorrhagic stroke, and they say they’re willing to accept the risk” of having an ischemic stroke by coming off anticoagulation. “This is a way for them to do it safely,” Dr. Marchlinski said in an interview. He stressed that he only allows his patients to go this route if they understand the risk and accept their shared responsibility for vigilant, twice-daily pulse monitoring to detect resumption of an irregular heart beat.

Since 2011, Dr. Marchlinski’s program ablated 1,216 patients with AFib who then remained arrhythmia free during 3 weeks of continuous ECG monitoring following their procedure. Among these patients, 443 had a CHA2DS2-VAScscore of either 0 (men) or 1 (women) that indicated no ongoing need for oral anticoagulation according to current guidelines. Of the remaining 773 patients with a CHA2DS2-VASc score of at least 1 in men and 2 in women, the clinicians determined 583 to be ineligible for the program because of their unwillingness to accept the risk, unwillingness to comply with daily pulse checks, a history of asymptomatic AFib, a CHA2DS2-VASc score greater than 4, or a resting pulse above 90 beats per minute, leaving 190 patients eligible to participate. Among these patients, 105 (55%) had a CHA2DS2-VASc score of 2-4, which should prompt anticoagulation according to current guidelines.Participating patients committed to check their resting pulse by palpation at least twice daily and to contacting the program immediately if their resting rate spiked by more than 20 beats per minutes or in another way seemed irregular. Patients were also instructed to restart their oral anticoagulation immediately if they experienced AFib symptoms that persisted for more than 5 minutes. Many patients in the program also use a wearable device (usually a watch) to monitor their resting pulse and to generate a 30-second ECG recording that they can send as an electronic file to the University of Pennsylvania staff. “We embrace wearables,” Dr. Marchlinski said. Those without a wearable can undergo transtelephonic EEG monitoring to document a suspected arrhythmia recurrence, and all patients undergo annual monitoring by continuous ECG for at least 2 weeks.During follow-up, in addition to the 1 patient free from recurrent AFib who had an atherosclerotic embolism, 34 patients resumed anticoagulant treatment because of AFib recurrence; 12 withdrew from the program because of noncompliance or preference, or because an exclusion appeared; 29 resumed oral anticoagulation transiently but then discontinued the drug a second time when their AFib recurrence resolved; and 114 patients (60% of the starting cohort of 190) remained completely off anticoagulation during a median of 37 months. These data updated a published report from Dr. Marchlinski and his associates on their first 99 patients followed for a median of 30 months (J Cardiovasc Electrophysiol. 2019 May;30[5]:631-8).

This experience underscored the need for ongoing rhythm monitoring even in the absence of AFib symptoms, as six patients developed asymptomatic AFib detected by monitoring, including one patient whose recurrence occurred 30 months after the ablation procedure.

Dr. Marchlinski stressed the stringent selection process he applies to limit this approach to patients who are willing to faithfully monitor their pulse and symptoms daily, and who accept the risk that this approach may pose and their responsibility to stay in contact with the clinical team. The program calls patients at the 6-month mark between annual monitoring to remind them of their need for daily attention.

“Being off anticoagulants is very important to these patients,” he explained, and he highlighted the added workload this strategy places on his staff. “I think this has legs” for adoption by other cardiac arrhythmia programs, “but it depends on the time the staff is willing to spend” monitoring and following these patients, some of whom regularly send in ECG traces from their wearable devices for assessment. “It takes a village” to make this program work, he said.

Dr. Marchlinski has been a consultant to or has received honoraria from Abbott EP/St. Jude, Biosense Webster, Biotronik, Boston Scientific, and Medtronic.

mzoler@mdedge.com

The prevalence of Zika virus–related birth defects rose fourfold over preoutbreak levels in the areas of the United States hardest hit by the infection in 2016 and 2017, according to the Centers for Disease Control and Prevention.

That spike in the prevalence of brain abnormalities and/or microcephaly or eye abnormalities without brain abnormalities came during January through March 2017, about 6 months after the Zika outbreak’s reported peak in the jurisdictions with widespread local transmission, Puerto Rico and the U.S. Virgin Islands, wrote Ashley N. Smoots, MPH, of the CDC’s National Center on Birth Defects and Developmental Disabilities and associates in the Morbidity and Mortality Weekly Report.

In those two territories, the prevalence of birth defects potentially related to Zika virus infection was 5.6 per 1,000 live births during January through March 2017, compared with 1.3 per 1,000 in January through March 2016, they reported.

In the southern areas of Florida and Texas, where there was limited local Zika transmission, the highest prevalence of birth defects, 2.7 per 1,000, occurred during October through December 2016, and was only slightly greater than the baseline rate of 2.2 per 1,000 in January through March 2016, the investigators reported.

Among the other 19 jurisdictions (including Illinois, Louisiana, New Jersey, South Carolina, and Virginia) involved in the analysis, the rate of Zika virus–related birth defects never reached any higher than the 1.7 per 1,000 recorded at the start of the study period in January through March 2016, they said.

“Population-based birth defects surveillance is critical for identifying infants and fetuses with birth defects potentially related to Zika virus regardless of whether Zika virus testing was conducted, especially given the high prevalence of asymptomatic disease. These data can be used to inform follow-up care and services as well as strengthen surveillance,” the investigators wrote.

rfranki@mdedge.com

SOURCE: Smoots AN et al. MMWR. 2020 Jan 24;69(3):67-71.

The prevalence of Zika virus–related birth defects rose fourfold over preoutbreak levels in the areas of the United States hardest hit by the infection in 2016 and 2017, according to the Centers for Disease Control and Prevention.

That spike in the prevalence of brain abnormalities and/or microcephaly or eye abnormalities without brain abnormalities came during January through March 2017, about 6 months after the Zika outbreak’s reported peak in the jurisdictions with widespread local transmission, Puerto Rico and the U.S. Virgin Islands, wrote Ashley N. Smoots, MPH, of the CDC’s National Center on Birth Defects and Developmental Disabilities and associates in the Morbidity and Mortality Weekly Report.

In those two territories, the prevalence of birth defects potentially related to Zika virus infection was 5.6 per 1,000 live births during January through March 2017, compared with 1.3 per 1,000 in January through March 2016, they reported.

In the southern areas of Florida and Texas, where there was limited local Zika transmission, the highest prevalence of birth defects, 2.7 per 1,000, occurred during October through December 2016, and was only slightly greater than the baseline rate of 2.2 per 1,000 in January through March 2016, the investigators reported.

Among the other 19 jurisdictions (including Illinois, Louisiana, New Jersey, South Carolina, and Virginia) involved in the analysis, the rate of Zika virus–related birth defects never reached any higher than the 1.7 per 1,000 recorded at the start of the study period in January through March 2016, they said.

“Population-based birth defects surveillance is critical for identifying infants and fetuses with birth defects potentially related to Zika virus regardless of whether Zika virus testing was conducted, especially given the high prevalence of asymptomatic disease. These data can be used to inform follow-up care and services as well as strengthen surveillance,” the investigators wrote.

rfranki@mdedge.com

SOURCE: Smoots AN et al. MMWR. 2020 Jan 24;69(3):67-71.

The prevalence of Zika virus–related birth defects rose fourfold over preoutbreak levels in the areas of the United States hardest hit by the infection in 2016 and 2017, according to the Centers for Disease Control and Prevention.

That spike in the prevalence of brain abnormalities and/or microcephaly or eye abnormalities without brain abnormalities came during January through March 2017, about 6 months after the Zika outbreak’s reported peak in the jurisdictions with widespread local transmission, Puerto Rico and the U.S. Virgin Islands, wrote Ashley N. Smoots, MPH, of the CDC’s National Center on Birth Defects and Developmental Disabilities and associates in the Morbidity and Mortality Weekly Report.

In those two territories, the prevalence of birth defects potentially related to Zika virus infection was 5.6 per 1,000 live births during January through March 2017, compared with 1.3 per 1,000 in January through March 2016, they reported.

In the southern areas of Florida and Texas, where there was limited local Zika transmission, the highest prevalence of birth defects, 2.7 per 1,000, occurred during October through December 2016, and was only slightly greater than the baseline rate of 2.2 per 1,000 in January through March 2016, the investigators reported.

Among the other 19 jurisdictions (including Illinois, Louisiana, New Jersey, South Carolina, and Virginia) involved in the analysis, the rate of Zika virus–related birth defects never reached any higher than the 1.7 per 1,000 recorded at the start of the study period in January through March 2016, they said.

“Population-based birth defects surveillance is critical for identifying infants and fetuses with birth defects potentially related to Zika virus regardless of whether Zika virus testing was conducted, especially given the high prevalence of asymptomatic disease. These data can be used to inform follow-up care and services as well as strengthen surveillance,” the investigators wrote.

rfranki@mdedge.com

SOURCE: Smoots AN et al. MMWR. 2020 Jan 24;69(3):67-71.