Voters this year have told pollsters in no uncertain terms that health care is important to them. In particular, maintaining insurance protections for preexisting conditions is the top issue to many.

hermosawave/ThinkStock

But the results of the midterm elections are likely to have a major impact on a broad array of other health issues that touch every single American. And how those issues are addressed will depend in large part on which party controls the U.S. House and Senate, governors’ mansions, and state legislatures around the country.

All politics is local, and no single race is likely to determine national or even state action. But some key contests can provide something of a barometer of what’s likely to happen – or not happen – over the next 2 years.

For example, keep an eye on Kansas. The razor-tight race for governor could determine whether the state expands Medicaid to all people with low incomes, as allowed under the Affordable Care Act. The legislature in that deep-red state passed a bill to accept expansion in 2017, but it could not override the veto of then-Gov. Sam Brownback. Of the candidates running for governor in 2018, Democrat Laura Kelly supports expansion, while Republican Kris Kobach does not.

Here are three big health issues that could be dramatically affected by Tuesday’s vote.

1. The Affordable Care Act

Protections for preexisting conditions are only a small part of the ACA. The law also made big changes to Medicare and Medicaid, employer-provided health plans, and the generic drug approval process, among other things.

Republicans ran hard on promises to get rid of the law in every election since it passed in 2010. But when the GOP finally got control of the House, the Senate, and the White House in 2017, Republicans found they could not reach agreement on how to “repeal and replace” the law.

This year has Democrats on the attack over the votes Republicans took on various proposals to remake the health law. Probably the most endangered Democrat in the Senate, Heidi Heitkamp of North Dakota, has hammered her Republican opponent, U.S. Rep. Kevin Cramer, over his votes in the House for the unsuccessful repeal-and-replace bills. Rep. Cramer said that despite his votes he supports protections for preexisting conditions, but he has not said what he would do or get behind that could have that effect.

Polls suggest Rep. Cramer has a healthy lead in that race, but if Sen. Heitkamp pulled off a surprise win, health care might well get some of the credit.

And in New Jersey, Rep. Tom MacArthur, the moderate Republican who wrote the language that got the GOP health bill passed in the House in 2017, is in a heated race with Democrat Andy Kim, who has never held elective office. The overriding issue in that race, too, is health care.

It is not just congressional action that has Republicans playing defense on the ACA. In February, 18 GOP attorneys general and 2 GOP governors filed a lawsuit seeking a judgment that the law is now unconstitutional because Congress in the 2017 tax bill repealed the penalty for not having insurance. Two of those attorneys general – Missouri’s Josh Hawley and West Virginia’s Patrick Morrisey – are running for the Senate. Both states overwhelmingly supported President Donald Trump in 2016.

The attorneys general are running against Democratic incumbents – Claire McCaskill of Missouri and Joe Manchin of West Virginia. And both Republicans are being hotly criticized by their opponents for their participation in the lawsuit.

Although Sen. Manchin appears to have taken a lead, the Hawley-McCaskill race is rated a toss-up by political analysts.

But in the end the fate of the ACA depends less on an individual race than on which party winds up in control of Congress.

“If Democrats take the House ... then any attempt at repeal-and-replace will be kaput,” said John McDonough, a former Democratic Senate aide who helped write the ACA and now teaches at the Harvard School of Public Health, Boston.

Conservative health care strategist Chris Jacobs, who worked for Republicans on Capitol Hill, said a new repeal-and-replace effort might not happen even if Republicans are successful Tuesday.

“Republicans, if they maintain the majority in the House, will have a margin of a half-dozen seats – if they are lucky,” he said. That likely would not allow the party to push through another controversial effort to change the law. Currently there are 42 more Republicans than Democrats in the House. Even so, the GOP barely got its health bill passed out of the House in 2017.

And political strategists say that, when the dust clears after voting, the numbers in the Senate may not be much different so change could be hard there too. Republicans, even with a small majority last year, could not pass a repeal bill there.

2. Medicaid expansion

The Supreme Court in 2012 made optional the ACA’s expansion of Medicaid to cover all low-income Americans up to 138% of the poverty line ($16,753 for an individual in 2018). Most states have now expanded, particularly since the federal government is paying the vast majority of the cost: 94% in 2018, gradually dropping to 90% in 2020.

Still, 17 states, all with GOP governors or state legislatures (or both), have yet to expand Medicaid.

Mr. McDonough is confident that’s about to change. “I’m wondering if we’re on the cusp of a Medicaid wave,” he said.

Four states – Idaho, Montana, Nebraska, and Utah – have Medicaid expansion questions on their ballots. All but Montana have yet to expand the program. Montana’s question would eliminate the 2019 sunset date included in its expansion in 2016. But it will be interesting to watch results because the measure has run into big-pocketed opposition: the tobacco industry. The initiative would increase taxes on cigarettes and other tobacco products to fund the state’s increased Medicaid costs.

In Idaho, the ballot measure is being embraced by a number of Republican leaders. GOP Gov. Butch Otter, who is retiring after three terms, endorsed it Oct. 30.

But the issue is in play in other states, too. Several nonexpansion states have close or closer-than-expected races for governor where the Democrat has made Medicaid expansion a priority.

In Florida, one of the largest states not to have expanded Medicaid, the Republican candidate for governor, former U.S. Rep. Ron DeSantis, opposes expansion. His Democratic opponent, Tallahassee Mayor Andrew Gillum, supports it.

In Georgia, the gubernatorial candidates, Democrat Stacey Abrams and Republican Brian Kemp, are also on opposite sides of the Medicaid expansion debate.

However, the legislatures in both states have opposed the expansion, and it’s not clear if they would be swayed by arguments from a new governor.
 

3. Medicare

Until recently, Republicans have remained relatively quiet about efforts to change the popular Medicare program for seniors and people with disabilities.

Their new talking point is that proposals to expand the program – such as the often-touted “Medicare-for-all,” which an increasing number of Democrats are embracing – could threaten the existing program.

“Medicare is at significant risk of being cut if Democrats take over the House,” Rep. Greg Gianforte (R-Mont.) told the Lee Montana Newspapers. “Medicare-for-all is Medicare for none. It will gut Medicare, end the VA [Department of Veterans Affairs] as we know it, and force Montana seniors to the back of the line.”

Gianforte’s Democratic opponent, Kathleen Williams, is proposing another idea popular with Democrats: allowing people aged 55 years and over to “buy into” Medicare coverage. That race, too, is very tight.

Meanwhile, back in Washington, congressional Republicans are more concerned with how Medicare and other large government social programs are threatening the budget.

“Sooner or later we are going to run out of other people’s money,” said Mr. Jacobs.

Senate Majority Leader Mitch McConnell (R-Ky.) suggested in an Oct. 16 interview with Bloomberg News that entitlement programs like Medicare are “the real driver of the debt by any objective standard,” but that bipartisan cooperation will be needed to address that problem

Republican Mr. Jacobs and Democrat Mr. McDonough think that’s unlikely any time soon.

“Why would Democrats give that up as an issue heading into 2020?” asked Mr. McDonough, especially because Republicans in recent years have been proposing deep cuts to the Medicare program.

Agreed Mr. Jacobs, “Trump may not want that to be the centerpiece of a reelection campaign.”

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

Voters this year have told pollsters in no uncertain terms that health care is important to them. In particular, maintaining insurance protections for preexisting conditions is the top issue to many.

hermosawave/ThinkStock

But the results of the midterm elections are likely to have a major impact on a broad array of other health issues that touch every single American. And how those issues are addressed will depend in large part on which party controls the U.S. House and Senate, governors’ mansions, and state legislatures around the country.

All politics is local, and no single race is likely to determine national or even state action. But some key contests can provide something of a barometer of what’s likely to happen – or not happen – over the next 2 years.

For example, keep an eye on Kansas. The razor-tight race for governor could determine whether the state expands Medicaid to all people with low incomes, as allowed under the Affordable Care Act. The legislature in that deep-red state passed a bill to accept expansion in 2017, but it could not override the veto of then-Gov. Sam Brownback. Of the candidates running for governor in 2018, Democrat Laura Kelly supports expansion, while Republican Kris Kobach does not.

Here are three big health issues that could be dramatically affected by Tuesday’s vote.

1. The Affordable Care Act

Protections for preexisting conditions are only a small part of the ACA. The law also made big changes to Medicare and Medicaid, employer-provided health plans, and the generic drug approval process, among other things.

Republicans ran hard on promises to get rid of the law in every election since it passed in 2010. But when the GOP finally got control of the House, the Senate, and the White House in 2017, Republicans found they could not reach agreement on how to “repeal and replace” the law.

This year has Democrats on the attack over the votes Republicans took on various proposals to remake the health law. Probably the most endangered Democrat in the Senate, Heidi Heitkamp of North Dakota, has hammered her Republican opponent, U.S. Rep. Kevin Cramer, over his votes in the House for the unsuccessful repeal-and-replace bills. Rep. Cramer said that despite his votes he supports protections for preexisting conditions, but he has not said what he would do or get behind that could have that effect.

Polls suggest Rep. Cramer has a healthy lead in that race, but if Sen. Heitkamp pulled off a surprise win, health care might well get some of the credit.

And in New Jersey, Rep. Tom MacArthur, the moderate Republican who wrote the language that got the GOP health bill passed in the House in 2017, is in a heated race with Democrat Andy Kim, who has never held elective office. The overriding issue in that race, too, is health care.

It is not just congressional action that has Republicans playing defense on the ACA. In February, 18 GOP attorneys general and 2 GOP governors filed a lawsuit seeking a judgment that the law is now unconstitutional because Congress in the 2017 tax bill repealed the penalty for not having insurance. Two of those attorneys general – Missouri’s Josh Hawley and West Virginia’s Patrick Morrisey – are running for the Senate. Both states overwhelmingly supported President Donald Trump in 2016.

The attorneys general are running against Democratic incumbents – Claire McCaskill of Missouri and Joe Manchin of West Virginia. And both Republicans are being hotly criticized by their opponents for their participation in the lawsuit.

Although Sen. Manchin appears to have taken a lead, the Hawley-McCaskill race is rated a toss-up by political analysts.

But in the end the fate of the ACA depends less on an individual race than on which party winds up in control of Congress.

“If Democrats take the House ... then any attempt at repeal-and-replace will be kaput,” said John McDonough, a former Democratic Senate aide who helped write the ACA and now teaches at the Harvard School of Public Health, Boston.

Conservative health care strategist Chris Jacobs, who worked for Republicans on Capitol Hill, said a new repeal-and-replace effort might not happen even if Republicans are successful Tuesday.

“Republicans, if they maintain the majority in the House, will have a margin of a half-dozen seats – if they are lucky,” he said. That likely would not allow the party to push through another controversial effort to change the law. Currently there are 42 more Republicans than Democrats in the House. Even so, the GOP barely got its health bill passed out of the House in 2017.

And political strategists say that, when the dust clears after voting, the numbers in the Senate may not be much different so change could be hard there too. Republicans, even with a small majority last year, could not pass a repeal bill there.

2. Medicaid expansion

The Supreme Court in 2012 made optional the ACA’s expansion of Medicaid to cover all low-income Americans up to 138% of the poverty line ($16,753 for an individual in 2018). Most states have now expanded, particularly since the federal government is paying the vast majority of the cost: 94% in 2018, gradually dropping to 90% in 2020.

Still, 17 states, all with GOP governors or state legislatures (or both), have yet to expand Medicaid.

Mr. McDonough is confident that’s about to change. “I’m wondering if we’re on the cusp of a Medicaid wave,” he said.

Four states – Idaho, Montana, Nebraska, and Utah – have Medicaid expansion questions on their ballots. All but Montana have yet to expand the program. Montana’s question would eliminate the 2019 sunset date included in its expansion in 2016. But it will be interesting to watch results because the measure has run into big-pocketed opposition: the tobacco industry. The initiative would increase taxes on cigarettes and other tobacco products to fund the state’s increased Medicaid costs.

In Idaho, the ballot measure is being embraced by a number of Republican leaders. GOP Gov. Butch Otter, who is retiring after three terms, endorsed it Oct. 30.

But the issue is in play in other states, too. Several nonexpansion states have close or closer-than-expected races for governor where the Democrat has made Medicaid expansion a priority.

In Florida, one of the largest states not to have expanded Medicaid, the Republican candidate for governor, former U.S. Rep. Ron DeSantis, opposes expansion. His Democratic opponent, Tallahassee Mayor Andrew Gillum, supports it.

In Georgia, the gubernatorial candidates, Democrat Stacey Abrams and Republican Brian Kemp, are also on opposite sides of the Medicaid expansion debate.

However, the legislatures in both states have opposed the expansion, and it’s not clear if they would be swayed by arguments from a new governor.
 

3. Medicare

Until recently, Republicans have remained relatively quiet about efforts to change the popular Medicare program for seniors and people with disabilities.

Their new talking point is that proposals to expand the program – such as the often-touted “Medicare-for-all,” which an increasing number of Democrats are embracing – could threaten the existing program.

“Medicare is at significant risk of being cut if Democrats take over the House,” Rep. Greg Gianforte (R-Mont.) told the Lee Montana Newspapers. “Medicare-for-all is Medicare for none. It will gut Medicare, end the VA [Department of Veterans Affairs] as we know it, and force Montana seniors to the back of the line.”

Gianforte’s Democratic opponent, Kathleen Williams, is proposing another idea popular with Democrats: allowing people aged 55 years and over to “buy into” Medicare coverage. That race, too, is very tight.

Meanwhile, back in Washington, congressional Republicans are more concerned with how Medicare and other large government social programs are threatening the budget.

“Sooner or later we are going to run out of other people’s money,” said Mr. Jacobs.

Senate Majority Leader Mitch McConnell (R-Ky.) suggested in an Oct. 16 interview with Bloomberg News that entitlement programs like Medicare are “the real driver of the debt by any objective standard,” but that bipartisan cooperation will be needed to address that problem

Republican Mr. Jacobs and Democrat Mr. McDonough think that’s unlikely any time soon.

“Why would Democrats give that up as an issue heading into 2020?” asked Mr. McDonough, especially because Republicans in recent years have been proposing deep cuts to the Medicare program.

Agreed Mr. Jacobs, “Trump may not want that to be the centerpiece of a reelection campaign.”

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

Voters this year have told pollsters in no uncertain terms that health care is important to them. In particular, maintaining insurance protections for preexisting conditions is the top issue to many.

hermosawave/ThinkStock

But the results of the midterm elections are likely to have a major impact on a broad array of other health issues that touch every single American. And how those issues are addressed will depend in large part on which party controls the U.S. House and Senate, governors’ mansions, and state legislatures around the country.

All politics is local, and no single race is likely to determine national or even state action. But some key contests can provide something of a barometer of what’s likely to happen – or not happen – over the next 2 years.

For example, keep an eye on Kansas. The razor-tight race for governor could determine whether the state expands Medicaid to all people with low incomes, as allowed under the Affordable Care Act. The legislature in that deep-red state passed a bill to accept expansion in 2017, but it could not override the veto of then-Gov. Sam Brownback. Of the candidates running for governor in 2018, Democrat Laura Kelly supports expansion, while Republican Kris Kobach does not.

Here are three big health issues that could be dramatically affected by Tuesday’s vote.

1. The Affordable Care Act

Protections for preexisting conditions are only a small part of the ACA. The law also made big changes to Medicare and Medicaid, employer-provided health plans, and the generic drug approval process, among other things.

Republicans ran hard on promises to get rid of the law in every election since it passed in 2010. But when the GOP finally got control of the House, the Senate, and the White House in 2017, Republicans found they could not reach agreement on how to “repeal and replace” the law.

This year has Democrats on the attack over the votes Republicans took on various proposals to remake the health law. Probably the most endangered Democrat in the Senate, Heidi Heitkamp of North Dakota, has hammered her Republican opponent, U.S. Rep. Kevin Cramer, over his votes in the House for the unsuccessful repeal-and-replace bills. Rep. Cramer said that despite his votes he supports protections for preexisting conditions, but he has not said what he would do or get behind that could have that effect.

Polls suggest Rep. Cramer has a healthy lead in that race, but if Sen. Heitkamp pulled off a surprise win, health care might well get some of the credit.

And in New Jersey, Rep. Tom MacArthur, the moderate Republican who wrote the language that got the GOP health bill passed in the House in 2017, is in a heated race with Democrat Andy Kim, who has never held elective office. The overriding issue in that race, too, is health care.

It is not just congressional action that has Republicans playing defense on the ACA. In February, 18 GOP attorneys general and 2 GOP governors filed a lawsuit seeking a judgment that the law is now unconstitutional because Congress in the 2017 tax bill repealed the penalty for not having insurance. Two of those attorneys general – Missouri’s Josh Hawley and West Virginia’s Patrick Morrisey – are running for the Senate. Both states overwhelmingly supported President Donald Trump in 2016.

The attorneys general are running against Democratic incumbents – Claire McCaskill of Missouri and Joe Manchin of West Virginia. And both Republicans are being hotly criticized by their opponents for their participation in the lawsuit.

Although Sen. Manchin appears to have taken a lead, the Hawley-McCaskill race is rated a toss-up by political analysts.

But in the end the fate of the ACA depends less on an individual race than on which party winds up in control of Congress.

“If Democrats take the House ... then any attempt at repeal-and-replace will be kaput,” said John McDonough, a former Democratic Senate aide who helped write the ACA and now teaches at the Harvard School of Public Health, Boston.

Conservative health care strategist Chris Jacobs, who worked for Republicans on Capitol Hill, said a new repeal-and-replace effort might not happen even if Republicans are successful Tuesday.

“Republicans, if they maintain the majority in the House, will have a margin of a half-dozen seats – if they are lucky,” he said. That likely would not allow the party to push through another controversial effort to change the law. Currently there are 42 more Republicans than Democrats in the House. Even so, the GOP barely got its health bill passed out of the House in 2017.

And political strategists say that, when the dust clears after voting, the numbers in the Senate may not be much different so change could be hard there too. Republicans, even with a small majority last year, could not pass a repeal bill there.

2. Medicaid expansion

The Supreme Court in 2012 made optional the ACA’s expansion of Medicaid to cover all low-income Americans up to 138% of the poverty line ($16,753 for an individual in 2018). Most states have now expanded, particularly since the federal government is paying the vast majority of the cost: 94% in 2018, gradually dropping to 90% in 2020.

Still, 17 states, all with GOP governors or state legislatures (or both), have yet to expand Medicaid.

Mr. McDonough is confident that’s about to change. “I’m wondering if we’re on the cusp of a Medicaid wave,” he said.

Four states – Idaho, Montana, Nebraska, and Utah – have Medicaid expansion questions on their ballots. All but Montana have yet to expand the program. Montana’s question would eliminate the 2019 sunset date included in its expansion in 2016. But it will be interesting to watch results because the measure has run into big-pocketed opposition: the tobacco industry. The initiative would increase taxes on cigarettes and other tobacco products to fund the state’s increased Medicaid costs.

In Idaho, the ballot measure is being embraced by a number of Republican leaders. GOP Gov. Butch Otter, who is retiring after three terms, endorsed it Oct. 30.

But the issue is in play in other states, too. Several nonexpansion states have close or closer-than-expected races for governor where the Democrat has made Medicaid expansion a priority.

In Florida, one of the largest states not to have expanded Medicaid, the Republican candidate for governor, former U.S. Rep. Ron DeSantis, opposes expansion. His Democratic opponent, Tallahassee Mayor Andrew Gillum, supports it.

In Georgia, the gubernatorial candidates, Democrat Stacey Abrams and Republican Brian Kemp, are also on opposite sides of the Medicaid expansion debate.

However, the legislatures in both states have opposed the expansion, and it’s not clear if they would be swayed by arguments from a new governor.
 

3. Medicare

Until recently, Republicans have remained relatively quiet about efforts to change the popular Medicare program for seniors and people with disabilities.

Their new talking point is that proposals to expand the program – such as the often-touted “Medicare-for-all,” which an increasing number of Democrats are embracing – could threaten the existing program.

“Medicare is at significant risk of being cut if Democrats take over the House,” Rep. Greg Gianforte (R-Mont.) told the Lee Montana Newspapers. “Medicare-for-all is Medicare for none. It will gut Medicare, end the VA [Department of Veterans Affairs] as we know it, and force Montana seniors to the back of the line.”

Gianforte’s Democratic opponent, Kathleen Williams, is proposing another idea popular with Democrats: allowing people aged 55 years and over to “buy into” Medicare coverage. That race, too, is very tight.

Meanwhile, back in Washington, congressional Republicans are more concerned with how Medicare and other large government social programs are threatening the budget.

“Sooner or later we are going to run out of other people’s money,” said Mr. Jacobs.

Senate Majority Leader Mitch McConnell (R-Ky.) suggested in an Oct. 16 interview with Bloomberg News that entitlement programs like Medicare are “the real driver of the debt by any objective standard,” but that bipartisan cooperation will be needed to address that problem

Republican Mr. Jacobs and Democrat Mr. McDonough think that’s unlikely any time soon.

“Why would Democrats give that up as an issue heading into 2020?” asked Mr. McDonough, especially because Republicans in recent years have been proposing deep cuts to the Medicare program.

Agreed Mr. Jacobs, “Trump may not want that to be the centerpiece of a reelection campaign.”

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

Doctor Stephen Bergman now goes by Samuel Shem and lives outside Boston, but in the 1970s, he published arguably one of the most impactful books on medicine in recent memory -- the cult classic, the House of God.  Newsweek named the House of God the second best satirical piece of fiction of all time behind Don Quixote. In this conversation, Shem tells me about his motivation for the House of God and reveals that there will be a sequel in 2019 on the current state of medicine.
 

Doctor Stephen Bergman now goes by Samuel Shem and lives outside Boston, but in the 1970s, he published arguably one of the most impactful books on medicine in recent memory -- the cult classic, the House of God.  Newsweek named the House of God the second best satirical piece of fiction of all time behind Don Quixote. In this conversation, Shem tells me about his motivation for the House of God and reveals that there will be a sequel in 2019 on the current state of medicine.
 

Doctor Stephen Bergman now goes by Samuel Shem and lives outside Boston, but in the 1970s, he published arguably one of the most impactful books on medicine in recent memory -- the cult classic, the House of God.  Newsweek named the House of God the second best satirical piece of fiction of all time behind Don Quixote. In this conversation, Shem tells me about his motivation for the House of God and reveals that there will be a sequel in 2019 on the current state of medicine.
 

LAS VEGAS – It’s time to start thinking about barrier repair in acne patients, Hilary E. Baldwin, MD, asserts.

“We think about barrier repair with our psoriasis patients, with our dermatitis patients, and our rosacea patients, but we don’t talk about it much with our acne patients,” Dr. Baldwin said at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar. “Now there is increasing evidence that acne pathophysiology may include a barrier defect.”

Both topical and systemic medications exacerbate the problem, because they are so drying, added Dr. Baldwin, medical director of the Acne Treatment & Research Center in Morristown, N.J. Benzoyl peroxide has been shown to increase transepidermal water loss (TEWL) and deplete tocopherol levels in the stratum corneum, while topical retinoids thin the stratum corneum, increase epidermal fragility, and increase TEWL.

The barrier defect may actually decrease medication use – patients are irritated and they stop taking their medication. “An improved barrier may increase the use of medication and also improve acne,” she said.

She described the results of an Internet-based survey of 200 acne patients aged 15-40 years who had been prescribed clindamycin/benzoyl peroxide 5% within the last 6 months (J Drugs Dermatol. 2011 Jun;10[6]:605-8). The researchers found that side effects lead to suboptimal use of the topical medication, as patients reported spot application, use only in flares, infrequent use, and discontinuation.

Further, 31% of patients complained to their doctors’ offices about dryness, 23% said their doctors did not understand the potential side effects, 21% lost confidence in their doctors, 11% said they were less likely to see their doctors again, and 41% reported using moisturizer to combat dryness and erythema.

“No acne visit is complete without a discussion of skin care,” Dr. Baldwin said. Quality moisturization is a must for acne patients and has been shown to improve TEWL, normalize ceramides, and repair the microbiome.

“I recommend moisturizers with ceramides, hyaluronic acid, and certainly moisturizers that have been shown to be noncomedogenic,” Dr. Baldwin said. “Most acne patients aren’t willing to use a cream moisturizer during the day – they just feel too greasy – so I have them use a cream in the evening when they are home and a lotion in the morning.”

PainterSaba/iStock/Getty Images

[email protected]

LAS VEGAS – It’s time to start thinking about barrier repair in acne patients, Hilary E. Baldwin, MD, asserts.

“We think about barrier repair with our psoriasis patients, with our dermatitis patients, and our rosacea patients, but we don’t talk about it much with our acne patients,” Dr. Baldwin said at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar. “Now there is increasing evidence that acne pathophysiology may include a barrier defect.”

Both topical and systemic medications exacerbate the problem, because they are so drying, added Dr. Baldwin, medical director of the Acne Treatment & Research Center in Morristown, N.J. Benzoyl peroxide has been shown to increase transepidermal water loss (TEWL) and deplete tocopherol levels in the stratum corneum, while topical retinoids thin the stratum corneum, increase epidermal fragility, and increase TEWL.

The barrier defect may actually decrease medication use – patients are irritated and they stop taking their medication. “An improved barrier may increase the use of medication and also improve acne,” she said.

She described the results of an Internet-based survey of 200 acne patients aged 15-40 years who had been prescribed clindamycin/benzoyl peroxide 5% within the last 6 months (J Drugs Dermatol. 2011 Jun;10[6]:605-8). The researchers found that side effects lead to suboptimal use of the topical medication, as patients reported spot application, use only in flares, infrequent use, and discontinuation.

Further, 31% of patients complained to their doctors’ offices about dryness, 23% said their doctors did not understand the potential side effects, 21% lost confidence in their doctors, 11% said they were less likely to see their doctors again, and 41% reported using moisturizer to combat dryness and erythema.

“No acne visit is complete without a discussion of skin care,” Dr. Baldwin said. Quality moisturization is a must for acne patients and has been shown to improve TEWL, normalize ceramides, and repair the microbiome.

“I recommend moisturizers with ceramides, hyaluronic acid, and certainly moisturizers that have been shown to be noncomedogenic,” Dr. Baldwin said. “Most acne patients aren’t willing to use a cream moisturizer during the day – they just feel too greasy – so I have them use a cream in the evening when they are home and a lotion in the morning.”

PainterSaba/iStock/Getty Images

[email protected]

LAS VEGAS – It’s time to start thinking about barrier repair in acne patients, Hilary E. Baldwin, MD, asserts.

“We think about barrier repair with our psoriasis patients, with our dermatitis patients, and our rosacea patients, but we don’t talk about it much with our acne patients,” Dr. Baldwin said at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar. “Now there is increasing evidence that acne pathophysiology may include a barrier defect.”

Both topical and systemic medications exacerbate the problem, because they are so drying, added Dr. Baldwin, medical director of the Acne Treatment & Research Center in Morristown, N.J. Benzoyl peroxide has been shown to increase transepidermal water loss (TEWL) and deplete tocopherol levels in the stratum corneum, while topical retinoids thin the stratum corneum, increase epidermal fragility, and increase TEWL.

The barrier defect may actually decrease medication use – patients are irritated and they stop taking their medication. “An improved barrier may increase the use of medication and also improve acne,” she said.

She described the results of an Internet-based survey of 200 acne patients aged 15-40 years who had been prescribed clindamycin/benzoyl peroxide 5% within the last 6 months (J Drugs Dermatol. 2011 Jun;10[6]:605-8). The researchers found that side effects lead to suboptimal use of the topical medication, as patients reported spot application, use only in flares, infrequent use, and discontinuation.

Further, 31% of patients complained to their doctors’ offices about dryness, 23% said their doctors did not understand the potential side effects, 21% lost confidence in their doctors, 11% said they were less likely to see their doctors again, and 41% reported using moisturizer to combat dryness and erythema.

“No acne visit is complete without a discussion of skin care,” Dr. Baldwin said. Quality moisturization is a must for acne patients and has been shown to improve TEWL, normalize ceramides, and repair the microbiome.

“I recommend moisturizers with ceramides, hyaluronic acid, and certainly moisturizers that have been shown to be noncomedogenic,” Dr. Baldwin said. “Most acne patients aren’t willing to use a cream moisturizer during the day – they just feel too greasy – so I have them use a cream in the evening when they are home and a lotion in the morning.”

PainterSaba/iStock/Getty Images

[email protected]

BARCELONA – Four potent clinical predictors of treatment-resistant depression have been confirmed in a validation study that showed the four factors collectively have a predictive accuracy of 87%, Alexander Kautzky, MD, reported at the annual congress of the European College of Neuropsychopharmacology.

The four predictors – all easily assessed – are symptom severity, which was independently associated with a 3.3-fold increased likelihood of treatment-resistant depression (TRD) in a study of 916 patients with major depression at 10 referral centers in eight European countries; suicidal risk, with a 1.74-fold increased risk; comorbid anxiety disorder, with a 1.68-fold increased risk; and the lifetime number of major depressive episodes, for which the associated TRD risk climbs by 15% per prior episode, according to Dr. Kautzky of the Medical University of Vienna.

When these four predictors were put to the test in an independent validation cohort of 314 patients with major depression, the four clinical markers of TRD exhibited a sensitivity of 86%, a specificity of 88%, and an overall predictive accuracy of 87%.

In these studies, TRD was defined as a Montgomery-Åsberg Depression Rating Scale (MADRS) score of 22 or more despite at least two adequate trials of antidepressants. Response was defined as at least a 50% drop in MADRS score to below 22 points.

The validation of these clinical predictors of TRD is a welcome development in psychiatry. The World Health Organization ranks major depressive disorder as the No. 4 cause of disease burden worldwide, and an impressive number of antidepressant medications are available, but up to 60% of patients do not respond sufficiently to their first round of antidepressant therapy. And there is a notable absence of biological markers to aid in selecting the best initial antidepressant for a given individual, Dr. Kautzky observed.

The validation study was supported by an unrestricted research grant from Lundbeck to a European research consortium known as the Group for the Study of Resistant Depression. Dr. Kautzky reported having no financial conflicts of interest.

[email protected]

BARCELONA – Four potent clinical predictors of treatment-resistant depression have been confirmed in a validation study that showed the four factors collectively have a predictive accuracy of 87%, Alexander Kautzky, MD, reported at the annual congress of the European College of Neuropsychopharmacology.

The four predictors – all easily assessed – are symptom severity, which was independently associated with a 3.3-fold increased likelihood of treatment-resistant depression (TRD) in a study of 916 patients with major depression at 10 referral centers in eight European countries; suicidal risk, with a 1.74-fold increased risk; comorbid anxiety disorder, with a 1.68-fold increased risk; and the lifetime number of major depressive episodes, for which the associated TRD risk climbs by 15% per prior episode, according to Dr. Kautzky of the Medical University of Vienna.

When these four predictors were put to the test in an independent validation cohort of 314 patients with major depression, the four clinical markers of TRD exhibited a sensitivity of 86%, a specificity of 88%, and an overall predictive accuracy of 87%.

In these studies, TRD was defined as a Montgomery-Åsberg Depression Rating Scale (MADRS) score of 22 or more despite at least two adequate trials of antidepressants. Response was defined as at least a 50% drop in MADRS score to below 22 points.

The validation of these clinical predictors of TRD is a welcome development in psychiatry. The World Health Organization ranks major depressive disorder as the No. 4 cause of disease burden worldwide, and an impressive number of antidepressant medications are available, but up to 60% of patients do not respond sufficiently to their first round of antidepressant therapy. And there is a notable absence of biological markers to aid in selecting the best initial antidepressant for a given individual, Dr. Kautzky observed.

The validation study was supported by an unrestricted research grant from Lundbeck to a European research consortium known as the Group for the Study of Resistant Depression. Dr. Kautzky reported having no financial conflicts of interest.

[email protected]

BARCELONA – Four potent clinical predictors of treatment-resistant depression have been confirmed in a validation study that showed the four factors collectively have a predictive accuracy of 87%, Alexander Kautzky, MD, reported at the annual congress of the European College of Neuropsychopharmacology.

The four predictors – all easily assessed – are symptom severity, which was independently associated with a 3.3-fold increased likelihood of treatment-resistant depression (TRD) in a study of 916 patients with major depression at 10 referral centers in eight European countries; suicidal risk, with a 1.74-fold increased risk; comorbid anxiety disorder, with a 1.68-fold increased risk; and the lifetime number of major depressive episodes, for which the associated TRD risk climbs by 15% per prior episode, according to Dr. Kautzky of the Medical University of Vienna.

When these four predictors were put to the test in an independent validation cohort of 314 patients with major depression, the four clinical markers of TRD exhibited a sensitivity of 86%, a specificity of 88%, and an overall predictive accuracy of 87%.

In these studies, TRD was defined as a Montgomery-Åsberg Depression Rating Scale (MADRS) score of 22 or more despite at least two adequate trials of antidepressants. Response was defined as at least a 50% drop in MADRS score to below 22 points.

The validation of these clinical predictors of TRD is a welcome development in psychiatry. The World Health Organization ranks major depressive disorder as the No. 4 cause of disease burden worldwide, and an impressive number of antidepressant medications are available, but up to 60% of patients do not respond sufficiently to their first round of antidepressant therapy. And there is a notable absence of biological markers to aid in selecting the best initial antidepressant for a given individual, Dr. Kautzky observed.

The validation study was supported by an unrestricted research grant from Lundbeck to a European research consortium known as the Group for the Study of Resistant Depression. Dr. Kautzky reported having no financial conflicts of interest.

[email protected]

CHICAGO – Vascular ultrasound showed high sensitivity and specificity for diagnosing large-vessel giant-cell arteritis (LV-GCA) in a prospective study of patients with suspected new-onset disease.

Sharon Worcester/MDedge News

The findings highlight the value of vascular ultrasound – in the hands of experienced sonographers – as a first-line imaging test in this setting, Berit Dalsgaard Nielsen, MD, reported at the annual meeting of the American College of Rheumatology.

Of 41 control subjects without LV-GCA, none had a positive ultrasound, whereas 36 of 45 LV-GCA patients had a positive ultrasound, which gives the test a specificity of 100% and sensitivity of 80%, Dr. Nielsen of Aarhus (Denmark) University Hospital said during a press briefing at the meeting.

Ultrasound was performed on the carotid artery in the neck and axillary arteries under the arm, which are easily accessible by ultrasound.

“These patients also had temporal arteries evaluated, and if we included this evaluation in the diagnostic performance, it showed a sensitivity of 91%,” she noted, explaining that temporal artery ultrasound alone conferred 71% sensitivity. “So it actually helped us identify more GCA patients.”

The study subjects were adults with suspected GCA. Inclusion criteria included age of at least 50 years, C-reactive protein of more than 15 mg/L or erythrocyte sedimentation rate of more than 40 mm, and either cranial symptoms, new-onset limb claudication, protracted constitutional symptoms, or polymyalgia rheumatica (PMR) symptoms. Patients were excluded if they had recent or ongoing glucocorticoid or disease-modifying antirheumatic drug treatment, a previous GCA or PMR diagnosis, or a large vessel inflammation that mimicked LV-GCA.

Clinical evaluations and imaging tests were performed prior to treatment initiation. The reference diagnosis was a clinical diagnosis of GCA and a positive 18F-FDG PET/CT scan, Dr Nielsen said, adding that ultrasound examinations were performed by experienced sonographers who were blinded to the PET/CT results.

Of the 86 patients included, 45 had LV-GCA with or without concomitant cranial GCA, 10 had isolated cranial GCA, 21 had PMR, and 10 were diagnosed with other diseases. The patients found to not have LV-GCA were considered control subjects.

The findings are notable because, while PET is considered the gold standard, it is very expensive and not always readily available, Dr. Nielsen said.

Additionally, while cranial-GCA patients generally present with symptoms such as headache, jaw claudication, and visual disturbances that are considered typical for GCA, LV-GCA patients rarely present with these symptoms.

Rather, these LV-GCA patients tend to present with constitutional symptoms mimicking infection or cancer, and they undergo extensive examination programs before the diagnosis is established. For this reason, diagnosis is often delayed for several months in LV-GCA patients until late in the disease course.

“During this time they often experience a decline in physical ability,” she said. “So in this disease subset of patients with GCA, there’s an unmet need for earlier recognition and earlier diagnosis.”

New recommendations from the European League Against Rheumatism call for early diagnostic imaging in all cases of suspected GCA, she added, noting that, for cranial-GCA symptoms, temporal artery ultrasound is recommended first line, but for those who present without cranial symptoms, no particular imaging modality is recommended because of a lack of comparative and diagnostic accuracy data in LV-GCA.

Biopsy has traditionally been used in these cases, but now imaging can be substituted – and vascular ultrasound is an attractive first-line option given its affordability and availability.

Indeed, the current findings support its use in this setting, she said.

“We think that these results indicate that ultrasound should not only be the first-line imaging test in patients presenting with cranial symptoms, but also in patients suspected of GCA presenting with constitutional symptoms, and if this examination is included in the standard examinations in fast-track clinics, it may overcome the delay in diagnosis and the patients can be treated earlier. It may also spare the unneeded examinations performed in these patients,” she concluded.

Dr. Nielsen disclosed a relationship with Roche.

[email protected]

SOURCE: Nielsen B et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 2905.

CHICAGO – Vascular ultrasound showed high sensitivity and specificity for diagnosing large-vessel giant-cell arteritis (LV-GCA) in a prospective study of patients with suspected new-onset disease.

Sharon Worcester/MDedge News

The findings highlight the value of vascular ultrasound – in the hands of experienced sonographers – as a first-line imaging test in this setting, Berit Dalsgaard Nielsen, MD, reported at the annual meeting of the American College of Rheumatology.

Of 41 control subjects without LV-GCA, none had a positive ultrasound, whereas 36 of 45 LV-GCA patients had a positive ultrasound, which gives the test a specificity of 100% and sensitivity of 80%, Dr. Nielsen of Aarhus (Denmark) University Hospital said during a press briefing at the meeting.

Ultrasound was performed on the carotid artery in the neck and axillary arteries under the arm, which are easily accessible by ultrasound.

“These patients also had temporal arteries evaluated, and if we included this evaluation in the diagnostic performance, it showed a sensitivity of 91%,” she noted, explaining that temporal artery ultrasound alone conferred 71% sensitivity. “So it actually helped us identify more GCA patients.”

The study subjects were adults with suspected GCA. Inclusion criteria included age of at least 50 years, C-reactive protein of more than 15 mg/L or erythrocyte sedimentation rate of more than 40 mm, and either cranial symptoms, new-onset limb claudication, protracted constitutional symptoms, or polymyalgia rheumatica (PMR) symptoms. Patients were excluded if they had recent or ongoing glucocorticoid or disease-modifying antirheumatic drug treatment, a previous GCA or PMR diagnosis, or a large vessel inflammation that mimicked LV-GCA.

Clinical evaluations and imaging tests were performed prior to treatment initiation. The reference diagnosis was a clinical diagnosis of GCA and a positive 18F-FDG PET/CT scan, Dr Nielsen said, adding that ultrasound examinations were performed by experienced sonographers who were blinded to the PET/CT results.

Of the 86 patients included, 45 had LV-GCA with or without concomitant cranial GCA, 10 had isolated cranial GCA, 21 had PMR, and 10 were diagnosed with other diseases. The patients found to not have LV-GCA were considered control subjects.

The findings are notable because, while PET is considered the gold standard, it is very expensive and not always readily available, Dr. Nielsen said.

Additionally, while cranial-GCA patients generally present with symptoms such as headache, jaw claudication, and visual disturbances that are considered typical for GCA, LV-GCA patients rarely present with these symptoms.

Rather, these LV-GCA patients tend to present with constitutional symptoms mimicking infection or cancer, and they undergo extensive examination programs before the diagnosis is established. For this reason, diagnosis is often delayed for several months in LV-GCA patients until late in the disease course.

“During this time they often experience a decline in physical ability,” she said. “So in this disease subset of patients with GCA, there’s an unmet need for earlier recognition and earlier diagnosis.”

New recommendations from the European League Against Rheumatism call for early diagnostic imaging in all cases of suspected GCA, she added, noting that, for cranial-GCA symptoms, temporal artery ultrasound is recommended first line, but for those who present without cranial symptoms, no particular imaging modality is recommended because of a lack of comparative and diagnostic accuracy data in LV-GCA.

Biopsy has traditionally been used in these cases, but now imaging can be substituted – and vascular ultrasound is an attractive first-line option given its affordability and availability.

Indeed, the current findings support its use in this setting, she said.

“We think that these results indicate that ultrasound should not only be the first-line imaging test in patients presenting with cranial symptoms, but also in patients suspected of GCA presenting with constitutional symptoms, and if this examination is included in the standard examinations in fast-track clinics, it may overcome the delay in diagnosis and the patients can be treated earlier. It may also spare the unneeded examinations performed in these patients,” she concluded.

Dr. Nielsen disclosed a relationship with Roche.

[email protected]

SOURCE: Nielsen B et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 2905.

CHICAGO – Vascular ultrasound showed high sensitivity and specificity for diagnosing large-vessel giant-cell arteritis (LV-GCA) in a prospective study of patients with suspected new-onset disease.

Sharon Worcester/MDedge News

The findings highlight the value of vascular ultrasound – in the hands of experienced sonographers – as a first-line imaging test in this setting, Berit Dalsgaard Nielsen, MD, reported at the annual meeting of the American College of Rheumatology.

Of 41 control subjects without LV-GCA, none had a positive ultrasound, whereas 36 of 45 LV-GCA patients had a positive ultrasound, which gives the test a specificity of 100% and sensitivity of 80%, Dr. Nielsen of Aarhus (Denmark) University Hospital said during a press briefing at the meeting.

Ultrasound was performed on the carotid artery in the neck and axillary arteries under the arm, which are easily accessible by ultrasound.

“These patients also had temporal arteries evaluated, and if we included this evaluation in the diagnostic performance, it showed a sensitivity of 91%,” she noted, explaining that temporal artery ultrasound alone conferred 71% sensitivity. “So it actually helped us identify more GCA patients.”

The study subjects were adults with suspected GCA. Inclusion criteria included age of at least 50 years, C-reactive protein of more than 15 mg/L or erythrocyte sedimentation rate of more than 40 mm, and either cranial symptoms, new-onset limb claudication, protracted constitutional symptoms, or polymyalgia rheumatica (PMR) symptoms. Patients were excluded if they had recent or ongoing glucocorticoid or disease-modifying antirheumatic drug treatment, a previous GCA or PMR diagnosis, or a large vessel inflammation that mimicked LV-GCA.

Clinical evaluations and imaging tests were performed prior to treatment initiation. The reference diagnosis was a clinical diagnosis of GCA and a positive 18F-FDG PET/CT scan, Dr Nielsen said, adding that ultrasound examinations were performed by experienced sonographers who were blinded to the PET/CT results.

Of the 86 patients included, 45 had LV-GCA with or without concomitant cranial GCA, 10 had isolated cranial GCA, 21 had PMR, and 10 were diagnosed with other diseases. The patients found to not have LV-GCA were considered control subjects.

The findings are notable because, while PET is considered the gold standard, it is very expensive and not always readily available, Dr. Nielsen said.

Additionally, while cranial-GCA patients generally present with symptoms such as headache, jaw claudication, and visual disturbances that are considered typical for GCA, LV-GCA patients rarely present with these symptoms.

Rather, these LV-GCA patients tend to present with constitutional symptoms mimicking infection or cancer, and they undergo extensive examination programs before the diagnosis is established. For this reason, diagnosis is often delayed for several months in LV-GCA patients until late in the disease course.

“During this time they often experience a decline in physical ability,” she said. “So in this disease subset of patients with GCA, there’s an unmet need for earlier recognition and earlier diagnosis.”

New recommendations from the European League Against Rheumatism call for early diagnostic imaging in all cases of suspected GCA, she added, noting that, for cranial-GCA symptoms, temporal artery ultrasound is recommended first line, but for those who present without cranial symptoms, no particular imaging modality is recommended because of a lack of comparative and diagnostic accuracy data in LV-GCA.

Biopsy has traditionally been used in these cases, but now imaging can be substituted – and vascular ultrasound is an attractive first-line option given its affordability and availability.

Indeed, the current findings support its use in this setting, she said.

“We think that these results indicate that ultrasound should not only be the first-line imaging test in patients presenting with cranial symptoms, but also in patients suspected of GCA presenting with constitutional symptoms, and if this examination is included in the standard examinations in fast-track clinics, it may overcome the delay in diagnosis and the patients can be treated earlier. It may also spare the unneeded examinations performed in these patients,” she concluded.

Dr. Nielsen disclosed a relationship with Roche.

[email protected]

SOURCE: Nielsen B et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 2905.

BERLIN—Gray matter–white matter (GM/WM) contrast ratio on T1 magnetization prepared rapid gradient echo (MPRAGE) is sensitive to multiple sclerosis (MS), but not to migraine pathology, according to research presented at ECTRIMS 2018. The diagnostic and prognostic value of this MRI marker could be subjects for future investigations, said the study authors.

Researchers have suggested that MRI brain T1 GM/WM contrast may be a marker of neurodegeneration in Alzheimer’s disease. Whether this contrast has diagnostic value in MS remains unknown, however. Tina Mitrovic, a research assistant at the University of Basel in Switzerland, and colleagues conducted a study to compare the T1 GM/WM contrast in patients with MS, migraineurs, and healthy controls. They also investigated whether the contrast was associated with disability outcomes in MS.

BERLIN—Gray matter–white matter (GM/WM) contrast ratio on T1 magnetization prepared rapid gradient echo (MPRAGE) is sensitive to multiple sclerosis (MS), but not to migraine pathology, according to research presented at ECTRIMS 2018. The diagnostic and prognostic value of this MRI marker could be subjects for future investigations, said the study authors.

Researchers have suggested that MRI brain T1 GM/WM contrast may be a marker of neurodegeneration in Alzheimer’s disease. Whether this contrast has diagnostic value in MS remains unknown, however. Tina Mitrovic, a research assistant at the University of Basel in Switzerland, and colleagues conducted a study to compare the T1 GM/WM contrast in patients with MS, migraineurs, and healthy controls. They also investigated whether the contrast was associated with disability outcomes in MS.

BERLIN—Gray matter–white matter (GM/WM) contrast ratio on T1 magnetization prepared rapid gradient echo (MPRAGE) is sensitive to multiple sclerosis (MS), but not to migraine pathology, according to research presented at ECTRIMS 2018. The diagnostic and prognostic value of this MRI marker could be subjects for future investigations, said the study authors.

Researchers have suggested that MRI brain T1 GM/WM contrast may be a marker of neurodegeneration in Alzheimer’s disease. Whether this contrast has diagnostic value in MS remains unknown, however. Tina Mitrovic, a research assistant at the University of Basel in Switzerland, and colleagues conducted a study to compare the T1 GM/WM contrast in patients with MS, migraineurs, and healthy controls. They also investigated whether the contrast was associated with disability outcomes in MS.

High expression of karyopherin alpha 2 (KPNA2), a carrier protein that helps shuttle cancer-associated proteins from the nucleus to the cytoplasm, is an adverse prognostic factor in patients with clear cell or papillary renal cell carcinoma (RCC), according to a retrospective cohort study.

Senior author Glen Kristiansen, MD, director of the Institute of Pathology at the University Hospital Bonn (Germany), and his colleagues assessed tumor levels of KPNA2 protein by immunohistochemistry in 240 clinic patients with RCC (217 with clear cell histology, 23 with papillary histology). They also assessed tumor levels of KPNA2 mRNA in 771 patients with RCC (481 with clear cell histology, 290 with papillary cell histology) using publicly available gene expression data from the Cancer Genome Atlas (CGA).

Overall, 19% of the clinic patients’ tumors showed high expression of KPNA2 protein, according to results reported in Clinical Genitourinary Cancer. In addition, 26% of the CGA patients’ tumors showed high expression of KPNA2 mRNA.

Among patients with clear cell RCC, those with high tumor levels of KPNA2 protein survived roughly half as long as counterparts with low levels or none (74 months vs. 171 months); the difference was significant in univariate analysis (P = .012) but not in multivariate analysis that included well-known prognostic factors (HR, 1.491; P = .237). On the other hand, those with high tumor levels of KPNA2 mRNA had an elevated risk of death in both univariate analysis (HR, 2.31; P less than .001) and multivariate analysis (HR, 1.45; P = .035).

Among patients with papillary RCC, tumor levels of KPNA2 protein were not significantly associated with survival. However, those with high tumor levels of KPNA2 mRNA had a sharply elevated risk of death in both univariate analysis (HR, 9.7; P less than .001) and multivariate analysis (HR, 6.2; P = .004).

KPNA2 expression “represents a novel prognostic factor in these subtypes of RCC,” concluded Dr. Kristiansen and his coinvestigators. Therefore, this biomarker “could be used to stratify risk groups within RCC.” Collectively, the study’s findings suggest that KPNA2 is involved in both the pathogenesis and the progression of RCC. Given evidence that it helps transport p53 and fibroblast growth factor 2 at least in tumors with clear cell histology, “investigation of the nucleocytoplasmic transport through KPNA2 in [clear cell] RCC is an important task for future studies to better understand the link between elevated KPNA2 expression and altered biological processes like proliferation, cell growth, migration, invasion and tumor formation in RCC. In addition, examination of other members of [the] karyopherin-alpha family could elucidate the role of the nucleocytoplasmic transport system in pathogenesis of RCC.”

The authors reported that they had no conflict of interests.

SOURCE: Kristiansen G et al. Clin Genitourin Cancer. 2018 Oct 22. doi: 10.1016/j.clgc.2018.10.008.

High expression of karyopherin alpha 2 (KPNA2), a carrier protein that helps shuttle cancer-associated proteins from the nucleus to the cytoplasm, is an adverse prognostic factor in patients with clear cell or papillary renal cell carcinoma (RCC), according to a retrospective cohort study.

Senior author Glen Kristiansen, MD, director of the Institute of Pathology at the University Hospital Bonn (Germany), and his colleagues assessed tumor levels of KPNA2 protein by immunohistochemistry in 240 clinic patients with RCC (217 with clear cell histology, 23 with papillary histology). They also assessed tumor levels of KPNA2 mRNA in 771 patients with RCC (481 with clear cell histology, 290 with papillary cell histology) using publicly available gene expression data from the Cancer Genome Atlas (CGA).

Overall, 19% of the clinic patients’ tumors showed high expression of KPNA2 protein, according to results reported in Clinical Genitourinary Cancer. In addition, 26% of the CGA patients’ tumors showed high expression of KPNA2 mRNA.

Among patients with clear cell RCC, those with high tumor levels of KPNA2 protein survived roughly half as long as counterparts with low levels or none (74 months vs. 171 months); the difference was significant in univariate analysis (P = .012) but not in multivariate analysis that included well-known prognostic factors (HR, 1.491; P = .237). On the other hand, those with high tumor levels of KPNA2 mRNA had an elevated risk of death in both univariate analysis (HR, 2.31; P less than .001) and multivariate analysis (HR, 1.45; P = .035).

Among patients with papillary RCC, tumor levels of KPNA2 protein were not significantly associated with survival. However, those with high tumor levels of KPNA2 mRNA had a sharply elevated risk of death in both univariate analysis (HR, 9.7; P less than .001) and multivariate analysis (HR, 6.2; P = .004).

KPNA2 expression “represents a novel prognostic factor in these subtypes of RCC,” concluded Dr. Kristiansen and his coinvestigators. Therefore, this biomarker “could be used to stratify risk groups within RCC.” Collectively, the study’s findings suggest that KPNA2 is involved in both the pathogenesis and the progression of RCC. Given evidence that it helps transport p53 and fibroblast growth factor 2 at least in tumors with clear cell histology, “investigation of the nucleocytoplasmic transport through KPNA2 in [clear cell] RCC is an important task for future studies to better understand the link between elevated KPNA2 expression and altered biological processes like proliferation, cell growth, migration, invasion and tumor formation in RCC. In addition, examination of other members of [the] karyopherin-alpha family could elucidate the role of the nucleocytoplasmic transport system in pathogenesis of RCC.”

The authors reported that they had no conflict of interests.

SOURCE: Kristiansen G et al. Clin Genitourin Cancer. 2018 Oct 22. doi: 10.1016/j.clgc.2018.10.008.

High expression of karyopherin alpha 2 (KPNA2), a carrier protein that helps shuttle cancer-associated proteins from the nucleus to the cytoplasm, is an adverse prognostic factor in patients with clear cell or papillary renal cell carcinoma (RCC), according to a retrospective cohort study.

Senior author Glen Kristiansen, MD, director of the Institute of Pathology at the University Hospital Bonn (Germany), and his colleagues assessed tumor levels of KPNA2 protein by immunohistochemistry in 240 clinic patients with RCC (217 with clear cell histology, 23 with papillary histology). They also assessed tumor levels of KPNA2 mRNA in 771 patients with RCC (481 with clear cell histology, 290 with papillary cell histology) using publicly available gene expression data from the Cancer Genome Atlas (CGA).

Overall, 19% of the clinic patients’ tumors showed high expression of KPNA2 protein, according to results reported in Clinical Genitourinary Cancer. In addition, 26% of the CGA patients’ tumors showed high expression of KPNA2 mRNA.

Among patients with clear cell RCC, those with high tumor levels of KPNA2 protein survived roughly half as long as counterparts with low levels or none (74 months vs. 171 months); the difference was significant in univariate analysis (P = .012) but not in multivariate analysis that included well-known prognostic factors (HR, 1.491; P = .237). On the other hand, those with high tumor levels of KPNA2 mRNA had an elevated risk of death in both univariate analysis (HR, 2.31; P less than .001) and multivariate analysis (HR, 1.45; P = .035).

Among patients with papillary RCC, tumor levels of KPNA2 protein were not significantly associated with survival. However, those with high tumor levels of KPNA2 mRNA had a sharply elevated risk of death in both univariate analysis (HR, 9.7; P less than .001) and multivariate analysis (HR, 6.2; P = .004).

KPNA2 expression “represents a novel prognostic factor in these subtypes of RCC,” concluded Dr. Kristiansen and his coinvestigators. Therefore, this biomarker “could be used to stratify risk groups within RCC.” Collectively, the study’s findings suggest that KPNA2 is involved in both the pathogenesis and the progression of RCC. Given evidence that it helps transport p53 and fibroblast growth factor 2 at least in tumors with clear cell histology, “investigation of the nucleocytoplasmic transport through KPNA2 in [clear cell] RCC is an important task for future studies to better understand the link between elevated KPNA2 expression and altered biological processes like proliferation, cell growth, migration, invasion and tumor formation in RCC. In addition, examination of other members of [the] karyopherin-alpha family could elucidate the role of the nucleocytoplasmic transport system in pathogenesis of RCC.”

The authors reported that they had no conflict of interests.

SOURCE: Kristiansen G et al. Clin Genitourin Cancer. 2018 Oct 22. doi: 10.1016/j.clgc.2018.10.008.

ATLANTA—Individuals with higher levels of systemic inflammation during midlife experience greater rates of cognitive decline over the subsequent 20-year period, according to results from a long-term analysis presented at the 143rd Annual Meeting of the American Neurological Association.

“There is considerable evidence suggesting that abnormal immune functioning and inflammation may influence cognitive functioning and promote dementia,” said lead study author Keenan Walker, PhD, a clinical neuropsychology postdoctoral fellow at the Johns Hopkins University School of Medicine in Baltimore. “For example, several studies have found higher levels of inflammatory markers in the blood and CSF of patients with dementia, compared to nondemented individuals of a comparable age. What is less clear, however, is whether inflammation actually promotes cognitive decline or occurs simply as a result of the brain changes underlying dementia.”

To help answer this question, Dr. Walker and his colleagues evaluated blood biomarkers of inflammation in 12,727 middle-aged participants during visits one and two of the Atherosclerosis Risk in Communities (ARIC) study, a prospective epidemiologic analysis conducted in four US communities and funded by the National Heart, Lung, and Blood Institute. Visit 1 occurred between 1987 and 1989, and Visit 2 took place between 1990 and 1992. The researchers related these markers to cognitive change over the subsequent decades. Specifically, they used four biomarkers (ie, fibrinogen, white blood cell count, von Willebrand factor, and Factor VIII) to create an inflammation composite score at Visit 1 and measured C-reactive protein (CRP) at Visit 2. Next, they used measures of memory, executive function, and language to assess cognition over three visits spanning 20 years.

The average age of study participants at the first cognitive assessment was 57, 56% were women, and 21% were black. After controlling for differences in demographic variables, vascular risk factors, and comorbidities, the researchers observed that each standard deviation (SD) increase in the midlife inflammation composite score was associated with an additional 20-year global cognitive decline of –0.035 SD. They found a similar association between each SD higher midlife CRP level and additional 20-year decline in global cognition (–0.038 SD). In addition, study participants with a midlife inflammation composite score in the top quartile had a 7.6% steeper decline in global cognition, compared with participants in the lowest quartile. A similar association was observed for CRP.

“We were surprised at what we found when we looked at inflammation’s effect on individual cognitive domains,” said Dr. Walker. “Specifically, we found that inflammation was associated with declines in memory, but not declines in other domains, such as executive function or language. One possible interpretation for these findings is that inflammation may selectively influence brain regions such as the hippocampus that are necessary for memory consolidation and are also most vulnerable to Alzheimer’s disease.” He added that the current findings “provide support for the idea that systemic inflammation may have an early pathogenic role in the cognitive decline that occurs in the decades leading up to older adulthood.”

Dr. Walker acknowledged certain limitations of the study, including the attrition of participants because of deaths and dropouts over the 20-year follow-up period. “Because high levels of inflammation and comorbid disease are related to death and risk of study dropout, the sample of participants who completed the entirety of the study may represent a group that is healthier overall than the general population,” he said. “However, we took several steps to reduce any potential attrition bias using advanced statistical techniques.”

—Doug Brunk

ATLANTA—Individuals with higher levels of systemic inflammation during midlife experience greater rates of cognitive decline over the subsequent 20-year period, according to results from a long-term analysis presented at the 143rd Annual Meeting of the American Neurological Association.

“There is considerable evidence suggesting that abnormal immune functioning and inflammation may influence cognitive functioning and promote dementia,” said lead study author Keenan Walker, PhD, a clinical neuropsychology postdoctoral fellow at the Johns Hopkins University School of Medicine in Baltimore. “For example, several studies have found higher levels of inflammatory markers in the blood and CSF of patients with dementia, compared to nondemented individuals of a comparable age. What is less clear, however, is whether inflammation actually promotes cognitive decline or occurs simply as a result of the brain changes underlying dementia.”

To help answer this question, Dr. Walker and his colleagues evaluated blood biomarkers of inflammation in 12,727 middle-aged participants during visits one and two of the Atherosclerosis Risk in Communities (ARIC) study, a prospective epidemiologic analysis conducted in four US communities and funded by the National Heart, Lung, and Blood Institute. Visit 1 occurred between 1987 and 1989, and Visit 2 took place between 1990 and 1992. The researchers related these markers to cognitive change over the subsequent decades. Specifically, they used four biomarkers (ie, fibrinogen, white blood cell count, von Willebrand factor, and Factor VIII) to create an inflammation composite score at Visit 1 and measured C-reactive protein (CRP) at Visit 2. Next, they used measures of memory, executive function, and language to assess cognition over three visits spanning 20 years.

The average age of study participants at the first cognitive assessment was 57, 56% were women, and 21% were black. After controlling for differences in demographic variables, vascular risk factors, and comorbidities, the researchers observed that each standard deviation (SD) increase in the midlife inflammation composite score was associated with an additional 20-year global cognitive decline of –0.035 SD. They found a similar association between each SD higher midlife CRP level and additional 20-year decline in global cognition (–0.038 SD). In addition, study participants with a midlife inflammation composite score in the top quartile had a 7.6% steeper decline in global cognition, compared with participants in the lowest quartile. A similar association was observed for CRP.

“We were surprised at what we found when we looked at inflammation’s effect on individual cognitive domains,” said Dr. Walker. “Specifically, we found that inflammation was associated with declines in memory, but not declines in other domains, such as executive function or language. One possible interpretation for these findings is that inflammation may selectively influence brain regions such as the hippocampus that are necessary for memory consolidation and are also most vulnerable to Alzheimer’s disease.” He added that the current findings “provide support for the idea that systemic inflammation may have an early pathogenic role in the cognitive decline that occurs in the decades leading up to older adulthood.”

Dr. Walker acknowledged certain limitations of the study, including the attrition of participants because of deaths and dropouts over the 20-year follow-up period. “Because high levels of inflammation and comorbid disease are related to death and risk of study dropout, the sample of participants who completed the entirety of the study may represent a group that is healthier overall than the general population,” he said. “However, we took several steps to reduce any potential attrition bias using advanced statistical techniques.”

—Doug Brunk

ATLANTA—Individuals with higher levels of systemic inflammation during midlife experience greater rates of cognitive decline over the subsequent 20-year period, according to results from a long-term analysis presented at the 143rd Annual Meeting of the American Neurological Association.

“There is considerable evidence suggesting that abnormal immune functioning and inflammation may influence cognitive functioning and promote dementia,” said lead study author Keenan Walker, PhD, a clinical neuropsychology postdoctoral fellow at the Johns Hopkins University School of Medicine in Baltimore. “For example, several studies have found higher levels of inflammatory markers in the blood and CSF of patients with dementia, compared to nondemented individuals of a comparable age. What is less clear, however, is whether inflammation actually promotes cognitive decline or occurs simply as a result of the brain changes underlying dementia.”

To help answer this question, Dr. Walker and his colleagues evaluated blood biomarkers of inflammation in 12,727 middle-aged participants during visits one and two of the Atherosclerosis Risk in Communities (ARIC) study, a prospective epidemiologic analysis conducted in four US communities and funded by the National Heart, Lung, and Blood Institute. Visit 1 occurred between 1987 and 1989, and Visit 2 took place between 1990 and 1992. The researchers related these markers to cognitive change over the subsequent decades. Specifically, they used four biomarkers (ie, fibrinogen, white blood cell count, von Willebrand factor, and Factor VIII) to create an inflammation composite score at Visit 1 and measured C-reactive protein (CRP) at Visit 2. Next, they used measures of memory, executive function, and language to assess cognition over three visits spanning 20 years.

The average age of study participants at the first cognitive assessment was 57, 56% were women, and 21% were black. After controlling for differences in demographic variables, vascular risk factors, and comorbidities, the researchers observed that each standard deviation (SD) increase in the midlife inflammation composite score was associated with an additional 20-year global cognitive decline of –0.035 SD. They found a similar association between each SD higher midlife CRP level and additional 20-year decline in global cognition (–0.038 SD). In addition, study participants with a midlife inflammation composite score in the top quartile had a 7.6% steeper decline in global cognition, compared with participants in the lowest quartile. A similar association was observed for CRP.

“We were surprised at what we found when we looked at inflammation’s effect on individual cognitive domains,” said Dr. Walker. “Specifically, we found that inflammation was associated with declines in memory, but not declines in other domains, such as executive function or language. One possible interpretation for these findings is that inflammation may selectively influence brain regions such as the hippocampus that are necessary for memory consolidation and are also most vulnerable to Alzheimer’s disease.” He added that the current findings “provide support for the idea that systemic inflammation may have an early pathogenic role in the cognitive decline that occurs in the decades leading up to older adulthood.”

Dr. Walker acknowledged certain limitations of the study, including the attrition of participants because of deaths and dropouts over the 20-year follow-up period. “Because high levels of inflammation and comorbid disease are related to death and risk of study dropout, the sample of participants who completed the entirety of the study may represent a group that is healthier overall than the general population,” he said. “However, we took several steps to reduce any potential attrition bias using advanced statistical techniques.”

—Doug Brunk

Myth: Pick Psoriasis Scales to Remove Them

Patients may be inclined to pick psoriasis scales that appear in noticeable areas or on the scalp. However, they should be counseled to avoid this practice, which could cause an infection. Instead, Dr. Steven Feldman (Winston-Salem, North Carolina) suggests putting on an ointment or oil-like medication to soften the scale. “Almost any kind of moisturizer will change the reflective properties of the scale so that you don’t see the scale,” he advised. He also suggested descaling agents such as topical salicylic acid or lactic acid. His patient education video is available on the American Academy of Dermatology website should you wish to direct your patients to it.

Because salicylic acid is a keratolytic (or peeling agent), it works by causing the outer layer of skin to shed. When applied topically, it helps to soften and lift psoriasis scales. Coal tar over-the-counter products also can be used for the same purpose. The over-the-counter product guide from the National Psoriasis Foundation is a valuable resource to share with patients.

Expert Commentary

I agree that it is very important to treat scale very gently. In addition to risk for infection, picking and traumatizing scale can lead to worsening of the psoriasis. This is known as the Koebner phenomenon. The phenomenon was first described by Heinrich Koebner in 1876 as the formation of psoriatic lesions in uninvolved skin of patients with psoriasis after cutaneous trauma. This isomorphic phenomenon is now known to involve numerous diseases, among them vitiligo, lichen planus, and Darier disease.

—Jeffrey M. Weinberg, MD (New York, New York)

Myth: Pick Psoriasis Scales to Remove Them

Patients may be inclined to pick psoriasis scales that appear in noticeable areas or on the scalp. However, they should be counseled to avoid this practice, which could cause an infection. Instead, Dr. Steven Feldman (Winston-Salem, North Carolina) suggests putting on an ointment or oil-like medication to soften the scale. “Almost any kind of moisturizer will change the reflective properties of the scale so that you don’t see the scale,” he advised. He also suggested descaling agents such as topical salicylic acid or lactic acid. His patient education video is available on the American Academy of Dermatology website should you wish to direct your patients to it.

Because salicylic acid is a keratolytic (or peeling agent), it works by causing the outer layer of skin to shed. When applied topically, it helps to soften and lift psoriasis scales. Coal tar over-the-counter products also can be used for the same purpose. The over-the-counter product guide from the National Psoriasis Foundation is a valuable resource to share with patients.

Expert Commentary

I agree that it is very important to treat scale very gently. In addition to risk for infection, picking and traumatizing scale can lead to worsening of the psoriasis. This is known as the Koebner phenomenon. The phenomenon was first described by Heinrich Koebner in 1876 as the formation of psoriatic lesions in uninvolved skin of patients with psoriasis after cutaneous trauma. This isomorphic phenomenon is now known to involve numerous diseases, among them vitiligo, lichen planus, and Darier disease.

—Jeffrey M. Weinberg, MD (New York, New York)

Myth: Pick Psoriasis Scales to Remove Them

Patients may be inclined to pick psoriasis scales that appear in noticeable areas or on the scalp. However, they should be counseled to avoid this practice, which could cause an infection. Instead, Dr. Steven Feldman (Winston-Salem, North Carolina) suggests putting on an ointment or oil-like medication to soften the scale. “Almost any kind of moisturizer will change the reflective properties of the scale so that you don’t see the scale,” he advised. He also suggested descaling agents such as topical salicylic acid or lactic acid. His patient education video is available on the American Academy of Dermatology website should you wish to direct your patients to it.

Because salicylic acid is a keratolytic (or peeling agent), it works by causing the outer layer of skin to shed. When applied topically, it helps to soften and lift psoriasis scales. Coal tar over-the-counter products also can be used for the same purpose. The over-the-counter product guide from the National Psoriasis Foundation is a valuable resource to share with patients.

Expert Commentary

I agree that it is very important to treat scale very gently. In addition to risk for infection, picking and traumatizing scale can lead to worsening of the psoriasis. This is known as the Koebner phenomenon. The phenomenon was first described by Heinrich Koebner in 1876 as the formation of psoriatic lesions in uninvolved skin of patients with psoriasis after cutaneous trauma. This isomorphic phenomenon is now known to involve numerous diseases, among them vitiligo, lichen planus, and Darier disease.

—Jeffrey M. Weinberg, MD (New York, New York)

Immediate treatment of a first unprovoked seizure may be preferable to delayed treatment over a wide range of patients, including those who are at low risk of recurrent seizures, results of a decision analysis suggest.

Taking into account quality of life, seizure risk, and antiepileptic drug (AED) side effects, a model favored treatment of a patient with a single unprovoked seizure who did not meet the International League Against Epilepsy (ILAE) definition of epilepsy, investigators reported.

The model also favored treatment of patients who did meet ILAE criteria, namely, a 10-year recurrence risk greater than 60% in a patient with a single unprovoked seizure, according to the analysis, which was published in the October 9 issue of Neurology.

Together, these findings suggest that the current ILAE epilepsy definition is “too simplistic” for deciding whether to start or withhold AED treatment after a first unprovoked seizure, said M. Brandon Westover, MD, PhD, Associate Professor of Neurology at Massachusetts General Hospital in Boston, and his coauthors.

“A more precise and patient-personalized definition of epilepsy should encompass not only seizure recurrence probability but also a multitude of other risks and benefits associated with AED treatment,” they said.

Weighing Risks and Benefits

To determine which patients with a first unprovoked seizure might benefit from immediate AED treatment, Dr. Westover and his colleagues used a decision model with measures constructed from retrospective clinical trial data.

The goal of the simulation was to determine which treatment strategy—immediate or delayed AED treatment—would maximize the patient’s expected quality-adjusted life years (QALYs). Toward that end, Dr. Westover and his coinvestigators considered three base cases, which represented various degrees of seizure-recurrence risk.

The first case was a 30-year-old man with no risk factors for recurrent seizure other than having had a first seizure. In that case, immediate and deferred AED treatment resulted in 19.04 and 18.65 QALYs, respectively.

“In dollar values, using the conservative approximation of $50,000/QALY gained, this difference in treatment outcomes would amount to $19,500 gained per individual,” Dr. Westover and his coauthors wrote in their report.

The second case was a 30-year-old woman who presented with a first unprovoked seizure and had positive MRI results that establish a high risk of recurrence. As expected, because of the high recurrence risk, this scenario also favored immediate treatment, with 15.23 and 14.75 QALYs, respectively, for the immediate and deferred strategies.

The final case was a wheelchair-bound 60-year-old woman with a first unprovoked seizure and high risk of recurrence, but also a high risk of AED adverse effects and a smaller expected quality of life reduction from further seizures. In this scenario, in which treatment might be “intuitively discouraged” because of the AED side-effect risk, the cohort simulation favored deferred AED treatment by a small margin, the investigators said.

“A high baseline risk for recurrent seizures does not by itself always favor immediate AED treatment,” they said.

Findings May Shift Discussions About Therapy

The conclusion of this decision analysis by Dr. Westover and colleagues is “likely correct” that early treatment of a first unprovoked seizure could be favorable in a wide range of clinical scenarios, according to the authors of an accompanying editorial.

The decision analysis is based on a reasonable, though not comprehensive, set of parameters to simulate base cases representative of common first-ever seizure clinical scenarios, said editorialists Claire S. Jacobs, MD, PhD, and Jong Woo Lee, MD, PhD, both with the Department of Neurology at Brigham and Women’s Hospital in Boston.

Potentially the most controversial scenario addressed in the decision model, they noted, is the patient with low seizure recurrence risk but substantial quality of life decline upon recurrence. While that patient would not meet the commonly accepted 60% recurrence risk threshold that would indicate that treatment is warranted, this model favors immediate treatment because of the potentially disruptive effect of recurrence.

This study does not address important issues such as the cost of medication and patient preferences, they pointed out, and furthermore, QALYs can be difficult to integrate into clinical decision making.

Nonetheless, the findings are worth considering in clinical practice, the authors suggested. “At the very least, this study should, however subtly, shift the starting point of discussion with the patient toward a default of immediate, rather than deferred, treatment after a first unprovoked seizure and apparent absence of disease,” said Drs. Jacob and Lee.

The study was supported by NINDS.

—Andrew D. Bowser

Suggested Reading

Bao EL, Chao LY, Ni P, et al. Antiepileptic drug treatment after an unprovoked first seizure: a decision analysis. Neurology. 2018;91(15):e1429-e1439.

Jacobs CS, Lee JW. Immediate vs delayed treatment of first unprovoked seizure: to treat, or not to treat? Neurology. 2018;91(15):684-685.

Immediate treatment of a first unprovoked seizure may be preferable to delayed treatment over a wide range of patients, including those who are at low risk of recurrent seizures, results of a decision analysis suggest.

Taking into account quality of life, seizure risk, and antiepileptic drug (AED) side effects, a model favored treatment of a patient with a single unprovoked seizure who did not meet the International League Against Epilepsy (ILAE) definition of epilepsy, investigators reported.

The model also favored treatment of patients who did meet ILAE criteria, namely, a 10-year recurrence risk greater than 60% in a patient with a single unprovoked seizure, according to the analysis, which was published in the October 9 issue of Neurology.

Together, these findings suggest that the current ILAE epilepsy definition is “too simplistic” for deciding whether to start or withhold AED treatment after a first unprovoked seizure, said M. Brandon Westover, MD, PhD, Associate Professor of Neurology at Massachusetts General Hospital in Boston, and his coauthors.

“A more precise and patient-personalized definition of epilepsy should encompass not only seizure recurrence probability but also a multitude of other risks and benefits associated with AED treatment,” they said.

Weighing Risks and Benefits

To determine which patients with a first unprovoked seizure might benefit from immediate AED treatment, Dr. Westover and his colleagues used a decision model with measures constructed from retrospective clinical trial data.

The goal of the simulation was to determine which treatment strategy—immediate or delayed AED treatment—would maximize the patient’s expected quality-adjusted life years (QALYs). Toward that end, Dr. Westover and his coinvestigators considered three base cases, which represented various degrees of seizure-recurrence risk.

The first case was a 30-year-old man with no risk factors for recurrent seizure other than having had a first seizure. In that case, immediate and deferred AED treatment resulted in 19.04 and 18.65 QALYs, respectively.

“In dollar values, using the conservative approximation of $50,000/QALY gained, this difference in treatment outcomes would amount to $19,500 gained per individual,” Dr. Westover and his coauthors wrote in their report.

The second case was a 30-year-old woman who presented with a first unprovoked seizure and had positive MRI results that establish a high risk of recurrence. As expected, because of the high recurrence risk, this scenario also favored immediate treatment, with 15.23 and 14.75 QALYs, respectively, for the immediate and deferred strategies.

The final case was a wheelchair-bound 60-year-old woman with a first unprovoked seizure and high risk of recurrence, but also a high risk of AED adverse effects and a smaller expected quality of life reduction from further seizures. In this scenario, in which treatment might be “intuitively discouraged” because of the AED side-effect risk, the cohort simulation favored deferred AED treatment by a small margin, the investigators said.

“A high baseline risk for recurrent seizures does not by itself always favor immediate AED treatment,” they said.

Findings May Shift Discussions About Therapy

The conclusion of this decision analysis by Dr. Westover and colleagues is “likely correct” that early treatment of a first unprovoked seizure could be favorable in a wide range of clinical scenarios, according to the authors of an accompanying editorial.

The decision analysis is based on a reasonable, though not comprehensive, set of parameters to simulate base cases representative of common first-ever seizure clinical scenarios, said editorialists Claire S. Jacobs, MD, PhD, and Jong Woo Lee, MD, PhD, both with the Department of Neurology at Brigham and Women’s Hospital in Boston.

Potentially the most controversial scenario addressed in the decision model, they noted, is the patient with low seizure recurrence risk but substantial quality of life decline upon recurrence. While that patient would not meet the commonly accepted 60% recurrence risk threshold that would indicate that treatment is warranted, this model favors immediate treatment because of the potentially disruptive effect of recurrence.

This study does not address important issues such as the cost of medication and patient preferences, they pointed out, and furthermore, QALYs can be difficult to integrate into clinical decision making.

Nonetheless, the findings are worth considering in clinical practice, the authors suggested. “At the very least, this study should, however subtly, shift the starting point of discussion with the patient toward a default of immediate, rather than deferred, treatment after a first unprovoked seizure and apparent absence of disease,” said Drs. Jacob and Lee.

The study was supported by NINDS.

—Andrew D. Bowser

Suggested Reading

Bao EL, Chao LY, Ni P, et al. Antiepileptic drug treatment after an unprovoked first seizure: a decision analysis. Neurology. 2018;91(15):e1429-e1439.

Jacobs CS, Lee JW. Immediate vs delayed treatment of first unprovoked seizure: to treat, or not to treat? Neurology. 2018;91(15):684-685.

Immediate treatment of a first unprovoked seizure may be preferable to delayed treatment over a wide range of patients, including those who are at low risk of recurrent seizures, results of a decision analysis suggest.

Taking into account quality of life, seizure risk, and antiepileptic drug (AED) side effects, a model favored treatment of a patient with a single unprovoked seizure who did not meet the International League Against Epilepsy (ILAE) definition of epilepsy, investigators reported.

The model also favored treatment of patients who did meet ILAE criteria, namely, a 10-year recurrence risk greater than 60% in a patient with a single unprovoked seizure, according to the analysis, which was published in the October 9 issue of Neurology.

Together, these findings suggest that the current ILAE epilepsy definition is “too simplistic” for deciding whether to start or withhold AED treatment after a first unprovoked seizure, said M. Brandon Westover, MD, PhD, Associate Professor of Neurology at Massachusetts General Hospital in Boston, and his coauthors.

“A more precise and patient-personalized definition of epilepsy should encompass not only seizure recurrence probability but also a multitude of other risks and benefits associated with AED treatment,” they said.

Weighing Risks and Benefits

To determine which patients with a first unprovoked seizure might benefit from immediate AED treatment, Dr. Westover and his colleagues used a decision model with measures constructed from retrospective clinical trial data.

The goal of the simulation was to determine which treatment strategy—immediate or delayed AED treatment—would maximize the patient’s expected quality-adjusted life years (QALYs). Toward that end, Dr. Westover and his coinvestigators considered three base cases, which represented various degrees of seizure-recurrence risk.

The first case was a 30-year-old man with no risk factors for recurrent seizure other than having had a first seizure. In that case, immediate and deferred AED treatment resulted in 19.04 and 18.65 QALYs, respectively.

“In dollar values, using the conservative approximation of $50,000/QALY gained, this difference in treatment outcomes would amount to $19,500 gained per individual,” Dr. Westover and his coauthors wrote in their report.

The second case was a 30-year-old woman who presented with a first unprovoked seizure and had positive MRI results that establish a high risk of recurrence. As expected, because of the high recurrence risk, this scenario also favored immediate treatment, with 15.23 and 14.75 QALYs, respectively, for the immediate and deferred strategies.

The final case was a wheelchair-bound 60-year-old woman with a first unprovoked seizure and high risk of recurrence, but also a high risk of AED adverse effects and a smaller expected quality of life reduction from further seizures. In this scenario, in which treatment might be “intuitively discouraged” because of the AED side-effect risk, the cohort simulation favored deferred AED treatment by a small margin, the investigators said.

“A high baseline risk for recurrent seizures does not by itself always favor immediate AED treatment,” they said.

Findings May Shift Discussions About Therapy

The conclusion of this decision analysis by Dr. Westover and colleagues is “likely correct” that early treatment of a first unprovoked seizure could be favorable in a wide range of clinical scenarios, according to the authors of an accompanying editorial.

The decision analysis is based on a reasonable, though not comprehensive, set of parameters to simulate base cases representative of common first-ever seizure clinical scenarios, said editorialists Claire S. Jacobs, MD, PhD, and Jong Woo Lee, MD, PhD, both with the Department of Neurology at Brigham and Women’s Hospital in Boston.

Potentially the most controversial scenario addressed in the decision model, they noted, is the patient with low seizure recurrence risk but substantial quality of life decline upon recurrence. While that patient would not meet the commonly accepted 60% recurrence risk threshold that would indicate that treatment is warranted, this model favors immediate treatment because of the potentially disruptive effect of recurrence.

This study does not address important issues such as the cost of medication and patient preferences, they pointed out, and furthermore, QALYs can be difficult to integrate into clinical decision making.

Nonetheless, the findings are worth considering in clinical practice, the authors suggested. “At the very least, this study should, however subtly, shift the starting point of discussion with the patient toward a default of immediate, rather than deferred, treatment after a first unprovoked seizure and apparent absence of disease,” said Drs. Jacob and Lee.

The study was supported by NINDS.

—Andrew D. Bowser

Suggested Reading

Bao EL, Chao LY, Ni P, et al. Antiepileptic drug treatment after an unprovoked first seizure: a decision analysis. Neurology. 2018;91(15):e1429-e1439.

Jacobs CS, Lee JW. Immediate vs delayed treatment of first unprovoked seizure: to treat, or not to treat? Neurology. 2018;91(15):684-685.