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Experts: Kavanaugh may have lasting impact on health care
As the Supreme Court sits for its second session on Oct. 29, legal analysts question what impact its newest Associate Justice, Brett M. Kavanaugh, may have on health care cases that might come before the court.
The addition of Justice Kavanaugh cements a conservative majority on the high court, said Eric J. Segall, a constitutional law professor at Georgia State University in Atlanta.
“Where Justice Kennedy was moderate or liberal, Justice Kavanaugh will move the court dramatically to the right in most areas of law,” Mr. Segall said in an interview.
One area drawing considerable attention is abortion, with abortion rights advocates raising concerns that Justice Kavanaugh’s appointment may mean the reversal of Roe v. Wade. Legal analysts, however, say fall of the momentous ruling is not probable.
Based on his decisions written while he sat on the Court of Appeals for the District of Columbia Circuit, it’s more likely that Justice Kavanaugh would attempt to narrow the instances in which state abortion restrictions are considered to impede a woman’s constitutional right to an abortion, according to Timothy S. Jost, a legal analyst and retired health law professor at Washington and Lee University in Lexington, Va.
In Garza v. Hargan for example, then-Judge Kavanaugh dissented from a majority decision which ultimately allowed a teenage immigrant in U.S. custody to have an abortion. Judge Kavanaugh argued that it was wrong for unlawful immigrant minors in U.S. detention to obtain “immediate abortion on demand.” However, his dissent was not as far-reaching as that of another judge who argued that a minor undocumented immigrant had no constitutional right to an abortion.
“[Justice] Kavanaugh certainly could vote to overturn Roe v. Wade, but based on his past opinions, I think it much more likely that he would simply expand Roe’s undue burden exception on a case by case basis until it was meaningless,” Mr. Jost said in an interview. “He doesn’t have to overturn Roe v. Wade to allow states that want to effectively bar abortion [to succeed].”
Mr. Segall agrees that Justice Kavanaugh will likely water down the undue burden test for abortion and through this softening, essentially dismantle Roe and return the issue of abortion to states.
As for the fate of the Affordable Care Act, legal experts foresee a restrained stance by Justice Kavanaugh, rather than a strong rejection of the entire law. In 2011, Judge Kavanaugh wrote a dissenting opinion in Seven-Sky v. Holder, a case that challenged the constitutionality of the health law’s individual mandate. While his fellow judges ruled that Congress had the authority to enact the mandate, Judge Kavanaugh argued the mandate was a tax and thus, it was too early for the court to hear the case since the tax had not yet been levied.
The dissent by Judge Kavanaugh in this case amounted to a “procedural cop-out,” according to Thomas P. Miller, a resident fellow at the conservative American Enterprise Institute and a health care policy scholar.
“That tells you he is a relatively cautious judge as opposed to going right to the metal because other circuit court of appeals judges were able to say this is an unconstitutional mandate,” Mr. Miller said in an interview. “That suggests a degree of tactical caution on these issues, very similar to [Supreme Court Chief Justice John] Roberts.”
Justice Kavanaugh may get his first chance to rule on the ACA’s future through Texas v. United States. The case centers on a challenge by 20 Republican state attorneys general over the constitutionality of the health law’s individual mandate. The Trump administration has reduced the penalty for failing to have health insurance to $0 starting in 2019. The plaintiffs allege that the mandate cannot be severed from the rest of the ACA and that if the mandate is eliminated, the rest of the law should fall. Because the Trump administration has opted not to protect the ACA, Democratic state attorneys general in 16 states have intervened to defend the health law. Arguments were heard before the federal district court in the Northern District of Texas in September and a decision is expected any day.
If appealed, the Fifth Circuit would next take on the case, but the challenge could eventually reach the Supreme Court, Mr. Jost said.
“Chief Justice Roberts could save [the ACA] one more time, but I could see [Justice] Kavanaugh voting to uphold the ACA as the question would likely be a question of severability of the individual mandate from the rest of the ACA, and I can see [Kavanaugh] holding it severable,” he said.
Justice Kavanaugh may also weigh in on a handful of Medicaid cases that could go before the Supreme Court. The first case involves how much deference the federal government should have in allowing states to impose work requirements on Medicaid patients. In June, a federal judge in Washington D.C. struck down the federal government’s approval of a Kentucky Medicaid waiver that would have imposed work requirements and other rules for eligibility. That judge ruled that the Centers for Medicare & Medicaid Services did not adequately evaluate whether Kentucky’s requirements were consistent with federal Medicaid law.
Mr. Miller said it is too early to tell which way Justice Kavanaugh would vote on a Medicaid work requirements case, and that the decision depends on the context of the case and the reading of the law involved.
“[Justice] Kavanaugh has a less predictable record in this more narrow area of administrative law,” Mr. Miller said. “I doubt he alone is going to drive the court anywhere on this issue it doesn’t otherwise want to go – or at least drift.”
Two other Medicaid cases pending before the Supreme Court revolve around the right of a private Medicaid patient to sue a state over the exclusion of Planned Parenthood in its Medicaid program. Gee v. Planned Parenthood of Gulf Coast Inc. and its sister case, Anderson v. Planned Parenthood of Kansas and Mid-Missouri, stem from separate efforts by Kansas and Louisiana to remove Planned Parenthood from their Medicaid programs. The question is whether the Medicaid patients have a right to challenge the exclusions.
If the Supreme Court accepts the cases, Mr. Jost said it’s likely that Justice Kavanaugh would side with the states and bar the patients from suing.
“I could see him holding that Medicaid recipients can’t sue if a state violates federal law, which would effectively end Medicaid as an entitlement,” Mr. Jost said. “This would have disastrous consequences for low-income Americans.”
Justice Kavanaugh also could make an impact on gun control, Mr. Segall noted. The Supreme Court has not taken a Second Amendment case in several years; in the past, there was uncertainty about how Justice Kennedy would vote on a gun control case. Not so with Justice Kavanaugh, Mr. Segall said. In Heller v. District of Columbia (known as Heller II), Judge Kavanaugh dissented from the majority, writing that the District’s ban on semiautomatic rifles and its requirement that handguns be registered were unconstitutional.
“[The dissent] gave the Second Amendment as broad a reading as any judge has ever given,” Mr. Segall said. “Gun control, gun reform, and gun limits ... this is where [Kavanaugh] is going to make the biggest difference.”
As the Supreme Court sits for its second session on Oct. 29, legal analysts question what impact its newest Associate Justice, Brett M. Kavanaugh, may have on health care cases that might come before the court.
The addition of Justice Kavanaugh cements a conservative majority on the high court, said Eric J. Segall, a constitutional law professor at Georgia State University in Atlanta.
“Where Justice Kennedy was moderate or liberal, Justice Kavanaugh will move the court dramatically to the right in most areas of law,” Mr. Segall said in an interview.
One area drawing considerable attention is abortion, with abortion rights advocates raising concerns that Justice Kavanaugh’s appointment may mean the reversal of Roe v. Wade. Legal analysts, however, say fall of the momentous ruling is not probable.
Based on his decisions written while he sat on the Court of Appeals for the District of Columbia Circuit, it’s more likely that Justice Kavanaugh would attempt to narrow the instances in which state abortion restrictions are considered to impede a woman’s constitutional right to an abortion, according to Timothy S. Jost, a legal analyst and retired health law professor at Washington and Lee University in Lexington, Va.
In Garza v. Hargan for example, then-Judge Kavanaugh dissented from a majority decision which ultimately allowed a teenage immigrant in U.S. custody to have an abortion. Judge Kavanaugh argued that it was wrong for unlawful immigrant minors in U.S. detention to obtain “immediate abortion on demand.” However, his dissent was not as far-reaching as that of another judge who argued that a minor undocumented immigrant had no constitutional right to an abortion.
“[Justice] Kavanaugh certainly could vote to overturn Roe v. Wade, but based on his past opinions, I think it much more likely that he would simply expand Roe’s undue burden exception on a case by case basis until it was meaningless,” Mr. Jost said in an interview. “He doesn’t have to overturn Roe v. Wade to allow states that want to effectively bar abortion [to succeed].”
Mr. Segall agrees that Justice Kavanaugh will likely water down the undue burden test for abortion and through this softening, essentially dismantle Roe and return the issue of abortion to states.
As for the fate of the Affordable Care Act, legal experts foresee a restrained stance by Justice Kavanaugh, rather than a strong rejection of the entire law. In 2011, Judge Kavanaugh wrote a dissenting opinion in Seven-Sky v. Holder, a case that challenged the constitutionality of the health law’s individual mandate. While his fellow judges ruled that Congress had the authority to enact the mandate, Judge Kavanaugh argued the mandate was a tax and thus, it was too early for the court to hear the case since the tax had not yet been levied.
The dissent by Judge Kavanaugh in this case amounted to a “procedural cop-out,” according to Thomas P. Miller, a resident fellow at the conservative American Enterprise Institute and a health care policy scholar.
“That tells you he is a relatively cautious judge as opposed to going right to the metal because other circuit court of appeals judges were able to say this is an unconstitutional mandate,” Mr. Miller said in an interview. “That suggests a degree of tactical caution on these issues, very similar to [Supreme Court Chief Justice John] Roberts.”
Justice Kavanaugh may get his first chance to rule on the ACA’s future through Texas v. United States. The case centers on a challenge by 20 Republican state attorneys general over the constitutionality of the health law’s individual mandate. The Trump administration has reduced the penalty for failing to have health insurance to $0 starting in 2019. The plaintiffs allege that the mandate cannot be severed from the rest of the ACA and that if the mandate is eliminated, the rest of the law should fall. Because the Trump administration has opted not to protect the ACA, Democratic state attorneys general in 16 states have intervened to defend the health law. Arguments were heard before the federal district court in the Northern District of Texas in September and a decision is expected any day.
If appealed, the Fifth Circuit would next take on the case, but the challenge could eventually reach the Supreme Court, Mr. Jost said.
“Chief Justice Roberts could save [the ACA] one more time, but I could see [Justice] Kavanaugh voting to uphold the ACA as the question would likely be a question of severability of the individual mandate from the rest of the ACA, and I can see [Kavanaugh] holding it severable,” he said.
Justice Kavanaugh may also weigh in on a handful of Medicaid cases that could go before the Supreme Court. The first case involves how much deference the federal government should have in allowing states to impose work requirements on Medicaid patients. In June, a federal judge in Washington D.C. struck down the federal government’s approval of a Kentucky Medicaid waiver that would have imposed work requirements and other rules for eligibility. That judge ruled that the Centers for Medicare & Medicaid Services did not adequately evaluate whether Kentucky’s requirements were consistent with federal Medicaid law.
Mr. Miller said it is too early to tell which way Justice Kavanaugh would vote on a Medicaid work requirements case, and that the decision depends on the context of the case and the reading of the law involved.
“[Justice] Kavanaugh has a less predictable record in this more narrow area of administrative law,” Mr. Miller said. “I doubt he alone is going to drive the court anywhere on this issue it doesn’t otherwise want to go – or at least drift.”
Two other Medicaid cases pending before the Supreme Court revolve around the right of a private Medicaid patient to sue a state over the exclusion of Planned Parenthood in its Medicaid program. Gee v. Planned Parenthood of Gulf Coast Inc. and its sister case, Anderson v. Planned Parenthood of Kansas and Mid-Missouri, stem from separate efforts by Kansas and Louisiana to remove Planned Parenthood from their Medicaid programs. The question is whether the Medicaid patients have a right to challenge the exclusions.
If the Supreme Court accepts the cases, Mr. Jost said it’s likely that Justice Kavanaugh would side with the states and bar the patients from suing.
“I could see him holding that Medicaid recipients can’t sue if a state violates federal law, which would effectively end Medicaid as an entitlement,” Mr. Jost said. “This would have disastrous consequences for low-income Americans.”
Justice Kavanaugh also could make an impact on gun control, Mr. Segall noted. The Supreme Court has not taken a Second Amendment case in several years; in the past, there was uncertainty about how Justice Kennedy would vote on a gun control case. Not so with Justice Kavanaugh, Mr. Segall said. In Heller v. District of Columbia (known as Heller II), Judge Kavanaugh dissented from the majority, writing that the District’s ban on semiautomatic rifles and its requirement that handguns be registered were unconstitutional.
“[The dissent] gave the Second Amendment as broad a reading as any judge has ever given,” Mr. Segall said. “Gun control, gun reform, and gun limits ... this is where [Kavanaugh] is going to make the biggest difference.”
As the Supreme Court sits for its second session on Oct. 29, legal analysts question what impact its newest Associate Justice, Brett M. Kavanaugh, may have on health care cases that might come before the court.
The addition of Justice Kavanaugh cements a conservative majority on the high court, said Eric J. Segall, a constitutional law professor at Georgia State University in Atlanta.
“Where Justice Kennedy was moderate or liberal, Justice Kavanaugh will move the court dramatically to the right in most areas of law,” Mr. Segall said in an interview.
One area drawing considerable attention is abortion, with abortion rights advocates raising concerns that Justice Kavanaugh’s appointment may mean the reversal of Roe v. Wade. Legal analysts, however, say fall of the momentous ruling is not probable.
Based on his decisions written while he sat on the Court of Appeals for the District of Columbia Circuit, it’s more likely that Justice Kavanaugh would attempt to narrow the instances in which state abortion restrictions are considered to impede a woman’s constitutional right to an abortion, according to Timothy S. Jost, a legal analyst and retired health law professor at Washington and Lee University in Lexington, Va.
In Garza v. Hargan for example, then-Judge Kavanaugh dissented from a majority decision which ultimately allowed a teenage immigrant in U.S. custody to have an abortion. Judge Kavanaugh argued that it was wrong for unlawful immigrant minors in U.S. detention to obtain “immediate abortion on demand.” However, his dissent was not as far-reaching as that of another judge who argued that a minor undocumented immigrant had no constitutional right to an abortion.
“[Justice] Kavanaugh certainly could vote to overturn Roe v. Wade, but based on his past opinions, I think it much more likely that he would simply expand Roe’s undue burden exception on a case by case basis until it was meaningless,” Mr. Jost said in an interview. “He doesn’t have to overturn Roe v. Wade to allow states that want to effectively bar abortion [to succeed].”
Mr. Segall agrees that Justice Kavanaugh will likely water down the undue burden test for abortion and through this softening, essentially dismantle Roe and return the issue of abortion to states.
As for the fate of the Affordable Care Act, legal experts foresee a restrained stance by Justice Kavanaugh, rather than a strong rejection of the entire law. In 2011, Judge Kavanaugh wrote a dissenting opinion in Seven-Sky v. Holder, a case that challenged the constitutionality of the health law’s individual mandate. While his fellow judges ruled that Congress had the authority to enact the mandate, Judge Kavanaugh argued the mandate was a tax and thus, it was too early for the court to hear the case since the tax had not yet been levied.
The dissent by Judge Kavanaugh in this case amounted to a “procedural cop-out,” according to Thomas P. Miller, a resident fellow at the conservative American Enterprise Institute and a health care policy scholar.
“That tells you he is a relatively cautious judge as opposed to going right to the metal because other circuit court of appeals judges were able to say this is an unconstitutional mandate,” Mr. Miller said in an interview. “That suggests a degree of tactical caution on these issues, very similar to [Supreme Court Chief Justice John] Roberts.”
Justice Kavanaugh may get his first chance to rule on the ACA’s future through Texas v. United States. The case centers on a challenge by 20 Republican state attorneys general over the constitutionality of the health law’s individual mandate. The Trump administration has reduced the penalty for failing to have health insurance to $0 starting in 2019. The plaintiffs allege that the mandate cannot be severed from the rest of the ACA and that if the mandate is eliminated, the rest of the law should fall. Because the Trump administration has opted not to protect the ACA, Democratic state attorneys general in 16 states have intervened to defend the health law. Arguments were heard before the federal district court in the Northern District of Texas in September and a decision is expected any day.
If appealed, the Fifth Circuit would next take on the case, but the challenge could eventually reach the Supreme Court, Mr. Jost said.
“Chief Justice Roberts could save [the ACA] one more time, but I could see [Justice] Kavanaugh voting to uphold the ACA as the question would likely be a question of severability of the individual mandate from the rest of the ACA, and I can see [Kavanaugh] holding it severable,” he said.
Justice Kavanaugh may also weigh in on a handful of Medicaid cases that could go before the Supreme Court. The first case involves how much deference the federal government should have in allowing states to impose work requirements on Medicaid patients. In June, a federal judge in Washington D.C. struck down the federal government’s approval of a Kentucky Medicaid waiver that would have imposed work requirements and other rules for eligibility. That judge ruled that the Centers for Medicare & Medicaid Services did not adequately evaluate whether Kentucky’s requirements were consistent with federal Medicaid law.
Mr. Miller said it is too early to tell which way Justice Kavanaugh would vote on a Medicaid work requirements case, and that the decision depends on the context of the case and the reading of the law involved.
“[Justice] Kavanaugh has a less predictable record in this more narrow area of administrative law,” Mr. Miller said. “I doubt he alone is going to drive the court anywhere on this issue it doesn’t otherwise want to go – or at least drift.”
Two other Medicaid cases pending before the Supreme Court revolve around the right of a private Medicaid patient to sue a state over the exclusion of Planned Parenthood in its Medicaid program. Gee v. Planned Parenthood of Gulf Coast Inc. and its sister case, Anderson v. Planned Parenthood of Kansas and Mid-Missouri, stem from separate efforts by Kansas and Louisiana to remove Planned Parenthood from their Medicaid programs. The question is whether the Medicaid patients have a right to challenge the exclusions.
If the Supreme Court accepts the cases, Mr. Jost said it’s likely that Justice Kavanaugh would side with the states and bar the patients from suing.
“I could see him holding that Medicaid recipients can’t sue if a state violates federal law, which would effectively end Medicaid as an entitlement,” Mr. Jost said. “This would have disastrous consequences for low-income Americans.”
Justice Kavanaugh also could make an impact on gun control, Mr. Segall noted. The Supreme Court has not taken a Second Amendment case in several years; in the past, there was uncertainty about how Justice Kennedy would vote on a gun control case. Not so with Justice Kavanaugh, Mr. Segall said. In Heller v. District of Columbia (known as Heller II), Judge Kavanaugh dissented from the majority, writing that the District’s ban on semiautomatic rifles and its requirement that handguns be registered were unconstitutional.
“[The dissent] gave the Second Amendment as broad a reading as any judge has ever given,” Mr. Segall said. “Gun control, gun reform, and gun limits ... this is where [Kavanaugh] is going to make the biggest difference.”
IDEAS study meets first aim of changing 3-month clinical management, health outcomes
BARCELONA – Amyloid PET brain imaging changed clinical management in 60% of patients with a diagnosis of mild cognitive impairment or dementia and confirmed a presumptive Alzheimer’s diagnosis in 95% of those with positive scans.
But the scans also benefited amyloid-negative patients, Gil Rabinovici, MD, said at the Clinical Trials on Alzheimer’s Disease conference. Before the test, 71% carried an Alzheimer’s disease (AD) diagnosis; after the test, just 10% did, opening the way for an accurate diagnosis and more effective treatment.
“These patients were saved from unnecessary treatment for Alzheimer’s,” said Dr. Rabinovici, the Edward Fein and Pearl Landrith Endowed Professor in Memory & Aging at the University of California, San Francisco. They received more suitable care plans because of the confirmation.
He presented final results of aim one of the IDEAS (Imaging Dementia–Evidence for Amyloid Scanning) study, which seeks to prove that amyloid imaging changes clinical management and improves health outcomes in Medicare beneficiaries who have been diagnosed with mild cognitive impairment (MCI) or dementia of uncertain cause. Its two aims are to show that amyloid PET imaging affects a patient’s care plan within 3 months of the scan and that this impacts major medical outcomes 12 months later. In diagnostically uncertain cases, investigators theorized, amyloid PET imaging would lead to significant changes in patient management, which would then translate into improved medical outcomes.
Ultimately, investigators hope the U.S.-wide, open-label study will prove the clinical value of amyloid PET scanning and convince the Centers for Medicare & Medicaid Services to make the test a fully covered service.
So far, IDEAS has accrued data on 11,409 patients and is quickly closing in on the 18,000-patient target. The patients reported on at CTAD were aged a mean of 75 years and were largely white; only 4% were black and 4% Hispanic. The mean Mini-Mental Scale Exam score was 26. AD was the leading suspect pathology in 73% of the 6,905 with MCI and in 83% of those with dementia of uncertain etiology. Overall, 44% were taking AD medications at baseline.
Scans were positive in 55% of those with MCI and in 70% of those with dementia. Overall, the scans changed clinical management in 61% (7,018), including 60% of those with MCI and 63% of those with dementia.
“We also asked physicians how much the scan results contributed to these changes, and 86.7% replied that they ‘contributed significantly,’ ” Dr. Rabinovici said.
Most changes involved adjustments to medication. AD drugs were started in 44% of MCI patients and in 45% of dementia patients, and non-AD drugs started in 22% and 25%, respectively. About a fifth of the patients received counseling in wake of the scan results.
Medication adjustments also varied by scan result. Among amyloid-positive MCI patients, AD drug use increased from 40% before imaging to 81% after; among amyloid-negative MCI patients, drug use decreased slightly from 27% to 24%. Among amyloid-positive dementia patients, AD drug use increased from 63% to 91%, and among amyloid-negative patients, it dropped from 50% to 44%. All these changes were statistically significant.
The primary diagnosis changed from AD to non-AD in 25%, and from non-AD to AD in 10%. Among amyloid-positive patients, the diagnosis prevalence jumped from 80.0% to 95.5%; among amyloid-negative patients, it dropped from 71% to just 10%.
“IDEAS now provides the strongest data we have supporting the beneficial impact of amyloid PET on patient management,” said Dr. Rabinovici. “Aim two, which is the 12-month health outcomes, we expect to be completed by the end of next year.”
The IDEAS team is also looking at a furthering the investigation with a study called, aptly, “NEW IDEAS.” That would reach out to recruit the minorities that were so underrepresented in the main study and include patients with early-onset MCI or dementia. Building up a library of DNA and blood plasma samples might also fit into the new project.
IDEAS is a funding collaboration of the CMS, the Alzheimer’s Association, Avid Radiopharmaceuticals/Eli Lilly, General Electric Healthcare, Piramal Imaging, and the American College of Radiology. Dr. Rabinovici had no financial disclosures.
BARCELONA – Amyloid PET brain imaging changed clinical management in 60% of patients with a diagnosis of mild cognitive impairment or dementia and confirmed a presumptive Alzheimer’s diagnosis in 95% of those with positive scans.
But the scans also benefited amyloid-negative patients, Gil Rabinovici, MD, said at the Clinical Trials on Alzheimer’s Disease conference. Before the test, 71% carried an Alzheimer’s disease (AD) diagnosis; after the test, just 10% did, opening the way for an accurate diagnosis and more effective treatment.
“These patients were saved from unnecessary treatment for Alzheimer’s,” said Dr. Rabinovici, the Edward Fein and Pearl Landrith Endowed Professor in Memory & Aging at the University of California, San Francisco. They received more suitable care plans because of the confirmation.
He presented final results of aim one of the IDEAS (Imaging Dementia–Evidence for Amyloid Scanning) study, which seeks to prove that amyloid imaging changes clinical management and improves health outcomes in Medicare beneficiaries who have been diagnosed with mild cognitive impairment (MCI) or dementia of uncertain cause. Its two aims are to show that amyloid PET imaging affects a patient’s care plan within 3 months of the scan and that this impacts major medical outcomes 12 months later. In diagnostically uncertain cases, investigators theorized, amyloid PET imaging would lead to significant changes in patient management, which would then translate into improved medical outcomes.
Ultimately, investigators hope the U.S.-wide, open-label study will prove the clinical value of amyloid PET scanning and convince the Centers for Medicare & Medicaid Services to make the test a fully covered service.
So far, IDEAS has accrued data on 11,409 patients and is quickly closing in on the 18,000-patient target. The patients reported on at CTAD were aged a mean of 75 years and were largely white; only 4% were black and 4% Hispanic. The mean Mini-Mental Scale Exam score was 26. AD was the leading suspect pathology in 73% of the 6,905 with MCI and in 83% of those with dementia of uncertain etiology. Overall, 44% were taking AD medications at baseline.
Scans were positive in 55% of those with MCI and in 70% of those with dementia. Overall, the scans changed clinical management in 61% (7,018), including 60% of those with MCI and 63% of those with dementia.
“We also asked physicians how much the scan results contributed to these changes, and 86.7% replied that they ‘contributed significantly,’ ” Dr. Rabinovici said.
Most changes involved adjustments to medication. AD drugs were started in 44% of MCI patients and in 45% of dementia patients, and non-AD drugs started in 22% and 25%, respectively. About a fifth of the patients received counseling in wake of the scan results.
Medication adjustments also varied by scan result. Among amyloid-positive MCI patients, AD drug use increased from 40% before imaging to 81% after; among amyloid-negative MCI patients, drug use decreased slightly from 27% to 24%. Among amyloid-positive dementia patients, AD drug use increased from 63% to 91%, and among amyloid-negative patients, it dropped from 50% to 44%. All these changes were statistically significant.
The primary diagnosis changed from AD to non-AD in 25%, and from non-AD to AD in 10%. Among amyloid-positive patients, the diagnosis prevalence jumped from 80.0% to 95.5%; among amyloid-negative patients, it dropped from 71% to just 10%.
“IDEAS now provides the strongest data we have supporting the beneficial impact of amyloid PET on patient management,” said Dr. Rabinovici. “Aim two, which is the 12-month health outcomes, we expect to be completed by the end of next year.”
The IDEAS team is also looking at a furthering the investigation with a study called, aptly, “NEW IDEAS.” That would reach out to recruit the minorities that were so underrepresented in the main study and include patients with early-onset MCI or dementia. Building up a library of DNA and blood plasma samples might also fit into the new project.
IDEAS is a funding collaboration of the CMS, the Alzheimer’s Association, Avid Radiopharmaceuticals/Eli Lilly, General Electric Healthcare, Piramal Imaging, and the American College of Radiology. Dr. Rabinovici had no financial disclosures.
BARCELONA – Amyloid PET brain imaging changed clinical management in 60% of patients with a diagnosis of mild cognitive impairment or dementia and confirmed a presumptive Alzheimer’s diagnosis in 95% of those with positive scans.
But the scans also benefited amyloid-negative patients, Gil Rabinovici, MD, said at the Clinical Trials on Alzheimer’s Disease conference. Before the test, 71% carried an Alzheimer’s disease (AD) diagnosis; after the test, just 10% did, opening the way for an accurate diagnosis and more effective treatment.
“These patients were saved from unnecessary treatment for Alzheimer’s,” said Dr. Rabinovici, the Edward Fein and Pearl Landrith Endowed Professor in Memory & Aging at the University of California, San Francisco. They received more suitable care plans because of the confirmation.
He presented final results of aim one of the IDEAS (Imaging Dementia–Evidence for Amyloid Scanning) study, which seeks to prove that amyloid imaging changes clinical management and improves health outcomes in Medicare beneficiaries who have been diagnosed with mild cognitive impairment (MCI) or dementia of uncertain cause. Its two aims are to show that amyloid PET imaging affects a patient’s care plan within 3 months of the scan and that this impacts major medical outcomes 12 months later. In diagnostically uncertain cases, investigators theorized, amyloid PET imaging would lead to significant changes in patient management, which would then translate into improved medical outcomes.
Ultimately, investigators hope the U.S.-wide, open-label study will prove the clinical value of amyloid PET scanning and convince the Centers for Medicare & Medicaid Services to make the test a fully covered service.
So far, IDEAS has accrued data on 11,409 patients and is quickly closing in on the 18,000-patient target. The patients reported on at CTAD were aged a mean of 75 years and were largely white; only 4% were black and 4% Hispanic. The mean Mini-Mental Scale Exam score was 26. AD was the leading suspect pathology in 73% of the 6,905 with MCI and in 83% of those with dementia of uncertain etiology. Overall, 44% were taking AD medications at baseline.
Scans were positive in 55% of those with MCI and in 70% of those with dementia. Overall, the scans changed clinical management in 61% (7,018), including 60% of those with MCI and 63% of those with dementia.
“We also asked physicians how much the scan results contributed to these changes, and 86.7% replied that they ‘contributed significantly,’ ” Dr. Rabinovici said.
Most changes involved adjustments to medication. AD drugs were started in 44% of MCI patients and in 45% of dementia patients, and non-AD drugs started in 22% and 25%, respectively. About a fifth of the patients received counseling in wake of the scan results.
Medication adjustments also varied by scan result. Among amyloid-positive MCI patients, AD drug use increased from 40% before imaging to 81% after; among amyloid-negative MCI patients, drug use decreased slightly from 27% to 24%. Among amyloid-positive dementia patients, AD drug use increased from 63% to 91%, and among amyloid-negative patients, it dropped from 50% to 44%. All these changes were statistically significant.
The primary diagnosis changed from AD to non-AD in 25%, and from non-AD to AD in 10%. Among amyloid-positive patients, the diagnosis prevalence jumped from 80.0% to 95.5%; among amyloid-negative patients, it dropped from 71% to just 10%.
“IDEAS now provides the strongest data we have supporting the beneficial impact of amyloid PET on patient management,” said Dr. Rabinovici. “Aim two, which is the 12-month health outcomes, we expect to be completed by the end of next year.”
The IDEAS team is also looking at a furthering the investigation with a study called, aptly, “NEW IDEAS.” That would reach out to recruit the minorities that were so underrepresented in the main study and include patients with early-onset MCI or dementia. Building up a library of DNA and blood plasma samples might also fit into the new project.
IDEAS is a funding collaboration of the CMS, the Alzheimer’s Association, Avid Radiopharmaceuticals/Eli Lilly, General Electric Healthcare, Piramal Imaging, and the American College of Radiology. Dr. Rabinovici had no financial disclosures.
REPORTING FROM CTAD
Key clinical point: Amyloid PET imaging can refine equivocal dementia diagnoses.
Major finding:
Study details: The IDEAS study has thus far accrued data on 11,409 subjects.
Disclosures: IDEAS is a funding collaboration of the Centers for Medicare & Medicaid Services, the Alzheimer’s Association, Avid Radiopharmaceuticals/Eli Lilly, General Electric Healthcare, Piramal Imaging, and the American College of Radiology. Dr. Rabinovici had no financial disclosures.
Transition to high-sensitivity troponin T assay helped boost ED discharge rates
SAN DIEGO – After transitioning to using the high-sensitivity troponin T assay for patients over the age of 35 years who presented to the ED with chest pain or tightness, an increased number of patients were discharged, yet no impact was observed on the time to admission and/or observation, according to a study conducted at two Philadelphia-based hospitals.
“Biomarkers have been a cornerstone of evaluating patients who present with chest pain,” Frederick T. Randolph, MD, said at the annual meeting of the American College of Emergency Physicians. “Recently in the United States, fifth-generation or high-sensitivity troponin [assays] have been approved for use. Our institution made the plan to transition to utilization of high-sensitivity troponins. At that time, we were aware of European studies that they were able to discharge a higher percentage of patients from the ED. There have been no prior studies of the clinical impact of transition to high-sensitivity troponin [assays] in the U.S.”
Dr. Randolph, director of the Chest Pain Center at Thomas Jefferson University, Philadelphia, and his colleagues performed a before and after study assessing all patients over age 35 years who presented to two hospitals with chest pain or tightness and who received a troponin assay draw in the ED. They conducted two town halls, in-services with cardiology and emergency medicine, and distributed a slide set to all providers. “There was no guidance as to who to order the troponin on,” said Dr. Randolph, who is also vice chief of emergency medicine at the university. “Essentially, the recommendation was, ‘Keep using troponins the same way you’ve been using troponins for years.’ The education was centered on how frequently we were going to order repeat troponins and how to interpret those results.”
The researchers used a 0- and 2-hour sampling strategy (unless the first value was less than 6 ng/L) and used a cut-point of 19 ng/L to define “ruled out” and a cut-point of 53 ng/L to define “consistent with acute myocardial infarction.” Indeterminate values were repeated every 2 hours. Dr. Randolph and his associates collected data for 1 year prior to transition to high-sensitivity troponins in 4,295 patients, and 2 months post transition in 769 patients. The primary outcome was discharge rate from the ED. Secondary outcome was time from presentation to admission/observation decision.
There were no statistically significant differences between the pre- and posttransition groups in the percentage of those aged 36-64 years (74% vs. 76%, respectively) or in the percentage of those who were nonwhite (61% vs. 59%). The only statistically significant difference was a higher percentage of females in the preimplementation group (49% vs. 46%; P = .02).
In all, the researchers were able to discharge 45.2% of all patients during the pretransition period, compared with 58.7% of patients in the posttransition period, for an absolute increase of 13% (P less than .001). There was no difference between the two groups in time to decision to admit or to observe (a mean of 199.1 vs. 192.2 minutes, respectively; P = .96). “Areas of future study would be to evaluate those patients who were discharged and monitor them for any changes in outcomes, to see if there is any increase in morbidity or complications,” said Dr. Randolph. “An additional research curiosity would be the downstream consequences on cost or revenue to the institution given the increased number of admissions and the decreased use of diagnostic testing such as coronary computed tomography angiography and stress testing.”
Dr. Randolph disclosed that some of the study authors have participated in multiple biomarker studies over the years. He reported having no financial disclosures.
Source: Randolph FT et al. Ann Emerg Med. 2018 Oct;72;4:S2-3. doi. 10.1016/j.annemergmed.2018.08.009.
SAN DIEGO – After transitioning to using the high-sensitivity troponin T assay for patients over the age of 35 years who presented to the ED with chest pain or tightness, an increased number of patients were discharged, yet no impact was observed on the time to admission and/or observation, according to a study conducted at two Philadelphia-based hospitals.
“Biomarkers have been a cornerstone of evaluating patients who present with chest pain,” Frederick T. Randolph, MD, said at the annual meeting of the American College of Emergency Physicians. “Recently in the United States, fifth-generation or high-sensitivity troponin [assays] have been approved for use. Our institution made the plan to transition to utilization of high-sensitivity troponins. At that time, we were aware of European studies that they were able to discharge a higher percentage of patients from the ED. There have been no prior studies of the clinical impact of transition to high-sensitivity troponin [assays] in the U.S.”
Dr. Randolph, director of the Chest Pain Center at Thomas Jefferson University, Philadelphia, and his colleagues performed a before and after study assessing all patients over age 35 years who presented to two hospitals with chest pain or tightness and who received a troponin assay draw in the ED. They conducted two town halls, in-services with cardiology and emergency medicine, and distributed a slide set to all providers. “There was no guidance as to who to order the troponin on,” said Dr. Randolph, who is also vice chief of emergency medicine at the university. “Essentially, the recommendation was, ‘Keep using troponins the same way you’ve been using troponins for years.’ The education was centered on how frequently we were going to order repeat troponins and how to interpret those results.”
The researchers used a 0- and 2-hour sampling strategy (unless the first value was less than 6 ng/L) and used a cut-point of 19 ng/L to define “ruled out” and a cut-point of 53 ng/L to define “consistent with acute myocardial infarction.” Indeterminate values were repeated every 2 hours. Dr. Randolph and his associates collected data for 1 year prior to transition to high-sensitivity troponins in 4,295 patients, and 2 months post transition in 769 patients. The primary outcome was discharge rate from the ED. Secondary outcome was time from presentation to admission/observation decision.
There were no statistically significant differences between the pre- and posttransition groups in the percentage of those aged 36-64 years (74% vs. 76%, respectively) or in the percentage of those who were nonwhite (61% vs. 59%). The only statistically significant difference was a higher percentage of females in the preimplementation group (49% vs. 46%; P = .02).
In all, the researchers were able to discharge 45.2% of all patients during the pretransition period, compared with 58.7% of patients in the posttransition period, for an absolute increase of 13% (P less than .001). There was no difference between the two groups in time to decision to admit or to observe (a mean of 199.1 vs. 192.2 minutes, respectively; P = .96). “Areas of future study would be to evaluate those patients who were discharged and monitor them for any changes in outcomes, to see if there is any increase in morbidity or complications,” said Dr. Randolph. “An additional research curiosity would be the downstream consequences on cost or revenue to the institution given the increased number of admissions and the decreased use of diagnostic testing such as coronary computed tomography angiography and stress testing.”
Dr. Randolph disclosed that some of the study authors have participated in multiple biomarker studies over the years. He reported having no financial disclosures.
Source: Randolph FT et al. Ann Emerg Med. 2018 Oct;72;4:S2-3. doi. 10.1016/j.annemergmed.2018.08.009.
SAN DIEGO – After transitioning to using the high-sensitivity troponin T assay for patients over the age of 35 years who presented to the ED with chest pain or tightness, an increased number of patients were discharged, yet no impact was observed on the time to admission and/or observation, according to a study conducted at two Philadelphia-based hospitals.
“Biomarkers have been a cornerstone of evaluating patients who present with chest pain,” Frederick T. Randolph, MD, said at the annual meeting of the American College of Emergency Physicians. “Recently in the United States, fifth-generation or high-sensitivity troponin [assays] have been approved for use. Our institution made the plan to transition to utilization of high-sensitivity troponins. At that time, we were aware of European studies that they were able to discharge a higher percentage of patients from the ED. There have been no prior studies of the clinical impact of transition to high-sensitivity troponin [assays] in the U.S.”
Dr. Randolph, director of the Chest Pain Center at Thomas Jefferson University, Philadelphia, and his colleagues performed a before and after study assessing all patients over age 35 years who presented to two hospitals with chest pain or tightness and who received a troponin assay draw in the ED. They conducted two town halls, in-services with cardiology and emergency medicine, and distributed a slide set to all providers. “There was no guidance as to who to order the troponin on,” said Dr. Randolph, who is also vice chief of emergency medicine at the university. “Essentially, the recommendation was, ‘Keep using troponins the same way you’ve been using troponins for years.’ The education was centered on how frequently we were going to order repeat troponins and how to interpret those results.”
The researchers used a 0- and 2-hour sampling strategy (unless the first value was less than 6 ng/L) and used a cut-point of 19 ng/L to define “ruled out” and a cut-point of 53 ng/L to define “consistent with acute myocardial infarction.” Indeterminate values were repeated every 2 hours. Dr. Randolph and his associates collected data for 1 year prior to transition to high-sensitivity troponins in 4,295 patients, and 2 months post transition in 769 patients. The primary outcome was discharge rate from the ED. Secondary outcome was time from presentation to admission/observation decision.
There were no statistically significant differences between the pre- and posttransition groups in the percentage of those aged 36-64 years (74% vs. 76%, respectively) or in the percentage of those who were nonwhite (61% vs. 59%). The only statistically significant difference was a higher percentage of females in the preimplementation group (49% vs. 46%; P = .02).
In all, the researchers were able to discharge 45.2% of all patients during the pretransition period, compared with 58.7% of patients in the posttransition period, for an absolute increase of 13% (P less than .001). There was no difference between the two groups in time to decision to admit or to observe (a mean of 199.1 vs. 192.2 minutes, respectively; P = .96). “Areas of future study would be to evaluate those patients who were discharged and monitor them for any changes in outcomes, to see if there is any increase in morbidity or complications,” said Dr. Randolph. “An additional research curiosity would be the downstream consequences on cost or revenue to the institution given the increased number of admissions and the decreased use of diagnostic testing such as coronary computed tomography angiography and stress testing.”
Dr. Randolph disclosed that some of the study authors have participated in multiple biomarker studies over the years. He reported having no financial disclosures.
Source: Randolph FT et al. Ann Emerg Med. 2018 Oct;72;4:S2-3. doi. 10.1016/j.annemergmed.2018.08.009.
AT ACEP18
Key clinical point: .
Major finding: After conversion to using the high-sensitivity troponin T assay, the ED discharge rate increased to 58.7%, from 45.2% (P less than 0.001).
Study details: A before and after study of 5,064 patients aged 35 and older who presented to the ED with chest pain or tightness.
Disclosures: Dr. Randolph disclosed that some of the study authors have participated in multiple biomarker studies over the years. He reported having no financial disclosures.
Source: Randolph FT et al. Ann Emerg Med. 2018 Oct;72;4:S2-3. doi: 10.1016/j.annemergmed.2018.08.009.
Serlopitant quells prurigo nodularis in phase 2 study
PARIS – The in a 127-patient, randomized, placebo-controlled trial, Sonja Stander, MD, said at the annual congress of the European Academy of Dermatology and Venereology.
She used her speaker’s platform not only to present key outcomes of the phase 2 study, but also to explain some of the underappreciated aspects of prurigo nodularis and how the results shed new light on the pathogenesis of the disease.
“There is a knowledge gap regarding this disease,” observed Dr. Stander, professor of dermatology at the University of Munster (Germany).
Prurigo nodularis is a chronic skin condition characterized by numerous intensely pruritic, symmetrically distributed, erosive nodular lesions. As Dr. Stander and her fellow members of the EADV Task Force Pruritus recently reported, prurigo nodularis should be considered as one of the clinical manifestations of chronic prurigo, hallmarks of which include neuronal sensitization to itch and development of an itch-scratch cycle (J Eur Acad Dermatol Venereol. 2018 Jul;32[7]:1059-65). At present, there is no approved treatment for prurigo nodularis in the United States or Europe.
Despite its name, prurigo nodularis is not just about the itch. Additional symptoms were frequently reported by participants in the serlopitant study. Indeed, while 97% of participants reported experiencing devilish pruritus, 52% reported a burning sensation on involved skin, 41% said the lesions were painful, and 36% indicated they were plagued by a stinging sensation. All of these disturbing sensations were significantly reduced with 8 weeks of serlopitant in the trial.
The clinical implications of these baseline findings are clear: “We have to ask not only about itch, but also about pain and burning and stinging, which are really an issue with these patients,” the dermatologist said.
Dr. Stander noted that prurigo nodularis has a large negative impact on quality of life as reflected in study participants’ mean baseline Dermatology Life Quality Index score of 61. And it’s a disease that sticks around: At enrollment, 38% of subjects had a 1- to 5-year history of prurigo nodularis, 20% had had the disease for 5-10 years, and fully 29% had had prurigo nodularis for longer than 10 years.
“This is not a chronic relapsing disease. These patients had prurigo nodularis all the time,” Dr. Stander said.
Consistent with the findings of other studies, half of patients with prurigo nodularis had an atopic predisposition as defined by an Erlangen Atopy Questionnaire score of 10 or higher.
Patients in the phase 2 study were randomized to either a 15-mg loading dose of oral serlopitant followed by 5 mg/day for 8 weeks or to placebo. All four of the most common manifestations of prurigo nodularis – itching, burning, pain, and stinging – were reduced to a significantly greater extent in the serlopitant group than with placebo. For example, the proportion of serlopitant-treated patients who rated their itching as none or mild went from zero at baseline to 54% at week 8, as compared with 26% among placebo-treated controls. After 8 weeks, 46% of serlopitant-treated patients rated their itching as moderate, severe, or very severe, as did 71% of controls.
Similarly, the proportion of patients in the serlopitant group who reported no or only a mild burning sensation climbed from 41% at baseline to 73% after 8 weeks. In the control group, the proportion improved from 36% to 47% over the course of 8 weeks. At week 8, 27% of patients on serlopitant characterized themselves as experiencing a moderate, severe, or very severe burning sensation; the rate was twice as high in controls.
Although the stinging sensation associated with prurigo nodularis was significantly reduced by serlopitant, the effect was less robust than with the other common sensory expressions of the disease. The proportion of patients with no or mild stinging increased by an absolute 23% after 8 weeks on serlopitant and by 6% with placebo. At week 8, 22% of patients treated with the neurokinin-1 receptor antagonist complained of a moderate to very severe stinging sensation, as did 40% of controls.
As a neurokinin-1 receptor antagonist, serlopitant inhibits substance P. The drug’s efficacy suggests that substance P plays a role in inducing the itch and other sensory symptoms of prurigo nodularis, according to Dr. Stander.
Based upon the favorable phase 2 results, multiple phase 3 clinical trials of serlopitant for prurigo nodularis are underway in the United States and elsewhere, including a year-long safety study.
Serlopitant is being developed by Menlo Therapeutics. Dr. Stander reported receiving research funding from and serving as a consultant to the company.
PARIS – The in a 127-patient, randomized, placebo-controlled trial, Sonja Stander, MD, said at the annual congress of the European Academy of Dermatology and Venereology.
She used her speaker’s platform not only to present key outcomes of the phase 2 study, but also to explain some of the underappreciated aspects of prurigo nodularis and how the results shed new light on the pathogenesis of the disease.
“There is a knowledge gap regarding this disease,” observed Dr. Stander, professor of dermatology at the University of Munster (Germany).
Prurigo nodularis is a chronic skin condition characterized by numerous intensely pruritic, symmetrically distributed, erosive nodular lesions. As Dr. Stander and her fellow members of the EADV Task Force Pruritus recently reported, prurigo nodularis should be considered as one of the clinical manifestations of chronic prurigo, hallmarks of which include neuronal sensitization to itch and development of an itch-scratch cycle (J Eur Acad Dermatol Venereol. 2018 Jul;32[7]:1059-65). At present, there is no approved treatment for prurigo nodularis in the United States or Europe.
Despite its name, prurigo nodularis is not just about the itch. Additional symptoms were frequently reported by participants in the serlopitant study. Indeed, while 97% of participants reported experiencing devilish pruritus, 52% reported a burning sensation on involved skin, 41% said the lesions were painful, and 36% indicated they were plagued by a stinging sensation. All of these disturbing sensations were significantly reduced with 8 weeks of serlopitant in the trial.
The clinical implications of these baseline findings are clear: “We have to ask not only about itch, but also about pain and burning and stinging, which are really an issue with these patients,” the dermatologist said.
Dr. Stander noted that prurigo nodularis has a large negative impact on quality of life as reflected in study participants’ mean baseline Dermatology Life Quality Index score of 61. And it’s a disease that sticks around: At enrollment, 38% of subjects had a 1- to 5-year history of prurigo nodularis, 20% had had the disease for 5-10 years, and fully 29% had had prurigo nodularis for longer than 10 years.
“This is not a chronic relapsing disease. These patients had prurigo nodularis all the time,” Dr. Stander said.
Consistent with the findings of other studies, half of patients with prurigo nodularis had an atopic predisposition as defined by an Erlangen Atopy Questionnaire score of 10 or higher.
Patients in the phase 2 study were randomized to either a 15-mg loading dose of oral serlopitant followed by 5 mg/day for 8 weeks or to placebo. All four of the most common manifestations of prurigo nodularis – itching, burning, pain, and stinging – were reduced to a significantly greater extent in the serlopitant group than with placebo. For example, the proportion of serlopitant-treated patients who rated their itching as none or mild went from zero at baseline to 54% at week 8, as compared with 26% among placebo-treated controls. After 8 weeks, 46% of serlopitant-treated patients rated their itching as moderate, severe, or very severe, as did 71% of controls.
Similarly, the proportion of patients in the serlopitant group who reported no or only a mild burning sensation climbed from 41% at baseline to 73% after 8 weeks. In the control group, the proportion improved from 36% to 47% over the course of 8 weeks. At week 8, 27% of patients on serlopitant characterized themselves as experiencing a moderate, severe, or very severe burning sensation; the rate was twice as high in controls.
Although the stinging sensation associated with prurigo nodularis was significantly reduced by serlopitant, the effect was less robust than with the other common sensory expressions of the disease. The proportion of patients with no or mild stinging increased by an absolute 23% after 8 weeks on serlopitant and by 6% with placebo. At week 8, 22% of patients treated with the neurokinin-1 receptor antagonist complained of a moderate to very severe stinging sensation, as did 40% of controls.
As a neurokinin-1 receptor antagonist, serlopitant inhibits substance P. The drug’s efficacy suggests that substance P plays a role in inducing the itch and other sensory symptoms of prurigo nodularis, according to Dr. Stander.
Based upon the favorable phase 2 results, multiple phase 3 clinical trials of serlopitant for prurigo nodularis are underway in the United States and elsewhere, including a year-long safety study.
Serlopitant is being developed by Menlo Therapeutics. Dr. Stander reported receiving research funding from and serving as a consultant to the company.
PARIS – The in a 127-patient, randomized, placebo-controlled trial, Sonja Stander, MD, said at the annual congress of the European Academy of Dermatology and Venereology.
She used her speaker’s platform not only to present key outcomes of the phase 2 study, but also to explain some of the underappreciated aspects of prurigo nodularis and how the results shed new light on the pathogenesis of the disease.
“There is a knowledge gap regarding this disease,” observed Dr. Stander, professor of dermatology at the University of Munster (Germany).
Prurigo nodularis is a chronic skin condition characterized by numerous intensely pruritic, symmetrically distributed, erosive nodular lesions. As Dr. Stander and her fellow members of the EADV Task Force Pruritus recently reported, prurigo nodularis should be considered as one of the clinical manifestations of chronic prurigo, hallmarks of which include neuronal sensitization to itch and development of an itch-scratch cycle (J Eur Acad Dermatol Venereol. 2018 Jul;32[7]:1059-65). At present, there is no approved treatment for prurigo nodularis in the United States or Europe.
Despite its name, prurigo nodularis is not just about the itch. Additional symptoms were frequently reported by participants in the serlopitant study. Indeed, while 97% of participants reported experiencing devilish pruritus, 52% reported a burning sensation on involved skin, 41% said the lesions were painful, and 36% indicated they were plagued by a stinging sensation. All of these disturbing sensations were significantly reduced with 8 weeks of serlopitant in the trial.
The clinical implications of these baseline findings are clear: “We have to ask not only about itch, but also about pain and burning and stinging, which are really an issue with these patients,” the dermatologist said.
Dr. Stander noted that prurigo nodularis has a large negative impact on quality of life as reflected in study participants’ mean baseline Dermatology Life Quality Index score of 61. And it’s a disease that sticks around: At enrollment, 38% of subjects had a 1- to 5-year history of prurigo nodularis, 20% had had the disease for 5-10 years, and fully 29% had had prurigo nodularis for longer than 10 years.
“This is not a chronic relapsing disease. These patients had prurigo nodularis all the time,” Dr. Stander said.
Consistent with the findings of other studies, half of patients with prurigo nodularis had an atopic predisposition as defined by an Erlangen Atopy Questionnaire score of 10 or higher.
Patients in the phase 2 study were randomized to either a 15-mg loading dose of oral serlopitant followed by 5 mg/day for 8 weeks or to placebo. All four of the most common manifestations of prurigo nodularis – itching, burning, pain, and stinging – were reduced to a significantly greater extent in the serlopitant group than with placebo. For example, the proportion of serlopitant-treated patients who rated their itching as none or mild went from zero at baseline to 54% at week 8, as compared with 26% among placebo-treated controls. After 8 weeks, 46% of serlopitant-treated patients rated their itching as moderate, severe, or very severe, as did 71% of controls.
Similarly, the proportion of patients in the serlopitant group who reported no or only a mild burning sensation climbed from 41% at baseline to 73% after 8 weeks. In the control group, the proportion improved from 36% to 47% over the course of 8 weeks. At week 8, 27% of patients on serlopitant characterized themselves as experiencing a moderate, severe, or very severe burning sensation; the rate was twice as high in controls.
Although the stinging sensation associated with prurigo nodularis was significantly reduced by serlopitant, the effect was less robust than with the other common sensory expressions of the disease. The proportion of patients with no or mild stinging increased by an absolute 23% after 8 weeks on serlopitant and by 6% with placebo. At week 8, 22% of patients treated with the neurokinin-1 receptor antagonist complained of a moderate to very severe stinging sensation, as did 40% of controls.
As a neurokinin-1 receptor antagonist, serlopitant inhibits substance P. The drug’s efficacy suggests that substance P plays a role in inducing the itch and other sensory symptoms of prurigo nodularis, according to Dr. Stander.
Based upon the favorable phase 2 results, multiple phase 3 clinical trials of serlopitant for prurigo nodularis are underway in the United States and elsewhere, including a year-long safety study.
Serlopitant is being developed by Menlo Therapeutics. Dr. Stander reported receiving research funding from and serving as a consultant to the company.
REPORTING FROM THE EADV CONGRESS
Key clinical point: Serlopitant decreases the disruptive itch, burning, pain, and stinging of prurigo nodularis.
Major finding: The proportion of prurigo nodularis patients who rated their itching as none or mild went from zero at baseline to 54% after 8 weeks on oral serlopitant.
Study details: This 8-week, randomized, double-blind phase 2 study included 127 patients with prurigo nodularis who were randomized to oral serlopitant or placebo.
Disclosures: Serlopitant is being developed by Menlo Therapeutics. The presenter reported receiving research funding from and serving as a consultant to the company.
Collaborative approach for suicidal youth helps providers, too
SEATTLE – When it comes to treating children and adolescents who have experienced trauma and present suicidality, it is not just the patients who need support. Clinicians also experience grave anxiety when dealing with a traumatized child exhibiting suicidal behavior. The Collaborative Assessment and Management of Suicide (CAMS) framework can help clinicians or health care workers manage the care of these challenging patients.
CAMS is well established in adults with suicidal behavior, but it is unproven in youth and adolescents. The key is to its success in younger patients will be whether the program is developmentally appropriate, according to Molly C. Adrian, PhD, assistant professor of psychiatry and behavioral medicine at the University of Washington, Seattle. Dr. Adrian discussed CAMS and its potential applications at the annual meeting of the American Academy of Child and Adolescent Psychiatry.
The CAMS approach emphasizes cooperation between the therapist and patient. “Adolescents are seeking autonomy and independence, and so it’s a good fit philosophically that you would partner alongside the teen as opposed to starting in a more adversarial sort of way – not that we as therapists ever do that. But it can be more tense when suicide is on the table and you feel unprepared,” Dr. Adrian said.
Seattle Children’s Hospital is persuaded enough to make CAMS part of its standard of care, Dr. Adrian said.
CAMS is a framework for patient management that has no prerequisites for the therapeutic approach. “It’s principle driven, not protocol driven. Clinicians can use whatever specific interventions they feel are appropriate for the drivers (of the suicidality). What we’re trying to change is the approach to the suicidal patient, so that it is not an anxiety-provoking, terrifying experience for the clinician – because we know that a suicidal patient is the most anxiety-provoking task for clinicians,” Dr. Adrian said. “We want clinicians to feel prepared and protected in providing the elements of care,” Dr. Adrian said in an interview.
The framework incorporates a suicide-status form (SSF), which assesses theory-driven and epidemiologically guided risk factors and helps to identify the drivers or the reasons why suicide is compelling to the patient. Those drivers then help inform crisis prevention efforts and the selection of interventions.
Three randomized, controlled trials have demonstrated the efficacy of CAMS over standard of care in adult patients, showing that the SSF is an effective assessment tool and that CAMS reduces suicidal ideation and leads to decreases in distress, depression, and hopelessness. There are no randomized, controlled trials showing its efficacy in children, but Seattle Children’s Hospital is conducting a pilot study in 12 youth and have found a 40% response rate at 8 weeks.
The SSF gauges the patient’s status and trajectory, while the CAMS therapeutic worksheet helps to distinguish direct and indirect drivers of suicidal behavior. In cases in which trauma symptoms or experiences are tied to suicidal behavior, they receive priority for treatment. The framework provides for discussion of options and treatment choice through collaboration between the clinician and the patient.
The patient and clinician fill out an SSF in the first session and use it to create a crisis convention plan, which includes gaining a commitment to treatment, removing or restricting access to lethal means, and incorporating parental monitoring.
Dr. Adrian is hopeful that the CAMS framework will help health care workers address suicidality in traumatized youth and adolescents. Currently, they may feel intimidated by a stricken child’s issues. “You don’t want to be responsible for a child dying, so you may overrespond with an intervention like an emergency department evaluation or an inpatient hospitalization that may be iatrogenic – there are data coming out from adults that hospitalization contributes to suicide risk above and beyond other risk factors,” Dr. Adrian said.
CAMS is simple and flexible, according to Dr. Adrian, and can be used by psychiatrists, social workers, substance use counselors, and others. At Seattle Children’s Hospital, clinicians have embraced it. “They feel it changes their practice. It gets to the heart of the matter quickly, and they feel more confident having that framework,” Dr. Adrian said.
Dr. Adrian has no conflicts of interest or disclosures.
SEATTLE – When it comes to treating children and adolescents who have experienced trauma and present suicidality, it is not just the patients who need support. Clinicians also experience grave anxiety when dealing with a traumatized child exhibiting suicidal behavior. The Collaborative Assessment and Management of Suicide (CAMS) framework can help clinicians or health care workers manage the care of these challenging patients.
CAMS is well established in adults with suicidal behavior, but it is unproven in youth and adolescents. The key is to its success in younger patients will be whether the program is developmentally appropriate, according to Molly C. Adrian, PhD, assistant professor of psychiatry and behavioral medicine at the University of Washington, Seattle. Dr. Adrian discussed CAMS and its potential applications at the annual meeting of the American Academy of Child and Adolescent Psychiatry.
The CAMS approach emphasizes cooperation between the therapist and patient. “Adolescents are seeking autonomy and independence, and so it’s a good fit philosophically that you would partner alongside the teen as opposed to starting in a more adversarial sort of way – not that we as therapists ever do that. But it can be more tense when suicide is on the table and you feel unprepared,” Dr. Adrian said.
Seattle Children’s Hospital is persuaded enough to make CAMS part of its standard of care, Dr. Adrian said.
CAMS is a framework for patient management that has no prerequisites for the therapeutic approach. “It’s principle driven, not protocol driven. Clinicians can use whatever specific interventions they feel are appropriate for the drivers (of the suicidality). What we’re trying to change is the approach to the suicidal patient, so that it is not an anxiety-provoking, terrifying experience for the clinician – because we know that a suicidal patient is the most anxiety-provoking task for clinicians,” Dr. Adrian said. “We want clinicians to feel prepared and protected in providing the elements of care,” Dr. Adrian said in an interview.
The framework incorporates a suicide-status form (SSF), which assesses theory-driven and epidemiologically guided risk factors and helps to identify the drivers or the reasons why suicide is compelling to the patient. Those drivers then help inform crisis prevention efforts and the selection of interventions.
Three randomized, controlled trials have demonstrated the efficacy of CAMS over standard of care in adult patients, showing that the SSF is an effective assessment tool and that CAMS reduces suicidal ideation and leads to decreases in distress, depression, and hopelessness. There are no randomized, controlled trials showing its efficacy in children, but Seattle Children’s Hospital is conducting a pilot study in 12 youth and have found a 40% response rate at 8 weeks.
The SSF gauges the patient’s status and trajectory, while the CAMS therapeutic worksheet helps to distinguish direct and indirect drivers of suicidal behavior. In cases in which trauma symptoms or experiences are tied to suicidal behavior, they receive priority for treatment. The framework provides for discussion of options and treatment choice through collaboration between the clinician and the patient.
The patient and clinician fill out an SSF in the first session and use it to create a crisis convention plan, which includes gaining a commitment to treatment, removing or restricting access to lethal means, and incorporating parental monitoring.
Dr. Adrian is hopeful that the CAMS framework will help health care workers address suicidality in traumatized youth and adolescents. Currently, they may feel intimidated by a stricken child’s issues. “You don’t want to be responsible for a child dying, so you may overrespond with an intervention like an emergency department evaluation or an inpatient hospitalization that may be iatrogenic – there are data coming out from adults that hospitalization contributes to suicide risk above and beyond other risk factors,” Dr. Adrian said.
CAMS is simple and flexible, according to Dr. Adrian, and can be used by psychiatrists, social workers, substance use counselors, and others. At Seattle Children’s Hospital, clinicians have embraced it. “They feel it changes their practice. It gets to the heart of the matter quickly, and they feel more confident having that framework,” Dr. Adrian said.
Dr. Adrian has no conflicts of interest or disclosures.
SEATTLE – When it comes to treating children and adolescents who have experienced trauma and present suicidality, it is not just the patients who need support. Clinicians also experience grave anxiety when dealing with a traumatized child exhibiting suicidal behavior. The Collaborative Assessment and Management of Suicide (CAMS) framework can help clinicians or health care workers manage the care of these challenging patients.
CAMS is well established in adults with suicidal behavior, but it is unproven in youth and adolescents. The key is to its success in younger patients will be whether the program is developmentally appropriate, according to Molly C. Adrian, PhD, assistant professor of psychiatry and behavioral medicine at the University of Washington, Seattle. Dr. Adrian discussed CAMS and its potential applications at the annual meeting of the American Academy of Child and Adolescent Psychiatry.
The CAMS approach emphasizes cooperation between the therapist and patient. “Adolescents are seeking autonomy and independence, and so it’s a good fit philosophically that you would partner alongside the teen as opposed to starting in a more adversarial sort of way – not that we as therapists ever do that. But it can be more tense when suicide is on the table and you feel unprepared,” Dr. Adrian said.
Seattle Children’s Hospital is persuaded enough to make CAMS part of its standard of care, Dr. Adrian said.
CAMS is a framework for patient management that has no prerequisites for the therapeutic approach. “It’s principle driven, not protocol driven. Clinicians can use whatever specific interventions they feel are appropriate for the drivers (of the suicidality). What we’re trying to change is the approach to the suicidal patient, so that it is not an anxiety-provoking, terrifying experience for the clinician – because we know that a suicidal patient is the most anxiety-provoking task for clinicians,” Dr. Adrian said. “We want clinicians to feel prepared and protected in providing the elements of care,” Dr. Adrian said in an interview.
The framework incorporates a suicide-status form (SSF), which assesses theory-driven and epidemiologically guided risk factors and helps to identify the drivers or the reasons why suicide is compelling to the patient. Those drivers then help inform crisis prevention efforts and the selection of interventions.
Three randomized, controlled trials have demonstrated the efficacy of CAMS over standard of care in adult patients, showing that the SSF is an effective assessment tool and that CAMS reduces suicidal ideation and leads to decreases in distress, depression, and hopelessness. There are no randomized, controlled trials showing its efficacy in children, but Seattle Children’s Hospital is conducting a pilot study in 12 youth and have found a 40% response rate at 8 weeks.
The SSF gauges the patient’s status and trajectory, while the CAMS therapeutic worksheet helps to distinguish direct and indirect drivers of suicidal behavior. In cases in which trauma symptoms or experiences are tied to suicidal behavior, they receive priority for treatment. The framework provides for discussion of options and treatment choice through collaboration between the clinician and the patient.
The patient and clinician fill out an SSF in the first session and use it to create a crisis convention plan, which includes gaining a commitment to treatment, removing or restricting access to lethal means, and incorporating parental monitoring.
Dr. Adrian is hopeful that the CAMS framework will help health care workers address suicidality in traumatized youth and adolescents. Currently, they may feel intimidated by a stricken child’s issues. “You don’t want to be responsible for a child dying, so you may overrespond with an intervention like an emergency department evaluation or an inpatient hospitalization that may be iatrogenic – there are data coming out from adults that hospitalization contributes to suicide risk above and beyond other risk factors,” Dr. Adrian said.
CAMS is simple and flexible, according to Dr. Adrian, and can be used by psychiatrists, social workers, substance use counselors, and others. At Seattle Children’s Hospital, clinicians have embraced it. “They feel it changes their practice. It gets to the heart of the matter quickly, and they feel more confident having that framework,” Dr. Adrian said.
Dr. Adrian has no conflicts of interest or disclosures.
FROM AACAP 2018
Heather Yeo: Surgical Residency Attrition
When Dr. Yeo was a resident, one of her co-residents left surgery. Dr. Yeo says that this resident was highly talented technically and on-point clinically. After this resident left, Dr. Yeo began investigating this and looking into what can be done to keep surgical trainees in surgery.
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When Dr. Yeo was a resident, one of her co-residents left surgery. Dr. Yeo says that this resident was highly talented technically and on-point clinically. After this resident left, Dr. Yeo began investigating this and looking into what can be done to keep surgical trainees in surgery.
Subscribe here:
When Dr. Yeo was a resident, one of her co-residents left surgery. Dr. Yeo says that this resident was highly talented technically and on-point clinically. After this resident left, Dr. Yeo began investigating this and looking into what can be done to keep surgical trainees in surgery.
Subscribe here:
Validation for SLE low-disease definition
Click here to listen to the MDedge Postcall Podcast.
Also today, if you see a swollen knee in a kid, remember: above 9, treat for lyme, FDA approves Xofluza for treatment of influenza, and there are still problems with APMs.
Amazon Alexa
Apple Podcasts
Spotify
Click here to listen to the MDedge Postcall Podcast.
Also today, if you see a swollen knee in a kid, remember: above 9, treat for lyme, FDA approves Xofluza for treatment of influenza, and there are still problems with APMs.
Amazon Alexa
Apple Podcasts
Spotify
Click here to listen to the MDedge Postcall Podcast.
Also today, if you see a swollen knee in a kid, remember: above 9, treat for lyme, FDA approves Xofluza for treatment of influenza, and there are still problems with APMs.
Amazon Alexa
Apple Podcasts
Spotify
Lnk deficiency boosts HSC replication in Fanconi anemia
A novel approach can restore hematopoietic stem cell (HSC) function in Fanconi anemia (FA), according to preclinical research published in Nature Communications.
The investigators showed that Lnk (Sh2b3) deficiency restores HSC proliferation and survival in Fancd2-deficient mice.
And it does so, in part, by alleviating blocks to cytokine-mediated JAK2 signaling.
These findings, the researchers wrote, “highlight a new role for cytokine/JAK signaling” and have therapeutic implications for FA.
The investigators noted that FA is caused by mutations in genes that are essential for DNA interstrand crosslink repair and replication stress tolerance.
Allogeneic transplant can replace defective HSCs in patients with FA, the researchers said, but there are no interventions that mitigate defects in HSCs. So the investigators decided to test whether Lnk deficiency ameliorates HSC defects in FA.
Using a model of FA in which mice lacked Fancd2, the researchers inhibited the regulatory protein Sh2b3/Lnk.
The investigators said Lnk deficiency restored the proliferation and survival of Fancd2−/− HSCs while also reducing replication stress and genomic instability. Lnk deficiency did not, however, affect DNA interstrand crosslink repair.
“We expected that inhibiting Lnk would restore the ability of FA cells to repair DNA damage, but this was not the case,” said study author Wei Tong, PhD, of Children’s Hospital of Philadelphia in Pennsylvania.
“Instead, inhibiting Lnk stabilized the stalled replication machinery, allowing affected cells to continue to copy DNA, and to prevent small errors from cascading into a catastrophic failure. The most exciting aspect of this discovery is that Lnk is part of a well-known growth pathway that can be manipulated by existing drugs in other diseases.”
That pathway is the TPO/MPL/JAK2 pathway, which is already targeted by eltrombopag and romiplostin for immune thrombocytopenia and eltrombopag for aplastic anemia.
The researchers plan to continue their work with animal models of FA and Lnk.
“Our ultimate goal is to translate our knowledge into treatments for both Fanconi anemia and for the broader problem of bone marrow failure,” Dr. Tong said.
This research was supported by the National Institutes of Health, the Fanconi Anemia Research Fund, the Department of Defense, the Basser Center for BRCA Team Science Grant, the Leukemia Lymphoma Society Scholar Award, and the Patel Family Award.
The researchers declared no competing interests.
A novel approach can restore hematopoietic stem cell (HSC) function in Fanconi anemia (FA), according to preclinical research published in Nature Communications.
The investigators showed that Lnk (Sh2b3) deficiency restores HSC proliferation and survival in Fancd2-deficient mice.
And it does so, in part, by alleviating blocks to cytokine-mediated JAK2 signaling.
These findings, the researchers wrote, “highlight a new role for cytokine/JAK signaling” and have therapeutic implications for FA.
The investigators noted that FA is caused by mutations in genes that are essential for DNA interstrand crosslink repair and replication stress tolerance.
Allogeneic transplant can replace defective HSCs in patients with FA, the researchers said, but there are no interventions that mitigate defects in HSCs. So the investigators decided to test whether Lnk deficiency ameliorates HSC defects in FA.
Using a model of FA in which mice lacked Fancd2, the researchers inhibited the regulatory protein Sh2b3/Lnk.
The investigators said Lnk deficiency restored the proliferation and survival of Fancd2−/− HSCs while also reducing replication stress and genomic instability. Lnk deficiency did not, however, affect DNA interstrand crosslink repair.
“We expected that inhibiting Lnk would restore the ability of FA cells to repair DNA damage, but this was not the case,” said study author Wei Tong, PhD, of Children’s Hospital of Philadelphia in Pennsylvania.
“Instead, inhibiting Lnk stabilized the stalled replication machinery, allowing affected cells to continue to copy DNA, and to prevent small errors from cascading into a catastrophic failure. The most exciting aspect of this discovery is that Lnk is part of a well-known growth pathway that can be manipulated by existing drugs in other diseases.”
That pathway is the TPO/MPL/JAK2 pathway, which is already targeted by eltrombopag and romiplostin for immune thrombocytopenia and eltrombopag for aplastic anemia.
The researchers plan to continue their work with animal models of FA and Lnk.
“Our ultimate goal is to translate our knowledge into treatments for both Fanconi anemia and for the broader problem of bone marrow failure,” Dr. Tong said.
This research was supported by the National Institutes of Health, the Fanconi Anemia Research Fund, the Department of Defense, the Basser Center for BRCA Team Science Grant, the Leukemia Lymphoma Society Scholar Award, and the Patel Family Award.
The researchers declared no competing interests.
A novel approach can restore hematopoietic stem cell (HSC) function in Fanconi anemia (FA), according to preclinical research published in Nature Communications.
The investigators showed that Lnk (Sh2b3) deficiency restores HSC proliferation and survival in Fancd2-deficient mice.
And it does so, in part, by alleviating blocks to cytokine-mediated JAK2 signaling.
These findings, the researchers wrote, “highlight a new role for cytokine/JAK signaling” and have therapeutic implications for FA.
The investigators noted that FA is caused by mutations in genes that are essential for DNA interstrand crosslink repair and replication stress tolerance.
Allogeneic transplant can replace defective HSCs in patients with FA, the researchers said, but there are no interventions that mitigate defects in HSCs. So the investigators decided to test whether Lnk deficiency ameliorates HSC defects in FA.
Using a model of FA in which mice lacked Fancd2, the researchers inhibited the regulatory protein Sh2b3/Lnk.
The investigators said Lnk deficiency restored the proliferation and survival of Fancd2−/− HSCs while also reducing replication stress and genomic instability. Lnk deficiency did not, however, affect DNA interstrand crosslink repair.
“We expected that inhibiting Lnk would restore the ability of FA cells to repair DNA damage, but this was not the case,” said study author Wei Tong, PhD, of Children’s Hospital of Philadelphia in Pennsylvania.
“Instead, inhibiting Lnk stabilized the stalled replication machinery, allowing affected cells to continue to copy DNA, and to prevent small errors from cascading into a catastrophic failure. The most exciting aspect of this discovery is that Lnk is part of a well-known growth pathway that can be manipulated by existing drugs in other diseases.”
That pathway is the TPO/MPL/JAK2 pathway, which is already targeted by eltrombopag and romiplostin for immune thrombocytopenia and eltrombopag for aplastic anemia.
The researchers plan to continue their work with animal models of FA and Lnk.
“Our ultimate goal is to translate our knowledge into treatments for both Fanconi anemia and for the broader problem of bone marrow failure,” Dr. Tong said.
This research was supported by the National Institutes of Health, the Fanconi Anemia Research Fund, the Department of Defense, the Basser Center for BRCA Team Science Grant, the Leukemia Lymphoma Society Scholar Award, and the Patel Family Award.
The researchers declared no competing interests.
Aspirin prevents VTE as well as anticoagulants, study suggests
Putting patients on aspirin following a knee replacement is a safe, cost-effective alternative to treatment with anticoagulants, according to researchers.
A study of more than 40,000 patients revealed a similar incidence of venous thromboembolism (VTE) or death after total knee arthroplasty (TKA) in patients receiving aspirin and patients receiving anticoagulants.
“Aspirin alone may provide similar protection compared to anticoagulation treatments,” said Brian R. Hallstrom, MD, of the University of Michigan in Ann Arbor.
He and his colleagues compared aspirin to anticoagulants after TKA and detailed their findings in JAMA Surgery.
The researchers evaluated 41,537 patients who underwent TKA and received:
- No pharmacological VTE prophylaxis (n=668; 1.6%)
- Aspirin only (n=12,831; 30.9%)
- Only an anticoagulant (n=22,620; 54.5%)
- Both aspirin and an anticoagulant (n=5418; 13.0%).
Anticoagulants included low-molecular-weight heparin, warfarin, and factor Xa inhibitors.
About 87% of all patients (n=36,113) were also using intermittent pneumatic compression stockings.
Safety and efficacy
The study’s primary outcome was a composite of VTE and death. It occurred in:
- 4.79% (32/668) of patients not on pharmacological prophylaxis
- 1.16% (149/12,831) of patients who received aspirin alone
- 1.42% (321/22,620) of patients on anticoagulation alone
- 1.31% (71/5418) of patients who received both aspirin and anticoagulation.
In a multivariable analysis adjusted for confounding, aspirin was noninferior to the other prophylaxis regimens for the outcome of VTE or death. The adjusted odds ratio was 0.85 (P=0.007).
Bleeding was a secondary outcome of this study, and it occurred in:
- 1.50% (10/668) of patients not on pharmacological prophylaxis
- 0.90% (116/12,831) of patients who received aspirin alone
- 1.14% (258/22,620) of patients who received anticoagulation
- 1.35% (73/5,418) of patients who received both aspirin and anticoagulation.
In an adjusted analysis, aspirin was noninferior to the other prophylaxis regimens for the outcome of bleeding. The adjusted odds ratio was 0.80 (P<0.001).
Other benefits
Aspirin provides other benefits aside from similar safety and efficacy as anticoagulants, according to the researchers.
“Aspirin is easy to take and much less expensive,” Dr. Hallstrom noted. “Patients can get it over the counter for pennies, while the other anticoagulants require monitoring, injections, frequent dose adjustments and are extremely expensive.”
Dr. Hallstrom and his colleagues said the reported cost for a 30-day supply of rivaroxaban is approximately $379 to $450, and the estimated cost of heparin is $450 to $890.
Although warfarin costs a few dollars for a 30-day supply, its cost approaches that of the other anticoagulants when doctor visits for monitoring are factored in, the researchers noted.
In contrast, aspirin costs approximately $2 a month.
Dr. Hallstrom and his colleagues did note that, although this study suggests aspirin can prevent VTE as well as anticoagulants, doctors need to consider factors such as a patient’s history of clots, obesity, and ability to mobilize after surgery.
Putting patients on aspirin following a knee replacement is a safe, cost-effective alternative to treatment with anticoagulants, according to researchers.
A study of more than 40,000 patients revealed a similar incidence of venous thromboembolism (VTE) or death after total knee arthroplasty (TKA) in patients receiving aspirin and patients receiving anticoagulants.
“Aspirin alone may provide similar protection compared to anticoagulation treatments,” said Brian R. Hallstrom, MD, of the University of Michigan in Ann Arbor.
He and his colleagues compared aspirin to anticoagulants after TKA and detailed their findings in JAMA Surgery.
The researchers evaluated 41,537 patients who underwent TKA and received:
- No pharmacological VTE prophylaxis (n=668; 1.6%)
- Aspirin only (n=12,831; 30.9%)
- Only an anticoagulant (n=22,620; 54.5%)
- Both aspirin and an anticoagulant (n=5418; 13.0%).
Anticoagulants included low-molecular-weight heparin, warfarin, and factor Xa inhibitors.
About 87% of all patients (n=36,113) were also using intermittent pneumatic compression stockings.
Safety and efficacy
The study’s primary outcome was a composite of VTE and death. It occurred in:
- 4.79% (32/668) of patients not on pharmacological prophylaxis
- 1.16% (149/12,831) of patients who received aspirin alone
- 1.42% (321/22,620) of patients on anticoagulation alone
- 1.31% (71/5418) of patients who received both aspirin and anticoagulation.
In a multivariable analysis adjusted for confounding, aspirin was noninferior to the other prophylaxis regimens for the outcome of VTE or death. The adjusted odds ratio was 0.85 (P=0.007).
Bleeding was a secondary outcome of this study, and it occurred in:
- 1.50% (10/668) of patients not on pharmacological prophylaxis
- 0.90% (116/12,831) of patients who received aspirin alone
- 1.14% (258/22,620) of patients who received anticoagulation
- 1.35% (73/5,418) of patients who received both aspirin and anticoagulation.
In an adjusted analysis, aspirin was noninferior to the other prophylaxis regimens for the outcome of bleeding. The adjusted odds ratio was 0.80 (P<0.001).
Other benefits
Aspirin provides other benefits aside from similar safety and efficacy as anticoagulants, according to the researchers.
“Aspirin is easy to take and much less expensive,” Dr. Hallstrom noted. “Patients can get it over the counter for pennies, while the other anticoagulants require monitoring, injections, frequent dose adjustments and are extremely expensive.”
Dr. Hallstrom and his colleagues said the reported cost for a 30-day supply of rivaroxaban is approximately $379 to $450, and the estimated cost of heparin is $450 to $890.
Although warfarin costs a few dollars for a 30-day supply, its cost approaches that of the other anticoagulants when doctor visits for monitoring are factored in, the researchers noted.
In contrast, aspirin costs approximately $2 a month.
Dr. Hallstrom and his colleagues did note that, although this study suggests aspirin can prevent VTE as well as anticoagulants, doctors need to consider factors such as a patient’s history of clots, obesity, and ability to mobilize after surgery.
Putting patients on aspirin following a knee replacement is a safe, cost-effective alternative to treatment with anticoagulants, according to researchers.
A study of more than 40,000 patients revealed a similar incidence of venous thromboembolism (VTE) or death after total knee arthroplasty (TKA) in patients receiving aspirin and patients receiving anticoagulants.
“Aspirin alone may provide similar protection compared to anticoagulation treatments,” said Brian R. Hallstrom, MD, of the University of Michigan in Ann Arbor.
He and his colleagues compared aspirin to anticoagulants after TKA and detailed their findings in JAMA Surgery.
The researchers evaluated 41,537 patients who underwent TKA and received:
- No pharmacological VTE prophylaxis (n=668; 1.6%)
- Aspirin only (n=12,831; 30.9%)
- Only an anticoagulant (n=22,620; 54.5%)
- Both aspirin and an anticoagulant (n=5418; 13.0%).
Anticoagulants included low-molecular-weight heparin, warfarin, and factor Xa inhibitors.
About 87% of all patients (n=36,113) were also using intermittent pneumatic compression stockings.
Safety and efficacy
The study’s primary outcome was a composite of VTE and death. It occurred in:
- 4.79% (32/668) of patients not on pharmacological prophylaxis
- 1.16% (149/12,831) of patients who received aspirin alone
- 1.42% (321/22,620) of patients on anticoagulation alone
- 1.31% (71/5418) of patients who received both aspirin and anticoagulation.
In a multivariable analysis adjusted for confounding, aspirin was noninferior to the other prophylaxis regimens for the outcome of VTE or death. The adjusted odds ratio was 0.85 (P=0.007).
Bleeding was a secondary outcome of this study, and it occurred in:
- 1.50% (10/668) of patients not on pharmacological prophylaxis
- 0.90% (116/12,831) of patients who received aspirin alone
- 1.14% (258/22,620) of patients who received anticoagulation
- 1.35% (73/5,418) of patients who received both aspirin and anticoagulation.
In an adjusted analysis, aspirin was noninferior to the other prophylaxis regimens for the outcome of bleeding. The adjusted odds ratio was 0.80 (P<0.001).
Other benefits
Aspirin provides other benefits aside from similar safety and efficacy as anticoagulants, according to the researchers.
“Aspirin is easy to take and much less expensive,” Dr. Hallstrom noted. “Patients can get it over the counter for pennies, while the other anticoagulants require monitoring, injections, frequent dose adjustments and are extremely expensive.”
Dr. Hallstrom and his colleagues said the reported cost for a 30-day supply of rivaroxaban is approximately $379 to $450, and the estimated cost of heparin is $450 to $890.
Although warfarin costs a few dollars for a 30-day supply, its cost approaches that of the other anticoagulants when doctor visits for monitoring are factored in, the researchers noted.
In contrast, aspirin costs approximately $2 a month.
Dr. Hallstrom and his colleagues did note that, although this study suggests aspirin can prevent VTE as well as anticoagulants, doctors need to consider factors such as a patient’s history of clots, obesity, and ability to mobilize after surgery.
OMS721 receives orphan designation for HSCT-TMA
The U.S. Food and Drug Administration (FDA) has granted OMS721 orphan designation for the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA).
OMS721 is a monoclonal antibody targeting MASP-2, the effector enzyme of the lectin pathway of the complement system.
The FDA previously granted OMS721 breakthrough therapy designation for HSCT-TMA and orphan designation for the prevention of complement-mediated TMA, including HSCT-TMA.
Omeros Corporation, the company developing OMS721, has established a compassionate-use program for OMS721, which is active in the United States and Europe.
Clinical trials
Phase 3 clinical programs are in progress for OMS721 in atypical hemolytic uremic syndrome, immunoglobulin A nephropathy, and HSCT-TMA. Two phase 2 trials of OMS721—one in TMA and one in immunoglobulin A nephropathy—are ongoing.
Omeros released results from the phase 2 TMA trial (NCT02222545) in February.
The study includes adults with HSCT-TMA persisting for at least 2 weeks following immunosuppressive regimen modification or more than 30 days post-transplant. Patients receive weekly OMS721 treatments for 4 to 8 weeks at the discretion of the investigator.
At the time of Omeros’s announcement, 18 HSCT-TMA patients had been treated on this study.
These patients had a significantly longer median overall survival than historical controls—347 days and 21 days, respectively (P<0.0001).
Omeros also reported that markers of TMA activity significantly improved following OMS721 treatment.
The mean platelet count increased from 18,100 x 106/mL at baseline to 52,300 x 106/mL (P=0.017). The mean lactate dehydrogenase decreased from 591 U/L to 250 U/L (P<0.001). And the mean haptoglobin increased from 8 mg/dL to 141 mg/dL (P=0.003).
Mean creatinine remained stable—at approximately 120 μmol/L—but a majority of patients had co-existing conditions for which they were receiving nephrotoxic medications. These conditions included graft-versus-host disease, cytomegalovirus and human herpes virus 6 infections, prior sepsis, diffuse alveolar hemorrhage, and residual underlying malignancies.
The most commonly reported adverse events were diarrhea and neutropenia.
Four deaths occurred. One of these—due to acute renal and respiratory failure—was considered possibly related to OMS721. The other deaths were due to progression of acute myeloid leukemia (n=1) and neutropenic sepsis (n=2).
About orphan and breakthrough designations
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the United States.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.
The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.
To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
The U.S. Food and Drug Administration (FDA) has granted OMS721 orphan designation for the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA).
OMS721 is a monoclonal antibody targeting MASP-2, the effector enzyme of the lectin pathway of the complement system.
The FDA previously granted OMS721 breakthrough therapy designation for HSCT-TMA and orphan designation for the prevention of complement-mediated TMA, including HSCT-TMA.
Omeros Corporation, the company developing OMS721, has established a compassionate-use program for OMS721, which is active in the United States and Europe.
Clinical trials
Phase 3 clinical programs are in progress for OMS721 in atypical hemolytic uremic syndrome, immunoglobulin A nephropathy, and HSCT-TMA. Two phase 2 trials of OMS721—one in TMA and one in immunoglobulin A nephropathy—are ongoing.
Omeros released results from the phase 2 TMA trial (NCT02222545) in February.
The study includes adults with HSCT-TMA persisting for at least 2 weeks following immunosuppressive regimen modification or more than 30 days post-transplant. Patients receive weekly OMS721 treatments for 4 to 8 weeks at the discretion of the investigator.
At the time of Omeros’s announcement, 18 HSCT-TMA patients had been treated on this study.
These patients had a significantly longer median overall survival than historical controls—347 days and 21 days, respectively (P<0.0001).
Omeros also reported that markers of TMA activity significantly improved following OMS721 treatment.
The mean platelet count increased from 18,100 x 106/mL at baseline to 52,300 x 106/mL (P=0.017). The mean lactate dehydrogenase decreased from 591 U/L to 250 U/L (P<0.001). And the mean haptoglobin increased from 8 mg/dL to 141 mg/dL (P=0.003).
Mean creatinine remained stable—at approximately 120 μmol/L—but a majority of patients had co-existing conditions for which they were receiving nephrotoxic medications. These conditions included graft-versus-host disease, cytomegalovirus and human herpes virus 6 infections, prior sepsis, diffuse alveolar hemorrhage, and residual underlying malignancies.
The most commonly reported adverse events were diarrhea and neutropenia.
Four deaths occurred. One of these—due to acute renal and respiratory failure—was considered possibly related to OMS721. The other deaths were due to progression of acute myeloid leukemia (n=1) and neutropenic sepsis (n=2).
About orphan and breakthrough designations
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the United States.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.
The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.
To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
The U.S. Food and Drug Administration (FDA) has granted OMS721 orphan designation for the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA).
OMS721 is a monoclonal antibody targeting MASP-2, the effector enzyme of the lectin pathway of the complement system.
The FDA previously granted OMS721 breakthrough therapy designation for HSCT-TMA and orphan designation for the prevention of complement-mediated TMA, including HSCT-TMA.
Omeros Corporation, the company developing OMS721, has established a compassionate-use program for OMS721, which is active in the United States and Europe.
Clinical trials
Phase 3 clinical programs are in progress for OMS721 in atypical hemolytic uremic syndrome, immunoglobulin A nephropathy, and HSCT-TMA. Two phase 2 trials of OMS721—one in TMA and one in immunoglobulin A nephropathy—are ongoing.
Omeros released results from the phase 2 TMA trial (NCT02222545) in February.
The study includes adults with HSCT-TMA persisting for at least 2 weeks following immunosuppressive regimen modification or more than 30 days post-transplant. Patients receive weekly OMS721 treatments for 4 to 8 weeks at the discretion of the investigator.
At the time of Omeros’s announcement, 18 HSCT-TMA patients had been treated on this study.
These patients had a significantly longer median overall survival than historical controls—347 days and 21 days, respectively (P<0.0001).
Omeros also reported that markers of TMA activity significantly improved following OMS721 treatment.
The mean platelet count increased from 18,100 x 106/mL at baseline to 52,300 x 106/mL (P=0.017). The mean lactate dehydrogenase decreased from 591 U/L to 250 U/L (P<0.001). And the mean haptoglobin increased from 8 mg/dL to 141 mg/dL (P=0.003).
Mean creatinine remained stable—at approximately 120 μmol/L—but a majority of patients had co-existing conditions for which they were receiving nephrotoxic medications. These conditions included graft-versus-host disease, cytomegalovirus and human herpes virus 6 infections, prior sepsis, diffuse alveolar hemorrhage, and residual underlying malignancies.
The most commonly reported adverse events were diarrhea and neutropenia.
Four deaths occurred. One of these—due to acute renal and respiratory failure—was considered possibly related to OMS721. The other deaths were due to progression of acute myeloid leukemia (n=1) and neutropenic sepsis (n=2).
About orphan and breakthrough designations
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the United States.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.
The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.
To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.