MDedge Cardiology

April 5 is the official start date of a U.S. law requiring health care organizations to provide patients with free, full, and immediate electronic access to their doctor’s clinical notes as well as test results and reports from pathology and imaging.

The mandate, called “open notes” by many, is part of the 21st Century Cures Act, a wide-ranging piece of federal health care legislation. The previous deadline of Nov. 2, 2020, for enacting open notes was extended last year because of the exigencies of the COVID-19 pandemic.

Organizations must provide access via patient portals to the following types of notes: consultations, discharge summaries, histories, physical examination findings, imaging narratives, laboratory and pathology report narratives, and procedure and progress notes. Noncompliant organizations will eventually be subject to fines from the Department of Health & Human Services for “information blocking.”

This news organization reported on the mandate in 2020, and some readers said it was an unwelcome intrusion into practice. Since then, this news organization has run additional open notes stories about physician concerns, a perspective essay addressing those fears, and a reader poll about the phenomenon.

Now, as the legislation turns into a practical clinical matter, there are five key points clinicians should consider.
 

Clinicians don’t have to change writing style.

The new law mandates timely patient access to notes and test results, but it doesn’t require that clinicians alter their writing, said Scott MacDonald, MD, an internist and electronic health record medical director at University of California Davis Health in Sacramento.

“You don’t have to change your notes,” he said. However, patients are now part of the note audience and some health care systems are directing clinicians to make patient-friendly style changes.

Everyday experience should guide clinicians when writing notes, said one expert.

“When you’re not sure [of how to write a note], just mirror the way you would speak in the office – that’s going to get you right, including for mental health issues,” advised Leonor Fernandez, MD, an internist at Beth Deaconess Israel Medical Center, Boston, in her “take-away” comments in the online video, How to Write an Open Note.

According to a 2020 Medscape poll of 1,050 physicians, a majority (56%) anticipate that they will write notes differently, knowing that patients can read them via open notes. Nearly two-thirds (64%) believe that this new wrinkle in medical records will increase their workload. However, actual practice suggests that this is true for a minority of practitioners, according to the results from a recent study of more than 1,000 physicians in Boston, Seattle, and rural Pennsylvania, who already work in open notes settings. Only about one-third (37%) reported “spending more time on documentation.”

Note writing is going to change because of the addition of the patient reader, and something will be lost, argued Steven Reidbord, MD, a psychiatrist in private practice in San Francisco. By watering down the language for patients, “you are trading away the technical precision and other advantages of having a professional language,” commented Dr. Reidbord, who blogs for Psychology Today and has criticized the open notes movement in the past.

However, years of investigation from OpenNotes, the Boston-based advocacy and research organization, indicates that there are many gains with patient-accessible notes, including improved medical record accuracy, greater medication adherence, and potentially improved health care disparities among a range of patient types. In a 2019 study, researchers said that worry and confusion among note-reading patients are uncommon (5% and 3%, respectively), which addresses two criticisms voiced by multiple people last year.
 

Some clinical notes can be withheld. 

The new rules from the federal government permit information blocking if there is clear evidence that doing so “will substantially reduce the risk of harm” to patients or to other third parties, Tom Delbanco, MD, and Charlotte Blease, PhD, of OpenNotes in Boston wrote in a commentary in February 2021.

There are also state-level laws that can supersede the new U.S. law and block access to notes, points out MacDonald. For example, California law dictates that providers cannot post cancer test results without talking with the patient first.

The OpenNotes organization also points out that, with regard to sensitive psychotherapy notes that are separated from the rest of a medical record, those notes “can be kept from patients without their permission, and such rules vary state by state.”
 

Some patients are more likely readers. 

Some patients are more likely to peer into their files than others, said Liz Salmi, senior strategist at OpenNotes, who is also a brain cancer patient.

“Those patients who have more serious or chronic conditions ... are more likely to read their notes,” she said in an interview.

A new study of nearly 6,000 medical oncology patients at the University of Wisconsin confirmed that opinion. Patients with incurable metastatic disease were much more likely than those with early-stage, curable disease to read notes. Notably, younger patients were more likely than older ones to access notes, likely the result of generational tech savvy.

Despite the unpredictability of serious disease such as cancer, oncology patients find satisfaction in reading their notes, say experts. “We’ve overwhelmingly heard that patients like it,” Thomas LeBlanc, MD, medical oncologist at Duke University, Durham, N.C., where all patients already have access to clinicians’ notes, told this news organization in 2018.
 

You are part of the avant garde. 

The United States and Scandinavian countries are the world leaders in implementing open notes in clinical practice, Dr. Blease said in an interview.

“It’s a phenomenal achievement” to have enacted open notes nationally, she said. For example, there are no open notes in Northern Ireland, Dr. Blease’s home country, or most of Europe.

In the United States, there are more than 200 medical organizations, including at least one in every state, that were voluntarily providing open notes before April 5, including interstate giants such as Banner Health and big-name medical centers such as Cleveland Clinic.

It may be hard for the United States to top Sweden’s embrace of the practice. The national open notes program now has 7.2 million patient accounts in a country of 10 million people, noted Maria Häggland, PhD, of Uppsala (Sweden) MedTech Science Innovation Center during a webinar last year.
 

The start day will come, and you may not notice. 

“When April 5 happens, something brand new is going to happen symbolically,” Ms. Salmi said. Its importance is hard to measure.

“Patients say they trust their doctor more because they understand their thinking with open notes. How do you value that? We don’t have metrics for that,” she said.

Dr. MacDonald suggested that open notes are both new and not new. In the fall of 2020, he predicted that the launch day would come, and few clinicians would notice, in part because many patients already access truncated information via patient portals.

However, there are “sensitive issues,” such as with adolescents and reproductive health, where “we know that some parents have sign-in information for their teen’s portal,” he commented. With clinical notes now on full display, potential problems “may be out of our control.”

Still, the Sacramento-based physician and IT officer acknowledged that concerns about open notes may be a bit inflated. “I’ve been more worried about reassuring physicians that everything will be okay than what’s actually going to happen [as the law takes effect],” Dr. MacDonald said.

The OpenNotes organization is grant funded, and staff disclosed no relevant financial relationships.

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

April 5 is the official start date of a U.S. law requiring health care organizations to provide patients with free, full, and immediate electronic access to their doctor’s clinical notes as well as test results and reports from pathology and imaging.

The mandate, called “open notes” by many, is part of the 21st Century Cures Act, a wide-ranging piece of federal health care legislation. The previous deadline of Nov. 2, 2020, for enacting open notes was extended last year because of the exigencies of the COVID-19 pandemic.

Organizations must provide access via patient portals to the following types of notes: consultations, discharge summaries, histories, physical examination findings, imaging narratives, laboratory and pathology report narratives, and procedure and progress notes. Noncompliant organizations will eventually be subject to fines from the Department of Health & Human Services for “information blocking.”

This news organization reported on the mandate in 2020, and some readers said it was an unwelcome intrusion into practice. Since then, this news organization has run additional open notes stories about physician concerns, a perspective essay addressing those fears, and a reader poll about the phenomenon.

Now, as the legislation turns into a practical clinical matter, there are five key points clinicians should consider.
 

Clinicians don’t have to change writing style.

The new law mandates timely patient access to notes and test results, but it doesn’t require that clinicians alter their writing, said Scott MacDonald, MD, an internist and electronic health record medical director at University of California Davis Health in Sacramento.

“You don’t have to change your notes,” he said. However, patients are now part of the note audience and some health care systems are directing clinicians to make patient-friendly style changes.

Everyday experience should guide clinicians when writing notes, said one expert.

“When you’re not sure [of how to write a note], just mirror the way you would speak in the office – that’s going to get you right, including for mental health issues,” advised Leonor Fernandez, MD, an internist at Beth Deaconess Israel Medical Center, Boston, in her “take-away” comments in the online video, How to Write an Open Note.

According to a 2020 Medscape poll of 1,050 physicians, a majority (56%) anticipate that they will write notes differently, knowing that patients can read them via open notes. Nearly two-thirds (64%) believe that this new wrinkle in medical records will increase their workload. However, actual practice suggests that this is true for a minority of practitioners, according to the results from a recent study of more than 1,000 physicians in Boston, Seattle, and rural Pennsylvania, who already work in open notes settings. Only about one-third (37%) reported “spending more time on documentation.”

Note writing is going to change because of the addition of the patient reader, and something will be lost, argued Steven Reidbord, MD, a psychiatrist in private practice in San Francisco. By watering down the language for patients, “you are trading away the technical precision and other advantages of having a professional language,” commented Dr. Reidbord, who blogs for Psychology Today and has criticized the open notes movement in the past.

However, years of investigation from OpenNotes, the Boston-based advocacy and research organization, indicates that there are many gains with patient-accessible notes, including improved medical record accuracy, greater medication adherence, and potentially improved health care disparities among a range of patient types. In a 2019 study, researchers said that worry and confusion among note-reading patients are uncommon (5% and 3%, respectively), which addresses two criticisms voiced by multiple people last year.
 

Some clinical notes can be withheld. 

The new rules from the federal government permit information blocking if there is clear evidence that doing so “will substantially reduce the risk of harm” to patients or to other third parties, Tom Delbanco, MD, and Charlotte Blease, PhD, of OpenNotes in Boston wrote in a commentary in February 2021.

There are also state-level laws that can supersede the new U.S. law and block access to notes, points out MacDonald. For example, California law dictates that providers cannot post cancer test results without talking with the patient first.

The OpenNotes organization also points out that, with regard to sensitive psychotherapy notes that are separated from the rest of a medical record, those notes “can be kept from patients without their permission, and such rules vary state by state.”
 

Some patients are more likely readers. 

Some patients are more likely to peer into their files than others, said Liz Salmi, senior strategist at OpenNotes, who is also a brain cancer patient.

“Those patients who have more serious or chronic conditions ... are more likely to read their notes,” she said in an interview.

A new study of nearly 6,000 medical oncology patients at the University of Wisconsin confirmed that opinion. Patients with incurable metastatic disease were much more likely than those with early-stage, curable disease to read notes. Notably, younger patients were more likely than older ones to access notes, likely the result of generational tech savvy.

Despite the unpredictability of serious disease such as cancer, oncology patients find satisfaction in reading their notes, say experts. “We’ve overwhelmingly heard that patients like it,” Thomas LeBlanc, MD, medical oncologist at Duke University, Durham, N.C., where all patients already have access to clinicians’ notes, told this news organization in 2018.
 

You are part of the avant garde. 

The United States and Scandinavian countries are the world leaders in implementing open notes in clinical practice, Dr. Blease said in an interview.

“It’s a phenomenal achievement” to have enacted open notes nationally, she said. For example, there are no open notes in Northern Ireland, Dr. Blease’s home country, or most of Europe.

In the United States, there are more than 200 medical organizations, including at least one in every state, that were voluntarily providing open notes before April 5, including interstate giants such as Banner Health and big-name medical centers such as Cleveland Clinic.

It may be hard for the United States to top Sweden’s embrace of the practice. The national open notes program now has 7.2 million patient accounts in a country of 10 million people, noted Maria Häggland, PhD, of Uppsala (Sweden) MedTech Science Innovation Center during a webinar last year.
 

The start day will come, and you may not notice. 

“When April 5 happens, something brand new is going to happen symbolically,” Ms. Salmi said. Its importance is hard to measure.

“Patients say they trust their doctor more because they understand their thinking with open notes. How do you value that? We don’t have metrics for that,” she said.

Dr. MacDonald suggested that open notes are both new and not new. In the fall of 2020, he predicted that the launch day would come, and few clinicians would notice, in part because many patients already access truncated information via patient portals.

However, there are “sensitive issues,” such as with adolescents and reproductive health, where “we know that some parents have sign-in information for their teen’s portal,” he commented. With clinical notes now on full display, potential problems “may be out of our control.”

Still, the Sacramento-based physician and IT officer acknowledged that concerns about open notes may be a bit inflated. “I’ve been more worried about reassuring physicians that everything will be okay than what’s actually going to happen [as the law takes effect],” Dr. MacDonald said.

The OpenNotes organization is grant funded, and staff disclosed no relevant financial relationships.

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

April 5 is the official start date of a U.S. law requiring health care organizations to provide patients with free, full, and immediate electronic access to their doctor’s clinical notes as well as test results and reports from pathology and imaging.

The mandate, called “open notes” by many, is part of the 21st Century Cures Act, a wide-ranging piece of federal health care legislation. The previous deadline of Nov. 2, 2020, for enacting open notes was extended last year because of the exigencies of the COVID-19 pandemic.

Organizations must provide access via patient portals to the following types of notes: consultations, discharge summaries, histories, physical examination findings, imaging narratives, laboratory and pathology report narratives, and procedure and progress notes. Noncompliant organizations will eventually be subject to fines from the Department of Health & Human Services for “information blocking.”

This news organization reported on the mandate in 2020, and some readers said it was an unwelcome intrusion into practice. Since then, this news organization has run additional open notes stories about physician concerns, a perspective essay addressing those fears, and a reader poll about the phenomenon.

Now, as the legislation turns into a practical clinical matter, there are five key points clinicians should consider.
 

Clinicians don’t have to change writing style.

The new law mandates timely patient access to notes and test results, but it doesn’t require that clinicians alter their writing, said Scott MacDonald, MD, an internist and electronic health record medical director at University of California Davis Health in Sacramento.

“You don’t have to change your notes,” he said. However, patients are now part of the note audience and some health care systems are directing clinicians to make patient-friendly style changes.

Everyday experience should guide clinicians when writing notes, said one expert.

“When you’re not sure [of how to write a note], just mirror the way you would speak in the office – that’s going to get you right, including for mental health issues,” advised Leonor Fernandez, MD, an internist at Beth Deaconess Israel Medical Center, Boston, in her “take-away” comments in the online video, How to Write an Open Note.

According to a 2020 Medscape poll of 1,050 physicians, a majority (56%) anticipate that they will write notes differently, knowing that patients can read them via open notes. Nearly two-thirds (64%) believe that this new wrinkle in medical records will increase their workload. However, actual practice suggests that this is true for a minority of practitioners, according to the results from a recent study of more than 1,000 physicians in Boston, Seattle, and rural Pennsylvania, who already work in open notes settings. Only about one-third (37%) reported “spending more time on documentation.”

Note writing is going to change because of the addition of the patient reader, and something will be lost, argued Steven Reidbord, MD, a psychiatrist in private practice in San Francisco. By watering down the language for patients, “you are trading away the technical precision and other advantages of having a professional language,” commented Dr. Reidbord, who blogs for Psychology Today and has criticized the open notes movement in the past.

However, years of investigation from OpenNotes, the Boston-based advocacy and research organization, indicates that there are many gains with patient-accessible notes, including improved medical record accuracy, greater medication adherence, and potentially improved health care disparities among a range of patient types. In a 2019 study, researchers said that worry and confusion among note-reading patients are uncommon (5% and 3%, respectively), which addresses two criticisms voiced by multiple people last year.
 

Some clinical notes can be withheld. 

The new rules from the federal government permit information blocking if there is clear evidence that doing so “will substantially reduce the risk of harm” to patients or to other third parties, Tom Delbanco, MD, and Charlotte Blease, PhD, of OpenNotes in Boston wrote in a commentary in February 2021.

There are also state-level laws that can supersede the new U.S. law and block access to notes, points out MacDonald. For example, California law dictates that providers cannot post cancer test results without talking with the patient first.

The OpenNotes organization also points out that, with regard to sensitive psychotherapy notes that are separated from the rest of a medical record, those notes “can be kept from patients without their permission, and such rules vary state by state.”
 

Some patients are more likely readers. 

Some patients are more likely to peer into their files than others, said Liz Salmi, senior strategist at OpenNotes, who is also a brain cancer patient.

“Those patients who have more serious or chronic conditions ... are more likely to read their notes,” she said in an interview.

A new study of nearly 6,000 medical oncology patients at the University of Wisconsin confirmed that opinion. Patients with incurable metastatic disease were much more likely than those with early-stage, curable disease to read notes. Notably, younger patients were more likely than older ones to access notes, likely the result of generational tech savvy.

Despite the unpredictability of serious disease such as cancer, oncology patients find satisfaction in reading their notes, say experts. “We’ve overwhelmingly heard that patients like it,” Thomas LeBlanc, MD, medical oncologist at Duke University, Durham, N.C., where all patients already have access to clinicians’ notes, told this news organization in 2018.
 

You are part of the avant garde. 

The United States and Scandinavian countries are the world leaders in implementing open notes in clinical practice, Dr. Blease said in an interview.

“It’s a phenomenal achievement” to have enacted open notes nationally, she said. For example, there are no open notes in Northern Ireland, Dr. Blease’s home country, or most of Europe.

In the United States, there are more than 200 medical organizations, including at least one in every state, that were voluntarily providing open notes before April 5, including interstate giants such as Banner Health and big-name medical centers such as Cleveland Clinic.

It may be hard for the United States to top Sweden’s embrace of the practice. The national open notes program now has 7.2 million patient accounts in a country of 10 million people, noted Maria Häggland, PhD, of Uppsala (Sweden) MedTech Science Innovation Center during a webinar last year.
 

The start day will come, and you may not notice. 

“When April 5 happens, something brand new is going to happen symbolically,” Ms. Salmi said. Its importance is hard to measure.

“Patients say they trust their doctor more because they understand their thinking with open notes. How do you value that? We don’t have metrics for that,” she said.

Dr. MacDonald suggested that open notes are both new and not new. In the fall of 2020, he predicted that the launch day would come, and few clinicians would notice, in part because many patients already access truncated information via patient portals.

However, there are “sensitive issues,” such as with adolescents and reproductive health, where “we know that some parents have sign-in information for their teen’s portal,” he commented. With clinical notes now on full display, potential problems “may be out of our control.”

Still, the Sacramento-based physician and IT officer acknowledged that concerns about open notes may be a bit inflated. “I’ve been more worried about reassuring physicians that everything will be okay than what’s actually going to happen [as the law takes effect],” Dr. MacDonald said.

The OpenNotes organization is grant funded, and staff disclosed no relevant financial relationships.

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

COVID-19 was the third-leading cause of death in the United States in 2020, but that mortality burden did not fall evenly along racial/ethnic lines, according to a provisional report from the Centers for Disease Control and Prevention.

Only heart disease and cancer caused more deaths than SARS-CoV-2, which took the lives of almost 378,000 Americans last year, Farida B. Ahmad, MPH, and associates at the National Center for Health Statistics noted March 31 in the Morbidity and Mortality Weekly Report.

That represents 11.2% of the almost 3.36 million total deaths recorded in 2020. The racial/ethnics demographics, however, show that 22.4% of all deaths among Hispanic Americans were COVID-19–related, as were 18.6% of deaths in American Indians/Alaska Natives. Deaths among Asian persons, at 14.7%, and African Americans, at 13.5%, were closer but still above the national figure, while Whites (9.3%) were the only major subgroup below it, based on data from the National Vital Statistics System.

Age-adjusted death rates tell a somewhat different story: American Indian/Alaska native persons were highest with a rate of 187.8 COVID-19–associated deaths per 100,000 standard population, with Hispanic persons second at 164.3 per 100,000. Blacks were next at 151.1 deaths per 100,000, but Whites had a higher rate (72.5) than did Asian Americans (66.7), the CDC investigators reported.

“During January-December 2020, the estimated 2020 age-adjusted death rate increased for the first time since 2017, with an increase of 15.9% compared with 2019, from 715.2 to 828.7 deaths per 100,000 population,” they wrote, noting that “certain categories of race (i.e., AI/AN and Asian) and Hispanic ethnicity reported on death certificates might have been misclassified, possibly resulting in underestimates of death rates for some groups.”

[email protected]

COVID-19 was the third-leading cause of death in the United States in 2020, but that mortality burden did not fall evenly along racial/ethnic lines, according to a provisional report from the Centers for Disease Control and Prevention.

Only heart disease and cancer caused more deaths than SARS-CoV-2, which took the lives of almost 378,000 Americans last year, Farida B. Ahmad, MPH, and associates at the National Center for Health Statistics noted March 31 in the Morbidity and Mortality Weekly Report.

That represents 11.2% of the almost 3.36 million total deaths recorded in 2020. The racial/ethnics demographics, however, show that 22.4% of all deaths among Hispanic Americans were COVID-19–related, as were 18.6% of deaths in American Indians/Alaska Natives. Deaths among Asian persons, at 14.7%, and African Americans, at 13.5%, were closer but still above the national figure, while Whites (9.3%) were the only major subgroup below it, based on data from the National Vital Statistics System.

Age-adjusted death rates tell a somewhat different story: American Indian/Alaska native persons were highest with a rate of 187.8 COVID-19–associated deaths per 100,000 standard population, with Hispanic persons second at 164.3 per 100,000. Blacks were next at 151.1 deaths per 100,000, but Whites had a higher rate (72.5) than did Asian Americans (66.7), the CDC investigators reported.

“During January-December 2020, the estimated 2020 age-adjusted death rate increased for the first time since 2017, with an increase of 15.9% compared with 2019, from 715.2 to 828.7 deaths per 100,000 population,” they wrote, noting that “certain categories of race (i.e., AI/AN and Asian) and Hispanic ethnicity reported on death certificates might have been misclassified, possibly resulting in underestimates of death rates for some groups.”

[email protected]

COVID-19 was the third-leading cause of death in the United States in 2020, but that mortality burden did not fall evenly along racial/ethnic lines, according to a provisional report from the Centers for Disease Control and Prevention.

Only heart disease and cancer caused more deaths than SARS-CoV-2, which took the lives of almost 378,000 Americans last year, Farida B. Ahmad, MPH, and associates at the National Center for Health Statistics noted March 31 in the Morbidity and Mortality Weekly Report.

That represents 11.2% of the almost 3.36 million total deaths recorded in 2020. The racial/ethnics demographics, however, show that 22.4% of all deaths among Hispanic Americans were COVID-19–related, as were 18.6% of deaths in American Indians/Alaska Natives. Deaths among Asian persons, at 14.7%, and African Americans, at 13.5%, were closer but still above the national figure, while Whites (9.3%) were the only major subgroup below it, based on data from the National Vital Statistics System.

Age-adjusted death rates tell a somewhat different story: American Indian/Alaska native persons were highest with a rate of 187.8 COVID-19–associated deaths per 100,000 standard population, with Hispanic persons second at 164.3 per 100,000. Blacks were next at 151.1 deaths per 100,000, but Whites had a higher rate (72.5) than did Asian Americans (66.7), the CDC investigators reported.

“During January-December 2020, the estimated 2020 age-adjusted death rate increased for the first time since 2017, with an increase of 15.9% compared with 2019, from 715.2 to 828.7 deaths per 100,000 population,” they wrote, noting that “certain categories of race (i.e., AI/AN and Asian) and Hispanic ethnicity reported on death certificates might have been misclassified, possibly resulting in underestimates of death rates for some groups.”

[email protected]

After losing at arbitration, as well as in federal court and partially on appeal, Tenet Healthcare is refusing to comment on whether it will continue to battle two Detroit-area cardiologists whom the hospital corporation fired from leadership positions in 2018.

The cardiologists were awarded $10.6 million from an arbitrator, who found that Detroit Medical Center (DMC) and its parent, Tenet, retaliated against Amir Kaki, MD, and Mahir Elder, MD, when the doctors repeatedly reported concerns about patient safety and potential fraud.

belchonock/Thinkstock

From respected to reviled

Both Dr. Kaki and Dr. Elder were respected at DMC, according to court filings.

Dr. Kaki was recruited from Weill Cornell Medical College by a Detroit mayor because of his expertise in interventional cardiology. He had staff privileges at DMC beginning in 2012 and was a clinical associate professor and assistant program director of the interventional cardiology fellowship program at Wayne State University in Detroit. He became director of the cardiac catheterization services unit at the new DMC Heart Hospital at Harper-Hutzel Hospital in Detroit in 2014, and 4 years later was appointed director of the facility’s anticoagulation clinic. Dr. Kaki was nominated for and completed Tenet’s Leadership Academy.

Dr. Elder was a clinical professor and assistant fellowship director at Wayne State and was a clinical professor of medicine at Michigan State University. Beginning in 2008, he held directorships at DMC’s cardiac care unit, ambulatory services program, cardiac CT angiogram program, PERT program, and carotid stenting program. Dr. Elder was voted Teacher of the Year for 10 consecutive years by DMC cardiology fellows.

The two doctors aimed high when it came to quality of care and ethics, according to legal filings. Over the years, Dr. Kaki and Dr. Elder repeatedly reported what they considered to be egregious violations of patient safety and of Medicare and Medicaid fraud laws. The clinicians complained about unsterile surgical instruments and the removal of a stat laboratory from the cardiac catheterization unit, noting that the removal would cause delays that would endanger lives.

At peer review meetings, as well as with administrators, they flagged colleagues who they said were performing unnecessary or dangerous procedures solely to generate revenue. At least one doctor falsified records of such a procedure after a patient died, alleged Dr. Kaki and Dr. Elder.

Tenet hired outside attorneys in the fall of 2018, telling Dr. Kaki and Dr. Elder that the legal team would investigate their complaints. However, the investigation was a sham: Filings allege that the investigation was used instead to build a case against Dr. Kaki and Dr. Elder and that Tenet leadership used the inquiry to pressure the cardiologists to resign.

They refused, and in October 2018, they were fired from their leadership positions. DMC and Tenet then held a press conference in which they said that Dr. Kaki and Dr. Elder had been dismissed for “violations” of the “Tenet Standards of Conduct.”
 

Cardiologists push back

Dr. Kaki and Dr. Elder, however, were not willing to just walk away. They sought reinstatement through an internal DMC appeals panel of their peers. The clinicians who participated on that panel ruled that neither firing was justified.

But DMC’s governing board voted in April 2020 to deny privileges to both cardiologists.

Tenet continued a campaign of retaliation, according to legal filings, by not paying the clinicians for being on call, by removing them from peer review committees, and by prohibiting them from teaching or giving lectures. DMC refused to give Dr. Kaki his personnel record, stating that he was never an employee when he was in the leadership position. Dr. Kaki sued, and a Wayne County Circuit Court judge granted his motion to get his file. DMC and Tenet appealed that ruling but lost.

Eventually, Ms. Gordon sued DMC and Tenet in federal court, alleging the hospital retaliated against the cardiologists, interfered with their ability to earn a living by disparaging them, refused to renew their privileges in 2019, and committed violations under multiple federal and state statutes, including the False Claims Act and the Fair Labor Standards Act.

Tenet successfully argued that the case should go to arbitration.

Arbitrator Mary Beth Kelly, though, ruled in December 2020 that the vast majority of the complaints compiled against the two physicians in the external investigation were not verified or supported and that Tenet and DMC had retaliated against Dr. Kaki and Dr. Elder.

For that harm, Ms. Kelly awarded each clinician $1 million, according to the final ruling shared in an interview.

In addition, she awarded Dr. Kaki $2.3 million in back pay and 2 years of front pay (slightly more than $1 million). She awarded Dr. Elder $2.3 million in back pay and $2.1 million in front pay for 4 years, noting that “his strong association with DMC may make it more difficult for him to successfully transition into the situation he enjoyed prior to termination and nonrenewal.”

The clinicians also were awarded legal fees of $623,816 and court costs of $110,673.
 

“Wholesale retrial”

To secure the award, Ms. Gordon had to seek a ruling from the U.S. District Court for Eastern Michigan. Tenet asked that court to overturn the arbitrator’s award and to keep it sealed from public view.

In his February ruling, Judge Arthur J. Tarnow wrote that Tenet and DMC “not only attempt to relitigate the legal issues, but also endeavor to introduce a factual counternarrative unmoored from the findings of the Arbitrator and including evidence which the Arbitrator specifically found inadmissible.

“By seeking a wholesale retrial of their case after forcing plaintiffs to arbitrate in the first place,” Tenet and DMC basically ignored the goal of arbitration, which is to relieve judicial congestion and provide a faster and cheaper alternative to litigation, he wrote.

Judge Tarnow also warned Tenet and DMC against taking too long to reinstate privileges for Dr. Kaki and Dr. Elder. If they “continue to delay the restoration of plaintiffs’ privileges in the hopes of a different result on appeal, they will be in violation of this Order,” said the judge.

Tenet, however, tried one more avenue to block the cardiologists from getting privileges, appealing to the Sixth Circuit, which again ordered the company to grant the 1-year privileges.

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

After losing at arbitration, as well as in federal court and partially on appeal, Tenet Healthcare is refusing to comment on whether it will continue to battle two Detroit-area cardiologists whom the hospital corporation fired from leadership positions in 2018.

The cardiologists were awarded $10.6 million from an arbitrator, who found that Detroit Medical Center (DMC) and its parent, Tenet, retaliated against Amir Kaki, MD, and Mahir Elder, MD, when the doctors repeatedly reported concerns about patient safety and potential fraud.

belchonock/Thinkstock

From respected to reviled

Both Dr. Kaki and Dr. Elder were respected at DMC, according to court filings.

Dr. Kaki was recruited from Weill Cornell Medical College by a Detroit mayor because of his expertise in interventional cardiology. He had staff privileges at DMC beginning in 2012 and was a clinical associate professor and assistant program director of the interventional cardiology fellowship program at Wayne State University in Detroit. He became director of the cardiac catheterization services unit at the new DMC Heart Hospital at Harper-Hutzel Hospital in Detroit in 2014, and 4 years later was appointed director of the facility’s anticoagulation clinic. Dr. Kaki was nominated for and completed Tenet’s Leadership Academy.

Dr. Elder was a clinical professor and assistant fellowship director at Wayne State and was a clinical professor of medicine at Michigan State University. Beginning in 2008, he held directorships at DMC’s cardiac care unit, ambulatory services program, cardiac CT angiogram program, PERT program, and carotid stenting program. Dr. Elder was voted Teacher of the Year for 10 consecutive years by DMC cardiology fellows.

The two doctors aimed high when it came to quality of care and ethics, according to legal filings. Over the years, Dr. Kaki and Dr. Elder repeatedly reported what they considered to be egregious violations of patient safety and of Medicare and Medicaid fraud laws. The clinicians complained about unsterile surgical instruments and the removal of a stat laboratory from the cardiac catheterization unit, noting that the removal would cause delays that would endanger lives.

At peer review meetings, as well as with administrators, they flagged colleagues who they said were performing unnecessary or dangerous procedures solely to generate revenue. At least one doctor falsified records of such a procedure after a patient died, alleged Dr. Kaki and Dr. Elder.

Tenet hired outside attorneys in the fall of 2018, telling Dr. Kaki and Dr. Elder that the legal team would investigate their complaints. However, the investigation was a sham: Filings allege that the investigation was used instead to build a case against Dr. Kaki and Dr. Elder and that Tenet leadership used the inquiry to pressure the cardiologists to resign.

They refused, and in October 2018, they were fired from their leadership positions. DMC and Tenet then held a press conference in which they said that Dr. Kaki and Dr. Elder had been dismissed for “violations” of the “Tenet Standards of Conduct.”
 

Cardiologists push back

Dr. Kaki and Dr. Elder, however, were not willing to just walk away. They sought reinstatement through an internal DMC appeals panel of their peers. The clinicians who participated on that panel ruled that neither firing was justified.

But DMC’s governing board voted in April 2020 to deny privileges to both cardiologists.

Tenet continued a campaign of retaliation, according to legal filings, by not paying the clinicians for being on call, by removing them from peer review committees, and by prohibiting them from teaching or giving lectures. DMC refused to give Dr. Kaki his personnel record, stating that he was never an employee when he was in the leadership position. Dr. Kaki sued, and a Wayne County Circuit Court judge granted his motion to get his file. DMC and Tenet appealed that ruling but lost.

Eventually, Ms. Gordon sued DMC and Tenet in federal court, alleging the hospital retaliated against the cardiologists, interfered with their ability to earn a living by disparaging them, refused to renew their privileges in 2019, and committed violations under multiple federal and state statutes, including the False Claims Act and the Fair Labor Standards Act.

Tenet successfully argued that the case should go to arbitration.

Arbitrator Mary Beth Kelly, though, ruled in December 2020 that the vast majority of the complaints compiled against the two physicians in the external investigation were not verified or supported and that Tenet and DMC had retaliated against Dr. Kaki and Dr. Elder.

For that harm, Ms. Kelly awarded each clinician $1 million, according to the final ruling shared in an interview.

In addition, she awarded Dr. Kaki $2.3 million in back pay and 2 years of front pay (slightly more than $1 million). She awarded Dr. Elder $2.3 million in back pay and $2.1 million in front pay for 4 years, noting that “his strong association with DMC may make it more difficult for him to successfully transition into the situation he enjoyed prior to termination and nonrenewal.”

The clinicians also were awarded legal fees of $623,816 and court costs of $110,673.
 

“Wholesale retrial”

To secure the award, Ms. Gordon had to seek a ruling from the U.S. District Court for Eastern Michigan. Tenet asked that court to overturn the arbitrator’s award and to keep it sealed from public view.

In his February ruling, Judge Arthur J. Tarnow wrote that Tenet and DMC “not only attempt to relitigate the legal issues, but also endeavor to introduce a factual counternarrative unmoored from the findings of the Arbitrator and including evidence which the Arbitrator specifically found inadmissible.

“By seeking a wholesale retrial of their case after forcing plaintiffs to arbitrate in the first place,” Tenet and DMC basically ignored the goal of arbitration, which is to relieve judicial congestion and provide a faster and cheaper alternative to litigation, he wrote.

Judge Tarnow also warned Tenet and DMC against taking too long to reinstate privileges for Dr. Kaki and Dr. Elder. If they “continue to delay the restoration of plaintiffs’ privileges in the hopes of a different result on appeal, they will be in violation of this Order,” said the judge.

Tenet, however, tried one more avenue to block the cardiologists from getting privileges, appealing to the Sixth Circuit, which again ordered the company to grant the 1-year privileges.

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

After losing at arbitration, as well as in federal court and partially on appeal, Tenet Healthcare is refusing to comment on whether it will continue to battle two Detroit-area cardiologists whom the hospital corporation fired from leadership positions in 2018.

The cardiologists were awarded $10.6 million from an arbitrator, who found that Detroit Medical Center (DMC) and its parent, Tenet, retaliated against Amir Kaki, MD, and Mahir Elder, MD, when the doctors repeatedly reported concerns about patient safety and potential fraud.

belchonock/Thinkstock

From respected to reviled

Both Dr. Kaki and Dr. Elder were respected at DMC, according to court filings.

Dr. Kaki was recruited from Weill Cornell Medical College by a Detroit mayor because of his expertise in interventional cardiology. He had staff privileges at DMC beginning in 2012 and was a clinical associate professor and assistant program director of the interventional cardiology fellowship program at Wayne State University in Detroit. He became director of the cardiac catheterization services unit at the new DMC Heart Hospital at Harper-Hutzel Hospital in Detroit in 2014, and 4 years later was appointed director of the facility’s anticoagulation clinic. Dr. Kaki was nominated for and completed Tenet’s Leadership Academy.

Dr. Elder was a clinical professor and assistant fellowship director at Wayne State and was a clinical professor of medicine at Michigan State University. Beginning in 2008, he held directorships at DMC’s cardiac care unit, ambulatory services program, cardiac CT angiogram program, PERT program, and carotid stenting program. Dr. Elder was voted Teacher of the Year for 10 consecutive years by DMC cardiology fellows.

The two doctors aimed high when it came to quality of care and ethics, according to legal filings. Over the years, Dr. Kaki and Dr. Elder repeatedly reported what they considered to be egregious violations of patient safety and of Medicare and Medicaid fraud laws. The clinicians complained about unsterile surgical instruments and the removal of a stat laboratory from the cardiac catheterization unit, noting that the removal would cause delays that would endanger lives.

At peer review meetings, as well as with administrators, they flagged colleagues who they said were performing unnecessary or dangerous procedures solely to generate revenue. At least one doctor falsified records of such a procedure after a patient died, alleged Dr. Kaki and Dr. Elder.

Tenet hired outside attorneys in the fall of 2018, telling Dr. Kaki and Dr. Elder that the legal team would investigate their complaints. However, the investigation was a sham: Filings allege that the investigation was used instead to build a case against Dr. Kaki and Dr. Elder and that Tenet leadership used the inquiry to pressure the cardiologists to resign.

They refused, and in October 2018, they were fired from their leadership positions. DMC and Tenet then held a press conference in which they said that Dr. Kaki and Dr. Elder had been dismissed for “violations” of the “Tenet Standards of Conduct.”
 

Cardiologists push back

Dr. Kaki and Dr. Elder, however, were not willing to just walk away. They sought reinstatement through an internal DMC appeals panel of their peers. The clinicians who participated on that panel ruled that neither firing was justified.

But DMC’s governing board voted in April 2020 to deny privileges to both cardiologists.

Tenet continued a campaign of retaliation, according to legal filings, by not paying the clinicians for being on call, by removing them from peer review committees, and by prohibiting them from teaching or giving lectures. DMC refused to give Dr. Kaki his personnel record, stating that he was never an employee when he was in the leadership position. Dr. Kaki sued, and a Wayne County Circuit Court judge granted his motion to get his file. DMC and Tenet appealed that ruling but lost.

Eventually, Ms. Gordon sued DMC and Tenet in federal court, alleging the hospital retaliated against the cardiologists, interfered with their ability to earn a living by disparaging them, refused to renew their privileges in 2019, and committed violations under multiple federal and state statutes, including the False Claims Act and the Fair Labor Standards Act.

Tenet successfully argued that the case should go to arbitration.

Arbitrator Mary Beth Kelly, though, ruled in December 2020 that the vast majority of the complaints compiled against the two physicians in the external investigation were not verified or supported and that Tenet and DMC had retaliated against Dr. Kaki and Dr. Elder.

For that harm, Ms. Kelly awarded each clinician $1 million, according to the final ruling shared in an interview.

In addition, she awarded Dr. Kaki $2.3 million in back pay and 2 years of front pay (slightly more than $1 million). She awarded Dr. Elder $2.3 million in back pay and $2.1 million in front pay for 4 years, noting that “his strong association with DMC may make it more difficult for him to successfully transition into the situation he enjoyed prior to termination and nonrenewal.”

The clinicians also were awarded legal fees of $623,816 and court costs of $110,673.
 

“Wholesale retrial”

To secure the award, Ms. Gordon had to seek a ruling from the U.S. District Court for Eastern Michigan. Tenet asked that court to overturn the arbitrator’s award and to keep it sealed from public view.

In his February ruling, Judge Arthur J. Tarnow wrote that Tenet and DMC “not only attempt to relitigate the legal issues, but also endeavor to introduce a factual counternarrative unmoored from the findings of the Arbitrator and including evidence which the Arbitrator specifically found inadmissible.

“By seeking a wholesale retrial of their case after forcing plaintiffs to arbitrate in the first place,” Tenet and DMC basically ignored the goal of arbitration, which is to relieve judicial congestion and provide a faster and cheaper alternative to litigation, he wrote.

Judge Tarnow also warned Tenet and DMC against taking too long to reinstate privileges for Dr. Kaki and Dr. Elder. If they “continue to delay the restoration of plaintiffs’ privileges in the hopes of a different result on appeal, they will be in violation of this Order,” said the judge.

Tenet, however, tried one more avenue to block the cardiologists from getting privileges, appealing to the Sixth Circuit, which again ordered the company to grant the 1-year privileges.

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

The evidence in favor of endovascular therapy for selected stroke patients who present in the late time window, from 6 to 24 hours after stroke onset, has been strengthened by the results of a new meta-analysis of data from six clinical trials.

Results of the AURORA analysis showed that for every 100 patients treated with thrombectomy, 33 patients will have less disability, and 27 patients will achieve an independent level of functioning compared with patients who receive only standard medical care.

The benefit of mechanical removal of the clot for selected patients who may have salvageable brain tissue, as identified through the use of various imaging modalities, was maintained whether the patient had a “wake-up stroke” or the onset of symptoms was witnessed, regardless of the point in time within the late window. In fact, the benefit of intervention was greater for patients who presented in the latter part of the late time window.

Never too late for urgent medical care

“While the findings of this analysis do not contradict the mantra that the earlier treatment is instituted, the higher the chance of a good outcome, they highlight the fact that it is never too late to seek urgent medical care,” said lead investigator Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey.

“The implications of the findings from AURORA are that they could lead to a change in guidelines from endorsement of thrombectomy as level 1a recommendation in eligible patients presenting in the 6- to 16-hour time window to a 6- to 24-hour time window,” said Dr. Jovin.

“Furthermore, there are strong signals of benefit of thrombectomy in patients who are not selected based on volumetric analysis of baseline infarct (core) or extent of tissue at risk (penumbra), such that when those imaging modalities are not available or contraindicated, selection based on noncontrast CT and clinical information only may be acceptable,” he added. “Finally, the possibility of benefit from thrombectomy performed beyond 24 hours from last seen well is real and should be explored in future studies.”

The AURORA findings were presented at the virtual International Stroke Conference (ISC) 2021.

The objective of the study was to provide a more precise estimate of the benefit of thrombectomy for patients with stroke when performed within 6-24 hours after the patient was last seen well, Dr. Jovin explained.

He said the 6-hour cutoff was chosen somewhat arbitrarily, but added, “It is highly consequential, as it marks the point of demarcation between the early and late time window, and virtually all guidelines recommend different approaches, dependent on whether patients present before or after 6 hours from symptom onset.”

The 6+ hour window

Dr. Jovin pointed out that for patients who present beyond 6 hours, treatment options are more restricted, because the data on thrombectomy in this later period come mainly from two North American trials (DEFUSE 3 and DAWN) that had very stringent imaging criteria for enrollment.

“We wanted to create a heterogeneous dataset with regard to geography and selection criteria by forming the AURORA collaboration,” he commented. Their study involved an individual-level pooled analysis of all patients who underwent randomization after 6 hours from the time that they were last seen well. Patients were randomly assigned to receive either best medical therapy alone or best medical therapy plus thrombectomy (either with stent retrievers or aspiration) for anterior circulation proximal large-vessel occlusion stroke.

The data came from six trials: DAWN (which enrolled patients 6-24 hours from stroke onset), DEFUSE 3 (6-16 hours), ESCAPE (0-12 hours), REVASCAT (0-8 hours), RESILIENT (0-8 hours), and POSITIVE (0-12 hours). In total, 505 patients were included in the meta-analysis, 266 in the intervention group, and 239 in the control group.

“By pooling data on patients presenting after 6 hours from all these trails, we achieve greater precision for treatment effect estimation and increased the power for subgroup analysis,” Dr. Jovin noted.

Although the majority of the patients were in the DAWN and DIFFUSE 3 trials (n = 388), “there are still a good number from the other four trials (n = 117),” Dr. Jovin reported.

Most of the trials used Modified Rankin Scale (mRS) ordinal or shift analysis as their primary endpoint, which was the also the endpoint chosen for this meta-analysis.

Imaging selection criteria ranged from fully automated software-generated quantitative volumetric analysis of baseline infarct (core) or tissue at risk to CT perfusion and plain CT/CTA. The minimum ASPECTS score was 5 or 6.

There were no imbalances in baseline characteristics. The median NIH Stroke Scale score was 16, and the median ASPECTS score was 8. The median time to randomization was 10.5 hours.

With regard to safety, there was no significant difference in rates of symptomatic intracerebral hemorrhage (5.3% in the intervention group vs. 3.3% in the control group; P = .23) or in mortality at 90 days (16.5% vs. 19.3%; P = .87). Jovin noted that these results are very similar to those from the HERMES meta-analysis of patients treated in the early time window.

The primary outcome – ordinal analysis of the mRS distribution – showed an adjusted odds ratio of 2.54 (P < .0001) for benefit in the intervention group. The number needed to treat to reduce disability was 3. “This is again very similar to the HERMES meta-analysis of patients in the early window,” Dr. Jovin said.

The P value for heterogeneity of treatment effect across the six studies was nonsignificant.

Secondary outcome analysis showed an “almost 27%” difference in good functional outcome (MRS, 0-2) between the two groups (45.9% in the intervention group vs. 19.3% in the control group), which translates into a number needed to treat of 3.8, Dr. Jovin reported.

Subgroup analysis showed a treatment effect favoring intervention across all prespecified subgroup factors, including age, sex, occlusion location, mode of presentation (wake-up vs. witnessed), and ASPECTS score, with the caveat that most of the patients were enrolled with ASPECTS scores of 7 or greater.

Early versus late

Surprisingly, although thrombectomy was found to be beneficial in both the 6- to 12-hour and 12- to 24-hour time window, the magnitude of benefit was significantly higher in the later rather than the earlier time window. The odds ratio of a better outcome with thrombectomy on the mRS shift analysis in those presenting in the 6- to 12-hour period was 1.78, compared with 5.86 in the 12- to 24-hour time window.

“This should not be interpreted as a higher chance of a good outcome if treated late. In fact, the rate of good outcomes were numerically higher in the earlier treated patients, but the difference comes from the control group, which did much worse in patients randomized in the later time period,” Dr. Jovin said.

“Aurora was the goddess of dawn [in ancient Roman mythology], so this is a very fitting name, as it reminds us that we are in the dawn of a new era where patients are selected based on physiological data rather than on time, and we certainly hope that this work has brought us closer to this reality,” Dr. Jovin concluded.

Commenting on the study, Michael Hill, MD, University of Calgary (Alta.), said: “The work provides pooled empiric data to support the concept that time to treatment is no longer the sole threshold variable to be used in treatment decision-making. Instead, time is now simply another variable to consider in the context of clinical and imaging factors.”

Dr. Hill, who headed up the ESCAPE trial and was also involved in the current meta-analysis, added: “This meta-analysis supports the concept of patient selection using the ‘good scan’ model, rather than using a time-based concept of patient eligibility for endovascular therapy. It will further push changes in care, because the implication is that all patients with more severe acute stroke presentations need emergency neurovascular imaging to decide if they are eligible for treatment.”

The AURORA meta-analysis was funded by Stryker Neurovascular. Dr. Jovin reports stock holdings in Anaconda, Route 92, VizAi, FreeOx, Blockade Medical, Methinks, and Corindus; personal fees from Cerenovus and Contego Medical; travel support from Fundacio Ictus; and grant support from Medtronic and Stryker Neurovascular.

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

The evidence in favor of endovascular therapy for selected stroke patients who present in the late time window, from 6 to 24 hours after stroke onset, has been strengthened by the results of a new meta-analysis of data from six clinical trials.

Results of the AURORA analysis showed that for every 100 patients treated with thrombectomy, 33 patients will have less disability, and 27 patients will achieve an independent level of functioning compared with patients who receive only standard medical care.

The benefit of mechanical removal of the clot for selected patients who may have salvageable brain tissue, as identified through the use of various imaging modalities, was maintained whether the patient had a “wake-up stroke” or the onset of symptoms was witnessed, regardless of the point in time within the late window. In fact, the benefit of intervention was greater for patients who presented in the latter part of the late time window.

Never too late for urgent medical care

“While the findings of this analysis do not contradict the mantra that the earlier treatment is instituted, the higher the chance of a good outcome, they highlight the fact that it is never too late to seek urgent medical care,” said lead investigator Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey.

“The implications of the findings from AURORA are that they could lead to a change in guidelines from endorsement of thrombectomy as level 1a recommendation in eligible patients presenting in the 6- to 16-hour time window to a 6- to 24-hour time window,” said Dr. Jovin.

“Furthermore, there are strong signals of benefit of thrombectomy in patients who are not selected based on volumetric analysis of baseline infarct (core) or extent of tissue at risk (penumbra), such that when those imaging modalities are not available or contraindicated, selection based on noncontrast CT and clinical information only may be acceptable,” he added. “Finally, the possibility of benefit from thrombectomy performed beyond 24 hours from last seen well is real and should be explored in future studies.”

The AURORA findings were presented at the virtual International Stroke Conference (ISC) 2021.

The objective of the study was to provide a more precise estimate of the benefit of thrombectomy for patients with stroke when performed within 6-24 hours after the patient was last seen well, Dr. Jovin explained.

He said the 6-hour cutoff was chosen somewhat arbitrarily, but added, “It is highly consequential, as it marks the point of demarcation between the early and late time window, and virtually all guidelines recommend different approaches, dependent on whether patients present before or after 6 hours from symptom onset.”

The 6+ hour window

Dr. Jovin pointed out that for patients who present beyond 6 hours, treatment options are more restricted, because the data on thrombectomy in this later period come mainly from two North American trials (DEFUSE 3 and DAWN) that had very stringent imaging criteria for enrollment.

“We wanted to create a heterogeneous dataset with regard to geography and selection criteria by forming the AURORA collaboration,” he commented. Their study involved an individual-level pooled analysis of all patients who underwent randomization after 6 hours from the time that they were last seen well. Patients were randomly assigned to receive either best medical therapy alone or best medical therapy plus thrombectomy (either with stent retrievers or aspiration) for anterior circulation proximal large-vessel occlusion stroke.

The data came from six trials: DAWN (which enrolled patients 6-24 hours from stroke onset), DEFUSE 3 (6-16 hours), ESCAPE (0-12 hours), REVASCAT (0-8 hours), RESILIENT (0-8 hours), and POSITIVE (0-12 hours). In total, 505 patients were included in the meta-analysis, 266 in the intervention group, and 239 in the control group.

“By pooling data on patients presenting after 6 hours from all these trails, we achieve greater precision for treatment effect estimation and increased the power for subgroup analysis,” Dr. Jovin noted.

Although the majority of the patients were in the DAWN and DIFFUSE 3 trials (n = 388), “there are still a good number from the other four trials (n = 117),” Dr. Jovin reported.

Most of the trials used Modified Rankin Scale (mRS) ordinal or shift analysis as their primary endpoint, which was the also the endpoint chosen for this meta-analysis.

Imaging selection criteria ranged from fully automated software-generated quantitative volumetric analysis of baseline infarct (core) or tissue at risk to CT perfusion and plain CT/CTA. The minimum ASPECTS score was 5 or 6.

There were no imbalances in baseline characteristics. The median NIH Stroke Scale score was 16, and the median ASPECTS score was 8. The median time to randomization was 10.5 hours.

With regard to safety, there was no significant difference in rates of symptomatic intracerebral hemorrhage (5.3% in the intervention group vs. 3.3% in the control group; P = .23) or in mortality at 90 days (16.5% vs. 19.3%; P = .87). Jovin noted that these results are very similar to those from the HERMES meta-analysis of patients treated in the early time window.

The primary outcome – ordinal analysis of the mRS distribution – showed an adjusted odds ratio of 2.54 (P < .0001) for benefit in the intervention group. The number needed to treat to reduce disability was 3. “This is again very similar to the HERMES meta-analysis of patients in the early window,” Dr. Jovin said.

The P value for heterogeneity of treatment effect across the six studies was nonsignificant.

Secondary outcome analysis showed an “almost 27%” difference in good functional outcome (MRS, 0-2) between the two groups (45.9% in the intervention group vs. 19.3% in the control group), which translates into a number needed to treat of 3.8, Dr. Jovin reported.

Subgroup analysis showed a treatment effect favoring intervention across all prespecified subgroup factors, including age, sex, occlusion location, mode of presentation (wake-up vs. witnessed), and ASPECTS score, with the caveat that most of the patients were enrolled with ASPECTS scores of 7 or greater.

Early versus late

Surprisingly, although thrombectomy was found to be beneficial in both the 6- to 12-hour and 12- to 24-hour time window, the magnitude of benefit was significantly higher in the later rather than the earlier time window. The odds ratio of a better outcome with thrombectomy on the mRS shift analysis in those presenting in the 6- to 12-hour period was 1.78, compared with 5.86 in the 12- to 24-hour time window.

“This should not be interpreted as a higher chance of a good outcome if treated late. In fact, the rate of good outcomes were numerically higher in the earlier treated patients, but the difference comes from the control group, which did much worse in patients randomized in the later time period,” Dr. Jovin said.

“Aurora was the goddess of dawn [in ancient Roman mythology], so this is a very fitting name, as it reminds us that we are in the dawn of a new era where patients are selected based on physiological data rather than on time, and we certainly hope that this work has brought us closer to this reality,” Dr. Jovin concluded.

Commenting on the study, Michael Hill, MD, University of Calgary (Alta.), said: “The work provides pooled empiric data to support the concept that time to treatment is no longer the sole threshold variable to be used in treatment decision-making. Instead, time is now simply another variable to consider in the context of clinical and imaging factors.”

Dr. Hill, who headed up the ESCAPE trial and was also involved in the current meta-analysis, added: “This meta-analysis supports the concept of patient selection using the ‘good scan’ model, rather than using a time-based concept of patient eligibility for endovascular therapy. It will further push changes in care, because the implication is that all patients with more severe acute stroke presentations need emergency neurovascular imaging to decide if they are eligible for treatment.”

The AURORA meta-analysis was funded by Stryker Neurovascular. Dr. Jovin reports stock holdings in Anaconda, Route 92, VizAi, FreeOx, Blockade Medical, Methinks, and Corindus; personal fees from Cerenovus and Contego Medical; travel support from Fundacio Ictus; and grant support from Medtronic and Stryker Neurovascular.

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

The evidence in favor of endovascular therapy for selected stroke patients who present in the late time window, from 6 to 24 hours after stroke onset, has been strengthened by the results of a new meta-analysis of data from six clinical trials.

Results of the AURORA analysis showed that for every 100 patients treated with thrombectomy, 33 patients will have less disability, and 27 patients will achieve an independent level of functioning compared with patients who receive only standard medical care.

The benefit of mechanical removal of the clot for selected patients who may have salvageable brain tissue, as identified through the use of various imaging modalities, was maintained whether the patient had a “wake-up stroke” or the onset of symptoms was witnessed, regardless of the point in time within the late window. In fact, the benefit of intervention was greater for patients who presented in the latter part of the late time window.

Never too late for urgent medical care

“While the findings of this analysis do not contradict the mantra that the earlier treatment is instituted, the higher the chance of a good outcome, they highlight the fact that it is never too late to seek urgent medical care,” said lead investigator Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey.

“The implications of the findings from AURORA are that they could lead to a change in guidelines from endorsement of thrombectomy as level 1a recommendation in eligible patients presenting in the 6- to 16-hour time window to a 6- to 24-hour time window,” said Dr. Jovin.

“Furthermore, there are strong signals of benefit of thrombectomy in patients who are not selected based on volumetric analysis of baseline infarct (core) or extent of tissue at risk (penumbra), such that when those imaging modalities are not available or contraindicated, selection based on noncontrast CT and clinical information only may be acceptable,” he added. “Finally, the possibility of benefit from thrombectomy performed beyond 24 hours from last seen well is real and should be explored in future studies.”

The AURORA findings were presented at the virtual International Stroke Conference (ISC) 2021.

The objective of the study was to provide a more precise estimate of the benefit of thrombectomy for patients with stroke when performed within 6-24 hours after the patient was last seen well, Dr. Jovin explained.

He said the 6-hour cutoff was chosen somewhat arbitrarily, but added, “It is highly consequential, as it marks the point of demarcation between the early and late time window, and virtually all guidelines recommend different approaches, dependent on whether patients present before or after 6 hours from symptom onset.”

The 6+ hour window

Dr. Jovin pointed out that for patients who present beyond 6 hours, treatment options are more restricted, because the data on thrombectomy in this later period come mainly from two North American trials (DEFUSE 3 and DAWN) that had very stringent imaging criteria for enrollment.

“We wanted to create a heterogeneous dataset with regard to geography and selection criteria by forming the AURORA collaboration,” he commented. Their study involved an individual-level pooled analysis of all patients who underwent randomization after 6 hours from the time that they were last seen well. Patients were randomly assigned to receive either best medical therapy alone or best medical therapy plus thrombectomy (either with stent retrievers or aspiration) for anterior circulation proximal large-vessel occlusion stroke.

The data came from six trials: DAWN (which enrolled patients 6-24 hours from stroke onset), DEFUSE 3 (6-16 hours), ESCAPE (0-12 hours), REVASCAT (0-8 hours), RESILIENT (0-8 hours), and POSITIVE (0-12 hours). In total, 505 patients were included in the meta-analysis, 266 in the intervention group, and 239 in the control group.

“By pooling data on patients presenting after 6 hours from all these trails, we achieve greater precision for treatment effect estimation and increased the power for subgroup analysis,” Dr. Jovin noted.

Although the majority of the patients were in the DAWN and DIFFUSE 3 trials (n = 388), “there are still a good number from the other four trials (n = 117),” Dr. Jovin reported.

Most of the trials used Modified Rankin Scale (mRS) ordinal or shift analysis as their primary endpoint, which was the also the endpoint chosen for this meta-analysis.

Imaging selection criteria ranged from fully automated software-generated quantitative volumetric analysis of baseline infarct (core) or tissue at risk to CT perfusion and plain CT/CTA. The minimum ASPECTS score was 5 or 6.

There were no imbalances in baseline characteristics. The median NIH Stroke Scale score was 16, and the median ASPECTS score was 8. The median time to randomization was 10.5 hours.

With regard to safety, there was no significant difference in rates of symptomatic intracerebral hemorrhage (5.3% in the intervention group vs. 3.3% in the control group; P = .23) or in mortality at 90 days (16.5% vs. 19.3%; P = .87). Jovin noted that these results are very similar to those from the HERMES meta-analysis of patients treated in the early time window.

The primary outcome – ordinal analysis of the mRS distribution – showed an adjusted odds ratio of 2.54 (P < .0001) for benefit in the intervention group. The number needed to treat to reduce disability was 3. “This is again very similar to the HERMES meta-analysis of patients in the early window,” Dr. Jovin said.

The P value for heterogeneity of treatment effect across the six studies was nonsignificant.

Secondary outcome analysis showed an “almost 27%” difference in good functional outcome (MRS, 0-2) between the two groups (45.9% in the intervention group vs. 19.3% in the control group), which translates into a number needed to treat of 3.8, Dr. Jovin reported.

Subgroup analysis showed a treatment effect favoring intervention across all prespecified subgroup factors, including age, sex, occlusion location, mode of presentation (wake-up vs. witnessed), and ASPECTS score, with the caveat that most of the patients were enrolled with ASPECTS scores of 7 or greater.

Early versus late

Surprisingly, although thrombectomy was found to be beneficial in both the 6- to 12-hour and 12- to 24-hour time window, the magnitude of benefit was significantly higher in the later rather than the earlier time window. The odds ratio of a better outcome with thrombectomy on the mRS shift analysis in those presenting in the 6- to 12-hour period was 1.78, compared with 5.86 in the 12- to 24-hour time window.

“This should not be interpreted as a higher chance of a good outcome if treated late. In fact, the rate of good outcomes were numerically higher in the earlier treated patients, but the difference comes from the control group, which did much worse in patients randomized in the later time period,” Dr. Jovin said.

“Aurora was the goddess of dawn [in ancient Roman mythology], so this is a very fitting name, as it reminds us that we are in the dawn of a new era where patients are selected based on physiological data rather than on time, and we certainly hope that this work has brought us closer to this reality,” Dr. Jovin concluded.

Commenting on the study, Michael Hill, MD, University of Calgary (Alta.), said: “The work provides pooled empiric data to support the concept that time to treatment is no longer the sole threshold variable to be used in treatment decision-making. Instead, time is now simply another variable to consider in the context of clinical and imaging factors.”

Dr. Hill, who headed up the ESCAPE trial and was also involved in the current meta-analysis, added: “This meta-analysis supports the concept of patient selection using the ‘good scan’ model, rather than using a time-based concept of patient eligibility for endovascular therapy. It will further push changes in care, because the implication is that all patients with more severe acute stroke presentations need emergency neurovascular imaging to decide if they are eligible for treatment.”

The AURORA meta-analysis was funded by Stryker Neurovascular. Dr. Jovin reports stock holdings in Anaconda, Route 92, VizAi, FreeOx, Blockade Medical, Methinks, and Corindus; personal fees from Cerenovus and Contego Medical; travel support from Fundacio Ictus; and grant support from Medtronic and Stryker Neurovascular.

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

The Centers for Disease Control and Prevention has added several new medical conditions to its list of those that predispose adults to more severe COVID-19 illness.

Conditions that had previously been categorized as “might be” placing individuals at increased risk – but now are listed as high risk – include type 1 diabetes (in addition to type 2), moderate-to-severe asthma, liver disease, dementia or other neurologic conditions, stroke/cerebrovascular disease, HIV infection, cystic fibrosis, and overweight (in addition to obesity).

Substance use disorders, which hadn’t been previously listed, are now also considered high risk.  

The new list groups together certain categories, such as chronic lung diseases (chronic obstructive pulmonary disease, asthma, cystic fibrosis, etc) and heart conditions (heart failure, coronary artery disease, hypertension, etc).

Both diabetes types are now grouped under “diabetes.”  

The added medical conditions were posted on the CDC website’s COVID-19 page on March 29.
 

Type 1 diabetes and other conditions now priority for vaccination

The CDC refers to the medical conditions list as phase 1c in regard to COVID-19 vaccine prioritization, which means that anyone with any of these conditions can now be prioritized for vaccination, following those in groups 1a (frontline essential workers and those in long-term care facilities) and 1b (people aged 65-74 years; other essential workers; and people aged 16-64 years with underlying conditions that increase the risk of serious, life-threatening complications from COVID-19).

But in many cases, multiple states have already either fully opened up vaccine eligibility to all adults or have created their own lists of underlying high-risk medical conditions, CDC spokeswoman Kristen Nordlund told this news organization.  

No conditions have been removed from the list.

In January, the American Diabetes Association and 18 other organizations sent a letter to the CDC requesting that type 1 diabetes be prioritized along with type 2, based on data from studies showing people with both types to be at high risk for severe COVID-19 illness.

Now, ADA says, “this updated guidance will help to address the fact that in many states, millions of people with type 1 diabetes have not been prioritized equally, slowing their access to critical vaccines.”

While awaiting this latest CDC move, ADA had been urging state governors to prioritize type 1 and type 2 diabetes equally. As of now, 38 states and the District of Columbia had either done so or announced that they would.

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

The Centers for Disease Control and Prevention has added several new medical conditions to its list of those that predispose adults to more severe COVID-19 illness.

Conditions that had previously been categorized as “might be” placing individuals at increased risk – but now are listed as high risk – include type 1 diabetes (in addition to type 2), moderate-to-severe asthma, liver disease, dementia or other neurologic conditions, stroke/cerebrovascular disease, HIV infection, cystic fibrosis, and overweight (in addition to obesity).

Substance use disorders, which hadn’t been previously listed, are now also considered high risk.  

The new list groups together certain categories, such as chronic lung diseases (chronic obstructive pulmonary disease, asthma, cystic fibrosis, etc) and heart conditions (heart failure, coronary artery disease, hypertension, etc).

Both diabetes types are now grouped under “diabetes.”  

The added medical conditions were posted on the CDC website’s COVID-19 page on March 29.
 

Type 1 diabetes and other conditions now priority for vaccination

The CDC refers to the medical conditions list as phase 1c in regard to COVID-19 vaccine prioritization, which means that anyone with any of these conditions can now be prioritized for vaccination, following those in groups 1a (frontline essential workers and those in long-term care facilities) and 1b (people aged 65-74 years; other essential workers; and people aged 16-64 years with underlying conditions that increase the risk of serious, life-threatening complications from COVID-19).

But in many cases, multiple states have already either fully opened up vaccine eligibility to all adults or have created their own lists of underlying high-risk medical conditions, CDC spokeswoman Kristen Nordlund told this news organization.  

No conditions have been removed from the list.

In January, the American Diabetes Association and 18 other organizations sent a letter to the CDC requesting that type 1 diabetes be prioritized along with type 2, based on data from studies showing people with both types to be at high risk for severe COVID-19 illness.

Now, ADA says, “this updated guidance will help to address the fact that in many states, millions of people with type 1 diabetes have not been prioritized equally, slowing their access to critical vaccines.”

While awaiting this latest CDC move, ADA had been urging state governors to prioritize type 1 and type 2 diabetes equally. As of now, 38 states and the District of Columbia had either done so or announced that they would.

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

The Centers for Disease Control and Prevention has added several new medical conditions to its list of those that predispose adults to more severe COVID-19 illness.

Conditions that had previously been categorized as “might be” placing individuals at increased risk – but now are listed as high risk – include type 1 diabetes (in addition to type 2), moderate-to-severe asthma, liver disease, dementia or other neurologic conditions, stroke/cerebrovascular disease, HIV infection, cystic fibrosis, and overweight (in addition to obesity).

Substance use disorders, which hadn’t been previously listed, are now also considered high risk.  

The new list groups together certain categories, such as chronic lung diseases (chronic obstructive pulmonary disease, asthma, cystic fibrosis, etc) and heart conditions (heart failure, coronary artery disease, hypertension, etc).

Both diabetes types are now grouped under “diabetes.”  

The added medical conditions were posted on the CDC website’s COVID-19 page on March 29.
 

Type 1 diabetes and other conditions now priority for vaccination

The CDC refers to the medical conditions list as phase 1c in regard to COVID-19 vaccine prioritization, which means that anyone with any of these conditions can now be prioritized for vaccination, following those in groups 1a (frontline essential workers and those in long-term care facilities) and 1b (people aged 65-74 years; other essential workers; and people aged 16-64 years with underlying conditions that increase the risk of serious, life-threatening complications from COVID-19).

But in many cases, multiple states have already either fully opened up vaccine eligibility to all adults or have created their own lists of underlying high-risk medical conditions, CDC spokeswoman Kristen Nordlund told this news organization.  

No conditions have been removed from the list.

In January, the American Diabetes Association and 18 other organizations sent a letter to the CDC requesting that type 1 diabetes be prioritized along with type 2, based on data from studies showing people with both types to be at high risk for severe COVID-19 illness.

Now, ADA says, “this updated guidance will help to address the fact that in many states, millions of people with type 1 diabetes have not been prioritized equally, slowing their access to critical vaccines.”

While awaiting this latest CDC move, ADA had been urging state governors to prioritize type 1 and type 2 diabetes equally. As of now, 38 states and the District of Columbia had either done so or announced that they would.

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

A radially adjustable stent retriever provided a high rate of substantial reperfusion and was associated with low rates of symptomatic intracranial hemorrhage and death in a new study. The novel device may increase the options for endovascular therapy, researchers say.

In this study, the Tigertriever (Rapid Medical) was noninferior to a prespecified performance goal and superior to established devices, as determined from historical rates derived from trials. The device achieved first-pass successful reperfusion in approximately 6 of 10 patients and final successful reperfusion in more than 9 of 10 patients.

“The Tigertriever is a highly effective and safe device to remove thrombus in patients with large-vessel occlusion who are eligible for mechanical thrombectomy,” Rishi Gupta, MD, a vascular neurologist at Wellstar Health System Kennestone Hospital, Marietta, Ga., said during his presentation.

Results of the TIGER trial were presented at the International Stroke Conference, sponsored by the American Heart Association, and were published online March 19, 2021, in Stroke.

Endovascular therapy significantly improves outcomes of acute ischemic stroke resulting from large-vessel occlusion. However, current devices fail to achieve successful reperfusion in approximately 27% of patients, the researchers noted. In addition, the devices are associated with complications such as embolization to a new territory and symptomatic intracranial hemorrhage.

The Tigertriever is a radially adjustable, fully visible stent retriever. The operator controls the device’s radial expansion and force, enabling the operator to minimize vessel tension. The Tigertriever is available in Europe.

Effective revascularization

Dr. Gupta and colleagues conducted the prospective, single-arm TIGER study to evaluate the safety and efficacy of the Tigertriever in restoring blood flow by removing clots for patients with ischemic stroke resulting from large-vessel occlusion. The investigators compared the performance of the Tigertriever with a composite performance goal criterion derived from six pivotal trials of the Solitaire and Trevo devices.

The researchers enrolled patients at 16 U.S. sites and one site in Israel. Eligible participants had acute ischemic stroke resulting from large-vessel occlusion and moderate to severe neurologic deficits within 8 hours of symptom onset.

The study’s primary efficacy endpoint was successful revascularization within three Tigertriever passes. The investigators defined successful revascularization as achieving a modified Thrombolysis in Cerebral Ischemia score of 2b-3. Secondary efficacy endpoints were first-pass successful revascularization and good clinical outcome, which was defined as a Modified Rankin Scale score of 0-2.

The primary safety endpoint was the composite of symptomatic intracranial hemorrhage at 24 hours and all-cause mortality at 3 months.

The researchers enrolled 160 patients between May 2018 and March 2020. The mean age of the patients was 65 years, and 61.5% were men. The median National Institutes of Health Stroke Scale score was 17. Approximately 66% of patients received tissue plasminogen activator, and the median time to tPA administration was 95 minutes.

Most occlusions were in the M1 segment of the middle cerebral artery (57.3%) or the M2 segment of the MCA (19.7%). Approximately 21% of occlusions were in the internal carotid artery.

Successful revascularization was achieved in 84.6% of participants within three passes of the Tigertriever device. This rate surpassed the 63.4% performance goal and the 73.4% historical rate.

Successful revascularization was achieved in 57.8% of cases on first pass. After three passes, the rate was 84.6%. The rate of good clinical outcome at 90 days was 58% with the Tigertriever and 43% with the historical control.

The rate of symptomatic intracranial hemorrhage at 24 hours and mortality at 90 days was 18.1% with the Tigertriever and 20.4% with the historical control.

The rates of symptomatic hemorrhage and of embolization to a new territory with the Tigertriever were lower than with other devices, despite the relatively infrequent use of balloon guide catheters in the study, said Dr. Gupta.

Unmeasured confounding

“I congratulate the TIGER investigators for an interesting study that looked at a novel stentriever with adjustable radial size and force,” said Adam de Havenon, MD, assistant professor of neurology at the University of Utah, Salt Lake City, who was asked to comment on the study. “This intuitive concept shows promise in comparison to historical controls, and I look forward to hearing more about this exciting technology.”

The major advantage of the use of a composite historical control in the study is that fewer patients are needed for a trial, said Dr. de Havenon. This design makes the trial more economical and enables it to be completed more quickly.

“The impact is that a real-world patient could receive a beneficial treatment even sooner if it was shown to be beneficial with this study design,” he added. “The disadvantage is that there is unmeasured confounding because the historical controls come from trials during different time periods and at different centers and countries, with unique demographics that may not match well with your cohort.”

Statistical methodology helps mitigate this unmeasured confounding, but it remains a concern in the quest for a high level of evidence, Dr. de Havenon added.

The data suggest that the Tigertriever is a viable alternative to other stent retrievers, but they do not support its preferential use. “If the goal is to have the Tigertriever be considered a viable treatment option for large-vessel occlusion stroke, then [the researchers] have accomplished that with this study, which provides the needed data for FDA approval of the device,” said Dr. de Havenon.

“However, these data introduce the possibility of superiority but do not definitely show that,” he concluded. “To do so, they would need a randomized trial with a comparator device or devices and, as a result, a larger sample size.”

The study was funded by Rapid Medical. Dr. Gupta was one of the principal investigators for this study and for studies sponsored by Stryker Neurovascular, Zoll, and Vesalio. He served on the clinical events committee of a trial sponsored by Penumbra and has acted as a consultant for Cerenovous. Dr de Havenon disclosed no relevant financial relationships.

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

A radially adjustable stent retriever provided a high rate of substantial reperfusion and was associated with low rates of symptomatic intracranial hemorrhage and death in a new study. The novel device may increase the options for endovascular therapy, researchers say.

In this study, the Tigertriever (Rapid Medical) was noninferior to a prespecified performance goal and superior to established devices, as determined from historical rates derived from trials. The device achieved first-pass successful reperfusion in approximately 6 of 10 patients and final successful reperfusion in more than 9 of 10 patients.

“The Tigertriever is a highly effective and safe device to remove thrombus in patients with large-vessel occlusion who are eligible for mechanical thrombectomy,” Rishi Gupta, MD, a vascular neurologist at Wellstar Health System Kennestone Hospital, Marietta, Ga., said during his presentation.

Results of the TIGER trial were presented at the International Stroke Conference, sponsored by the American Heart Association, and were published online March 19, 2021, in Stroke.

Endovascular therapy significantly improves outcomes of acute ischemic stroke resulting from large-vessel occlusion. However, current devices fail to achieve successful reperfusion in approximately 27% of patients, the researchers noted. In addition, the devices are associated with complications such as embolization to a new territory and symptomatic intracranial hemorrhage.

The Tigertriever is a radially adjustable, fully visible stent retriever. The operator controls the device’s radial expansion and force, enabling the operator to minimize vessel tension. The Tigertriever is available in Europe.

Effective revascularization

Dr. Gupta and colleagues conducted the prospective, single-arm TIGER study to evaluate the safety and efficacy of the Tigertriever in restoring blood flow by removing clots for patients with ischemic stroke resulting from large-vessel occlusion. The investigators compared the performance of the Tigertriever with a composite performance goal criterion derived from six pivotal trials of the Solitaire and Trevo devices.

The researchers enrolled patients at 16 U.S. sites and one site in Israel. Eligible participants had acute ischemic stroke resulting from large-vessel occlusion and moderate to severe neurologic deficits within 8 hours of symptom onset.

The study’s primary efficacy endpoint was successful revascularization within three Tigertriever passes. The investigators defined successful revascularization as achieving a modified Thrombolysis in Cerebral Ischemia score of 2b-3. Secondary efficacy endpoints were first-pass successful revascularization and good clinical outcome, which was defined as a Modified Rankin Scale score of 0-2.

The primary safety endpoint was the composite of symptomatic intracranial hemorrhage at 24 hours and all-cause mortality at 3 months.

The researchers enrolled 160 patients between May 2018 and March 2020. The mean age of the patients was 65 years, and 61.5% were men. The median National Institutes of Health Stroke Scale score was 17. Approximately 66% of patients received tissue plasminogen activator, and the median time to tPA administration was 95 minutes.

Most occlusions were in the M1 segment of the middle cerebral artery (57.3%) or the M2 segment of the MCA (19.7%). Approximately 21% of occlusions were in the internal carotid artery.

Successful revascularization was achieved in 84.6% of participants within three passes of the Tigertriever device. This rate surpassed the 63.4% performance goal and the 73.4% historical rate.

Successful revascularization was achieved in 57.8% of cases on first pass. After three passes, the rate was 84.6%. The rate of good clinical outcome at 90 days was 58% with the Tigertriever and 43% with the historical control.

The rate of symptomatic intracranial hemorrhage at 24 hours and mortality at 90 days was 18.1% with the Tigertriever and 20.4% with the historical control.

The rates of symptomatic hemorrhage and of embolization to a new territory with the Tigertriever were lower than with other devices, despite the relatively infrequent use of balloon guide catheters in the study, said Dr. Gupta.

Unmeasured confounding

“I congratulate the TIGER investigators for an interesting study that looked at a novel stentriever with adjustable radial size and force,” said Adam de Havenon, MD, assistant professor of neurology at the University of Utah, Salt Lake City, who was asked to comment on the study. “This intuitive concept shows promise in comparison to historical controls, and I look forward to hearing more about this exciting technology.”

The major advantage of the use of a composite historical control in the study is that fewer patients are needed for a trial, said Dr. de Havenon. This design makes the trial more economical and enables it to be completed more quickly.

“The impact is that a real-world patient could receive a beneficial treatment even sooner if it was shown to be beneficial with this study design,” he added. “The disadvantage is that there is unmeasured confounding because the historical controls come from trials during different time periods and at different centers and countries, with unique demographics that may not match well with your cohort.”

Statistical methodology helps mitigate this unmeasured confounding, but it remains a concern in the quest for a high level of evidence, Dr. de Havenon added.

The data suggest that the Tigertriever is a viable alternative to other stent retrievers, but they do not support its preferential use. “If the goal is to have the Tigertriever be considered a viable treatment option for large-vessel occlusion stroke, then [the researchers] have accomplished that with this study, which provides the needed data for FDA approval of the device,” said Dr. de Havenon.

“However, these data introduce the possibility of superiority but do not definitely show that,” he concluded. “To do so, they would need a randomized trial with a comparator device or devices and, as a result, a larger sample size.”

The study was funded by Rapid Medical. Dr. Gupta was one of the principal investigators for this study and for studies sponsored by Stryker Neurovascular, Zoll, and Vesalio. He served on the clinical events committee of a trial sponsored by Penumbra and has acted as a consultant for Cerenovous. Dr de Havenon disclosed no relevant financial relationships.

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

A radially adjustable stent retriever provided a high rate of substantial reperfusion and was associated with low rates of symptomatic intracranial hemorrhage and death in a new study. The novel device may increase the options for endovascular therapy, researchers say.

In this study, the Tigertriever (Rapid Medical) was noninferior to a prespecified performance goal and superior to established devices, as determined from historical rates derived from trials. The device achieved first-pass successful reperfusion in approximately 6 of 10 patients and final successful reperfusion in more than 9 of 10 patients.

“The Tigertriever is a highly effective and safe device to remove thrombus in patients with large-vessel occlusion who are eligible for mechanical thrombectomy,” Rishi Gupta, MD, a vascular neurologist at Wellstar Health System Kennestone Hospital, Marietta, Ga., said during his presentation.

Results of the TIGER trial were presented at the International Stroke Conference, sponsored by the American Heart Association, and were published online March 19, 2021, in Stroke.

Endovascular therapy significantly improves outcomes of acute ischemic stroke resulting from large-vessel occlusion. However, current devices fail to achieve successful reperfusion in approximately 27% of patients, the researchers noted. In addition, the devices are associated with complications such as embolization to a new territory and symptomatic intracranial hemorrhage.

The Tigertriever is a radially adjustable, fully visible stent retriever. The operator controls the device’s radial expansion and force, enabling the operator to minimize vessel tension. The Tigertriever is available in Europe.

Effective revascularization

Dr. Gupta and colleagues conducted the prospective, single-arm TIGER study to evaluate the safety and efficacy of the Tigertriever in restoring blood flow by removing clots for patients with ischemic stroke resulting from large-vessel occlusion. The investigators compared the performance of the Tigertriever with a composite performance goal criterion derived from six pivotal trials of the Solitaire and Trevo devices.

The researchers enrolled patients at 16 U.S. sites and one site in Israel. Eligible participants had acute ischemic stroke resulting from large-vessel occlusion and moderate to severe neurologic deficits within 8 hours of symptom onset.

The study’s primary efficacy endpoint was successful revascularization within three Tigertriever passes. The investigators defined successful revascularization as achieving a modified Thrombolysis in Cerebral Ischemia score of 2b-3. Secondary efficacy endpoints were first-pass successful revascularization and good clinical outcome, which was defined as a Modified Rankin Scale score of 0-2.

The primary safety endpoint was the composite of symptomatic intracranial hemorrhage at 24 hours and all-cause mortality at 3 months.

The researchers enrolled 160 patients between May 2018 and March 2020. The mean age of the patients was 65 years, and 61.5% were men. The median National Institutes of Health Stroke Scale score was 17. Approximately 66% of patients received tissue plasminogen activator, and the median time to tPA administration was 95 minutes.

Most occlusions were in the M1 segment of the middle cerebral artery (57.3%) or the M2 segment of the MCA (19.7%). Approximately 21% of occlusions were in the internal carotid artery.

Successful revascularization was achieved in 84.6% of participants within three passes of the Tigertriever device. This rate surpassed the 63.4% performance goal and the 73.4% historical rate.

Successful revascularization was achieved in 57.8% of cases on first pass. After three passes, the rate was 84.6%. The rate of good clinical outcome at 90 days was 58% with the Tigertriever and 43% with the historical control.

The rate of symptomatic intracranial hemorrhage at 24 hours and mortality at 90 days was 18.1% with the Tigertriever and 20.4% with the historical control.

The rates of symptomatic hemorrhage and of embolization to a new territory with the Tigertriever were lower than with other devices, despite the relatively infrequent use of balloon guide catheters in the study, said Dr. Gupta.

Unmeasured confounding

“I congratulate the TIGER investigators for an interesting study that looked at a novel stentriever with adjustable radial size and force,” said Adam de Havenon, MD, assistant professor of neurology at the University of Utah, Salt Lake City, who was asked to comment on the study. “This intuitive concept shows promise in comparison to historical controls, and I look forward to hearing more about this exciting technology.”

The major advantage of the use of a composite historical control in the study is that fewer patients are needed for a trial, said Dr. de Havenon. This design makes the trial more economical and enables it to be completed more quickly.

“The impact is that a real-world patient could receive a beneficial treatment even sooner if it was shown to be beneficial with this study design,” he added. “The disadvantage is that there is unmeasured confounding because the historical controls come from trials during different time periods and at different centers and countries, with unique demographics that may not match well with your cohort.”

Statistical methodology helps mitigate this unmeasured confounding, but it remains a concern in the quest for a high level of evidence, Dr. de Havenon added.

The data suggest that the Tigertriever is a viable alternative to other stent retrievers, but they do not support its preferential use. “If the goal is to have the Tigertriever be considered a viable treatment option for large-vessel occlusion stroke, then [the researchers] have accomplished that with this study, which provides the needed data for FDA approval of the device,” said Dr. de Havenon.

“However, these data introduce the possibility of superiority but do not definitely show that,” he concluded. “To do so, they would need a randomized trial with a comparator device or devices and, as a result, a larger sample size.”

The study was funded by Rapid Medical. Dr. Gupta was one of the principal investigators for this study and for studies sponsored by Stryker Neurovascular, Zoll, and Vesalio. He served on the clinical events committee of a trial sponsored by Penumbra and has acted as a consultant for Cerenovous. Dr de Havenon disclosed no relevant financial relationships.

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

Ideally, Americans receiving their Pfizer/BioNTech or Moderna COVID-19 vaccines will get both doses from the same manufacturer, said Gregory Poland, MD, a vaccinologist at the Mayo Clinic in Rochester, Minn.

After all, that’s how they were tested for efficacy and safety, and it was results from those studies that led to emergency use authorization (EUA) being granted by the Food and Drug Administration.

But states and countries have struggled to keep up with the demand for vaccine, and more flexible vaccination schedules could help.

So researchers are exploring whether it is safe and effective to get the first and second doses from different manufacturers. And they are even wondering whether mixing doses from different manufacturers could increase effectiveness, particularly in light of emerging variants.

It’s called the “interchangeability issue,” said Dr. Poland, who has gotten a steady stream of questions about it.

For example, a patient recently asked about options for his father, who had gotten his first dose of the AstraZeneca vaccine in Ecuador, but had since moved to the United States, where that product has not been approved for use.

Dr. Poland said in an interview that he prefaces each answer with: “I’ve got no science for what I’m about to tell you.”

In this particular case, he recommended that the man’s father talk with his doctor about his level of COVID-19 risk and consider whether he should gamble on the AstraZeneca vaccine getting approved in the United States soon, or whether he should ask for a second dose from one of the three vaccines currently approved.

On March 22, 2021, AstraZeneca released positive results from its phase 3 trial, which will likely speed its path toward use in the United States.

Although clinical trials have started to test combinations and boosters, there’s currently no definitive evidence from human trials on mixing COVID vaccines, Dr. Poland pointed out.

But a study of a mixed-vaccine regimen is currently underway in the United Kingdom.

Participants in that 13-month trial will be given the Oxford/AstraZeneca and Pfizer/BioNTech vaccines in different combinations and at different intervals. The first results from that trial are expected this summer.

And interim results from a trial combining Russia’s Sputnik V and the AstraZeneca vaccines are expected in 2 months, according to a Reuters report.
 

Mix only in ‘exceptional situations’

The Centers for Disease Control and Prevention has been hesitant to open the door to mixing Pfizer and Moderna vaccinations, noting that the two “are not interchangeable.” But CDC guidance has changed slightly. Now, instead of saying the two vaccines should not be mixed, CDC guidance says they can be mixed in “exceptional situations,” and that the second dose can be administered up to 6 weeks after the first dose.

It is reasonable to assume that mixing COVID-19 vaccines that use the same platform – such as the mRNA platform used by both the Pfizer and Moderna vaccines – will be acceptable, Dr. Poland said, although human trials have not proven that.

However, it is unclear whether vaccines that use different platforms can be mixed. Can the first dose of an mRNA vaccine be followed by an adenovirus-based vaccine, like the Johnson & Johnson product or Novavax, if that vaccine is granted an EUA?

Ross Kedl, PhD, a vaccine researcher and professor of immunology at the University of Colorado at Denver, Aurora, said matching vaccine platforms might not be the preferred vaccination strategy.

He disagreed that there’s a lack of science surrounding the issue, and said all signs point to mixing as not only a good option, but probably a better one.
 

Researcher says science backs mixing

A mix of two different vaccine platforms likely enhances immunity, Dr. Kedl said. The heterologous prime-boost strategy has been used in animal studies for decades, “and it is well known that this promotes a much better immune response than when immunizing with the same vaccine twice.

“If you think about it in a Venn diagram sort of way, it makes sense,” he said in an interview. “Each vaccine has a number of components in it that influence immunity in various ways, but between the two of them, they only have one component that is similar. In the case of the coronavirus vaccines, the one thing both have in common is the spike protein from SARS-CoV-2. In essence, this gives you two shots at generating immunity against the one thing in each vaccine you care most about, but only one shot for the other vaccine components in each platform, resulting in an amplified response against the common target.”

In fact, the heterologous prime-boost vaccination strategy has proven to be effective in humans in early studies.

For example, an Ebola regimen that consisted of an adenovirus vector, similar to the AstraZeneca COVID vaccine, and a modified vaccinia virus vector showed promise in a phase 1 study. And an HIV regimen that consisted of the combination of a DNA vaccine, similar to the Pfizer and Moderna mRNA vaccines, and another viral vector showed encouraging results in a proof-of-concept study.

In both these cases, the heterologous prime-boost strategy was far better than single-vaccine prime-boost regimens, Dr. Kedl pointed out. And neither study reported any safety issues with the combinations.

For now, it’s best to stick with the same manufacturer for both shots, as the CDC guidance suggests, he said, agreeing with Dr. Poland.

But “I would be very surprised if we didn’t move to a mixing of vaccine platforms for the population,” Dr. Kedl said.

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

Ideally, Americans receiving their Pfizer/BioNTech or Moderna COVID-19 vaccines will get both doses from the same manufacturer, said Gregory Poland, MD, a vaccinologist at the Mayo Clinic in Rochester, Minn.

After all, that’s how they were tested for efficacy and safety, and it was results from those studies that led to emergency use authorization (EUA) being granted by the Food and Drug Administration.

But states and countries have struggled to keep up with the demand for vaccine, and more flexible vaccination schedules could help.

So researchers are exploring whether it is safe and effective to get the first and second doses from different manufacturers. And they are even wondering whether mixing doses from different manufacturers could increase effectiveness, particularly in light of emerging variants.

It’s called the “interchangeability issue,” said Dr. Poland, who has gotten a steady stream of questions about it.

For example, a patient recently asked about options for his father, who had gotten his first dose of the AstraZeneca vaccine in Ecuador, but had since moved to the United States, where that product has not been approved for use.

Dr. Poland said in an interview that he prefaces each answer with: “I’ve got no science for what I’m about to tell you.”

In this particular case, he recommended that the man’s father talk with his doctor about his level of COVID-19 risk and consider whether he should gamble on the AstraZeneca vaccine getting approved in the United States soon, or whether he should ask for a second dose from one of the three vaccines currently approved.

On March 22, 2021, AstraZeneca released positive results from its phase 3 trial, which will likely speed its path toward use in the United States.

Although clinical trials have started to test combinations and boosters, there’s currently no definitive evidence from human trials on mixing COVID vaccines, Dr. Poland pointed out.

But a study of a mixed-vaccine regimen is currently underway in the United Kingdom.

Participants in that 13-month trial will be given the Oxford/AstraZeneca and Pfizer/BioNTech vaccines in different combinations and at different intervals. The first results from that trial are expected this summer.

And interim results from a trial combining Russia’s Sputnik V and the AstraZeneca vaccines are expected in 2 months, according to a Reuters report.
 

Mix only in ‘exceptional situations’

The Centers for Disease Control and Prevention has been hesitant to open the door to mixing Pfizer and Moderna vaccinations, noting that the two “are not interchangeable.” But CDC guidance has changed slightly. Now, instead of saying the two vaccines should not be mixed, CDC guidance says they can be mixed in “exceptional situations,” and that the second dose can be administered up to 6 weeks after the first dose.

It is reasonable to assume that mixing COVID-19 vaccines that use the same platform – such as the mRNA platform used by both the Pfizer and Moderna vaccines – will be acceptable, Dr. Poland said, although human trials have not proven that.

However, it is unclear whether vaccines that use different platforms can be mixed. Can the first dose of an mRNA vaccine be followed by an adenovirus-based vaccine, like the Johnson & Johnson product or Novavax, if that vaccine is granted an EUA?

Ross Kedl, PhD, a vaccine researcher and professor of immunology at the University of Colorado at Denver, Aurora, said matching vaccine platforms might not be the preferred vaccination strategy.

He disagreed that there’s a lack of science surrounding the issue, and said all signs point to mixing as not only a good option, but probably a better one.
 

Researcher says science backs mixing

A mix of two different vaccine platforms likely enhances immunity, Dr. Kedl said. The heterologous prime-boost strategy has been used in animal studies for decades, “and it is well known that this promotes a much better immune response than when immunizing with the same vaccine twice.

“If you think about it in a Venn diagram sort of way, it makes sense,” he said in an interview. “Each vaccine has a number of components in it that influence immunity in various ways, but between the two of them, they only have one component that is similar. In the case of the coronavirus vaccines, the one thing both have in common is the spike protein from SARS-CoV-2. In essence, this gives you two shots at generating immunity against the one thing in each vaccine you care most about, but only one shot for the other vaccine components in each platform, resulting in an amplified response against the common target.”

In fact, the heterologous prime-boost vaccination strategy has proven to be effective in humans in early studies.

For example, an Ebola regimen that consisted of an adenovirus vector, similar to the AstraZeneca COVID vaccine, and a modified vaccinia virus vector showed promise in a phase 1 study. And an HIV regimen that consisted of the combination of a DNA vaccine, similar to the Pfizer and Moderna mRNA vaccines, and another viral vector showed encouraging results in a proof-of-concept study.

In both these cases, the heterologous prime-boost strategy was far better than single-vaccine prime-boost regimens, Dr. Kedl pointed out. And neither study reported any safety issues with the combinations.

For now, it’s best to stick with the same manufacturer for both shots, as the CDC guidance suggests, he said, agreeing with Dr. Poland.

But “I would be very surprised if we didn’t move to a mixing of vaccine platforms for the population,” Dr. Kedl said.

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

Ideally, Americans receiving their Pfizer/BioNTech or Moderna COVID-19 vaccines will get both doses from the same manufacturer, said Gregory Poland, MD, a vaccinologist at the Mayo Clinic in Rochester, Minn.

After all, that’s how they were tested for efficacy and safety, and it was results from those studies that led to emergency use authorization (EUA) being granted by the Food and Drug Administration.

But states and countries have struggled to keep up with the demand for vaccine, and more flexible vaccination schedules could help.

So researchers are exploring whether it is safe and effective to get the first and second doses from different manufacturers. And they are even wondering whether mixing doses from different manufacturers could increase effectiveness, particularly in light of emerging variants.

It’s called the “interchangeability issue,” said Dr. Poland, who has gotten a steady stream of questions about it.

For example, a patient recently asked about options for his father, who had gotten his first dose of the AstraZeneca vaccine in Ecuador, but had since moved to the United States, where that product has not been approved for use.

Dr. Poland said in an interview that he prefaces each answer with: “I’ve got no science for what I’m about to tell you.”

In this particular case, he recommended that the man’s father talk with his doctor about his level of COVID-19 risk and consider whether he should gamble on the AstraZeneca vaccine getting approved in the United States soon, or whether he should ask for a second dose from one of the three vaccines currently approved.

On March 22, 2021, AstraZeneca released positive results from its phase 3 trial, which will likely speed its path toward use in the United States.

Although clinical trials have started to test combinations and boosters, there’s currently no definitive evidence from human trials on mixing COVID vaccines, Dr. Poland pointed out.

But a study of a mixed-vaccine regimen is currently underway in the United Kingdom.

Participants in that 13-month trial will be given the Oxford/AstraZeneca and Pfizer/BioNTech vaccines in different combinations and at different intervals. The first results from that trial are expected this summer.

And interim results from a trial combining Russia’s Sputnik V and the AstraZeneca vaccines are expected in 2 months, according to a Reuters report.
 

Mix only in ‘exceptional situations’

The Centers for Disease Control and Prevention has been hesitant to open the door to mixing Pfizer and Moderna vaccinations, noting that the two “are not interchangeable.” But CDC guidance has changed slightly. Now, instead of saying the two vaccines should not be mixed, CDC guidance says they can be mixed in “exceptional situations,” and that the second dose can be administered up to 6 weeks after the first dose.

It is reasonable to assume that mixing COVID-19 vaccines that use the same platform – such as the mRNA platform used by both the Pfizer and Moderna vaccines – will be acceptable, Dr. Poland said, although human trials have not proven that.

However, it is unclear whether vaccines that use different platforms can be mixed. Can the first dose of an mRNA vaccine be followed by an adenovirus-based vaccine, like the Johnson & Johnson product or Novavax, if that vaccine is granted an EUA?

Ross Kedl, PhD, a vaccine researcher and professor of immunology at the University of Colorado at Denver, Aurora, said matching vaccine platforms might not be the preferred vaccination strategy.

He disagreed that there’s a lack of science surrounding the issue, and said all signs point to mixing as not only a good option, but probably a better one.
 

Researcher says science backs mixing

A mix of two different vaccine platforms likely enhances immunity, Dr. Kedl said. The heterologous prime-boost strategy has been used in animal studies for decades, “and it is well known that this promotes a much better immune response than when immunizing with the same vaccine twice.

“If you think about it in a Venn diagram sort of way, it makes sense,” he said in an interview. “Each vaccine has a number of components in it that influence immunity in various ways, but between the two of them, they only have one component that is similar. In the case of the coronavirus vaccines, the one thing both have in common is the spike protein from SARS-CoV-2. In essence, this gives you two shots at generating immunity against the one thing in each vaccine you care most about, but only one shot for the other vaccine components in each platform, resulting in an amplified response against the common target.”

In fact, the heterologous prime-boost vaccination strategy has proven to be effective in humans in early studies.

For example, an Ebola regimen that consisted of an adenovirus vector, similar to the AstraZeneca COVID vaccine, and a modified vaccinia virus vector showed promise in a phase 1 study. And an HIV regimen that consisted of the combination of a DNA vaccine, similar to the Pfizer and Moderna mRNA vaccines, and another viral vector showed encouraging results in a proof-of-concept study.

In both these cases, the heterologous prime-boost strategy was far better than single-vaccine prime-boost regimens, Dr. Kedl pointed out. And neither study reported any safety issues with the combinations.

For now, it’s best to stick with the same manufacturer for both shots, as the CDC guidance suggests, he said, agreeing with Dr. Poland.

But “I would be very surprised if we didn’t move to a mixing of vaccine platforms for the population,” Dr. Kedl said.

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

Depression might be a disorder of the brain, but its harms aren’t confined to the cranium. Prolonged depression has been linked with a slew of health problems, from impaired immune function to gastrointestinal dysfunction. It’s also been linked with cardiovascular disease (CVD), even increasing the risk for heart attack and a disrupted heart rate. Now, researchers are exploring whether heart function could be a valuable biomarker in informing depression diagnosis and treatment.

Major depressive disorder has proved difficult to diagnose and treat, and biomarkers that indicate a depressive episode or suggest specific interventions would be an attractive solution to its clinically nebulous nature.

Currently, diagnosing depression relies on the patients effectively communicating their symptoms. If the patient does receive a diagnosis, treating it remains a matter of trial and error. It takes weeks to know whether a treatment is working, and in only one-third of cases does the condition go into remission after the patient is initially prescribed an antidepressant. Even after successful treatment, it’s challenging to identify who might be at risk for relapse, and when. Research now shows that cardiac biomarkers may be a way improve this picture. Clinicians could use changes in heart rate to both inform depression diagnosis and gauge a patient’s predicted response to treatment.

Given the increased risk for CVD among people with depression and the link between heart rate changes and CVD risk, these biomarkers could have implications for heart health, too. “We need more than just the current toolkit,” said Amit Shah, MD, a cardiologist and assistant professor of epidemiology at Emory University, Atlanta. “Ultimately, what we’re trying to do is develop interventions not only for depression but also for the associated physical health problems related to depression, in particular, cardiovascular disease,” he said. These overlapping interests – and the prospect of clinically considering both conditions in tandem – mean this research is “really worth its weight in gold,” added Dr. Shah.
 

The data on heart rate biomarkers

Patients with depression are often found to have lower heart rate variability (HRV) and higher heart rates. Scientists don’t know the mechanisms underpinning this relationship but think changes in the autonomic nervous system during depression, as well as stress generally, have a role.

Rébecca Robillard, PhD, is the head scientist of the Clinical Sleep Research Platform at the Royal’s Institute of Mental Health Research, Ottawa, Ont. In a 2019 study published in BMC Psychiatry, Dr. Robillard’s team used electrocardiogram recordings from sleep studies to see whether heart rate abnormalities were associated with depression. Using a profiling algorithm to analyze heart rate and HRV data, the team identified persons with depression with 80% accuracy among 174 people with sleep complaints.

“It’s still early days, but our work certainly suggests that [HRV and heart rate] could serve as potential biomarkers,” Dr. Robillard said.

In another study, Stephan Claes, MD, PhD, psychiatrist and professor of psychiatry at Katholieke Universiteit Leuven, Belgium, and his group tested the biomarker potential of heart rate and HRV data that were continuously recorded over several days. They too used an algorithm to distinguish 16 people with treatment-resistant depression from 16 without depression. Within the depression group, they used the algorithm to distinguish patients who had received ketamine treatment from those who had not.

The algorithm could differentiate between the depressed and nondepressed groups with 90% accuracy. Those with depression had higher overall heart rates, particularly at night, and lower HRV. Dr. Claes noted that, unlike in other studies, “the most reliable parameter that we had for this prediction was the heart rate, not the HRV.” After treatment, heart rates improved, but HRV remained the same.

Although their study has not yet been peer reviewed and more research is needed, Dr. Claes said that increased heart rate, especially during the night, could eventually serve as a warning sign of depression relapse. “That would allow a quicker referral to care and better care because of earlier intervention,” he said.
 

Finding a signal amid the noise

But heart rate and HRV aren’t foolproof biomarkers. Some studies have found that antidepressant use lowers HRV and that HRV changes aren’t unique to depression. There’s the added complication that depression often overlaps with other mental disorders.

“I think we’ve been very disappointed about the success of using particular biomarkers for particular disorders, because the majority of mental disorders are very heterogeneous,” said Andrew Kemp, PhD, psychology professor at Swansea University, Swansea, Wales. “A particular biomarker will, at the end of the day, be just one particular aspect of the overall profile that clinicians will have on particular individuals.”

The clinical utility of a heart rate–depression connection may go both ways.

For instance, depression could serve as a warning sign for atrial fibrillation, according to research from Parveen K. Garg, MD, associate professor of clinical medicine at the University of Southern California, Los Angeles. In a study involving more than 6,000 people, Dr. Garg showed that higher scores on depression scales correlated with a higher risk for the occurrence of atrial fibrillation over a follow-up period of about 13 years.

Depression is associated with other heart conditions as well. “A lot of data seem to suggest that just the presence of depression can increase risk for a whole range of cardiovascular problems,” said Dr. Garg. Epidemiologic studies have found associations between depression and the development of coronary heart disease and a modest increased risk for stroke.

“Things going on in your brain also have effects on the rest of your body,” said Dr. Garg. “Just recognizing this link, that maybe mental illness has an effect on other illnesses or diseases that can affect other parts of your body – I think that’s something we can share now.”

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

Depression might be a disorder of the brain, but its harms aren’t confined to the cranium. Prolonged depression has been linked with a slew of health problems, from impaired immune function to gastrointestinal dysfunction. It’s also been linked with cardiovascular disease (CVD), even increasing the risk for heart attack and a disrupted heart rate. Now, researchers are exploring whether heart function could be a valuable biomarker in informing depression diagnosis and treatment.

Major depressive disorder has proved difficult to diagnose and treat, and biomarkers that indicate a depressive episode or suggest specific interventions would be an attractive solution to its clinically nebulous nature.

Currently, diagnosing depression relies on the patients effectively communicating their symptoms. If the patient does receive a diagnosis, treating it remains a matter of trial and error. It takes weeks to know whether a treatment is working, and in only one-third of cases does the condition go into remission after the patient is initially prescribed an antidepressant. Even after successful treatment, it’s challenging to identify who might be at risk for relapse, and when. Research now shows that cardiac biomarkers may be a way improve this picture. Clinicians could use changes in heart rate to both inform depression diagnosis and gauge a patient’s predicted response to treatment.

Given the increased risk for CVD among people with depression and the link between heart rate changes and CVD risk, these biomarkers could have implications for heart health, too. “We need more than just the current toolkit,” said Amit Shah, MD, a cardiologist and assistant professor of epidemiology at Emory University, Atlanta. “Ultimately, what we’re trying to do is develop interventions not only for depression but also for the associated physical health problems related to depression, in particular, cardiovascular disease,” he said. These overlapping interests – and the prospect of clinically considering both conditions in tandem – mean this research is “really worth its weight in gold,” added Dr. Shah.
 

The data on heart rate biomarkers

Patients with depression are often found to have lower heart rate variability (HRV) and higher heart rates. Scientists don’t know the mechanisms underpinning this relationship but think changes in the autonomic nervous system during depression, as well as stress generally, have a role.

Rébecca Robillard, PhD, is the head scientist of the Clinical Sleep Research Platform at the Royal’s Institute of Mental Health Research, Ottawa, Ont. In a 2019 study published in BMC Psychiatry, Dr. Robillard’s team used electrocardiogram recordings from sleep studies to see whether heart rate abnormalities were associated with depression. Using a profiling algorithm to analyze heart rate and HRV data, the team identified persons with depression with 80% accuracy among 174 people with sleep complaints.

“It’s still early days, but our work certainly suggests that [HRV and heart rate] could serve as potential biomarkers,” Dr. Robillard said.

In another study, Stephan Claes, MD, PhD, psychiatrist and professor of psychiatry at Katholieke Universiteit Leuven, Belgium, and his group tested the biomarker potential of heart rate and HRV data that were continuously recorded over several days. They too used an algorithm to distinguish 16 people with treatment-resistant depression from 16 without depression. Within the depression group, they used the algorithm to distinguish patients who had received ketamine treatment from those who had not.

The algorithm could differentiate between the depressed and nondepressed groups with 90% accuracy. Those with depression had higher overall heart rates, particularly at night, and lower HRV. Dr. Claes noted that, unlike in other studies, “the most reliable parameter that we had for this prediction was the heart rate, not the HRV.” After treatment, heart rates improved, but HRV remained the same.

Although their study has not yet been peer reviewed and more research is needed, Dr. Claes said that increased heart rate, especially during the night, could eventually serve as a warning sign of depression relapse. “That would allow a quicker referral to care and better care because of earlier intervention,” he said.
 

Finding a signal amid the noise

But heart rate and HRV aren’t foolproof biomarkers. Some studies have found that antidepressant use lowers HRV and that HRV changes aren’t unique to depression. There’s the added complication that depression often overlaps with other mental disorders.

“I think we’ve been very disappointed about the success of using particular biomarkers for particular disorders, because the majority of mental disorders are very heterogeneous,” said Andrew Kemp, PhD, psychology professor at Swansea University, Swansea, Wales. “A particular biomarker will, at the end of the day, be just one particular aspect of the overall profile that clinicians will have on particular individuals.”

The clinical utility of a heart rate–depression connection may go both ways.

For instance, depression could serve as a warning sign for atrial fibrillation, according to research from Parveen K. Garg, MD, associate professor of clinical medicine at the University of Southern California, Los Angeles. In a study involving more than 6,000 people, Dr. Garg showed that higher scores on depression scales correlated with a higher risk for the occurrence of atrial fibrillation over a follow-up period of about 13 years.

Depression is associated with other heart conditions as well. “A lot of data seem to suggest that just the presence of depression can increase risk for a whole range of cardiovascular problems,” said Dr. Garg. Epidemiologic studies have found associations between depression and the development of coronary heart disease and a modest increased risk for stroke.

“Things going on in your brain also have effects on the rest of your body,” said Dr. Garg. “Just recognizing this link, that maybe mental illness has an effect on other illnesses or diseases that can affect other parts of your body – I think that’s something we can share now.”

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

Depression might be a disorder of the brain, but its harms aren’t confined to the cranium. Prolonged depression has been linked with a slew of health problems, from impaired immune function to gastrointestinal dysfunction. It’s also been linked with cardiovascular disease (CVD), even increasing the risk for heart attack and a disrupted heart rate. Now, researchers are exploring whether heart function could be a valuable biomarker in informing depression diagnosis and treatment.

Major depressive disorder has proved difficult to diagnose and treat, and biomarkers that indicate a depressive episode or suggest specific interventions would be an attractive solution to its clinically nebulous nature.

Currently, diagnosing depression relies on the patients effectively communicating their symptoms. If the patient does receive a diagnosis, treating it remains a matter of trial and error. It takes weeks to know whether a treatment is working, and in only one-third of cases does the condition go into remission after the patient is initially prescribed an antidepressant. Even after successful treatment, it’s challenging to identify who might be at risk for relapse, and when. Research now shows that cardiac biomarkers may be a way improve this picture. Clinicians could use changes in heart rate to both inform depression diagnosis and gauge a patient’s predicted response to treatment.

Given the increased risk for CVD among people with depression and the link between heart rate changes and CVD risk, these biomarkers could have implications for heart health, too. “We need more than just the current toolkit,” said Amit Shah, MD, a cardiologist and assistant professor of epidemiology at Emory University, Atlanta. “Ultimately, what we’re trying to do is develop interventions not only for depression but also for the associated physical health problems related to depression, in particular, cardiovascular disease,” he said. These overlapping interests – and the prospect of clinically considering both conditions in tandem – mean this research is “really worth its weight in gold,” added Dr. Shah.
 

The data on heart rate biomarkers

Patients with depression are often found to have lower heart rate variability (HRV) and higher heart rates. Scientists don’t know the mechanisms underpinning this relationship but think changes in the autonomic nervous system during depression, as well as stress generally, have a role.

Rébecca Robillard, PhD, is the head scientist of the Clinical Sleep Research Platform at the Royal’s Institute of Mental Health Research, Ottawa, Ont. In a 2019 study published in BMC Psychiatry, Dr. Robillard’s team used electrocardiogram recordings from sleep studies to see whether heart rate abnormalities were associated with depression. Using a profiling algorithm to analyze heart rate and HRV data, the team identified persons with depression with 80% accuracy among 174 people with sleep complaints.

“It’s still early days, but our work certainly suggests that [HRV and heart rate] could serve as potential biomarkers,” Dr. Robillard said.

In another study, Stephan Claes, MD, PhD, psychiatrist and professor of psychiatry at Katholieke Universiteit Leuven, Belgium, and his group tested the biomarker potential of heart rate and HRV data that were continuously recorded over several days. They too used an algorithm to distinguish 16 people with treatment-resistant depression from 16 without depression. Within the depression group, they used the algorithm to distinguish patients who had received ketamine treatment from those who had not.

The algorithm could differentiate between the depressed and nondepressed groups with 90% accuracy. Those with depression had higher overall heart rates, particularly at night, and lower HRV. Dr. Claes noted that, unlike in other studies, “the most reliable parameter that we had for this prediction was the heart rate, not the HRV.” After treatment, heart rates improved, but HRV remained the same.

Although their study has not yet been peer reviewed and more research is needed, Dr. Claes said that increased heart rate, especially during the night, could eventually serve as a warning sign of depression relapse. “That would allow a quicker referral to care and better care because of earlier intervention,” he said.
 

Finding a signal amid the noise

But heart rate and HRV aren’t foolproof biomarkers. Some studies have found that antidepressant use lowers HRV and that HRV changes aren’t unique to depression. There’s the added complication that depression often overlaps with other mental disorders.

“I think we’ve been very disappointed about the success of using particular biomarkers for particular disorders, because the majority of mental disorders are very heterogeneous,” said Andrew Kemp, PhD, psychology professor at Swansea University, Swansea, Wales. “A particular biomarker will, at the end of the day, be just one particular aspect of the overall profile that clinicians will have on particular individuals.”

The clinical utility of a heart rate–depression connection may go both ways.

For instance, depression could serve as a warning sign for atrial fibrillation, according to research from Parveen K. Garg, MD, associate professor of clinical medicine at the University of Southern California, Los Angeles. In a study involving more than 6,000 people, Dr. Garg showed that higher scores on depression scales correlated with a higher risk for the occurrence of atrial fibrillation over a follow-up period of about 13 years.

Depression is associated with other heart conditions as well. “A lot of data seem to suggest that just the presence of depression can increase risk for a whole range of cardiovascular problems,” said Dr. Garg. Epidemiologic studies have found associations between depression and the development of coronary heart disease and a modest increased risk for stroke.

“Things going on in your brain also have effects on the rest of your body,” said Dr. Garg. “Just recognizing this link, that maybe mental illness has an effect on other illnesses or diseases that can affect other parts of your body – I think that’s something we can share now.”

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

Two-thirds of epidemiologists from leading academic institutions say the world will need new or modified vaccines for COVID-19 within a year, new research shows.

South_agency/Getty Images

In a survey of 77 epidemiologists from 28 countries by the People’s Vaccine Alliance, 66.2% predicted that the world has a year or less before variants make current vaccines ineffective. The People’s Vaccine Alliance is a coalition of more than 50 organizations, including the African Alliance, Oxfam, Public Citizen, and UNAIDS (the Joint United Nations Programme on HIV/AIDS).

Almost a third (32.5%) of those surveyed said ineffectiveness would happen in 9 months or less; 18.2% said 6 months or less.

Paul A. Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, said in an interview that, while it’s hard to say whether vaccines could become ineffective in that time frame, “It’s perfectly reasonable to think it could happen.”

The good news, said Dr. Offit, who was not involved with the survey, is that SARS-CoV-2 mutates slowly, compared with other viruses such as influenza.

“To date,” he said, “the mutations that have occurred are not far enough away from the immunity induced by your natural infection or immunization such that one isn’t protected at least against severe and critical disease.”

That’s the goal of vaccines, he noted: “to keep people from suffering mightily.”
 

A line may be crossed

“And so far that’s happening, even with the variants,” Dr. Offit said. “That line has not been crossed. But I think we should assume that it might be.”

Dr. Offit said it will be critical to monitor anyone who gets hospitalized who is known to have been infected or fully vaccinated. Then countries need to get really good at sequencing those viruses.

The great majority of those surveyed (88%) said that persistently low vaccine coverage in many countries would make it more likely that vaccine-resistant mutations will appear.

Coverage comparisons between countries are stark.
 

Many countries haven’t given a single vaccine dose

While rich countries are giving COVID-19 vaccinations at the rate of a person a second, many of the poorest countries have given hardly any vaccines, the People’s Vaccine Alliance says.

Additionally, according to researchers at the Global Health Innovation Center at Duke University, Durham, N.C., high- and upper-middle–income countries, which represent one-fifth of the world’s population, have bought about 6 billion doses. But low- and lower-middle–income countries, which make up four-fifths of the population, have bought only about 2.6 billion, an article in Nature reports.

“You’re only as strong as your weakest country,” Dr. Offit said. “If we haven’t learned that what happens in other countries can [affect the global population], we haven’t been paying attention.”

Gregg Gonsalves, PhD, associate professor of epidemiology at Yale University, New Haven, Conn., one of the academic centers surveyed, didn’t specify a timeline for when vaccines would become ineffective, but said in a press release that the urgency for widespread global vaccination is real.

“Unless we vaccinate the world,” he said, “we leave the playing field open to more and more mutations, which could churn out variants that could evade our current vaccines and require booster shots to deal with them.”
 

“Dire, but not surprising”

Panagis Galiatsatos, MD, MHS, a pulmonologist at John Hopkins University, Baltimore, whose research focuses on health care disparities, said the survey findings were “dire, but not surprising.”

Johns Hopkins was another of the centers surveyed, but Dr. Galiatsatos wasn’t personally involved with the survey.

COVID-19, Dr. Galiatsatos pointed out, has laid bare disparities, both in who gets the vaccine and who’s involved in trials to develop the vaccines.

“It’s morally concerning and an ethical reckoning,” he said in an interview.

Recognition of the borderless swath of destruction the virus is exacting is critical, he said.

The United States “has to realize this can’t be a U.S.-centric issue,” he said. “We’re going to be back to the beginning if we don’t make sure that every country is doing well. We haven’t seen that level of uniform approach.”

He noted that scientists have always known that viruses mutate, but now the race is on to find the parts of SARS-CoV-2 that don’t mutate as much.

“My suspicion is we’ll probably need boosters instead of a whole different vaccine,” Dr. Galiatsatos said.

Among the strategies sought by the People’s Vaccine Alliance is for all pharmaceutical companies working on COVID-19 vaccines to openly share technology and intellectual property through the World Health Organization COVID-19 Technology Access Pool, to speed production and rollout of vaccines to all countries.

In the survey, 74% said that open sharing of technology and intellectual property could boost global vaccine coverage; 23% said maybe and 3% said it wouldn’t help.

The survey was carried out between Feb. 17 and March 25, 2021. Respondents included epidemiologists, virologists, and infection disease specialists from the following countries: Algeria, Argentina, Australia, Belgium, Bolivia, Canada, Denmark, Ethiopia, France, Guatemala, India, Italy, Kenya, Lebanon, Norway, Philippines, Senegal, Somalia, South Africa, South Sudan, Spain, United Arab Emirates, Uganda, United Kingdom, United States, Vietnam, Zambia, and Zimbabwe.

Dr. Offit and Dr. Galiatsatos reported no relevant financial relationships.

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

Two-thirds of epidemiologists from leading academic institutions say the world will need new or modified vaccines for COVID-19 within a year, new research shows.

South_agency/Getty Images

In a survey of 77 epidemiologists from 28 countries by the People’s Vaccine Alliance, 66.2% predicted that the world has a year or less before variants make current vaccines ineffective. The People’s Vaccine Alliance is a coalition of more than 50 organizations, including the African Alliance, Oxfam, Public Citizen, and UNAIDS (the Joint United Nations Programme on HIV/AIDS).

Almost a third (32.5%) of those surveyed said ineffectiveness would happen in 9 months or less; 18.2% said 6 months or less.

Paul A. Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, said in an interview that, while it’s hard to say whether vaccines could become ineffective in that time frame, “It’s perfectly reasonable to think it could happen.”

The good news, said Dr. Offit, who was not involved with the survey, is that SARS-CoV-2 mutates slowly, compared with other viruses such as influenza.

“To date,” he said, “the mutations that have occurred are not far enough away from the immunity induced by your natural infection or immunization such that one isn’t protected at least against severe and critical disease.”

That’s the goal of vaccines, he noted: “to keep people from suffering mightily.”
 

A line may be crossed

“And so far that’s happening, even with the variants,” Dr. Offit said. “That line has not been crossed. But I think we should assume that it might be.”

Dr. Offit said it will be critical to monitor anyone who gets hospitalized who is known to have been infected or fully vaccinated. Then countries need to get really good at sequencing those viruses.

The great majority of those surveyed (88%) said that persistently low vaccine coverage in many countries would make it more likely that vaccine-resistant mutations will appear.

Coverage comparisons between countries are stark.
 

Many countries haven’t given a single vaccine dose

While rich countries are giving COVID-19 vaccinations at the rate of a person a second, many of the poorest countries have given hardly any vaccines, the People’s Vaccine Alliance says.

Additionally, according to researchers at the Global Health Innovation Center at Duke University, Durham, N.C., high- and upper-middle–income countries, which represent one-fifth of the world’s population, have bought about 6 billion doses. But low- and lower-middle–income countries, which make up four-fifths of the population, have bought only about 2.6 billion, an article in Nature reports.

“You’re only as strong as your weakest country,” Dr. Offit said. “If we haven’t learned that what happens in other countries can [affect the global population], we haven’t been paying attention.”

Gregg Gonsalves, PhD, associate professor of epidemiology at Yale University, New Haven, Conn., one of the academic centers surveyed, didn’t specify a timeline for when vaccines would become ineffective, but said in a press release that the urgency for widespread global vaccination is real.

“Unless we vaccinate the world,” he said, “we leave the playing field open to more and more mutations, which could churn out variants that could evade our current vaccines and require booster shots to deal with them.”
 

“Dire, but not surprising”

Panagis Galiatsatos, MD, MHS, a pulmonologist at John Hopkins University, Baltimore, whose research focuses on health care disparities, said the survey findings were “dire, but not surprising.”

Johns Hopkins was another of the centers surveyed, but Dr. Galiatsatos wasn’t personally involved with the survey.

COVID-19, Dr. Galiatsatos pointed out, has laid bare disparities, both in who gets the vaccine and who’s involved in trials to develop the vaccines.

“It’s morally concerning and an ethical reckoning,” he said in an interview.

Recognition of the borderless swath of destruction the virus is exacting is critical, he said.

The United States “has to realize this can’t be a U.S.-centric issue,” he said. “We’re going to be back to the beginning if we don’t make sure that every country is doing well. We haven’t seen that level of uniform approach.”

He noted that scientists have always known that viruses mutate, but now the race is on to find the parts of SARS-CoV-2 that don’t mutate as much.

“My suspicion is we’ll probably need boosters instead of a whole different vaccine,” Dr. Galiatsatos said.

Among the strategies sought by the People’s Vaccine Alliance is for all pharmaceutical companies working on COVID-19 vaccines to openly share technology and intellectual property through the World Health Organization COVID-19 Technology Access Pool, to speed production and rollout of vaccines to all countries.

In the survey, 74% said that open sharing of technology and intellectual property could boost global vaccine coverage; 23% said maybe and 3% said it wouldn’t help.

The survey was carried out between Feb. 17 and March 25, 2021. Respondents included epidemiologists, virologists, and infection disease specialists from the following countries: Algeria, Argentina, Australia, Belgium, Bolivia, Canada, Denmark, Ethiopia, France, Guatemala, India, Italy, Kenya, Lebanon, Norway, Philippines, Senegal, Somalia, South Africa, South Sudan, Spain, United Arab Emirates, Uganda, United Kingdom, United States, Vietnam, Zambia, and Zimbabwe.

Dr. Offit and Dr. Galiatsatos reported no relevant financial relationships.

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

Two-thirds of epidemiologists from leading academic institutions say the world will need new or modified vaccines for COVID-19 within a year, new research shows.

South_agency/Getty Images

In a survey of 77 epidemiologists from 28 countries by the People’s Vaccine Alliance, 66.2% predicted that the world has a year or less before variants make current vaccines ineffective. The People’s Vaccine Alliance is a coalition of more than 50 organizations, including the African Alliance, Oxfam, Public Citizen, and UNAIDS (the Joint United Nations Programme on HIV/AIDS).

Almost a third (32.5%) of those surveyed said ineffectiveness would happen in 9 months or less; 18.2% said 6 months or less.

Paul A. Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, said in an interview that, while it’s hard to say whether vaccines could become ineffective in that time frame, “It’s perfectly reasonable to think it could happen.”

The good news, said Dr. Offit, who was not involved with the survey, is that SARS-CoV-2 mutates slowly, compared with other viruses such as influenza.

“To date,” he said, “the mutations that have occurred are not far enough away from the immunity induced by your natural infection or immunization such that one isn’t protected at least against severe and critical disease.”

That’s the goal of vaccines, he noted: “to keep people from suffering mightily.”
 

A line may be crossed

“And so far that’s happening, even with the variants,” Dr. Offit said. “That line has not been crossed. But I think we should assume that it might be.”

Dr. Offit said it will be critical to monitor anyone who gets hospitalized who is known to have been infected or fully vaccinated. Then countries need to get really good at sequencing those viruses.

The great majority of those surveyed (88%) said that persistently low vaccine coverage in many countries would make it more likely that vaccine-resistant mutations will appear.

Coverage comparisons between countries are stark.
 

Many countries haven’t given a single vaccine dose

While rich countries are giving COVID-19 vaccinations at the rate of a person a second, many of the poorest countries have given hardly any vaccines, the People’s Vaccine Alliance says.

Additionally, according to researchers at the Global Health Innovation Center at Duke University, Durham, N.C., high- and upper-middle–income countries, which represent one-fifth of the world’s population, have bought about 6 billion doses. But low- and lower-middle–income countries, which make up four-fifths of the population, have bought only about 2.6 billion, an article in Nature reports.

“You’re only as strong as your weakest country,” Dr. Offit said. “If we haven’t learned that what happens in other countries can [affect the global population], we haven’t been paying attention.”

Gregg Gonsalves, PhD, associate professor of epidemiology at Yale University, New Haven, Conn., one of the academic centers surveyed, didn’t specify a timeline for when vaccines would become ineffective, but said in a press release that the urgency for widespread global vaccination is real.

“Unless we vaccinate the world,” he said, “we leave the playing field open to more and more mutations, which could churn out variants that could evade our current vaccines and require booster shots to deal with them.”
 

“Dire, but not surprising”

Panagis Galiatsatos, MD, MHS, a pulmonologist at John Hopkins University, Baltimore, whose research focuses on health care disparities, said the survey findings were “dire, but not surprising.”

Johns Hopkins was another of the centers surveyed, but Dr. Galiatsatos wasn’t personally involved with the survey.

COVID-19, Dr. Galiatsatos pointed out, has laid bare disparities, both in who gets the vaccine and who’s involved in trials to develop the vaccines.

“It’s morally concerning and an ethical reckoning,” he said in an interview.

Recognition of the borderless swath of destruction the virus is exacting is critical, he said.

The United States “has to realize this can’t be a U.S.-centric issue,” he said. “We’re going to be back to the beginning if we don’t make sure that every country is doing well. We haven’t seen that level of uniform approach.”

He noted that scientists have always known that viruses mutate, but now the race is on to find the parts of SARS-CoV-2 that don’t mutate as much.

“My suspicion is we’ll probably need boosters instead of a whole different vaccine,” Dr. Galiatsatos said.

Among the strategies sought by the People’s Vaccine Alliance is for all pharmaceutical companies working on COVID-19 vaccines to openly share technology and intellectual property through the World Health Organization COVID-19 Technology Access Pool, to speed production and rollout of vaccines to all countries.

In the survey, 74% said that open sharing of technology and intellectual property could boost global vaccine coverage; 23% said maybe and 3% said it wouldn’t help.

The survey was carried out between Feb. 17 and March 25, 2021. Respondents included epidemiologists, virologists, and infection disease specialists from the following countries: Algeria, Argentina, Australia, Belgium, Bolivia, Canada, Denmark, Ethiopia, France, Guatemala, India, Italy, Kenya, Lebanon, Norway, Philippines, Senegal, Somalia, South Africa, South Sudan, Spain, United Arab Emirates, Uganda, United Kingdom, United States, Vietnam, Zambia, and Zimbabwe.

Dr. Offit and Dr. Galiatsatos reported no relevant financial relationships.

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

The National Psoriasis Foundation COVID-19 Task Force now recommends that certain patients on methotrexate consider stopping the drug for 2 weeks after receiving the Johnson & Johnson COVID-19 vaccine, Joel M. Gelfand, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.

Courtesy Dr. Joel M. Gelfand

The new guidance states: “Patients 60 or older who have at least one comorbidity associated with an increased risk for poor COVID-19 outcomes, and who are taking methotrexate with well-controlled psoriatic disease, may, in consultation with their prescriber, consider holding it for 2 weeks after receiving the Ad26.COV2.S [Johnson & Johnson] vaccine in order to potentially improve vaccine response.”

The key word here is “potentially.” There is no hard evidence that a 2-week hold on methotrexate after receiving the killed adenovirus vaccine will actually provide a clinically meaningful benefit. But it’s a hypothetical possibility. The rationale stems from a small randomized trial conducted in South Korea several years ago in which patients with rheumatoid arthritis were assigned to hold or continue their methotrexate for the first 2 weeks after receiving an inactivated-virus influenza vaccine. The antibody response to the vaccine was better in those who temporarily halted their methotrexate, explained Dr. Gelfand, cochair of the NPF COVID-19 Task Force and professor of dermatology and of epidemiology at the University of Pennsylvania, Philadelphia.

“If you have a patient on methotrexate who’s 60 or older and whose psoriasis is completely controlled and quiescent and the patient is concerned about how well the vaccine is going to work, this is a reasonable thing to consider in someone who’s at higher risk for poor outcomes if they get infected,” he said.

If the informed patient wants to continue on methotrexate without interruption, that’s fine, too, in light of the lack of compelling evidence on this issue, the dermatologist added at the conference, sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

The NPF task force does not extend the recommendation to consider holding methotrexate in recipients of the mRNA-based Moderna and Pfizer vaccines because of their very different mechanisms of action. Nor is it recommended to hold biologic agents after receiving any of the available COVID-19 vaccines. Studies have shown no altered immunologic response to influenza or pneumococcal vaccines in patients who continued on tumor necrosis factor inhibitors or interleukin-17 inhibitors. The interleukin-23 inhibitors haven’t been studied in this regard.

The task force recommends that most psoriasis patients should continue on treatment throughout the pandemic, and newly diagnosed patients should commence appropriate therapy as if there was no pandemic.

“We’ve learned that many patients who stopped their treatment for psoriatic disease early in the pandemic came to regret that decision because their psoriasis flared and got worse and required reinstitution of therapy,” Dr. Gelfand said. “The current data is largely reassuring that if there is an effect of our therapies on the risk of COVID, it must be rather small and therefore unlikely to be clinically meaningful for our patients.”

Dr. Gelfand reported serving as a consultant to and recipient of institutional research grants from Pfizer and numerous other pharmaceutical companies.

MedscapeLIVE and this news organization are owned by the same parent company.

[email protected]

The National Psoriasis Foundation COVID-19 Task Force now recommends that certain patients on methotrexate consider stopping the drug for 2 weeks after receiving the Johnson & Johnson COVID-19 vaccine, Joel M. Gelfand, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.

Courtesy Dr. Joel M. Gelfand

The new guidance states: “Patients 60 or older who have at least one comorbidity associated with an increased risk for poor COVID-19 outcomes, and who are taking methotrexate with well-controlled psoriatic disease, may, in consultation with their prescriber, consider holding it for 2 weeks after receiving the Ad26.COV2.S [Johnson & Johnson] vaccine in order to potentially improve vaccine response.”

The key word here is “potentially.” There is no hard evidence that a 2-week hold on methotrexate after receiving the killed adenovirus vaccine will actually provide a clinically meaningful benefit. But it’s a hypothetical possibility. The rationale stems from a small randomized trial conducted in South Korea several years ago in which patients with rheumatoid arthritis were assigned to hold or continue their methotrexate for the first 2 weeks after receiving an inactivated-virus influenza vaccine. The antibody response to the vaccine was better in those who temporarily halted their methotrexate, explained Dr. Gelfand, cochair of the NPF COVID-19 Task Force and professor of dermatology and of epidemiology at the University of Pennsylvania, Philadelphia.

“If you have a patient on methotrexate who’s 60 or older and whose psoriasis is completely controlled and quiescent and the patient is concerned about how well the vaccine is going to work, this is a reasonable thing to consider in someone who’s at higher risk for poor outcomes if they get infected,” he said.

If the informed patient wants to continue on methotrexate without interruption, that’s fine, too, in light of the lack of compelling evidence on this issue, the dermatologist added at the conference, sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

The NPF task force does not extend the recommendation to consider holding methotrexate in recipients of the mRNA-based Moderna and Pfizer vaccines because of their very different mechanisms of action. Nor is it recommended to hold biologic agents after receiving any of the available COVID-19 vaccines. Studies have shown no altered immunologic response to influenza or pneumococcal vaccines in patients who continued on tumor necrosis factor inhibitors or interleukin-17 inhibitors. The interleukin-23 inhibitors haven’t been studied in this regard.

The task force recommends that most psoriasis patients should continue on treatment throughout the pandemic, and newly diagnosed patients should commence appropriate therapy as if there was no pandemic.

“We’ve learned that many patients who stopped their treatment for psoriatic disease early in the pandemic came to regret that decision because their psoriasis flared and got worse and required reinstitution of therapy,” Dr. Gelfand said. “The current data is largely reassuring that if there is an effect of our therapies on the risk of COVID, it must be rather small and therefore unlikely to be clinically meaningful for our patients.”

Dr. Gelfand reported serving as a consultant to and recipient of institutional research grants from Pfizer and numerous other pharmaceutical companies.

MedscapeLIVE and this news organization are owned by the same parent company.

[email protected]

The National Psoriasis Foundation COVID-19 Task Force now recommends that certain patients on methotrexate consider stopping the drug for 2 weeks after receiving the Johnson & Johnson COVID-19 vaccine, Joel M. Gelfand, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.

Courtesy Dr. Joel M. Gelfand

The new guidance states: “Patients 60 or older who have at least one comorbidity associated with an increased risk for poor COVID-19 outcomes, and who are taking methotrexate with well-controlled psoriatic disease, may, in consultation with their prescriber, consider holding it for 2 weeks after receiving the Ad26.COV2.S [Johnson & Johnson] vaccine in order to potentially improve vaccine response.”

The key word here is “potentially.” There is no hard evidence that a 2-week hold on methotrexate after receiving the killed adenovirus vaccine will actually provide a clinically meaningful benefit. But it’s a hypothetical possibility. The rationale stems from a small randomized trial conducted in South Korea several years ago in which patients with rheumatoid arthritis were assigned to hold or continue their methotrexate for the first 2 weeks after receiving an inactivated-virus influenza vaccine. The antibody response to the vaccine was better in those who temporarily halted their methotrexate, explained Dr. Gelfand, cochair of the NPF COVID-19 Task Force and professor of dermatology and of epidemiology at the University of Pennsylvania, Philadelphia.

“If you have a patient on methotrexate who’s 60 or older and whose psoriasis is completely controlled and quiescent and the patient is concerned about how well the vaccine is going to work, this is a reasonable thing to consider in someone who’s at higher risk for poor outcomes if they get infected,” he said.

If the informed patient wants to continue on methotrexate without interruption, that’s fine, too, in light of the lack of compelling evidence on this issue, the dermatologist added at the conference, sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

The NPF task force does not extend the recommendation to consider holding methotrexate in recipients of the mRNA-based Moderna and Pfizer vaccines because of their very different mechanisms of action. Nor is it recommended to hold biologic agents after receiving any of the available COVID-19 vaccines. Studies have shown no altered immunologic response to influenza or pneumococcal vaccines in patients who continued on tumor necrosis factor inhibitors or interleukin-17 inhibitors. The interleukin-23 inhibitors haven’t been studied in this regard.

The task force recommends that most psoriasis patients should continue on treatment throughout the pandemic, and newly diagnosed patients should commence appropriate therapy as if there was no pandemic.

“We’ve learned that many patients who stopped their treatment for psoriatic disease early in the pandemic came to regret that decision because their psoriasis flared and got worse and required reinstitution of therapy,” Dr. Gelfand said. “The current data is largely reassuring that if there is an effect of our therapies on the risk of COVID, it must be rather small and therefore unlikely to be clinically meaningful for our patients.”

Dr. Gelfand reported serving as a consultant to and recipient of institutional research grants from Pfizer and numerous other pharmaceutical companies.

MedscapeLIVE and this news organization are owned by the same parent company.

[email protected]