Journal of Clinical Outcomes Management

Brain wave recordings obtained during cardiopulmonary resuscitation (CPR) offer support to near-death experiences subjectively reported by some people who survive cardiac arrest, according to a novel new study.

“These recalled experiences and brain wave changes may be the first signs of the so-called ‘near-death’ experience, and we have captured them for the first time in a large study,” lead investigator Sam Parnia, MD, PhD, with NYU Langone Health, said in a news release.

Identifying measurable electrical signs of lucid and heightened brain activity during CPR, coupled with stories of recalled near-death experiences, suggests that the human sense of self and consciousness, much like other biological body functions, may not stop completely around the time of death, Dr. Parnia added.

He presented the findings Nov. 6 at a resuscitation science symposium at the American Heart Association scientific sessions.
 

The AWARE II study

“For years, some people in cardiac arrest have reported being lucid, often with a heightened sense of consciousness, while seemingly unconscious and on the brink of death,” Dr. Parnia noted in an interview.

“Yet, no one’s ever be able to prove it and a lot of people have dismissed these experiences, thinking it’s all just a trick on the brain,” Dr. Parnia said.

In a first-of-its-kind study, Dr. Parnia and colleagues examined consciousness and its underlying electrocortical biomarkers during CPR for in-hospital cardiac arrest (IHCA).

They incorporated independent audiovisual testing of awareness with continuous real-time EEG and cerebral oxygenation (rSO₂) monitoring into CPR.

Only 53 of the 567 IHCA patients survived (9.3%). Among the 28 (52.8%) IHCA survivors who completed interviews, 11 (39.3%) reported unique, lucid experiences during resuscitation.

These experiences included a perception of separation from one’s body, observing events without pain or distress, and an awareness and meaningful evaluation of life, including of their actions, intentions, and thoughts toward others.

“These lucid experiences of death are not hallucinations or delusions. They cannot be considered a trick of a disordered or dying brain, but rather a unique human experience that emerges on the brink of death,” Dr. Parnia said. 

And what’s “fascinating,” he added, is that despite marked cerebral ischemia (mean regional oxygen saturation [rSO₂]  43%), near-normal/physiologic EEG activity (gamma, delta, theta, alpha, and beta rhythms) consistent with consciousness and a possible resumption of a network-level of cognitive and neuronal activity emerged for as long as 35-60 minutes into CPR.

Some of these brain waves normally occur when people are conscious and performing higher mental functions, including thinking, memory retrieval, and conscious perception, he said.
 

‘Seismic shift’ in understanding of death

This is the first time such biomarkers of consciousness have been identified during cardiac arrest and CPR, Dr. Parnia said.

He said further study is needed to more precisely define biomarkers of what is considered to be clinical consciousness and the recalled experience of death, and to monitor the long-term psychological effects of resuscitation after cardiac arrest.

“Our understanding of death has gone through a seismic shift in the last few years,” he said.

“The biological discoveries around death and the postmortem period are completely different to the social conventions that we have about death. That is, we perceive of death as being the end, but actually what we’re finding is that brain cells don’t die immediately. They die very slowly over many hours of time,” Dr. Parnia noted.

Reached for comment, Ajmal Zemmar, MD, PhD, of University of Louisville (Ky.), noted that several studies, including this one, “challenge the traditional way that we think of death – that when the heart stops beating that’s when we die.”

The observation that during cardiac arrest and CPR, the brain waves are still normal for up to an hour is “fairly remarkable,” Dr. Zemmar told this news organization.

“However, whether there is conscious perception or not is very hard to answer,” he cautioned. 

“This type of research tries to bridge the objective EEG recordings with the subjective description you get from the patient, but it’s hard to know when conscious perception stops,” he said.

Funding and support for the study were provided by NYU Langone Health, The John Templeton Foundation, and the UK Resuscitation Council, and National Institutes for Health Research. Dr. Parnia and Dr. Zemmar reported no relevant financial relationships.

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

Brain wave recordings obtained during cardiopulmonary resuscitation (CPR) offer support to near-death experiences subjectively reported by some people who survive cardiac arrest, according to a novel new study.

“These recalled experiences and brain wave changes may be the first signs of the so-called ‘near-death’ experience, and we have captured them for the first time in a large study,” lead investigator Sam Parnia, MD, PhD, with NYU Langone Health, said in a news release.

Identifying measurable electrical signs of lucid and heightened brain activity during CPR, coupled with stories of recalled near-death experiences, suggests that the human sense of self and consciousness, much like other biological body functions, may not stop completely around the time of death, Dr. Parnia added.

He presented the findings Nov. 6 at a resuscitation science symposium at the American Heart Association scientific sessions.
 

The AWARE II study

“For years, some people in cardiac arrest have reported being lucid, often with a heightened sense of consciousness, while seemingly unconscious and on the brink of death,” Dr. Parnia noted in an interview.

“Yet, no one’s ever be able to prove it and a lot of people have dismissed these experiences, thinking it’s all just a trick on the brain,” Dr. Parnia said.

In a first-of-its-kind study, Dr. Parnia and colleagues examined consciousness and its underlying electrocortical biomarkers during CPR for in-hospital cardiac arrest (IHCA).

They incorporated independent audiovisual testing of awareness with continuous real-time EEG and cerebral oxygenation (rSO₂) monitoring into CPR.

Only 53 of the 567 IHCA patients survived (9.3%). Among the 28 (52.8%) IHCA survivors who completed interviews, 11 (39.3%) reported unique, lucid experiences during resuscitation.

These experiences included a perception of separation from one’s body, observing events without pain or distress, and an awareness and meaningful evaluation of life, including of their actions, intentions, and thoughts toward others.

“These lucid experiences of death are not hallucinations or delusions. They cannot be considered a trick of a disordered or dying brain, but rather a unique human experience that emerges on the brink of death,” Dr. Parnia said. 

And what’s “fascinating,” he added, is that despite marked cerebral ischemia (mean regional oxygen saturation [rSO₂]  43%), near-normal/physiologic EEG activity (gamma, delta, theta, alpha, and beta rhythms) consistent with consciousness and a possible resumption of a network-level of cognitive and neuronal activity emerged for as long as 35-60 minutes into CPR.

Some of these brain waves normally occur when people are conscious and performing higher mental functions, including thinking, memory retrieval, and conscious perception, he said.
 

‘Seismic shift’ in understanding of death

This is the first time such biomarkers of consciousness have been identified during cardiac arrest and CPR, Dr. Parnia said.

He said further study is needed to more precisely define biomarkers of what is considered to be clinical consciousness and the recalled experience of death, and to monitor the long-term psychological effects of resuscitation after cardiac arrest.

“Our understanding of death has gone through a seismic shift in the last few years,” he said.

“The biological discoveries around death and the postmortem period are completely different to the social conventions that we have about death. That is, we perceive of death as being the end, but actually what we’re finding is that brain cells don’t die immediately. They die very slowly over many hours of time,” Dr. Parnia noted.

Reached for comment, Ajmal Zemmar, MD, PhD, of University of Louisville (Ky.), noted that several studies, including this one, “challenge the traditional way that we think of death – that when the heart stops beating that’s when we die.”

The observation that during cardiac arrest and CPR, the brain waves are still normal for up to an hour is “fairly remarkable,” Dr. Zemmar told this news organization.

“However, whether there is conscious perception or not is very hard to answer,” he cautioned. 

“This type of research tries to bridge the objective EEG recordings with the subjective description you get from the patient, but it’s hard to know when conscious perception stops,” he said.

Funding and support for the study were provided by NYU Langone Health, The John Templeton Foundation, and the UK Resuscitation Council, and National Institutes for Health Research. Dr. Parnia and Dr. Zemmar reported no relevant financial relationships.

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

Brain wave recordings obtained during cardiopulmonary resuscitation (CPR) offer support to near-death experiences subjectively reported by some people who survive cardiac arrest, according to a novel new study.

“These recalled experiences and brain wave changes may be the first signs of the so-called ‘near-death’ experience, and we have captured them for the first time in a large study,” lead investigator Sam Parnia, MD, PhD, with NYU Langone Health, said in a news release.

Identifying measurable electrical signs of lucid and heightened brain activity during CPR, coupled with stories of recalled near-death experiences, suggests that the human sense of self and consciousness, much like other biological body functions, may not stop completely around the time of death, Dr. Parnia added.

He presented the findings Nov. 6 at a resuscitation science symposium at the American Heart Association scientific sessions.
 

The AWARE II study

“For years, some people in cardiac arrest have reported being lucid, often with a heightened sense of consciousness, while seemingly unconscious and on the brink of death,” Dr. Parnia noted in an interview.

“Yet, no one’s ever be able to prove it and a lot of people have dismissed these experiences, thinking it’s all just a trick on the brain,” Dr. Parnia said.

In a first-of-its-kind study, Dr. Parnia and colleagues examined consciousness and its underlying electrocortical biomarkers during CPR for in-hospital cardiac arrest (IHCA).

They incorporated independent audiovisual testing of awareness with continuous real-time EEG and cerebral oxygenation (rSO₂) monitoring into CPR.

Only 53 of the 567 IHCA patients survived (9.3%). Among the 28 (52.8%) IHCA survivors who completed interviews, 11 (39.3%) reported unique, lucid experiences during resuscitation.

These experiences included a perception of separation from one’s body, observing events without pain or distress, and an awareness and meaningful evaluation of life, including of their actions, intentions, and thoughts toward others.

“These lucid experiences of death are not hallucinations or delusions. They cannot be considered a trick of a disordered or dying brain, but rather a unique human experience that emerges on the brink of death,” Dr. Parnia said. 

And what’s “fascinating,” he added, is that despite marked cerebral ischemia (mean regional oxygen saturation [rSO₂]  43%), near-normal/physiologic EEG activity (gamma, delta, theta, alpha, and beta rhythms) consistent with consciousness and a possible resumption of a network-level of cognitive and neuronal activity emerged for as long as 35-60 minutes into CPR.

Some of these brain waves normally occur when people are conscious and performing higher mental functions, including thinking, memory retrieval, and conscious perception, he said.
 

‘Seismic shift’ in understanding of death

This is the first time such biomarkers of consciousness have been identified during cardiac arrest and CPR, Dr. Parnia said.

He said further study is needed to more precisely define biomarkers of what is considered to be clinical consciousness and the recalled experience of death, and to monitor the long-term psychological effects of resuscitation after cardiac arrest.

“Our understanding of death has gone through a seismic shift in the last few years,” he said.

“The biological discoveries around death and the postmortem period are completely different to the social conventions that we have about death. That is, we perceive of death as being the end, but actually what we’re finding is that brain cells don’t die immediately. They die very slowly over many hours of time,” Dr. Parnia noted.

Reached for comment, Ajmal Zemmar, MD, PhD, of University of Louisville (Ky.), noted that several studies, including this one, “challenge the traditional way that we think of death – that when the heart stops beating that’s when we die.”

The observation that during cardiac arrest and CPR, the brain waves are still normal for up to an hour is “fairly remarkable,” Dr. Zemmar told this news organization.

“However, whether there is conscious perception or not is very hard to answer,” he cautioned. 

“This type of research tries to bridge the objective EEG recordings with the subjective description you get from the patient, but it’s hard to know when conscious perception stops,” he said.

Funding and support for the study were provided by NYU Langone Health, The John Templeton Foundation, and the UK Resuscitation Council, and National Institutes for Health Research. Dr. Parnia and Dr. Zemmar reported no relevant financial relationships.

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

A new antibiotic for urinary tract infections is heading toward government approval.

It would be the first new treatment in 20 years for UTIs, which affect more than half of women at least sometime in their lives, according to data compiled by the Department of Health and Human Services.

Called Gepotidacin, the antibiotic’s trial has halted enrollment early due to excellent effectiveness and safety results thus far, drugmaker GSK announced in a press release Nov. 3. GSK will seek approval and peer-reviewed publication early next year.

There is a need for new antibiotics such as this because of increasing antibiotic resistance. Antibiotic resistance to bacteria has become so prevalent that the World Health Organization recently began publishing a list of bacteria that pose the greatest public health threats.

“It’s definitely a big deal,” Cindy Liu, MD, MPH, PhD, of the Antibiotic Resistance Action Center at George Washington University, told CNN.

However, antibiotics are not a particularly profitable type of drug, The Wall Street Journal reported. The newspaper noted that they need to be used sparingly to limit resistance, and the cheapest option is usually prescribed. Some small companies that make antibiotics have even gone bankrupt recently, the Journal noted.

The U.S. government has invested in GSK’s development of Gepotidacin. The company predicts the drug could be a “blockbuster” and earn more than $1 billion due to UTI resistance to other drugs, the Journal reported.

“I think it will be really interesting and important to the field to see both how the drug companies sort of market this product and sort of how it does,” Dr. Liu said.

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

A new antibiotic for urinary tract infections is heading toward government approval.

It would be the first new treatment in 20 years for UTIs, which affect more than half of women at least sometime in their lives, according to data compiled by the Department of Health and Human Services.

Called Gepotidacin, the antibiotic’s trial has halted enrollment early due to excellent effectiveness and safety results thus far, drugmaker GSK announced in a press release Nov. 3. GSK will seek approval and peer-reviewed publication early next year.

There is a need for new antibiotics such as this because of increasing antibiotic resistance. Antibiotic resistance to bacteria has become so prevalent that the World Health Organization recently began publishing a list of bacteria that pose the greatest public health threats.

“It’s definitely a big deal,” Cindy Liu, MD, MPH, PhD, of the Antibiotic Resistance Action Center at George Washington University, told CNN.

However, antibiotics are not a particularly profitable type of drug, The Wall Street Journal reported. The newspaper noted that they need to be used sparingly to limit resistance, and the cheapest option is usually prescribed. Some small companies that make antibiotics have even gone bankrupt recently, the Journal noted.

The U.S. government has invested in GSK’s development of Gepotidacin. The company predicts the drug could be a “blockbuster” and earn more than $1 billion due to UTI resistance to other drugs, the Journal reported.

“I think it will be really interesting and important to the field to see both how the drug companies sort of market this product and sort of how it does,” Dr. Liu said.

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

A new antibiotic for urinary tract infections is heading toward government approval.

It would be the first new treatment in 20 years for UTIs, which affect more than half of women at least sometime in their lives, according to data compiled by the Department of Health and Human Services.

Called Gepotidacin, the antibiotic’s trial has halted enrollment early due to excellent effectiveness and safety results thus far, drugmaker GSK announced in a press release Nov. 3. GSK will seek approval and peer-reviewed publication early next year.

There is a need for new antibiotics such as this because of increasing antibiotic resistance. Antibiotic resistance to bacteria has become so prevalent that the World Health Organization recently began publishing a list of bacteria that pose the greatest public health threats.

“It’s definitely a big deal,” Cindy Liu, MD, MPH, PhD, of the Antibiotic Resistance Action Center at George Washington University, told CNN.

However, antibiotics are not a particularly profitable type of drug, The Wall Street Journal reported. The newspaper noted that they need to be used sparingly to limit resistance, and the cheapest option is usually prescribed. Some small companies that make antibiotics have even gone bankrupt recently, the Journal noted.

The U.S. government has invested in GSK’s development of Gepotidacin. The company predicts the drug could be a “blockbuster” and earn more than $1 billion due to UTI resistance to other drugs, the Journal reported.

“I think it will be really interesting and important to the field to see both how the drug companies sort of market this product and sort of how it does,” Dr. Liu said.

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

Women with polycystic ovary syndrome (PCOS) may be at a higher risk of developing pancreatic cancer, say researchers reporting a single-center case-control study.

A diagnosis of PCOS was associated with a 1.9-fold higher risk of pancreatic cancer after adjusting for age, race, ethnicity, estrogen level, and diabetes.

This is the second study to find such an association.

“Our study findings combined with those from the 2019 Swedish Registry study offer compelling evidence that PCOS may be a novel risk factor for pancreatic cancer,” said corresponding author Mengmeng Du, ScD, department of epidemiology and biostatistics, Memorial Sloan Kettering Cancer Center.

“These data suggest some individuals may have unknown metabolic derangements that may underlie the development of both conditions,” the team concluded.

The findings were published in JAMA Oncology.

Approached for comment, Srinivas Gaddam, MD, MPH, associate director of pancreatic biliary research medicine, Cedars-Sinai, suggested that the findings may pave the way for a better understanding of the two diseases, but he emphasized that more research is needed.

“I think there’s more research to be done because now we’re seeing more younger women get pancreatic cancer,” Dr. Gaddam said. “So that makes it interesting whether PCOS itself contributes to pancreatic cancer. I still think the jury is out there.”

Dr. Gaddam drew attention to the confidence interval for the finding – the adjusted odds ratio was 1.88 (95% confidence interval, 1.02-3.46). “Because their odds ratio includes 1, I’m left with the question as to whether or not this is truly associated. I’m not certain that we can draw any conclusions based on this,” he commented.

The investigators acknowledge that they did “not observe statistically significant interactions” and comment that “prospective studies are needed to examine underlying biologic mechanisms and confirm our findings.”

For the study, the team used data from the Memorial Sloan Kettering Cancer Center Pancreatic Tumor Registry. They identified patients with pancreatic cancer who also self-reported a diagnosis of PCOS.

The investigators compared data from 446 women with pathologically or cytologically confirmed pancreatic adenocarcinoma with 209 women who had no history of cancer. The mean age at cancer diagnosis or enrollment was 63.8 years among patients with pancreatic cancer and 57.7 years in the control group.

The study found that having PCOS nearly doubled a person’s risk of developing pancreatic cancer.

When adjusted for type 2 diabetes diagnosis, the odds ratio fell slightly to 1.78 (95% CI, 0.95-3.34).

Dr. Du, along with lead author Noah Peeri, PhD, were surprised that even after adjusting for body mass index and the presence of type 2 diabetes, PCOS remained strongly associated with pancreatic cancer risk.

“We originally thought type 2 diabetes may drive this association, given more than half of those with PCOS develop type 2 diabetes by age 40, according to the CDC, and type 2 diabetes has also been linked with increased pancreatic cancer risk,” said Dr. Du.

“While the association was slightly weaker and no longer statistically significant after we controlled for type 2 diabetes, the magnitude of the association remained largely unchanged,” he said.

Dr. Peeri believes that some of the factors that have been causally related to PCOS may increase an individual’s pancreatic cancer risk.

“PCOS itself does not likely cause pancreatic cancer, but metabolic problems (for example, improper breakdown of insulin) and chronic inflammation can contribute to both PCOS and pancreatic cancer risk,” Dr. Peeri said.

He concluded that the study results “suggest other underlying metabolic dysfunction may increase an individual’s pancreatic cancer risk.”

An important limitation of this study was that women in the study self-reported PCOS and may have incorrectly recalled their diagnosis. However, the authors believe it is unlikely that that had a bearing on the study findings.

The study was supported by National Cancer Institute grants, the Geoffrey Beene Foundation, and the Arnold and Arlene Goldstein Family Foundation.

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

Women with polycystic ovary syndrome (PCOS) may be at a higher risk of developing pancreatic cancer, say researchers reporting a single-center case-control study.

A diagnosis of PCOS was associated with a 1.9-fold higher risk of pancreatic cancer after adjusting for age, race, ethnicity, estrogen level, and diabetes.

This is the second study to find such an association.

“Our study findings combined with those from the 2019 Swedish Registry study offer compelling evidence that PCOS may be a novel risk factor for pancreatic cancer,” said corresponding author Mengmeng Du, ScD, department of epidemiology and biostatistics, Memorial Sloan Kettering Cancer Center.

“These data suggest some individuals may have unknown metabolic derangements that may underlie the development of both conditions,” the team concluded.

The findings were published in JAMA Oncology.

Approached for comment, Srinivas Gaddam, MD, MPH, associate director of pancreatic biliary research medicine, Cedars-Sinai, suggested that the findings may pave the way for a better understanding of the two diseases, but he emphasized that more research is needed.

“I think there’s more research to be done because now we’re seeing more younger women get pancreatic cancer,” Dr. Gaddam said. “So that makes it interesting whether PCOS itself contributes to pancreatic cancer. I still think the jury is out there.”

Dr. Gaddam drew attention to the confidence interval for the finding – the adjusted odds ratio was 1.88 (95% confidence interval, 1.02-3.46). “Because their odds ratio includes 1, I’m left with the question as to whether or not this is truly associated. I’m not certain that we can draw any conclusions based on this,” he commented.

The investigators acknowledge that they did “not observe statistically significant interactions” and comment that “prospective studies are needed to examine underlying biologic mechanisms and confirm our findings.”

For the study, the team used data from the Memorial Sloan Kettering Cancer Center Pancreatic Tumor Registry. They identified patients with pancreatic cancer who also self-reported a diagnosis of PCOS.

The investigators compared data from 446 women with pathologically or cytologically confirmed pancreatic adenocarcinoma with 209 women who had no history of cancer. The mean age at cancer diagnosis or enrollment was 63.8 years among patients with pancreatic cancer and 57.7 years in the control group.

The study found that having PCOS nearly doubled a person’s risk of developing pancreatic cancer.

When adjusted for type 2 diabetes diagnosis, the odds ratio fell slightly to 1.78 (95% CI, 0.95-3.34).

Dr. Du, along with lead author Noah Peeri, PhD, were surprised that even after adjusting for body mass index and the presence of type 2 diabetes, PCOS remained strongly associated with pancreatic cancer risk.

“We originally thought type 2 diabetes may drive this association, given more than half of those with PCOS develop type 2 diabetes by age 40, according to the CDC, and type 2 diabetes has also been linked with increased pancreatic cancer risk,” said Dr. Du.

“While the association was slightly weaker and no longer statistically significant after we controlled for type 2 diabetes, the magnitude of the association remained largely unchanged,” he said.

Dr. Peeri believes that some of the factors that have been causally related to PCOS may increase an individual’s pancreatic cancer risk.

“PCOS itself does not likely cause pancreatic cancer, but metabolic problems (for example, improper breakdown of insulin) and chronic inflammation can contribute to both PCOS and pancreatic cancer risk,” Dr. Peeri said.

He concluded that the study results “suggest other underlying metabolic dysfunction may increase an individual’s pancreatic cancer risk.”

An important limitation of this study was that women in the study self-reported PCOS and may have incorrectly recalled their diagnosis. However, the authors believe it is unlikely that that had a bearing on the study findings.

The study was supported by National Cancer Institute grants, the Geoffrey Beene Foundation, and the Arnold and Arlene Goldstein Family Foundation.

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

Women with polycystic ovary syndrome (PCOS) may be at a higher risk of developing pancreatic cancer, say researchers reporting a single-center case-control study.

A diagnosis of PCOS was associated with a 1.9-fold higher risk of pancreatic cancer after adjusting for age, race, ethnicity, estrogen level, and diabetes.

This is the second study to find such an association.

“Our study findings combined with those from the 2019 Swedish Registry study offer compelling evidence that PCOS may be a novel risk factor for pancreatic cancer,” said corresponding author Mengmeng Du, ScD, department of epidemiology and biostatistics, Memorial Sloan Kettering Cancer Center.

“These data suggest some individuals may have unknown metabolic derangements that may underlie the development of both conditions,” the team concluded.

The findings were published in JAMA Oncology.

Approached for comment, Srinivas Gaddam, MD, MPH, associate director of pancreatic biliary research medicine, Cedars-Sinai, suggested that the findings may pave the way for a better understanding of the two diseases, but he emphasized that more research is needed.

“I think there’s more research to be done because now we’re seeing more younger women get pancreatic cancer,” Dr. Gaddam said. “So that makes it interesting whether PCOS itself contributes to pancreatic cancer. I still think the jury is out there.”

Dr. Gaddam drew attention to the confidence interval for the finding – the adjusted odds ratio was 1.88 (95% confidence interval, 1.02-3.46). “Because their odds ratio includes 1, I’m left with the question as to whether or not this is truly associated. I’m not certain that we can draw any conclusions based on this,” he commented.

The investigators acknowledge that they did “not observe statistically significant interactions” and comment that “prospective studies are needed to examine underlying biologic mechanisms and confirm our findings.”

For the study, the team used data from the Memorial Sloan Kettering Cancer Center Pancreatic Tumor Registry. They identified patients with pancreatic cancer who also self-reported a diagnosis of PCOS.

The investigators compared data from 446 women with pathologically or cytologically confirmed pancreatic adenocarcinoma with 209 women who had no history of cancer. The mean age at cancer diagnosis or enrollment was 63.8 years among patients with pancreatic cancer and 57.7 years in the control group.

The study found that having PCOS nearly doubled a person’s risk of developing pancreatic cancer.

When adjusted for type 2 diabetes diagnosis, the odds ratio fell slightly to 1.78 (95% CI, 0.95-3.34).

Dr. Du, along with lead author Noah Peeri, PhD, were surprised that even after adjusting for body mass index and the presence of type 2 diabetes, PCOS remained strongly associated with pancreatic cancer risk.

“We originally thought type 2 diabetes may drive this association, given more than half of those with PCOS develop type 2 diabetes by age 40, according to the CDC, and type 2 diabetes has also been linked with increased pancreatic cancer risk,” said Dr. Du.

“While the association was slightly weaker and no longer statistically significant after we controlled for type 2 diabetes, the magnitude of the association remained largely unchanged,” he said.

Dr. Peeri believes that some of the factors that have been causally related to PCOS may increase an individual’s pancreatic cancer risk.

“PCOS itself does not likely cause pancreatic cancer, but metabolic problems (for example, improper breakdown of insulin) and chronic inflammation can contribute to both PCOS and pancreatic cancer risk,” Dr. Peeri said.

He concluded that the study results “suggest other underlying metabolic dysfunction may increase an individual’s pancreatic cancer risk.”

An important limitation of this study was that women in the study self-reported PCOS and may have incorrectly recalled their diagnosis. However, the authors believe it is unlikely that that had a bearing on the study findings.

The study was supported by National Cancer Institute grants, the Geoffrey Beene Foundation, and the Arnold and Arlene Goldstein Family Foundation.

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

The Centers for Disease Control and Prevention is warning of an early surge in respiratory disease caused by multiple viruses. As influenza viruses, respiratory syncytial virus (RSV), SARS-CoV-2, and rhinovirus/enterovirus simultaneously circulate, the agency cautioned that this confluence of viral activity could strain the health care system, according to a CDC Health Network Alert advisory issued Nov. 4.

“This early increase in disease incidence highlights the importance of optimizing respiratory virus prevention and treatment measures, including prompt vaccination and antiviral treatment,” the alert stated.

The CDC reports that RSV activity is increasing nationally, but in some areas – such as the South and Mountain West – cases appear to be trending downward.

Influenza cases continue to climb, with the virus activity being the highest in the South, Mid-Atlantic, and the south-central West Coast, according to CDC data. “In fact, we’re seeing the highest influenza hospitalization rates going back a decade,” said José Romero, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases, during a press briefing. The agency estimates that there have been 1.6 million illnesses, 13,000 hospitalizations, and 730 deaths from the flu so far this season. As of Nov. 4, there have been two pediatric deaths.

COVID-19 cases appear to have plateaued in the past three weeks, Dr. Romero said; however, the CDC expects that there will be “high-level circulation of SARS-CoV-2 this fall and winter,” the health alert stated.

The CDC advised that all eligible individuals aged 6-months or older should be vaccinated against COVID-19 and influenza. To protect against RSV-hospitalization, high-risk children should receive the monoclonal antibody drug palivizumab (Synagis). High-risk children include infants born before 29 weeks, children younger than age 2 with chronic lung disease or hemodynamically significant congenital heart disease, and children with suppressed immune systems or neuromuscular disorders.

Any patient with confirmed or suspected flu who is hospitalized, at higher risk for influenza complications, or who has a severe or progressive illness should be treated as early as possible with antivirals, such as oral oseltamivir (Tamiflu).

Patients with confirmed SARS-CoV-2 infection with increased risk of complications should also be treated with antivirals, such as nirmatrelvir and ritonavir (Paxlovid) or remdesivir (Veklury).

Patients should also be reminded to wash their hands frequently, cover coughs and sneezes, stay home when sick, and avoid close contact with people who are sick, the CDC advised.

“There’s no doubt that we will face some challenges this winter,” said Dawn O’Connell, HHS Assistant Secretary for Preparedness and Response, “but it’s important to remember that RSV and flu are not new, and we have safe and effective vaccines for COVID-19 and the flu.”

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

The Centers for Disease Control and Prevention is warning of an early surge in respiratory disease caused by multiple viruses. As influenza viruses, respiratory syncytial virus (RSV), SARS-CoV-2, and rhinovirus/enterovirus simultaneously circulate, the agency cautioned that this confluence of viral activity could strain the health care system, according to a CDC Health Network Alert advisory issued Nov. 4.

“This early increase in disease incidence highlights the importance of optimizing respiratory virus prevention and treatment measures, including prompt vaccination and antiviral treatment,” the alert stated.

The CDC reports that RSV activity is increasing nationally, but in some areas – such as the South and Mountain West – cases appear to be trending downward.

Influenza cases continue to climb, with the virus activity being the highest in the South, Mid-Atlantic, and the south-central West Coast, according to CDC data. “In fact, we’re seeing the highest influenza hospitalization rates going back a decade,” said José Romero, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases, during a press briefing. The agency estimates that there have been 1.6 million illnesses, 13,000 hospitalizations, and 730 deaths from the flu so far this season. As of Nov. 4, there have been two pediatric deaths.

COVID-19 cases appear to have plateaued in the past three weeks, Dr. Romero said; however, the CDC expects that there will be “high-level circulation of SARS-CoV-2 this fall and winter,” the health alert stated.

The CDC advised that all eligible individuals aged 6-months or older should be vaccinated against COVID-19 and influenza. To protect against RSV-hospitalization, high-risk children should receive the monoclonal antibody drug palivizumab (Synagis). High-risk children include infants born before 29 weeks, children younger than age 2 with chronic lung disease or hemodynamically significant congenital heart disease, and children with suppressed immune systems or neuromuscular disorders.

Any patient with confirmed or suspected flu who is hospitalized, at higher risk for influenza complications, or who has a severe or progressive illness should be treated as early as possible with antivirals, such as oral oseltamivir (Tamiflu).

Patients with confirmed SARS-CoV-2 infection with increased risk of complications should also be treated with antivirals, such as nirmatrelvir and ritonavir (Paxlovid) or remdesivir (Veklury).

Patients should also be reminded to wash their hands frequently, cover coughs and sneezes, stay home when sick, and avoid close contact with people who are sick, the CDC advised.

“There’s no doubt that we will face some challenges this winter,” said Dawn O’Connell, HHS Assistant Secretary for Preparedness and Response, “but it’s important to remember that RSV and flu are not new, and we have safe and effective vaccines for COVID-19 and the flu.”

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

The Centers for Disease Control and Prevention is warning of an early surge in respiratory disease caused by multiple viruses. As influenza viruses, respiratory syncytial virus (RSV), SARS-CoV-2, and rhinovirus/enterovirus simultaneously circulate, the agency cautioned that this confluence of viral activity could strain the health care system, according to a CDC Health Network Alert advisory issued Nov. 4.

“This early increase in disease incidence highlights the importance of optimizing respiratory virus prevention and treatment measures, including prompt vaccination and antiviral treatment,” the alert stated.

The CDC reports that RSV activity is increasing nationally, but in some areas – such as the South and Mountain West – cases appear to be trending downward.

Influenza cases continue to climb, with the virus activity being the highest in the South, Mid-Atlantic, and the south-central West Coast, according to CDC data. “In fact, we’re seeing the highest influenza hospitalization rates going back a decade,” said José Romero, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases, during a press briefing. The agency estimates that there have been 1.6 million illnesses, 13,000 hospitalizations, and 730 deaths from the flu so far this season. As of Nov. 4, there have been two pediatric deaths.

COVID-19 cases appear to have plateaued in the past three weeks, Dr. Romero said; however, the CDC expects that there will be “high-level circulation of SARS-CoV-2 this fall and winter,” the health alert stated.

The CDC advised that all eligible individuals aged 6-months or older should be vaccinated against COVID-19 and influenza. To protect against RSV-hospitalization, high-risk children should receive the monoclonal antibody drug palivizumab (Synagis). High-risk children include infants born before 29 weeks, children younger than age 2 with chronic lung disease or hemodynamically significant congenital heart disease, and children with suppressed immune systems or neuromuscular disorders.

Any patient with confirmed or suspected flu who is hospitalized, at higher risk for influenza complications, or who has a severe or progressive illness should be treated as early as possible with antivirals, such as oral oseltamivir (Tamiflu).

Patients with confirmed SARS-CoV-2 infection with increased risk of complications should also be treated with antivirals, such as nirmatrelvir and ritonavir (Paxlovid) or remdesivir (Veklury).

Patients should also be reminded to wash their hands frequently, cover coughs and sneezes, stay home when sick, and avoid close contact with people who are sick, the CDC advised.

“There’s no doubt that we will face some challenges this winter,” said Dawn O’Connell, HHS Assistant Secretary for Preparedness and Response, “but it’s important to remember that RSV and flu are not new, and we have safe and effective vaccines for COVID-19 and the flu.”

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

Epstein-Barr Virus (EBV) is a suspect in the development of multiple sclerosis (MS), and recent research developments have strengthened that connection. In 2022, two studies received quite a bit of attention. One showed that EBV seroconversion occurs in the years prior to MS diagnosis in virtually every patient, and that serum levels of the neuronal damage biomarker neurofilament light (NfL) rose following EBV infection. Another paper showed anti-EBNA (Epstein-Barr nuclear antigen) antibodies in the cerebrospinal fluid cross-react with the central nervous system antigen GlialCAM in some MS patients.

Based on those studies, “it’s tempting to speculate that primary EBV infection could be a trigger to the autoimmune process suspected for MS,” said Tilman Schneider-Hohendorf, PhD, during a presentation at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Dr. Schneider-Hohendorf, who is a postdoctoral fellow at the University of Münster, Germany, presented a new study that added more evidence that EBV may be a key player in MS pathogenesis. He and colleagues conducted a genetic analysis of patient T cells and found evidence that EBV viral activity may be occurring during MS.
 

A viral pathway to MS

Asked for comment, Bruce Cree, MD, PhD, said: “I think it is a very interesting one, because what we know about EBV is that it’s a risk factor for MS. So many studies performed over the last 20 years have shown a very strong association between EBV infection and the occurrence of MS. Studies have shown quite conclusively that EBV infection precedes MS in almost every patient, and that EBV infection is followed by a rise in serum NfL, which is a biomarker of neuronal damage. You have EBV infection, and then typically several years later a rise in serum concentrations of this marker of neuronal injury, and this is all in a presymptomatic state. Then that is followed by the onset of clinical symptoms in MS. That temporal sequence, I think, is very convincing,” said Dr. Cree, who is a professor of clinical neurology at the University of California, San Francisco.

He pointed out that EBV is not the sole causal pathway of MS, since genetic and environmental factors are known to be involved. “Nonetheless, it’s very strong evidence to indicate that this virus is involved in disease pathogenesis,” said Dr. Cree.

The new research takes the work a step further by revealing a population of T cells in MS patients that appear to be responding directly to EBV during active viral disease. That could be telling because most people who experience an EBV infection and experience mononucleosis recover, and some never even realize they have been infected. As a herpes virus, EBV remains in a latent state in B cells and other immune cells. “We know that you need an EBV infection (to trigger MS), but is EBV in some way continuing to be active in MS?” said Dr. Cree.

Other groups have looked for such evidence, but results have been mixed. Dr. Cree’s own group looked for evidence of EBV in spinal fluid of MS patients when they first present with symptoms, and could find no evidence. On the other hand, an autopsy study of MS patients has found evidence of chronic EBV infection in and around the brain, including the meninges, which could implicate the B cells found in that region. Another study found EBV-targeting antibodies that cross react with neuronal antigens in the cerebral spinal fluid of MS patients. “So depending on the assay used and the types of investigation, there is variable evidence to indicate that EBV has a role in ongoing MS pathogenesis – that it isn’t just a risk factor for MS that triggers the disease but potentially has a role in determining the course of MS,” said Dr. Cree.
 

IS EBV part of MS pathogenesis?

The new study presented at ECTRIMS by Dr. Schneider-Hohendorf offered evidence that MS patients have excess CD8-positive T cells that recognize EBV antigens typically shed during active viral infection. The results suggest “that the immune system is responding to that chronic infection,” said Dr. Cree.

The findings have some implications for a clinical study now in progress, called EMBOLD, which is looking at whether a heterologous infusion of T cells that have been primed to attack EBV could improve symptoms of progressive MS. “The hypothesis there is that chronically infected cells within the body are causing progressive MS and that if we could eradicate those cells, both within the central nervous system and within the periphery, perhaps we could see improvement in MS functional outcomes,” said Dr. Cree, who is a co-investigator for the EMBOLD study. The trial is using T cells from donors that are matched for the human leukocyte antigen complex, which is hoped will target and kill EBV-infected cells.

The study presented by Dr. Schneider-Hohendorf supports the approach. “There is an implication from this study that the trial that that’s currently being conducted might actually possibly have a benefit in the sense that there’s now another piece of evidence to indicate that EBV is not only a risk factor for MS, but may actually participate during the course of the disease as part of the pathogenesis,” said Dr. Cree.

In the new study, the researchers sequenced the T-cell receptor variable beta-chain (TRBV) peripheral repertoire among three cohorts of MS patients: A discovery cohort with 1,336 patients with MS and 229 controls; a validation cohort with 59 patients with MS and 51 controls; and 35 monozygotic twins who were discordant for MS. They identified sequences known to bind to EBV, SARS-CoV-2, cytomegalovirus, and influenza A, and used the latter three viruses as a proof of concept to demonstrate the validity of the approach. EBV-specific MHC-1 restricted CD8 TRBV in the serum of MS patients, with large effect sizes in the discovery (+2.2), validation (+2.1), and MS twin (+1.6) populations. The findings in the twin population rule out a genetic or environmental explanation for the findings in the discovery and validation cohorts, according to Dr. Schneider-Hohendorf.

The researchers also sequenced CSF among six healthy donors and five patients with MS and found significant differences. The T-cell populations had more lytic properties that suggested ongoing immune surveillance. “We can conclude that we found a broader response that could indicate an aberrant immune response. This could be a remnant of disease triggering an event or it could indicate an ongoing immune response to EBV. Is this EBV activity? We really don’t know. To find out, we would expand our pathogen-specific sequences, we would assess CNS tissue and lesions, and we would define the primary response in pediatric cohorts to better understand what might go wrong,” Dr. Schneider-Hohendorf concluded.

Dr. Cree has a financial relationship with Biogen and is a co-investigator for the EMBOLD trial. Dr. Schneider-Hohendorf has financial relationships with Biogen, Novartis, and Roche.

Epstein-Barr Virus (EBV) is a suspect in the development of multiple sclerosis (MS), and recent research developments have strengthened that connection. In 2022, two studies received quite a bit of attention. One showed that EBV seroconversion occurs in the years prior to MS diagnosis in virtually every patient, and that serum levels of the neuronal damage biomarker neurofilament light (NfL) rose following EBV infection. Another paper showed anti-EBNA (Epstein-Barr nuclear antigen) antibodies in the cerebrospinal fluid cross-react with the central nervous system antigen GlialCAM in some MS patients.

Based on those studies, “it’s tempting to speculate that primary EBV infection could be a trigger to the autoimmune process suspected for MS,” said Tilman Schneider-Hohendorf, PhD, during a presentation at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Dr. Schneider-Hohendorf, who is a postdoctoral fellow at the University of Münster, Germany, presented a new study that added more evidence that EBV may be a key player in MS pathogenesis. He and colleagues conducted a genetic analysis of patient T cells and found evidence that EBV viral activity may be occurring during MS.
 

A viral pathway to MS

Asked for comment, Bruce Cree, MD, PhD, said: “I think it is a very interesting one, because what we know about EBV is that it’s a risk factor for MS. So many studies performed over the last 20 years have shown a very strong association between EBV infection and the occurrence of MS. Studies have shown quite conclusively that EBV infection precedes MS in almost every patient, and that EBV infection is followed by a rise in serum NfL, which is a biomarker of neuronal damage. You have EBV infection, and then typically several years later a rise in serum concentrations of this marker of neuronal injury, and this is all in a presymptomatic state. Then that is followed by the onset of clinical symptoms in MS. That temporal sequence, I think, is very convincing,” said Dr. Cree, who is a professor of clinical neurology at the University of California, San Francisco.

He pointed out that EBV is not the sole causal pathway of MS, since genetic and environmental factors are known to be involved. “Nonetheless, it’s very strong evidence to indicate that this virus is involved in disease pathogenesis,” said Dr. Cree.

The new research takes the work a step further by revealing a population of T cells in MS patients that appear to be responding directly to EBV during active viral disease. That could be telling because most people who experience an EBV infection and experience mononucleosis recover, and some never even realize they have been infected. As a herpes virus, EBV remains in a latent state in B cells and other immune cells. “We know that you need an EBV infection (to trigger MS), but is EBV in some way continuing to be active in MS?” said Dr. Cree.

Other groups have looked for such evidence, but results have been mixed. Dr. Cree’s own group looked for evidence of EBV in spinal fluid of MS patients when they first present with symptoms, and could find no evidence. On the other hand, an autopsy study of MS patients has found evidence of chronic EBV infection in and around the brain, including the meninges, which could implicate the B cells found in that region. Another study found EBV-targeting antibodies that cross react with neuronal antigens in the cerebral spinal fluid of MS patients. “So depending on the assay used and the types of investigation, there is variable evidence to indicate that EBV has a role in ongoing MS pathogenesis – that it isn’t just a risk factor for MS that triggers the disease but potentially has a role in determining the course of MS,” said Dr. Cree.
 

IS EBV part of MS pathogenesis?

The new study presented at ECTRIMS by Dr. Schneider-Hohendorf offered evidence that MS patients have excess CD8-positive T cells that recognize EBV antigens typically shed during active viral infection. The results suggest “that the immune system is responding to that chronic infection,” said Dr. Cree.

The findings have some implications for a clinical study now in progress, called EMBOLD, which is looking at whether a heterologous infusion of T cells that have been primed to attack EBV could improve symptoms of progressive MS. “The hypothesis there is that chronically infected cells within the body are causing progressive MS and that if we could eradicate those cells, both within the central nervous system and within the periphery, perhaps we could see improvement in MS functional outcomes,” said Dr. Cree, who is a co-investigator for the EMBOLD study. The trial is using T cells from donors that are matched for the human leukocyte antigen complex, which is hoped will target and kill EBV-infected cells.

The study presented by Dr. Schneider-Hohendorf supports the approach. “There is an implication from this study that the trial that that’s currently being conducted might actually possibly have a benefit in the sense that there’s now another piece of evidence to indicate that EBV is not only a risk factor for MS, but may actually participate during the course of the disease as part of the pathogenesis,” said Dr. Cree.

In the new study, the researchers sequenced the T-cell receptor variable beta-chain (TRBV) peripheral repertoire among three cohorts of MS patients: A discovery cohort with 1,336 patients with MS and 229 controls; a validation cohort with 59 patients with MS and 51 controls; and 35 monozygotic twins who were discordant for MS. They identified sequences known to bind to EBV, SARS-CoV-2, cytomegalovirus, and influenza A, and used the latter three viruses as a proof of concept to demonstrate the validity of the approach. EBV-specific MHC-1 restricted CD8 TRBV in the serum of MS patients, with large effect sizes in the discovery (+2.2), validation (+2.1), and MS twin (+1.6) populations. The findings in the twin population rule out a genetic or environmental explanation for the findings in the discovery and validation cohorts, according to Dr. Schneider-Hohendorf.

The researchers also sequenced CSF among six healthy donors and five patients with MS and found significant differences. The T-cell populations had more lytic properties that suggested ongoing immune surveillance. “We can conclude that we found a broader response that could indicate an aberrant immune response. This could be a remnant of disease triggering an event or it could indicate an ongoing immune response to EBV. Is this EBV activity? We really don’t know. To find out, we would expand our pathogen-specific sequences, we would assess CNS tissue and lesions, and we would define the primary response in pediatric cohorts to better understand what might go wrong,” Dr. Schneider-Hohendorf concluded.

Dr. Cree has a financial relationship with Biogen and is a co-investigator for the EMBOLD trial. Dr. Schneider-Hohendorf has financial relationships with Biogen, Novartis, and Roche.

Epstein-Barr Virus (EBV) is a suspect in the development of multiple sclerosis (MS), and recent research developments have strengthened that connection. In 2022, two studies received quite a bit of attention. One showed that EBV seroconversion occurs in the years prior to MS diagnosis in virtually every patient, and that serum levels of the neuronal damage biomarker neurofilament light (NfL) rose following EBV infection. Another paper showed anti-EBNA (Epstein-Barr nuclear antigen) antibodies in the cerebrospinal fluid cross-react with the central nervous system antigen GlialCAM in some MS patients.

Based on those studies, “it’s tempting to speculate that primary EBV infection could be a trigger to the autoimmune process suspected for MS,” said Tilman Schneider-Hohendorf, PhD, during a presentation at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Dr. Schneider-Hohendorf, who is a postdoctoral fellow at the University of Münster, Germany, presented a new study that added more evidence that EBV may be a key player in MS pathogenesis. He and colleagues conducted a genetic analysis of patient T cells and found evidence that EBV viral activity may be occurring during MS.
 

A viral pathway to MS

Asked for comment, Bruce Cree, MD, PhD, said: “I think it is a very interesting one, because what we know about EBV is that it’s a risk factor for MS. So many studies performed over the last 20 years have shown a very strong association between EBV infection and the occurrence of MS. Studies have shown quite conclusively that EBV infection precedes MS in almost every patient, and that EBV infection is followed by a rise in serum NfL, which is a biomarker of neuronal damage. You have EBV infection, and then typically several years later a rise in serum concentrations of this marker of neuronal injury, and this is all in a presymptomatic state. Then that is followed by the onset of clinical symptoms in MS. That temporal sequence, I think, is very convincing,” said Dr. Cree, who is a professor of clinical neurology at the University of California, San Francisco.

He pointed out that EBV is not the sole causal pathway of MS, since genetic and environmental factors are known to be involved. “Nonetheless, it’s very strong evidence to indicate that this virus is involved in disease pathogenesis,” said Dr. Cree.

The new research takes the work a step further by revealing a population of T cells in MS patients that appear to be responding directly to EBV during active viral disease. That could be telling because most people who experience an EBV infection and experience mononucleosis recover, and some never even realize they have been infected. As a herpes virus, EBV remains in a latent state in B cells and other immune cells. “We know that you need an EBV infection (to trigger MS), but is EBV in some way continuing to be active in MS?” said Dr. Cree.

Other groups have looked for such evidence, but results have been mixed. Dr. Cree’s own group looked for evidence of EBV in spinal fluid of MS patients when they first present with symptoms, and could find no evidence. On the other hand, an autopsy study of MS patients has found evidence of chronic EBV infection in and around the brain, including the meninges, which could implicate the B cells found in that region. Another study found EBV-targeting antibodies that cross react with neuronal antigens in the cerebral spinal fluid of MS patients. “So depending on the assay used and the types of investigation, there is variable evidence to indicate that EBV has a role in ongoing MS pathogenesis – that it isn’t just a risk factor for MS that triggers the disease but potentially has a role in determining the course of MS,” said Dr. Cree.
 

IS EBV part of MS pathogenesis?

The new study presented at ECTRIMS by Dr. Schneider-Hohendorf offered evidence that MS patients have excess CD8-positive T cells that recognize EBV antigens typically shed during active viral infection. The results suggest “that the immune system is responding to that chronic infection,” said Dr. Cree.

The findings have some implications for a clinical study now in progress, called EMBOLD, which is looking at whether a heterologous infusion of T cells that have been primed to attack EBV could improve symptoms of progressive MS. “The hypothesis there is that chronically infected cells within the body are causing progressive MS and that if we could eradicate those cells, both within the central nervous system and within the periphery, perhaps we could see improvement in MS functional outcomes,” said Dr. Cree, who is a co-investigator for the EMBOLD study. The trial is using T cells from donors that are matched for the human leukocyte antigen complex, which is hoped will target and kill EBV-infected cells.

The study presented by Dr. Schneider-Hohendorf supports the approach. “There is an implication from this study that the trial that that’s currently being conducted might actually possibly have a benefit in the sense that there’s now another piece of evidence to indicate that EBV is not only a risk factor for MS, but may actually participate during the course of the disease as part of the pathogenesis,” said Dr. Cree.

In the new study, the researchers sequenced the T-cell receptor variable beta-chain (TRBV) peripheral repertoire among three cohorts of MS patients: A discovery cohort with 1,336 patients with MS and 229 controls; a validation cohort with 59 patients with MS and 51 controls; and 35 monozygotic twins who were discordant for MS. They identified sequences known to bind to EBV, SARS-CoV-2, cytomegalovirus, and influenza A, and used the latter three viruses as a proof of concept to demonstrate the validity of the approach. EBV-specific MHC-1 restricted CD8 TRBV in the serum of MS patients, with large effect sizes in the discovery (+2.2), validation (+2.1), and MS twin (+1.6) populations. The findings in the twin population rule out a genetic or environmental explanation for the findings in the discovery and validation cohorts, according to Dr. Schneider-Hohendorf.

The researchers also sequenced CSF among six healthy donors and five patients with MS and found significant differences. The T-cell populations had more lytic properties that suggested ongoing immune surveillance. “We can conclude that we found a broader response that could indicate an aberrant immune response. This could be a remnant of disease triggering an event or it could indicate an ongoing immune response to EBV. Is this EBV activity? We really don’t know. To find out, we would expand our pathogen-specific sequences, we would assess CNS tissue and lesions, and we would define the primary response in pediatric cohorts to better understand what might go wrong,” Dr. Schneider-Hohendorf concluded.

Dr. Cree has a financial relationship with Biogen and is a co-investigator for the EMBOLD trial. Dr. Schneider-Hohendorf has financial relationships with Biogen, Novartis, and Roche.

A new Japanese study of highly purified eicosapentaenoic acid (EPA; icosapent ethyl) has suggested a possible benefit in reducing adverse cardiovascular events in patients with chronic coronary artery disease taking statins.

The open-label randomized RESPECT-EPA study showed a reduction of borderline statistical significance in its primary endpoint of a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, unstable angina, and coronary revascularization in patients allocated to the EPA product at a dosage of 1,800 mg/day.

The results were presented at the American Heart Association scientific sessions by Hiroyuki Daida, MD, Juntendo University Graduate School of Medicine, Japan. 

However, the trial has several limitations, including a high number of patient withdrawals or protocol deviations, and as such, its conclusions are uncertain.  

Regardless, it has inevitably added to the debate on the cardiovascular benefits of EPA, which were shown in the REDUCE-IT trial. However, that trial has been dogged with controversy because of concerns that the mineral oil placebo used may have had an adverse effect.

Commenting on the new RESPECT-EPA trial for this article, lead investigator of the REDUCE-IT trial, Deepak Bhatt, MD, said the results were consistent with REDUCE-IT and another previous Japanese trial, the Japan EPA Lipid Intervention Study (JELIS), and added to the evidence supporting cardiovascular benefits of EPA.

“In isolation, this study may not be viewed as showing conclusive benefits, but looking at the totality of the data from this trial and from the field more widely, this together shows a convincing cardiovascular benefit with EPA,” Dr. Bhatt said. “We now have 3 randomized controlled trials all showing benefits of highly purified EPA in reducing cardiovascular events.”

However, long-time critic of the REDUCE-IT trial, Steve Nissen, MD, Cleveland Clinic, was not at all impressed with the RESPECT-EPA trial and does not believe it should be used to support the EPA data from REDUCE-IT. 

“The many limitations of the RESPECT-EPA trial make it uninterpretable. It just doesn’t meet contemporary standards for clinical trials,” Dr. Nissen said in an interview. “I don’t think it sheds any light at all on the debate over the efficacy of EPA in cardiovascular disease.”

Dr. Nissen was the lead investigator of another largescale trial, STRENGTH, which showed no benefit of a different high dose omega-3 fatty acid product including a combination of EPA and docosahexaenoic acid (DHA).  

In his AHA presentation on the RESPECT-EPA study, Dr. Daida explained as background that in 2005, JELIS first demonstrated a beneficial effect of highly purified EPA on cardiovascular outcomes in patients with and without coronary artery disease. 

Recently, optimal medical therapy, particularly with high-intensity statins, has become the gold standard of care for patients with coronary artery disease, but they are still at substantially high residual risk, he noted.

Despite of the evidence provided by JELIS, the conflicting results in recent omega-3 fatty acid trials (REDUCE-IT and STRENGTH) have led to an intense controversy regarding the relevance of EPA intervention on top of the latest optimal medical therapy, Dr. Daida said.

The current study – Randomized trial for Evaluating the Secondary Prevention Efficacy of Combination Therapy Statin and EPA (RESPECT-EPA) – was conducted to determine the effect of highly purified EPA on cardiovascular events in Japanese patients with chronic coronary artery disease and a low EPA/arachidonic acid (AA) ratio (< 0.4), who were already receiving statins.

They were randomly assigned to highly purified EPA (icosapent ethyl, 1,800 mg/day) plus statin therapy or to statin therapy alone.

The enrollment period started in 2013 and continued for 4 years. Patients were followed for a further 4 years from the end of the enrollment period.

The trial included 2,506 patients, 1,249 assigned to the EPA group and 1,257 to the control group. In both groups there were a high number of early withdrawals or protocol deviations (647 in the EPA group and 350 in the control group).

The analysis was conducted on 1,225 patients in the EPA group and 1,235 patients in the control group, although at 6 years’ follow-up there were fewer than 400 patients in each arm.  

Baseline characteristics showed median low-density lipoprotein (LDL) cholesterol levels of 80 mg/dL, EPA levels of 45 mcg/mL, and triglyceride levels of 120 mg/dL.

The primary endpoint, a composite of cardiovascular death, nonfatal MI, nonfatal ischemic stroke, unstable angina, and coronary revascularization showed a borderline significant reduction in the EPA group at 6 years since the start of randomization (10.9% vs. 14.9%; hazard ratio, 0.785; P = .0547).

The secondary endpoint, a composite of sudden cardiac death, MI, unstable angina, and coronary revascularization, showed a significant reduction in the EPA group (8.0% vs. 11.3%; HR, 0.734; P = .0306).

In terms of adverse events, there was an increase in gastrointestinal disorders (3.4% vs. 1.2%) and new-onset atrial fibrillation (3.1% vs. 1.6%) in the EPA group.

In a post hoc analysis, which excluded patients with an increase of more than 30 mcg/mL in the control group (182 patients) and those with an increase of less than 30 mcg/mL in the EPA group (259 patients), the primary endpoint showed a significant reduction the EPA group (HR, 0.725; P = .0202).

Dr. Daida noted that limitations of the study included a lower than expected event rate (suggesting that the study may be underpowered), an open-label design, and the fact that baseline levels of EPA in this Japanese population would be higher than those in Western countries.
 

‘Massive loss’ of patients

Critiquing the study, Dr. Nissen highlighted the large dropout and protocol violation rate.

“There was a massive loss of patients over the 6- to 8-year follow-up, and the Kaplan-Meier curves didn’t start to diverge until after 4 years, by which time many patients had dropped out. It would have been a very selective population that lasted 6 years in the study. Patients that drop out are different to those that stay in, so they are cherry-picking the patients that persist in the trial. There is enormous bias here,” he commented. 

“Another weakness is the open-label design. Everyone knew who is getting what. Blinding is important in a study. And there was no control treatment in this trial,” he noted.

The researchers also selected patients with low EPA levels at baseline, Dr. Nissen added. “That is completely different hypothesis to what was tested in the REDUCE-IT and STRENGTH trials. And even with all these problems, the results are still statistically insignificant.”  

On the post hoc subgroup analysis showing a significant benefit, Dr. Nissen said, “they compared a subgroup in the active treatment arm who had large increases in EPA to a subgroup of control patients who had the smallest increase in EPA. That would be like comparing patients who had the largest reductions in LDL in a statin trial to those in the control arm who had no reductions or increases in LDL. That’s scientifically totally inappropriate.”
 

Supportive data

But Dr. Bhatt argues that the RESPECT-EPA trial supports the two previous trials showing benefits of EPA.

“Some may quibble with the P value, but to me this study has shown clear results, with obvious separation of the Kaplan-Meier curves,” he said.  

“It is an investigator-initiated study, which is good in principle but has some of the usual caveats of such a study in that – probably as a consequence of budget constraints – it has an open-label design and is underpowered. But as they did not use a placebo and still showed a benefit of EPA, that helps resolve the issue of the placebo used in REDUCE-IT for those who were concerned about it,” Dr. Bhatt noted.  

He pointed out that the 1,800-mg dose of EPA is the same dose used in the JELIS trial and is the dose used in Japan. The REDUCE-IT trial used a higher dose (4 g), but in general, Japanese people have higher levels of EPA than Western populations, he explained.  

“While this trial included patients with lower levels of EPA, what is considered low in Japan is much higher than average American levels,” he added.
 

Magnitude of benefit uncertain?

Discussant of the study at the Late Breaking Clinical Trials session, Pam R. Taub, MD, professor of medicine at the University of California, San Diego School of Medicine, said, “Despite being underpowered with a sample size of 2,460, RESPECT-EPA shows benefit in decreasing composite coronary events.”

“There is benefit with EPA, but the magnitude of benefit is uncertain,” she stated.

Dr. Taub pointed out that there is a signal across studies for new-onset atrial fibrillation, but the absolute increase is “rather small.”

She noted that more mechanistic and clinical data are needed to hone in on which patients will derive the most benefit, such as those with elevated high-sensitivity C-reactive protein or highest change in EPA levels. But she concluded that in clinical practice, physicians could consider addition of EPA for reduction of residual risk in secondary prevention patients.

The RESPECT-EPA study was supported by the Japan Heart Foundation. Dr. Daida reports peakers’ bureau/honorarium fees from Novartis Pharma, Bayer Yakuhin, Sanofi, Kowa Company, Taisho Pharmaceutical, Abbott Medical Japan, Otsuka Pharmaceutical, Amgen, MSD, Daiichi Sankyo, Pfizer Japan, FUKUDA DENSHI, Tsumura, and TOA EIYO and research funding from Philips Japan, FUJIFILM Holdings, Asahi Kasei, Inter Reha, TOHO HOLDINGS, GLORY, BMS, Abbott Japan, and Boehringer Ingelheim Japan.

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

A new Japanese study of highly purified eicosapentaenoic acid (EPA; icosapent ethyl) has suggested a possible benefit in reducing adverse cardiovascular events in patients with chronic coronary artery disease taking statins.

The open-label randomized RESPECT-EPA study showed a reduction of borderline statistical significance in its primary endpoint of a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, unstable angina, and coronary revascularization in patients allocated to the EPA product at a dosage of 1,800 mg/day.

The results were presented at the American Heart Association scientific sessions by Hiroyuki Daida, MD, Juntendo University Graduate School of Medicine, Japan. 

However, the trial has several limitations, including a high number of patient withdrawals or protocol deviations, and as such, its conclusions are uncertain.  

Regardless, it has inevitably added to the debate on the cardiovascular benefits of EPA, which were shown in the REDUCE-IT trial. However, that trial has been dogged with controversy because of concerns that the mineral oil placebo used may have had an adverse effect.

Commenting on the new RESPECT-EPA trial for this article, lead investigator of the REDUCE-IT trial, Deepak Bhatt, MD, said the results were consistent with REDUCE-IT and another previous Japanese trial, the Japan EPA Lipid Intervention Study (JELIS), and added to the evidence supporting cardiovascular benefits of EPA.

“In isolation, this study may not be viewed as showing conclusive benefits, but looking at the totality of the data from this trial and from the field more widely, this together shows a convincing cardiovascular benefit with EPA,” Dr. Bhatt said. “We now have 3 randomized controlled trials all showing benefits of highly purified EPA in reducing cardiovascular events.”

However, long-time critic of the REDUCE-IT trial, Steve Nissen, MD, Cleveland Clinic, was not at all impressed with the RESPECT-EPA trial and does not believe it should be used to support the EPA data from REDUCE-IT. 

“The many limitations of the RESPECT-EPA trial make it uninterpretable. It just doesn’t meet contemporary standards for clinical trials,” Dr. Nissen said in an interview. “I don’t think it sheds any light at all on the debate over the efficacy of EPA in cardiovascular disease.”

Dr. Nissen was the lead investigator of another largescale trial, STRENGTH, which showed no benefit of a different high dose omega-3 fatty acid product including a combination of EPA and docosahexaenoic acid (DHA).  

In his AHA presentation on the RESPECT-EPA study, Dr. Daida explained as background that in 2005, JELIS first demonstrated a beneficial effect of highly purified EPA on cardiovascular outcomes in patients with and without coronary artery disease. 

Recently, optimal medical therapy, particularly with high-intensity statins, has become the gold standard of care for patients with coronary artery disease, but they are still at substantially high residual risk, he noted.

Despite of the evidence provided by JELIS, the conflicting results in recent omega-3 fatty acid trials (REDUCE-IT and STRENGTH) have led to an intense controversy regarding the relevance of EPA intervention on top of the latest optimal medical therapy, Dr. Daida said.

The current study – Randomized trial for Evaluating the Secondary Prevention Efficacy of Combination Therapy Statin and EPA (RESPECT-EPA) – was conducted to determine the effect of highly purified EPA on cardiovascular events in Japanese patients with chronic coronary artery disease and a low EPA/arachidonic acid (AA) ratio (< 0.4), who were already receiving statins.

They were randomly assigned to highly purified EPA (icosapent ethyl, 1,800 mg/day) plus statin therapy or to statin therapy alone.

The enrollment period started in 2013 and continued for 4 years. Patients were followed for a further 4 years from the end of the enrollment period.

The trial included 2,506 patients, 1,249 assigned to the EPA group and 1,257 to the control group. In both groups there were a high number of early withdrawals or protocol deviations (647 in the EPA group and 350 in the control group).

The analysis was conducted on 1,225 patients in the EPA group and 1,235 patients in the control group, although at 6 years’ follow-up there were fewer than 400 patients in each arm.  

Baseline characteristics showed median low-density lipoprotein (LDL) cholesterol levels of 80 mg/dL, EPA levels of 45 mcg/mL, and triglyceride levels of 120 mg/dL.

The primary endpoint, a composite of cardiovascular death, nonfatal MI, nonfatal ischemic stroke, unstable angina, and coronary revascularization showed a borderline significant reduction in the EPA group at 6 years since the start of randomization (10.9% vs. 14.9%; hazard ratio, 0.785; P = .0547).

The secondary endpoint, a composite of sudden cardiac death, MI, unstable angina, and coronary revascularization, showed a significant reduction in the EPA group (8.0% vs. 11.3%; HR, 0.734; P = .0306).

In terms of adverse events, there was an increase in gastrointestinal disorders (3.4% vs. 1.2%) and new-onset atrial fibrillation (3.1% vs. 1.6%) in the EPA group.

In a post hoc analysis, which excluded patients with an increase of more than 30 mcg/mL in the control group (182 patients) and those with an increase of less than 30 mcg/mL in the EPA group (259 patients), the primary endpoint showed a significant reduction the EPA group (HR, 0.725; P = .0202).

Dr. Daida noted that limitations of the study included a lower than expected event rate (suggesting that the study may be underpowered), an open-label design, and the fact that baseline levels of EPA in this Japanese population would be higher than those in Western countries.
 

‘Massive loss’ of patients

Critiquing the study, Dr. Nissen highlighted the large dropout and protocol violation rate.

“There was a massive loss of patients over the 6- to 8-year follow-up, and the Kaplan-Meier curves didn’t start to diverge until after 4 years, by which time many patients had dropped out. It would have been a very selective population that lasted 6 years in the study. Patients that drop out are different to those that stay in, so they are cherry-picking the patients that persist in the trial. There is enormous bias here,” he commented. 

“Another weakness is the open-label design. Everyone knew who is getting what. Blinding is important in a study. And there was no control treatment in this trial,” he noted.

The researchers also selected patients with low EPA levels at baseline, Dr. Nissen added. “That is completely different hypothesis to what was tested in the REDUCE-IT and STRENGTH trials. And even with all these problems, the results are still statistically insignificant.”  

On the post hoc subgroup analysis showing a significant benefit, Dr. Nissen said, “they compared a subgroup in the active treatment arm who had large increases in EPA to a subgroup of control patients who had the smallest increase in EPA. That would be like comparing patients who had the largest reductions in LDL in a statin trial to those in the control arm who had no reductions or increases in LDL. That’s scientifically totally inappropriate.”
 

Supportive data

But Dr. Bhatt argues that the RESPECT-EPA trial supports the two previous trials showing benefits of EPA.

“Some may quibble with the P value, but to me this study has shown clear results, with obvious separation of the Kaplan-Meier curves,” he said.  

“It is an investigator-initiated study, which is good in principle but has some of the usual caveats of such a study in that – probably as a consequence of budget constraints – it has an open-label design and is underpowered. But as they did not use a placebo and still showed a benefit of EPA, that helps resolve the issue of the placebo used in REDUCE-IT for those who were concerned about it,” Dr. Bhatt noted.  

He pointed out that the 1,800-mg dose of EPA is the same dose used in the JELIS trial and is the dose used in Japan. The REDUCE-IT trial used a higher dose (4 g), but in general, Japanese people have higher levels of EPA than Western populations, he explained.  

“While this trial included patients with lower levels of EPA, what is considered low in Japan is much higher than average American levels,” he added.
 

Magnitude of benefit uncertain?

Discussant of the study at the Late Breaking Clinical Trials session, Pam R. Taub, MD, professor of medicine at the University of California, San Diego School of Medicine, said, “Despite being underpowered with a sample size of 2,460, RESPECT-EPA shows benefit in decreasing composite coronary events.”

“There is benefit with EPA, but the magnitude of benefit is uncertain,” she stated.

Dr. Taub pointed out that there is a signal across studies for new-onset atrial fibrillation, but the absolute increase is “rather small.”

She noted that more mechanistic and clinical data are needed to hone in on which patients will derive the most benefit, such as those with elevated high-sensitivity C-reactive protein or highest change in EPA levels. But she concluded that in clinical practice, physicians could consider addition of EPA for reduction of residual risk in secondary prevention patients.

The RESPECT-EPA study was supported by the Japan Heart Foundation. Dr. Daida reports peakers’ bureau/honorarium fees from Novartis Pharma, Bayer Yakuhin, Sanofi, Kowa Company, Taisho Pharmaceutical, Abbott Medical Japan, Otsuka Pharmaceutical, Amgen, MSD, Daiichi Sankyo, Pfizer Japan, FUKUDA DENSHI, Tsumura, and TOA EIYO and research funding from Philips Japan, FUJIFILM Holdings, Asahi Kasei, Inter Reha, TOHO HOLDINGS, GLORY, BMS, Abbott Japan, and Boehringer Ingelheim Japan.

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

A new Japanese study of highly purified eicosapentaenoic acid (EPA; icosapent ethyl) has suggested a possible benefit in reducing adverse cardiovascular events in patients with chronic coronary artery disease taking statins.

The open-label randomized RESPECT-EPA study showed a reduction of borderline statistical significance in its primary endpoint of a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, unstable angina, and coronary revascularization in patients allocated to the EPA product at a dosage of 1,800 mg/day.

The results were presented at the American Heart Association scientific sessions by Hiroyuki Daida, MD, Juntendo University Graduate School of Medicine, Japan. 

However, the trial has several limitations, including a high number of patient withdrawals or protocol deviations, and as such, its conclusions are uncertain.  

Regardless, it has inevitably added to the debate on the cardiovascular benefits of EPA, which were shown in the REDUCE-IT trial. However, that trial has been dogged with controversy because of concerns that the mineral oil placebo used may have had an adverse effect.

Commenting on the new RESPECT-EPA trial for this article, lead investigator of the REDUCE-IT trial, Deepak Bhatt, MD, said the results were consistent with REDUCE-IT and another previous Japanese trial, the Japan EPA Lipid Intervention Study (JELIS), and added to the evidence supporting cardiovascular benefits of EPA.

“In isolation, this study may not be viewed as showing conclusive benefits, but looking at the totality of the data from this trial and from the field more widely, this together shows a convincing cardiovascular benefit with EPA,” Dr. Bhatt said. “We now have 3 randomized controlled trials all showing benefits of highly purified EPA in reducing cardiovascular events.”

However, long-time critic of the REDUCE-IT trial, Steve Nissen, MD, Cleveland Clinic, was not at all impressed with the RESPECT-EPA trial and does not believe it should be used to support the EPA data from REDUCE-IT. 

“The many limitations of the RESPECT-EPA trial make it uninterpretable. It just doesn’t meet contemporary standards for clinical trials,” Dr. Nissen said in an interview. “I don’t think it sheds any light at all on the debate over the efficacy of EPA in cardiovascular disease.”

Dr. Nissen was the lead investigator of another largescale trial, STRENGTH, which showed no benefit of a different high dose omega-3 fatty acid product including a combination of EPA and docosahexaenoic acid (DHA).  

In his AHA presentation on the RESPECT-EPA study, Dr. Daida explained as background that in 2005, JELIS first demonstrated a beneficial effect of highly purified EPA on cardiovascular outcomes in patients with and without coronary artery disease. 

Recently, optimal medical therapy, particularly with high-intensity statins, has become the gold standard of care for patients with coronary artery disease, but they are still at substantially high residual risk, he noted.

Despite of the evidence provided by JELIS, the conflicting results in recent omega-3 fatty acid trials (REDUCE-IT and STRENGTH) have led to an intense controversy regarding the relevance of EPA intervention on top of the latest optimal medical therapy, Dr. Daida said.

The current study – Randomized trial for Evaluating the Secondary Prevention Efficacy of Combination Therapy Statin and EPA (RESPECT-EPA) – was conducted to determine the effect of highly purified EPA on cardiovascular events in Japanese patients with chronic coronary artery disease and a low EPA/arachidonic acid (AA) ratio (< 0.4), who were already receiving statins.

They were randomly assigned to highly purified EPA (icosapent ethyl, 1,800 mg/day) plus statin therapy or to statin therapy alone.

The enrollment period started in 2013 and continued for 4 years. Patients were followed for a further 4 years from the end of the enrollment period.

The trial included 2,506 patients, 1,249 assigned to the EPA group and 1,257 to the control group. In both groups there were a high number of early withdrawals or protocol deviations (647 in the EPA group and 350 in the control group).

The analysis was conducted on 1,225 patients in the EPA group and 1,235 patients in the control group, although at 6 years’ follow-up there were fewer than 400 patients in each arm.  

Baseline characteristics showed median low-density lipoprotein (LDL) cholesterol levels of 80 mg/dL, EPA levels of 45 mcg/mL, and triglyceride levels of 120 mg/dL.

The primary endpoint, a composite of cardiovascular death, nonfatal MI, nonfatal ischemic stroke, unstable angina, and coronary revascularization showed a borderline significant reduction in the EPA group at 6 years since the start of randomization (10.9% vs. 14.9%; hazard ratio, 0.785; P = .0547).

The secondary endpoint, a composite of sudden cardiac death, MI, unstable angina, and coronary revascularization, showed a significant reduction in the EPA group (8.0% vs. 11.3%; HR, 0.734; P = .0306).

In terms of adverse events, there was an increase in gastrointestinal disorders (3.4% vs. 1.2%) and new-onset atrial fibrillation (3.1% vs. 1.6%) in the EPA group.

In a post hoc analysis, which excluded patients with an increase of more than 30 mcg/mL in the control group (182 patients) and those with an increase of less than 30 mcg/mL in the EPA group (259 patients), the primary endpoint showed a significant reduction the EPA group (HR, 0.725; P = .0202).

Dr. Daida noted that limitations of the study included a lower than expected event rate (suggesting that the study may be underpowered), an open-label design, and the fact that baseline levels of EPA in this Japanese population would be higher than those in Western countries.
 

‘Massive loss’ of patients

Critiquing the study, Dr. Nissen highlighted the large dropout and protocol violation rate.

“There was a massive loss of patients over the 6- to 8-year follow-up, and the Kaplan-Meier curves didn’t start to diverge until after 4 years, by which time many patients had dropped out. It would have been a very selective population that lasted 6 years in the study. Patients that drop out are different to those that stay in, so they are cherry-picking the patients that persist in the trial. There is enormous bias here,” he commented. 

“Another weakness is the open-label design. Everyone knew who is getting what. Blinding is important in a study. And there was no control treatment in this trial,” he noted.

The researchers also selected patients with low EPA levels at baseline, Dr. Nissen added. “That is completely different hypothesis to what was tested in the REDUCE-IT and STRENGTH trials. And even with all these problems, the results are still statistically insignificant.”  

On the post hoc subgroup analysis showing a significant benefit, Dr. Nissen said, “they compared a subgroup in the active treatment arm who had large increases in EPA to a subgroup of control patients who had the smallest increase in EPA. That would be like comparing patients who had the largest reductions in LDL in a statin trial to those in the control arm who had no reductions or increases in LDL. That’s scientifically totally inappropriate.”
 

Supportive data

But Dr. Bhatt argues that the RESPECT-EPA trial supports the two previous trials showing benefits of EPA.

“Some may quibble with the P value, but to me this study has shown clear results, with obvious separation of the Kaplan-Meier curves,” he said.  

“It is an investigator-initiated study, which is good in principle but has some of the usual caveats of such a study in that – probably as a consequence of budget constraints – it has an open-label design and is underpowered. But as they did not use a placebo and still showed a benefit of EPA, that helps resolve the issue of the placebo used in REDUCE-IT for those who were concerned about it,” Dr. Bhatt noted.  

He pointed out that the 1,800-mg dose of EPA is the same dose used in the JELIS trial and is the dose used in Japan. The REDUCE-IT trial used a higher dose (4 g), but in general, Japanese people have higher levels of EPA than Western populations, he explained.  

“While this trial included patients with lower levels of EPA, what is considered low in Japan is much higher than average American levels,” he added.
 

Magnitude of benefit uncertain?

Discussant of the study at the Late Breaking Clinical Trials session, Pam R. Taub, MD, professor of medicine at the University of California, San Diego School of Medicine, said, “Despite being underpowered with a sample size of 2,460, RESPECT-EPA shows benefit in decreasing composite coronary events.”

“There is benefit with EPA, but the magnitude of benefit is uncertain,” she stated.

Dr. Taub pointed out that there is a signal across studies for new-onset atrial fibrillation, but the absolute increase is “rather small.”

She noted that more mechanistic and clinical data are needed to hone in on which patients will derive the most benefit, such as those with elevated high-sensitivity C-reactive protein or highest change in EPA levels. But she concluded that in clinical practice, physicians could consider addition of EPA for reduction of residual risk in secondary prevention patients.

The RESPECT-EPA study was supported by the Japan Heart Foundation. Dr. Daida reports peakers’ bureau/honorarium fees from Novartis Pharma, Bayer Yakuhin, Sanofi, Kowa Company, Taisho Pharmaceutical, Abbott Medical Japan, Otsuka Pharmaceutical, Amgen, MSD, Daiichi Sankyo, Pfizer Japan, FUKUDA DENSHI, Tsumura, and TOA EIYO and research funding from Philips Japan, FUJIFILM Holdings, Asahi Kasei, Inter Reha, TOHO HOLDINGS, GLORY, BMS, Abbott Japan, and Boehringer Ingelheim Japan.

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

Response-adapted de-escalation of immunotherapy in patients with advanced melanoma may lead to considerable savings for payers – close to $20,000 per patient – compared with standard immunotherapy, an economic analysis found.

“The rising costs of cancer therapies are becoming untenable for both patients and payers, and there is both clinical and economic benefit to finding less expensive treatment alternatives,” Wolfgang Kunz, MD, University Hospital, Ludwig Maximilian University of Munich, told this news organization.

This economic analysis “highlights that leveraging modern diagnostic capabilities can do just that: Pairing drug regimens with CT-image analysis to optimize dosages can reduce health care costs and improve clinical outcomes,” Dr. Kunz said.

The study was published online in JAMA Dermatology.

While the use of immunotherapies over the past decade has improved the prognosis for patients with advanced melanoma, these drugs come with a hefty price tag.

One potential way to help reduce costs: de-escalate therapy. The ADAPT-IT trial demonstrated similar progression-free and overall survival among patients who received response-adapted ipilimumab discontinuation and those who received standard of care.

In the current analysis, Dr. Kunz and colleagues wanted to understand whether this response-adapted approach was also cost effective.

The team applied economic modeling to data from the ADAPT-IT trial as well as CheckMate 067, in which patients received standard of care four doses of combination ipilimumab-nivolumab followed by nivolumab monotherapy. In the ADAPT-IT trial, patients also initially received the immunotherapy combination but had CT scans to determine their response after two doses; if they responded, patients discontinued ipilimumab and continued with nivolumab monotherapy.

Overall, ADAPT-IT showed that responders could forgo the additional two doses of ipilimumab plus nivolumab while maintaining similar progression-free survival and overall survival seen at 18 months in the CheckMate 067 trial.

The current economic analysis, based on 41 patients from ADAPT-IT and 314 from CheckMate 067, showed a potential reduction in health care costs of $19,891 per patient with the response-adapted approach.

Response-adapted treatment was the cost-effective option in 94% of simulated scenarios.

When extrapolated to 2019 incidence rates of distant melanoma cases, yearly national savings could reach about $58 million.

“In the relatively small space of immunotherapies in advanced melanoma, we hope this analysis motivates clinicians to consider response-adapted treatment,” Dr. Kunz told this news organization.

“On the larger scale, this analysis serves as a stepping stone to more response-guided treatment protocols,” Dr. Kunz added. “With drug costs rising and imaging capabilities growing, more frequent image-guided adjustments are a perfect fit into the personalized care model.”

When applying the cost savings noted in this analysis across all treated patients, “the economic impact may be profound,” said Joseph Skitzki, MD, surgical oncologist, Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., who wasn’t involved in the study. The “financial toxicity of cancer care is increasingly recognized as a potential barrier to optimal outcomes and any measures to mitigate cost may be impactful.”

However, Dr. Skitzki said several caveats need to be considered.

One is that the data included from ADAPT-IT only included 41 patients, compared with 314 patients from CheckMate 067.

“It is possible that a larger real-world study utilizing the ADAPT-IT protocol may not be as favorable in terms of outcomes and could lessen the economic impact of de-escalation, although any form of de-escalation is likely to have a cost benefit,” Dr. Skitzki said in an interview.

A real-world response–adapted de-escalation clinical trial, with an emphasis on costs and a benchmark of similar progression-free and overall survival, should be conducted before the de-escalated option becomes “practice changing,” Dr. Skitzki said.

Jeffrey Weber, MD, PhD, deputy director, Perlmutter Cancer Center, NYU Langone Health, New York, also urged caution in interpreting the results.

“I would not base treatment decisions on a small sampling of 41 patients in the absence of a randomized comparison,” Dr. Weber told this news organization. “Without a proper comparison, I would not advocate using only two doses of ipilimumab-nivolumab to make decisions on treatment.”

Dr. Skitzki added that, while “studies like this one are desperately needed to lessen the economic impact of new and emerging combination immunotherapies,” there is likely also a “disincentive for pharmaceutical companies to conduct this type of research.”

This research had no specific funding. Dr. Kunz and Dr. Skitzki reported no relevant conflicts of interest. Dr. Weber disclosed relationships with Merck, Genentech, AstraZeneca, Pfizer, Regeneron, and GSK, among others, and holds equity in Cytomx, Biond, NexImmune, and Immunomax.

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

Response-adapted de-escalation of immunotherapy in patients with advanced melanoma may lead to considerable savings for payers – close to $20,000 per patient – compared with standard immunotherapy, an economic analysis found.

“The rising costs of cancer therapies are becoming untenable for both patients and payers, and there is both clinical and economic benefit to finding less expensive treatment alternatives,” Wolfgang Kunz, MD, University Hospital, Ludwig Maximilian University of Munich, told this news organization.

This economic analysis “highlights that leveraging modern diagnostic capabilities can do just that: Pairing drug regimens with CT-image analysis to optimize dosages can reduce health care costs and improve clinical outcomes,” Dr. Kunz said.

The study was published online in JAMA Dermatology.

While the use of immunotherapies over the past decade has improved the prognosis for patients with advanced melanoma, these drugs come with a hefty price tag.

One potential way to help reduce costs: de-escalate therapy. The ADAPT-IT trial demonstrated similar progression-free and overall survival among patients who received response-adapted ipilimumab discontinuation and those who received standard of care.

In the current analysis, Dr. Kunz and colleagues wanted to understand whether this response-adapted approach was also cost effective.

The team applied economic modeling to data from the ADAPT-IT trial as well as CheckMate 067, in which patients received standard of care four doses of combination ipilimumab-nivolumab followed by nivolumab monotherapy. In the ADAPT-IT trial, patients also initially received the immunotherapy combination but had CT scans to determine their response after two doses; if they responded, patients discontinued ipilimumab and continued with nivolumab monotherapy.

Overall, ADAPT-IT showed that responders could forgo the additional two doses of ipilimumab plus nivolumab while maintaining similar progression-free survival and overall survival seen at 18 months in the CheckMate 067 trial.

The current economic analysis, based on 41 patients from ADAPT-IT and 314 from CheckMate 067, showed a potential reduction in health care costs of $19,891 per patient with the response-adapted approach.

Response-adapted treatment was the cost-effective option in 94% of simulated scenarios.

When extrapolated to 2019 incidence rates of distant melanoma cases, yearly national savings could reach about $58 million.

“In the relatively small space of immunotherapies in advanced melanoma, we hope this analysis motivates clinicians to consider response-adapted treatment,” Dr. Kunz told this news organization.

“On the larger scale, this analysis serves as a stepping stone to more response-guided treatment protocols,” Dr. Kunz added. “With drug costs rising and imaging capabilities growing, more frequent image-guided adjustments are a perfect fit into the personalized care model.”

When applying the cost savings noted in this analysis across all treated patients, “the economic impact may be profound,” said Joseph Skitzki, MD, surgical oncologist, Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., who wasn’t involved in the study. The “financial toxicity of cancer care is increasingly recognized as a potential barrier to optimal outcomes and any measures to mitigate cost may be impactful.”

However, Dr. Skitzki said several caveats need to be considered.

One is that the data included from ADAPT-IT only included 41 patients, compared with 314 patients from CheckMate 067.

“It is possible that a larger real-world study utilizing the ADAPT-IT protocol may not be as favorable in terms of outcomes and could lessen the economic impact of de-escalation, although any form of de-escalation is likely to have a cost benefit,” Dr. Skitzki said in an interview.

A real-world response–adapted de-escalation clinical trial, with an emphasis on costs and a benchmark of similar progression-free and overall survival, should be conducted before the de-escalated option becomes “practice changing,” Dr. Skitzki said.

Jeffrey Weber, MD, PhD, deputy director, Perlmutter Cancer Center, NYU Langone Health, New York, also urged caution in interpreting the results.

“I would not base treatment decisions on a small sampling of 41 patients in the absence of a randomized comparison,” Dr. Weber told this news organization. “Without a proper comparison, I would not advocate using only two doses of ipilimumab-nivolumab to make decisions on treatment.”

Dr. Skitzki added that, while “studies like this one are desperately needed to lessen the economic impact of new and emerging combination immunotherapies,” there is likely also a “disincentive for pharmaceutical companies to conduct this type of research.”

This research had no specific funding. Dr. Kunz and Dr. Skitzki reported no relevant conflicts of interest. Dr. Weber disclosed relationships with Merck, Genentech, AstraZeneca, Pfizer, Regeneron, and GSK, among others, and holds equity in Cytomx, Biond, NexImmune, and Immunomax.

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

Response-adapted de-escalation of immunotherapy in patients with advanced melanoma may lead to considerable savings for payers – close to $20,000 per patient – compared with standard immunotherapy, an economic analysis found.

“The rising costs of cancer therapies are becoming untenable for both patients and payers, and there is both clinical and economic benefit to finding less expensive treatment alternatives,” Wolfgang Kunz, MD, University Hospital, Ludwig Maximilian University of Munich, told this news organization.

This economic analysis “highlights that leveraging modern diagnostic capabilities can do just that: Pairing drug regimens with CT-image analysis to optimize dosages can reduce health care costs and improve clinical outcomes,” Dr. Kunz said.

The study was published online in JAMA Dermatology.

While the use of immunotherapies over the past decade has improved the prognosis for patients with advanced melanoma, these drugs come with a hefty price tag.

One potential way to help reduce costs: de-escalate therapy. The ADAPT-IT trial demonstrated similar progression-free and overall survival among patients who received response-adapted ipilimumab discontinuation and those who received standard of care.

In the current analysis, Dr. Kunz and colleagues wanted to understand whether this response-adapted approach was also cost effective.

The team applied economic modeling to data from the ADAPT-IT trial as well as CheckMate 067, in which patients received standard of care four doses of combination ipilimumab-nivolumab followed by nivolumab monotherapy. In the ADAPT-IT trial, patients also initially received the immunotherapy combination but had CT scans to determine their response after two doses; if they responded, patients discontinued ipilimumab and continued with nivolumab monotherapy.

Overall, ADAPT-IT showed that responders could forgo the additional two doses of ipilimumab plus nivolumab while maintaining similar progression-free survival and overall survival seen at 18 months in the CheckMate 067 trial.

The current economic analysis, based on 41 patients from ADAPT-IT and 314 from CheckMate 067, showed a potential reduction in health care costs of $19,891 per patient with the response-adapted approach.

Response-adapted treatment was the cost-effective option in 94% of simulated scenarios.

When extrapolated to 2019 incidence rates of distant melanoma cases, yearly national savings could reach about $58 million.

“In the relatively small space of immunotherapies in advanced melanoma, we hope this analysis motivates clinicians to consider response-adapted treatment,” Dr. Kunz told this news organization.

“On the larger scale, this analysis serves as a stepping stone to more response-guided treatment protocols,” Dr. Kunz added. “With drug costs rising and imaging capabilities growing, more frequent image-guided adjustments are a perfect fit into the personalized care model.”

When applying the cost savings noted in this analysis across all treated patients, “the economic impact may be profound,” said Joseph Skitzki, MD, surgical oncologist, Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., who wasn’t involved in the study. The “financial toxicity of cancer care is increasingly recognized as a potential barrier to optimal outcomes and any measures to mitigate cost may be impactful.”

However, Dr. Skitzki said several caveats need to be considered.

One is that the data included from ADAPT-IT only included 41 patients, compared with 314 patients from CheckMate 067.

“It is possible that a larger real-world study utilizing the ADAPT-IT protocol may not be as favorable in terms of outcomes and could lessen the economic impact of de-escalation, although any form of de-escalation is likely to have a cost benefit,” Dr. Skitzki said in an interview.

A real-world response–adapted de-escalation clinical trial, with an emphasis on costs and a benchmark of similar progression-free and overall survival, should be conducted before the de-escalated option becomes “practice changing,” Dr. Skitzki said.

Jeffrey Weber, MD, PhD, deputy director, Perlmutter Cancer Center, NYU Langone Health, New York, also urged caution in interpreting the results.

“I would not base treatment decisions on a small sampling of 41 patients in the absence of a randomized comparison,” Dr. Weber told this news organization. “Without a proper comparison, I would not advocate using only two doses of ipilimumab-nivolumab to make decisions on treatment.”

Dr. Skitzki added that, while “studies like this one are desperately needed to lessen the economic impact of new and emerging combination immunotherapies,” there is likely also a “disincentive for pharmaceutical companies to conduct this type of research.”

This research had no specific funding. Dr. Kunz and Dr. Skitzki reported no relevant conflicts of interest. Dr. Weber disclosed relationships with Merck, Genentech, AstraZeneca, Pfizer, Regeneron, and GSK, among others, and holds equity in Cytomx, Biond, NexImmune, and Immunomax.

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

CHICAGO – A stepwise care pathway was associated with a substantial reduction in the number of invasive tests performed and a major improvement in outcomes, relative to usual management, in patients suspected of coronary artery disease (CAD), according to 1-year results of the multinational, randomized PRECISE trial.

The care pathway is appropriate for patients with nonacute chest pain or equivalent complaints that have raised suspicion of CAD, and it is extremely simple, according to the description from the principal investigator, Pamela S. Douglas, MD, given in her presentation at the annual scientific sessions of the American Heart Association.

Ted Bosworth/MDedge News

Unlike the highly complex diagnostic algorithms shunting suspected CAD patients to the vast array of potential evaluations, the newly tested protocol, characterized as a “precision strategy,” divides patients into those who are immediate candidates for invasive testing and those who are not. The discriminator is the PROMISE minimal risk assessment score, a tool already validated.

Those deemed candidates for testing on the basis of an elevated score undergo computed coronary CT angiography (cCTA). In those who are not, testing is deferred.
 

Strategy is simple but effective

Although simple, this pathway is highly effective, judging by the results of the PRECISE trial, which tested the strategy in 2,103 patients at 65 sites in North America and Europe. The primary outcome was a composite of major adverse cardiovascular events (MACE) that included death, nonfatal MI, and catheterization without observed CAD.

After a median follow-up of 11.8 months, the primary MACE endpoint was reached in about 11.3% of those in the usual-care group, which was more than twofold higher than the 4.2% in the precision strategy group. The unadjusted risk reduction was 65% but rose to more than 70% (hazard ratio, 0.29; P < .001) after adjustment for gender and baseline characteristics.

In the arm randomized to the precision strategy, 16% were characterized as low risk and received no further testing. Almost all the others underwent cCTA alone (48%) or cCTA with fractional flow reserve (FFR) (31%). Stress echocardiography, treadmill electrocardiography, and other functional studies were performed in the small proportion of remaining patients.
 

cCTA performed in just 15% of usual care

In the usual-care arm, cCTA with or without FFR was only performed in 15%. More than 80% of patients underwent evaluations with one or more of an array of functional tests. For example, one-third were evaluated with single photon emission CT/PET and nearly as many underwent stress echocardiography testing. Only 7% in usual care underwent no testing after referral.

Within the MACE composite endpoint, almost all the relative benefit in the precision strategy arm was derived from the endpoint of angiography performed without evidence of obstructive CAD (2.6% vs. 10.2%). Rates of all-cause mortality and MI were not significantly different.

Important for the safety and utility of the precision strategy, there “were no deaths or MI events among those assigned deferred testing ” in that experimental arm, according to Dr. Douglas, professor of research in cardiovascular diseases at Duke University, Durham, N.C.

Instead, those in the precision strategy arm were far less likely to undergo catheterization without finding CAD (20% vs. 60%) and far less likely to undergo catheterization without revascularization (28% vs. 70%).

In addition, the group randomized to the precision strategy were more likely to be placed on risk reducing therapies following testing. Although the higher proportion of patients placed on antihypertensive therapy did not reach statistical significance (P = .1), the increased proportions placed on lipid therapy (P < .001) and antiplatelet therapy (P < .001) did.

Citing a study in JAMA Cardiology that found that more than 25% of patients presenting with stable chest pain have normal coronary arteries, Dr. Douglas said that the precision strategy as shown in the PRECISE trial addresses several agreed-upon goals in guidelines from the AHA, the European Society of Cardiology and the U.K.’s National Institute for Health and Care Excellence. These goals include reducing unnecessary testing by risk stratification, improving diagnostic yield of the testing that is performed, and avoiding the costs and complications of unneeded invasive testing.

New protocol called preferred approach

On the basis of these results, Dr. Douglas called the precision strategy “a preferred approach in evaluating patients with stable symptoms and suspected coronary disease.”

Julie Indik, MD, PhD, a professor of medicine at the University of Arizona, Tuscon, said that application of this approach in routine care could have “a major impact on care” by avoiding unnecessary tests with no apparent adverse effect on outcomes.

Although not demonstrated in this study, Dr. Indik suggested that the large number of patients tested for CAD each year – she estimated 4 million visits – means that less testing is likely to have a major impact on the costs of care, and she praised “the practical, efficient” approach of the precision strategy.

Ted Bosworth/MDedge News

Ron Blankstein, MD, director of cardiac computed tomography, Brigham and Women’s Hospital, Boston, also said these data “have both economic and safety implications.” As an AHA-invited discussant of this study, he emphasized that this is a strategy that should only be applied to lower risk patients with no prior history of CAD, but, in this group, he believes these data “will inform future guidelines.”

Dr. Douglas declined to speculate on whether the precision strategy will be incorporated into future guidelines, but she did say that the PRECISE data demonstrate that this approach improves quality of care.

In an interview, Dr. Douglas suggested that this care pathway could provide a basis on which to demonstrate improved outcomes with more efficient use of resources, a common definition of quality care delivery.

Dr. Douglas reported financial relationships with Caption Health, Kowa, and Heartflow, which provided funding for the PRECISE trial. Dr. Indik reported no potential conflicts of interest. Dr. Blankstein reported financial relationships with Amgen, Caristo Diagnostics, and Novartis.

CHICAGO – A stepwise care pathway was associated with a substantial reduction in the number of invasive tests performed and a major improvement in outcomes, relative to usual management, in patients suspected of coronary artery disease (CAD), according to 1-year results of the multinational, randomized PRECISE trial.

The care pathway is appropriate for patients with nonacute chest pain or equivalent complaints that have raised suspicion of CAD, and it is extremely simple, according to the description from the principal investigator, Pamela S. Douglas, MD, given in her presentation at the annual scientific sessions of the American Heart Association.

Ted Bosworth/MDedge News

Unlike the highly complex diagnostic algorithms shunting suspected CAD patients to the vast array of potential evaluations, the newly tested protocol, characterized as a “precision strategy,” divides patients into those who are immediate candidates for invasive testing and those who are not. The discriminator is the PROMISE minimal risk assessment score, a tool already validated.

Those deemed candidates for testing on the basis of an elevated score undergo computed coronary CT angiography (cCTA). In those who are not, testing is deferred.
 

Strategy is simple but effective

Although simple, this pathway is highly effective, judging by the results of the PRECISE trial, which tested the strategy in 2,103 patients at 65 sites in North America and Europe. The primary outcome was a composite of major adverse cardiovascular events (MACE) that included death, nonfatal MI, and catheterization without observed CAD.

After a median follow-up of 11.8 months, the primary MACE endpoint was reached in about 11.3% of those in the usual-care group, which was more than twofold higher than the 4.2% in the precision strategy group. The unadjusted risk reduction was 65% but rose to more than 70% (hazard ratio, 0.29; P < .001) after adjustment for gender and baseline characteristics.

In the arm randomized to the precision strategy, 16% were characterized as low risk and received no further testing. Almost all the others underwent cCTA alone (48%) or cCTA with fractional flow reserve (FFR) (31%). Stress echocardiography, treadmill electrocardiography, and other functional studies were performed in the small proportion of remaining patients.
 

cCTA performed in just 15% of usual care

In the usual-care arm, cCTA with or without FFR was only performed in 15%. More than 80% of patients underwent evaluations with one or more of an array of functional tests. For example, one-third were evaluated with single photon emission CT/PET and nearly as many underwent stress echocardiography testing. Only 7% in usual care underwent no testing after referral.

Within the MACE composite endpoint, almost all the relative benefit in the precision strategy arm was derived from the endpoint of angiography performed without evidence of obstructive CAD (2.6% vs. 10.2%). Rates of all-cause mortality and MI were not significantly different.

Important for the safety and utility of the precision strategy, there “were no deaths or MI events among those assigned deferred testing ” in that experimental arm, according to Dr. Douglas, professor of research in cardiovascular diseases at Duke University, Durham, N.C.

Instead, those in the precision strategy arm were far less likely to undergo catheterization without finding CAD (20% vs. 60%) and far less likely to undergo catheterization without revascularization (28% vs. 70%).

In addition, the group randomized to the precision strategy were more likely to be placed on risk reducing therapies following testing. Although the higher proportion of patients placed on antihypertensive therapy did not reach statistical significance (P = .1), the increased proportions placed on lipid therapy (P < .001) and antiplatelet therapy (P < .001) did.

Citing a study in JAMA Cardiology that found that more than 25% of patients presenting with stable chest pain have normal coronary arteries, Dr. Douglas said that the precision strategy as shown in the PRECISE trial addresses several agreed-upon goals in guidelines from the AHA, the European Society of Cardiology and the U.K.’s National Institute for Health and Care Excellence. These goals include reducing unnecessary testing by risk stratification, improving diagnostic yield of the testing that is performed, and avoiding the costs and complications of unneeded invasive testing.

New protocol called preferred approach

On the basis of these results, Dr. Douglas called the precision strategy “a preferred approach in evaluating patients with stable symptoms and suspected coronary disease.”

Julie Indik, MD, PhD, a professor of medicine at the University of Arizona, Tuscon, said that application of this approach in routine care could have “a major impact on care” by avoiding unnecessary tests with no apparent adverse effect on outcomes.

Although not demonstrated in this study, Dr. Indik suggested that the large number of patients tested for CAD each year – she estimated 4 million visits – means that less testing is likely to have a major impact on the costs of care, and she praised “the practical, efficient” approach of the precision strategy.

Ted Bosworth/MDedge News

Ron Blankstein, MD, director of cardiac computed tomography, Brigham and Women’s Hospital, Boston, also said these data “have both economic and safety implications.” As an AHA-invited discussant of this study, he emphasized that this is a strategy that should only be applied to lower risk patients with no prior history of CAD, but, in this group, he believes these data “will inform future guidelines.”

Dr. Douglas declined to speculate on whether the precision strategy will be incorporated into future guidelines, but she did say that the PRECISE data demonstrate that this approach improves quality of care.

In an interview, Dr. Douglas suggested that this care pathway could provide a basis on which to demonstrate improved outcomes with more efficient use of resources, a common definition of quality care delivery.

Dr. Douglas reported financial relationships with Caption Health, Kowa, and Heartflow, which provided funding for the PRECISE trial. Dr. Indik reported no potential conflicts of interest. Dr. Blankstein reported financial relationships with Amgen, Caristo Diagnostics, and Novartis.

CHICAGO – A stepwise care pathway was associated with a substantial reduction in the number of invasive tests performed and a major improvement in outcomes, relative to usual management, in patients suspected of coronary artery disease (CAD), according to 1-year results of the multinational, randomized PRECISE trial.

The care pathway is appropriate for patients with nonacute chest pain or equivalent complaints that have raised suspicion of CAD, and it is extremely simple, according to the description from the principal investigator, Pamela S. Douglas, MD, given in her presentation at the annual scientific sessions of the American Heart Association.

Ted Bosworth/MDedge News

Unlike the highly complex diagnostic algorithms shunting suspected CAD patients to the vast array of potential evaluations, the newly tested protocol, characterized as a “precision strategy,” divides patients into those who are immediate candidates for invasive testing and those who are not. The discriminator is the PROMISE minimal risk assessment score, a tool already validated.

Those deemed candidates for testing on the basis of an elevated score undergo computed coronary CT angiography (cCTA). In those who are not, testing is deferred.
 

Strategy is simple but effective

Although simple, this pathway is highly effective, judging by the results of the PRECISE trial, which tested the strategy in 2,103 patients at 65 sites in North America and Europe. The primary outcome was a composite of major adverse cardiovascular events (MACE) that included death, nonfatal MI, and catheterization without observed CAD.

After a median follow-up of 11.8 months, the primary MACE endpoint was reached in about 11.3% of those in the usual-care group, which was more than twofold higher than the 4.2% in the precision strategy group. The unadjusted risk reduction was 65% but rose to more than 70% (hazard ratio, 0.29; P < .001) after adjustment for gender and baseline characteristics.

In the arm randomized to the precision strategy, 16% were characterized as low risk and received no further testing. Almost all the others underwent cCTA alone (48%) or cCTA with fractional flow reserve (FFR) (31%). Stress echocardiography, treadmill electrocardiography, and other functional studies were performed in the small proportion of remaining patients.
 

cCTA performed in just 15% of usual care

In the usual-care arm, cCTA with or without FFR was only performed in 15%. More than 80% of patients underwent evaluations with one or more of an array of functional tests. For example, one-third were evaluated with single photon emission CT/PET and nearly as many underwent stress echocardiography testing. Only 7% in usual care underwent no testing after referral.

Within the MACE composite endpoint, almost all the relative benefit in the precision strategy arm was derived from the endpoint of angiography performed without evidence of obstructive CAD (2.6% vs. 10.2%). Rates of all-cause mortality and MI were not significantly different.

Important for the safety and utility of the precision strategy, there “were no deaths or MI events among those assigned deferred testing ” in that experimental arm, according to Dr. Douglas, professor of research in cardiovascular diseases at Duke University, Durham, N.C.

Instead, those in the precision strategy arm were far less likely to undergo catheterization without finding CAD (20% vs. 60%) and far less likely to undergo catheterization without revascularization (28% vs. 70%).

In addition, the group randomized to the precision strategy were more likely to be placed on risk reducing therapies following testing. Although the higher proportion of patients placed on antihypertensive therapy did not reach statistical significance (P = .1), the increased proportions placed on lipid therapy (P < .001) and antiplatelet therapy (P < .001) did.

Citing a study in JAMA Cardiology that found that more than 25% of patients presenting with stable chest pain have normal coronary arteries, Dr. Douglas said that the precision strategy as shown in the PRECISE trial addresses several agreed-upon goals in guidelines from the AHA, the European Society of Cardiology and the U.K.’s National Institute for Health and Care Excellence. These goals include reducing unnecessary testing by risk stratification, improving diagnostic yield of the testing that is performed, and avoiding the costs and complications of unneeded invasive testing.

New protocol called preferred approach

On the basis of these results, Dr. Douglas called the precision strategy “a preferred approach in evaluating patients with stable symptoms and suspected coronary disease.”

Julie Indik, MD, PhD, a professor of medicine at the University of Arizona, Tuscon, said that application of this approach in routine care could have “a major impact on care” by avoiding unnecessary tests with no apparent adverse effect on outcomes.

Although not demonstrated in this study, Dr. Indik suggested that the large number of patients tested for CAD each year – she estimated 4 million visits – means that less testing is likely to have a major impact on the costs of care, and she praised “the practical, efficient” approach of the precision strategy.

Ted Bosworth/MDedge News

Ron Blankstein, MD, director of cardiac computed tomography, Brigham and Women’s Hospital, Boston, also said these data “have both economic and safety implications.” As an AHA-invited discussant of this study, he emphasized that this is a strategy that should only be applied to lower risk patients with no prior history of CAD, but, in this group, he believes these data “will inform future guidelines.”

Dr. Douglas declined to speculate on whether the precision strategy will be incorporated into future guidelines, but she did say that the PRECISE data demonstrate that this approach improves quality of care.

In an interview, Dr. Douglas suggested that this care pathway could provide a basis on which to demonstrate improved outcomes with more efficient use of resources, a common definition of quality care delivery.

Dr. Douglas reported financial relationships with Caption Health, Kowa, and Heartflow, which provided funding for the PRECISE trial. Dr. Indik reported no potential conflicts of interest. Dr. Blankstein reported financial relationships with Amgen, Caristo Diagnostics, and Novartis.

Medicare’s recently announced 2023 physician payment rule likely trims doctors’ pay even as it aims to expand patients’ access to behavioral health services, chronic pain management, and hearing screening. The rule also seeks to ease financial and administrative burdens on accountable care organizations (ACOs).

But physician groups’ initial reactions centered on what the American Medical Association describes as a “damaging across-the-board reduction” of 4.4% in a base calculation, known as a conversion factor.

The reduction is only one of the current threats to physician’s finances, Jack Resneck Jr, MD, AMA’s president, said in a statement. Medicare payment rates also fail to account for inflation in practice costs and COVID-related challenges. Physician’s Medicare payments could be cut by nearly 8.5% in 2023, factoring in other budget cuts, Dr. Resneck said in the statement.

That “would severely impede patient access to care due to the forced closure of physician practices and put further strain on those that remained open during the pandemic,” he said.

A key driver of these cuts is a law that was intended to resolve budget battles between Congress and physicians, while also transitioning Medicare away from fee-for-service payments and pegging reimbursement to judgments about value of care provided. The Centers for Medicare & Medicaid Services thus had little choice about cuts mandated by the Medicare Access and CHIP Reauthorization Act (MACRA) of 2015.

For AMA and other physician groups, the finalization of the Medicare rule served as a rallying point to build support for pending legislation intended to stave off at least some payment cuts.

Federal officials should act soon to block the expected cuts before this season of Congress ends in January, said Anders Gilberg, senior vice president for government affairs at the Medical Group Management Association, in a statement.

“This cannot wait until next Congress – there are claims-processing implications for retroactively applying these policies,” Mr. Gilberg said.

He said MGMA would work with Congress and CMS “to mitigate these cuts and develop sustainable payment policies to allow physician practices to focus on treating patients instead of scrambling to keep their doors open.”
 

Chronic budget battles

Once seen as a promising resolution to chronic annual budget battles between physicians and Medicare, MACRA has proven a near-universal disappointment. A federal advisory commission in 2018 recommended that Congress scrap MACRA’s  Merit-based Incentive Payment System (MIPS) and replace it with a new approach for attempting to tie reimbursement to judgments about the quality of medical care.

MACRA replaced an earlier budgeting approach on Medicare physician pay, known as the sustainable growth rate (SGR). Physician groups successfully lobbied Congress for many years to block threatened Medicare payment cuts. Between 2003 and April 2014, Congress passed 17 laws overriding the cuts to physician pay that the lawmakers earlier mandated through the SGR.

A similar pattern has emerged as Congress now acts on short-term fixes to stave off MACRA-mandated cuts. A law passed last December postponed cuts in physician pay from MACRA and federal budget laws.

And more than 70 members of the House support a bill (HR 8800) intended to block a slated 4.4% MACRA-related cut in physician pay for 2023. Two physicians, Rep. Ami Bera, MD, (D-CA) and Rep. Larry Bucshon (R-IN) sponsored the bill.

Among the groups backing the bill are the AMA, American Academy of Family Physicians, and American College of Physicians. The lawmakers may try to attach this bill to a large spending measure, known as an omnibus, that Congress will try to clear in December to avoid a partial government shutdown.

In a statement, Tochi Iroku-Malize, MD, MPH, MBA, the president of AAFP, urged Congress to factor in inflation in setting physician reimbursement and to reconsider Medicare’s approach to paying physicians.

“It’s past time to end the untenable physician payment cuts – which have now become an annual threat to the stability of physician practices – caused by Medicare budget neutrality requirements and the ongoing freeze in annual payment updates,” Dr. Iroku-Malize said.

Congress also needs to retool its approach to alternative payment models (APMs) intended to improve the quality of patient care, Dr. Iroku-Malize said.

“Physicians in APMs are better equipped to address unmet social needs and provide other enhanced services that are not supported by fee-for-service payment rates,” Dr. Iroku-Malize said. “However, insufficient Medicare fee-for-service payment rates, inadequate support, and burdensome timelines are undermining the move to value-based care and exacerbating our nation’s underinvestment in primary care.”
 

Policy changes

But the new rule did have some good news for family physicians, Dr. Iroku-Malize told this news organization in an email.

CMS said it will pay psychologists and social workers to help manage behavioral health needs as part of the primary care team, in addition to their own services. This change will give primary care practices more flexibility to coordinate with behavioral health professionals, Dr. Iroku-Malize noted.

“We know that primary care physicians are the first point of contact for many patients, and behavioral health integration increases critical access to mental health care, decreases stigma for patients, and can prevent more severe medical and behavioral health events,” she wrote.

CMS also eased a supervision requirement for nonphysicians providing behavioral health services.

It intends to allow certain health professionals to provide this care without requiring that a supervising physician or nurse practitioner be physically on site. This shift from direct supervision to what’s called general supervision applies to marriage and family therapists, licensed professional counselors, addiction counselors, certified peer recovery specialists, and behavioral health specialists, CMS said.

Other major policy changes include:

Medicare will pay for telehealth opioid treatment programs allowing patients to initiate treatment with buprenorphine. CMS also clarified that certain programs can bill for opioid use disorder treatment services provided through mobile units, such as vans.

Medicare enrollees may see audiologists for nonacute hearing conditions without an order from a physician or nurse practitioner. The policy is meant to allow audiologists to examine patients to prescribe, fit, or change hearing aids, or to provide hearing tests unrelated to disequilibrium.

CMS created new reimbursement codes for chronic pain management and treatment services to encourage clinicians to see patients with this condition. The codes also are meant to encourage practitioners already treating Medicare patients with chronic pain to spend more time helping them manage their condition “within a trusting, supportive, and ongoing care partnership,” CMS said.

CMS also made changes to the Medicare Shared Savings Program (MSSP) intended to reduce administrative burdens and offer more financial support to practices involved in ACOs. These steps include expanding opportunities for certain low-revenue ACOs to share in savings even if they do not meet a target rate.

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

Medicare’s recently announced 2023 physician payment rule likely trims doctors’ pay even as it aims to expand patients’ access to behavioral health services, chronic pain management, and hearing screening. The rule also seeks to ease financial and administrative burdens on accountable care organizations (ACOs).

But physician groups’ initial reactions centered on what the American Medical Association describes as a “damaging across-the-board reduction” of 4.4% in a base calculation, known as a conversion factor.

The reduction is only one of the current threats to physician’s finances, Jack Resneck Jr, MD, AMA’s president, said in a statement. Medicare payment rates also fail to account for inflation in practice costs and COVID-related challenges. Physician’s Medicare payments could be cut by nearly 8.5% in 2023, factoring in other budget cuts, Dr. Resneck said in the statement.

That “would severely impede patient access to care due to the forced closure of physician practices and put further strain on those that remained open during the pandemic,” he said.

A key driver of these cuts is a law that was intended to resolve budget battles between Congress and physicians, while also transitioning Medicare away from fee-for-service payments and pegging reimbursement to judgments about value of care provided. The Centers for Medicare & Medicaid Services thus had little choice about cuts mandated by the Medicare Access and CHIP Reauthorization Act (MACRA) of 2015.

For AMA and other physician groups, the finalization of the Medicare rule served as a rallying point to build support for pending legislation intended to stave off at least some payment cuts.

Federal officials should act soon to block the expected cuts before this season of Congress ends in January, said Anders Gilberg, senior vice president for government affairs at the Medical Group Management Association, in a statement.

“This cannot wait until next Congress – there are claims-processing implications for retroactively applying these policies,” Mr. Gilberg said.

He said MGMA would work with Congress and CMS “to mitigate these cuts and develop sustainable payment policies to allow physician practices to focus on treating patients instead of scrambling to keep their doors open.”
 

Chronic budget battles

Once seen as a promising resolution to chronic annual budget battles between physicians and Medicare, MACRA has proven a near-universal disappointment. A federal advisory commission in 2018 recommended that Congress scrap MACRA’s  Merit-based Incentive Payment System (MIPS) and replace it with a new approach for attempting to tie reimbursement to judgments about the quality of medical care.

MACRA replaced an earlier budgeting approach on Medicare physician pay, known as the sustainable growth rate (SGR). Physician groups successfully lobbied Congress for many years to block threatened Medicare payment cuts. Between 2003 and April 2014, Congress passed 17 laws overriding the cuts to physician pay that the lawmakers earlier mandated through the SGR.

A similar pattern has emerged as Congress now acts on short-term fixes to stave off MACRA-mandated cuts. A law passed last December postponed cuts in physician pay from MACRA and federal budget laws.

And more than 70 members of the House support a bill (HR 8800) intended to block a slated 4.4% MACRA-related cut in physician pay for 2023. Two physicians, Rep. Ami Bera, MD, (D-CA) and Rep. Larry Bucshon (R-IN) sponsored the bill.

Among the groups backing the bill are the AMA, American Academy of Family Physicians, and American College of Physicians. The lawmakers may try to attach this bill to a large spending measure, known as an omnibus, that Congress will try to clear in December to avoid a partial government shutdown.

In a statement, Tochi Iroku-Malize, MD, MPH, MBA, the president of AAFP, urged Congress to factor in inflation in setting physician reimbursement and to reconsider Medicare’s approach to paying physicians.

“It’s past time to end the untenable physician payment cuts – which have now become an annual threat to the stability of physician practices – caused by Medicare budget neutrality requirements and the ongoing freeze in annual payment updates,” Dr. Iroku-Malize said.

Congress also needs to retool its approach to alternative payment models (APMs) intended to improve the quality of patient care, Dr. Iroku-Malize said.

“Physicians in APMs are better equipped to address unmet social needs and provide other enhanced services that are not supported by fee-for-service payment rates,” Dr. Iroku-Malize said. “However, insufficient Medicare fee-for-service payment rates, inadequate support, and burdensome timelines are undermining the move to value-based care and exacerbating our nation’s underinvestment in primary care.”
 

Policy changes

But the new rule did have some good news for family physicians, Dr. Iroku-Malize told this news organization in an email.

CMS said it will pay psychologists and social workers to help manage behavioral health needs as part of the primary care team, in addition to their own services. This change will give primary care practices more flexibility to coordinate with behavioral health professionals, Dr. Iroku-Malize noted.

“We know that primary care physicians are the first point of contact for many patients, and behavioral health integration increases critical access to mental health care, decreases stigma for patients, and can prevent more severe medical and behavioral health events,” she wrote.

CMS also eased a supervision requirement for nonphysicians providing behavioral health services.

It intends to allow certain health professionals to provide this care without requiring that a supervising physician or nurse practitioner be physically on site. This shift from direct supervision to what’s called general supervision applies to marriage and family therapists, licensed professional counselors, addiction counselors, certified peer recovery specialists, and behavioral health specialists, CMS said.

Other major policy changes include:

Medicare will pay for telehealth opioid treatment programs allowing patients to initiate treatment with buprenorphine. CMS also clarified that certain programs can bill for opioid use disorder treatment services provided through mobile units, such as vans.

Medicare enrollees may see audiologists for nonacute hearing conditions without an order from a physician or nurse practitioner. The policy is meant to allow audiologists to examine patients to prescribe, fit, or change hearing aids, or to provide hearing tests unrelated to disequilibrium.

CMS created new reimbursement codes for chronic pain management and treatment services to encourage clinicians to see patients with this condition. The codes also are meant to encourage practitioners already treating Medicare patients with chronic pain to spend more time helping them manage their condition “within a trusting, supportive, and ongoing care partnership,” CMS said.

CMS also made changes to the Medicare Shared Savings Program (MSSP) intended to reduce administrative burdens and offer more financial support to practices involved in ACOs. These steps include expanding opportunities for certain low-revenue ACOs to share in savings even if they do not meet a target rate.

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

Medicare’s recently announced 2023 physician payment rule likely trims doctors’ pay even as it aims to expand patients’ access to behavioral health services, chronic pain management, and hearing screening. The rule also seeks to ease financial and administrative burdens on accountable care organizations (ACOs).

But physician groups’ initial reactions centered on what the American Medical Association describes as a “damaging across-the-board reduction” of 4.4% in a base calculation, known as a conversion factor.

The reduction is only one of the current threats to physician’s finances, Jack Resneck Jr, MD, AMA’s president, said in a statement. Medicare payment rates also fail to account for inflation in practice costs and COVID-related challenges. Physician’s Medicare payments could be cut by nearly 8.5% in 2023, factoring in other budget cuts, Dr. Resneck said in the statement.

That “would severely impede patient access to care due to the forced closure of physician practices and put further strain on those that remained open during the pandemic,” he said.

A key driver of these cuts is a law that was intended to resolve budget battles between Congress and physicians, while also transitioning Medicare away from fee-for-service payments and pegging reimbursement to judgments about value of care provided. The Centers for Medicare & Medicaid Services thus had little choice about cuts mandated by the Medicare Access and CHIP Reauthorization Act (MACRA) of 2015.

For AMA and other physician groups, the finalization of the Medicare rule served as a rallying point to build support for pending legislation intended to stave off at least some payment cuts.

Federal officials should act soon to block the expected cuts before this season of Congress ends in January, said Anders Gilberg, senior vice president for government affairs at the Medical Group Management Association, in a statement.

“This cannot wait until next Congress – there are claims-processing implications for retroactively applying these policies,” Mr. Gilberg said.

He said MGMA would work with Congress and CMS “to mitigate these cuts and develop sustainable payment policies to allow physician practices to focus on treating patients instead of scrambling to keep their doors open.”
 

Chronic budget battles

Once seen as a promising resolution to chronic annual budget battles between physicians and Medicare, MACRA has proven a near-universal disappointment. A federal advisory commission in 2018 recommended that Congress scrap MACRA’s  Merit-based Incentive Payment System (MIPS) and replace it with a new approach for attempting to tie reimbursement to judgments about the quality of medical care.

MACRA replaced an earlier budgeting approach on Medicare physician pay, known as the sustainable growth rate (SGR). Physician groups successfully lobbied Congress for many years to block threatened Medicare payment cuts. Between 2003 and April 2014, Congress passed 17 laws overriding the cuts to physician pay that the lawmakers earlier mandated through the SGR.

A similar pattern has emerged as Congress now acts on short-term fixes to stave off MACRA-mandated cuts. A law passed last December postponed cuts in physician pay from MACRA and federal budget laws.

And more than 70 members of the House support a bill (HR 8800) intended to block a slated 4.4% MACRA-related cut in physician pay for 2023. Two physicians, Rep. Ami Bera, MD, (D-CA) and Rep. Larry Bucshon (R-IN) sponsored the bill.

Among the groups backing the bill are the AMA, American Academy of Family Physicians, and American College of Physicians. The lawmakers may try to attach this bill to a large spending measure, known as an omnibus, that Congress will try to clear in December to avoid a partial government shutdown.

In a statement, Tochi Iroku-Malize, MD, MPH, MBA, the president of AAFP, urged Congress to factor in inflation in setting physician reimbursement and to reconsider Medicare’s approach to paying physicians.

“It’s past time to end the untenable physician payment cuts – which have now become an annual threat to the stability of physician practices – caused by Medicare budget neutrality requirements and the ongoing freeze in annual payment updates,” Dr. Iroku-Malize said.

Congress also needs to retool its approach to alternative payment models (APMs) intended to improve the quality of patient care, Dr. Iroku-Malize said.

“Physicians in APMs are better equipped to address unmet social needs and provide other enhanced services that are not supported by fee-for-service payment rates,” Dr. Iroku-Malize said. “However, insufficient Medicare fee-for-service payment rates, inadequate support, and burdensome timelines are undermining the move to value-based care and exacerbating our nation’s underinvestment in primary care.”
 

Policy changes

But the new rule did have some good news for family physicians, Dr. Iroku-Malize told this news organization in an email.

CMS said it will pay psychologists and social workers to help manage behavioral health needs as part of the primary care team, in addition to their own services. This change will give primary care practices more flexibility to coordinate with behavioral health professionals, Dr. Iroku-Malize noted.

“We know that primary care physicians are the first point of contact for many patients, and behavioral health integration increases critical access to mental health care, decreases stigma for patients, and can prevent more severe medical and behavioral health events,” she wrote.

CMS also eased a supervision requirement for nonphysicians providing behavioral health services.

It intends to allow certain health professionals to provide this care without requiring that a supervising physician or nurse practitioner be physically on site. This shift from direct supervision to what’s called general supervision applies to marriage and family therapists, licensed professional counselors, addiction counselors, certified peer recovery specialists, and behavioral health specialists, CMS said.

Other major policy changes include:

Medicare will pay for telehealth opioid treatment programs allowing patients to initiate treatment with buprenorphine. CMS also clarified that certain programs can bill for opioid use disorder treatment services provided through mobile units, such as vans.

Medicare enrollees may see audiologists for nonacute hearing conditions without an order from a physician or nurse practitioner. The policy is meant to allow audiologists to examine patients to prescribe, fit, or change hearing aids, or to provide hearing tests unrelated to disequilibrium.

CMS created new reimbursement codes for chronic pain management and treatment services to encourage clinicians to see patients with this condition. The codes also are meant to encourage practitioners already treating Medicare patients with chronic pain to spend more time helping them manage their condition “within a trusting, supportive, and ongoing care partnership,” CMS said.

CMS also made changes to the Medicare Shared Savings Program (MSSP) intended to reduce administrative burdens and offer more financial support to practices involved in ACOs. These steps include expanding opportunities for certain low-revenue ACOs to share in savings even if they do not meet a target rate.

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

A man in England who was infected with an early strain of COVID-19 was finally cleared 411 days after first testing positive, according to experts in the United Kingdom. 

The man was treated with a mixture of neutralizing monoclonal antibodies, King’s College London said in a news release.

The man, 59, tested positive in December 2020 and tested negative in January 2022. He had a weakened immune system because of a previous kidney transplant. He received three doses of vaccine and his symptoms lessened, but he kept testing positive for COVID.

To find out if the man had a persistent infection or had been infected several times, doctors did a genetic analysis of the virus.

“This revealed that the patient’s infection was a persistent infection with an early COVID variant – a variation of the original Wuhan variant that was dominant in the United Kingdom in the later months of 2020. Analysis found the patient’s virus had multiple mutations since he was first infected,” King’s College said.

The doctors treated him with a Regeneron treatment that is no longer widely used because it’s not effective against newer COVID variants.

“Some new variants of the virus are resistant to all the antibody treatments available in the United Kingdom and Europe. Some people with weakened immune systems are still at risk of severe illness and becoming persistently infected. We are still working to understand the best way to protect and treat them,” Luke Snell, MD, from the King’s College School of Immunology & Microbial Sciences, said in the news release.

This is one of the longest known cases of COVID infection. Another man in England was infected with COVID for 505 days before his death, which King’s College said was the longest known COVID infection.

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

A man in England who was infected with an early strain of COVID-19 was finally cleared 411 days after first testing positive, according to experts in the United Kingdom. 

The man was treated with a mixture of neutralizing monoclonal antibodies, King’s College London said in a news release.

The man, 59, tested positive in December 2020 and tested negative in January 2022. He had a weakened immune system because of a previous kidney transplant. He received three doses of vaccine and his symptoms lessened, but he kept testing positive for COVID.

To find out if the man had a persistent infection or had been infected several times, doctors did a genetic analysis of the virus.

“This revealed that the patient’s infection was a persistent infection with an early COVID variant – a variation of the original Wuhan variant that was dominant in the United Kingdom in the later months of 2020. Analysis found the patient’s virus had multiple mutations since he was first infected,” King’s College said.

The doctors treated him with a Regeneron treatment that is no longer widely used because it’s not effective against newer COVID variants.

“Some new variants of the virus are resistant to all the antibody treatments available in the United Kingdom and Europe. Some people with weakened immune systems are still at risk of severe illness and becoming persistently infected. We are still working to understand the best way to protect and treat them,” Luke Snell, MD, from the King’s College School of Immunology & Microbial Sciences, said in the news release.

This is one of the longest known cases of COVID infection. Another man in England was infected with COVID for 505 days before his death, which King’s College said was the longest known COVID infection.

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

A man in England who was infected with an early strain of COVID-19 was finally cleared 411 days after first testing positive, according to experts in the United Kingdom. 

The man was treated with a mixture of neutralizing monoclonal antibodies, King’s College London said in a news release.

The man, 59, tested positive in December 2020 and tested negative in January 2022. He had a weakened immune system because of a previous kidney transplant. He received three doses of vaccine and his symptoms lessened, but he kept testing positive for COVID.

To find out if the man had a persistent infection or had been infected several times, doctors did a genetic analysis of the virus.

“This revealed that the patient’s infection was a persistent infection with an early COVID variant – a variation of the original Wuhan variant that was dominant in the United Kingdom in the later months of 2020. Analysis found the patient’s virus had multiple mutations since he was first infected,” King’s College said.

The doctors treated him with a Regeneron treatment that is no longer widely used because it’s not effective against newer COVID variants.

“Some new variants of the virus are resistant to all the antibody treatments available in the United Kingdom and Europe. Some people with weakened immune systems are still at risk of severe illness and becoming persistently infected. We are still working to understand the best way to protect and treat them,” Luke Snell, MD, from the King’s College School of Immunology & Microbial Sciences, said in the news release.

This is one of the longest known cases of COVID infection. Another man in England was infected with COVID for 505 days before his death, which King’s College said was the longest known COVID infection.

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