Neurology Reviews

Anthony Fauci, MD, highlighting the latest COVID-19 developments on Friday, said, “It is now clear that about 40%-45% of infections are asymptomatic.”

NIH

Asymptomatic carriers can account for a large proportion — up to 50% — of virus transmissions, Fauci, director of the National Institute of Allergy and Infectious Diseases, told a virtual crowd of critical care clinicians gathered by the Society of Critical Care Medicine.

Such transmissions have made response strategies, such as contact tracing, extremely difficult, he said.

Lew Kaplan, MD, president of SCCM, told Medscape Medical News after the presentation: “That really supports the universal wearing of masks and the capstone message from that – you should protect one another.

“That kind of social responsibility that sits within the public health domain to me is as important as the vaccine candidates and the science behind the receptors. It underpins the necessary relationship and the interdependence of the medical community with the public,” Kaplan added.

Fauci’s plenary led the SCCM’s conference, “COVID-19: What’s Next/Preparing for the Second Wave,” running today and Saturday.
 

Why U.S. response lags behind Spain and Italy

“This virus has literally exploded upon the planet in a pandemic manner which is unparalleled to anything we’ve seen in the last 102 years since the pandemic of 1918,” Fauci said.

“Unfortunately, the United States has been hit harder than any other country in the world, with 6 million reported cases.”

He explained that in the European Union countries the disease spiked early on and returned to a low baseline. “Unfortunately for them,” Fauci said, “as they’re trying to open up their economy, it’s coming back up.”

The United States, he explained, plateaued at about 20,000 cases a day, then a surge of cases in Florida, California, Texas, and Arizona brought the cases to 70,000 a day. Now cases have returned to 35,000-40,000 a day.

The difference in the trajectory of the response, he said, is that, compared with Spain and Italy for example, the United States has not shut down mobility in parks, outdoor spaces, and grocery stores nearly as much as some European countries did.

He pointed to numerous clusters of cases, spread from social or work gatherings, including the well-known Skagit County Washington state choir practice in March, in which a symptomatic choir member infected 87% of the 61 people rehearsing.
 

Vaccine by end of the year

As for a vaccine timeline, Fauci told SCCM members, “We project that by the end of this year, namely November/December, we will know if we have a safe and effective vaccine and we are cautiously optimistic that we will be successful, based on promising data in the animal model as well as good immunological data that we see from the phase 1 and phase 2 trials.”

However, also on Friday, Fauci told MSNBC’s Andrea Mitchell that a sense of normalcy is not likely before the middle of next year.

“By the time you mobilize the distribution of the vaccinations, and you get the majority, or more, of the population vaccinated and protected, that’s likely not going to happen [until] the mid- or end of 2021,” he said.

According to the Centers for Disease Control and Prevention (CDC) case tracker, as of Thursday, COVID-19 had resulted in more than 190,000 deaths overall and more than 256,000 new cases in the United States in the past 7 days.

Fauci has warned that the next few months will be critical in the virus’ trajectory, with the double onslaught of COVID-19 and the flu season.

On Thursday, Fauci said, “We need to hunker down and get through this fall and winter because it’s not going to be easy.”

Fauci remains a top trusted source in COVID-19 information, poll numbers show.

A Kaiser Family Foundation poll released Thursday found that 68% of US adults had a fair amount or a great deal of trust that Fauci would provide reliable information on COVID-19, just slightly more that the 67% who said they trust the CDC information. About half (53%) say they trust Deborah Birx, MD, the coordinator for the White House Coronavirus Task Force, as a reliable source of information.

The poll also found that 54% of Americans said they would not get a COVID-19 vaccine if one was approved by the US Food and Drug Administration before the November election and was made available and free to all who wanted it.

Kaplan and Fauci report no relevant financial relationships.

This article first appeared on Medscape.com.

Anthony Fauci, MD, highlighting the latest COVID-19 developments on Friday, said, “It is now clear that about 40%-45% of infections are asymptomatic.”

NIH

Asymptomatic carriers can account for a large proportion — up to 50% — of virus transmissions, Fauci, director of the National Institute of Allergy and Infectious Diseases, told a virtual crowd of critical care clinicians gathered by the Society of Critical Care Medicine.

Such transmissions have made response strategies, such as contact tracing, extremely difficult, he said.

Lew Kaplan, MD, president of SCCM, told Medscape Medical News after the presentation: “That really supports the universal wearing of masks and the capstone message from that – you should protect one another.

“That kind of social responsibility that sits within the public health domain to me is as important as the vaccine candidates and the science behind the receptors. It underpins the necessary relationship and the interdependence of the medical community with the public,” Kaplan added.

Fauci’s plenary led the SCCM’s conference, “COVID-19: What’s Next/Preparing for the Second Wave,” running today and Saturday.
 

Why U.S. response lags behind Spain and Italy

“This virus has literally exploded upon the planet in a pandemic manner which is unparalleled to anything we’ve seen in the last 102 years since the pandemic of 1918,” Fauci said.

“Unfortunately, the United States has been hit harder than any other country in the world, with 6 million reported cases.”

He explained that in the European Union countries the disease spiked early on and returned to a low baseline. “Unfortunately for them,” Fauci said, “as they’re trying to open up their economy, it’s coming back up.”

The United States, he explained, plateaued at about 20,000 cases a day, then a surge of cases in Florida, California, Texas, and Arizona brought the cases to 70,000 a day. Now cases have returned to 35,000-40,000 a day.

The difference in the trajectory of the response, he said, is that, compared with Spain and Italy for example, the United States has not shut down mobility in parks, outdoor spaces, and grocery stores nearly as much as some European countries did.

He pointed to numerous clusters of cases, spread from social or work gatherings, including the well-known Skagit County Washington state choir practice in March, in which a symptomatic choir member infected 87% of the 61 people rehearsing.
 

Vaccine by end of the year

As for a vaccine timeline, Fauci told SCCM members, “We project that by the end of this year, namely November/December, we will know if we have a safe and effective vaccine and we are cautiously optimistic that we will be successful, based on promising data in the animal model as well as good immunological data that we see from the phase 1 and phase 2 trials.”

However, also on Friday, Fauci told MSNBC’s Andrea Mitchell that a sense of normalcy is not likely before the middle of next year.

“By the time you mobilize the distribution of the vaccinations, and you get the majority, or more, of the population vaccinated and protected, that’s likely not going to happen [until] the mid- or end of 2021,” he said.

According to the Centers for Disease Control and Prevention (CDC) case tracker, as of Thursday, COVID-19 had resulted in more than 190,000 deaths overall and more than 256,000 new cases in the United States in the past 7 days.

Fauci has warned that the next few months will be critical in the virus’ trajectory, with the double onslaught of COVID-19 and the flu season.

On Thursday, Fauci said, “We need to hunker down and get through this fall and winter because it’s not going to be easy.”

Fauci remains a top trusted source in COVID-19 information, poll numbers show.

A Kaiser Family Foundation poll released Thursday found that 68% of US adults had a fair amount or a great deal of trust that Fauci would provide reliable information on COVID-19, just slightly more that the 67% who said they trust the CDC information. About half (53%) say they trust Deborah Birx, MD, the coordinator for the White House Coronavirus Task Force, as a reliable source of information.

The poll also found that 54% of Americans said they would not get a COVID-19 vaccine if one was approved by the US Food and Drug Administration before the November election and was made available and free to all who wanted it.

Kaplan and Fauci report no relevant financial relationships.

This article first appeared on Medscape.com.

Anthony Fauci, MD, highlighting the latest COVID-19 developments on Friday, said, “It is now clear that about 40%-45% of infections are asymptomatic.”

NIH

Asymptomatic carriers can account for a large proportion — up to 50% — of virus transmissions, Fauci, director of the National Institute of Allergy and Infectious Diseases, told a virtual crowd of critical care clinicians gathered by the Society of Critical Care Medicine.

Such transmissions have made response strategies, such as contact tracing, extremely difficult, he said.

Lew Kaplan, MD, president of SCCM, told Medscape Medical News after the presentation: “That really supports the universal wearing of masks and the capstone message from that – you should protect one another.

“That kind of social responsibility that sits within the public health domain to me is as important as the vaccine candidates and the science behind the receptors. It underpins the necessary relationship and the interdependence of the medical community with the public,” Kaplan added.

Fauci’s plenary led the SCCM’s conference, “COVID-19: What’s Next/Preparing for the Second Wave,” running today and Saturday.
 

Why U.S. response lags behind Spain and Italy

“This virus has literally exploded upon the planet in a pandemic manner which is unparalleled to anything we’ve seen in the last 102 years since the pandemic of 1918,” Fauci said.

“Unfortunately, the United States has been hit harder than any other country in the world, with 6 million reported cases.”

He explained that in the European Union countries the disease spiked early on and returned to a low baseline. “Unfortunately for them,” Fauci said, “as they’re trying to open up their economy, it’s coming back up.”

The United States, he explained, plateaued at about 20,000 cases a day, then a surge of cases in Florida, California, Texas, and Arizona brought the cases to 70,000 a day. Now cases have returned to 35,000-40,000 a day.

The difference in the trajectory of the response, he said, is that, compared with Spain and Italy for example, the United States has not shut down mobility in parks, outdoor spaces, and grocery stores nearly as much as some European countries did.

He pointed to numerous clusters of cases, spread from social or work gatherings, including the well-known Skagit County Washington state choir practice in March, in which a symptomatic choir member infected 87% of the 61 people rehearsing.
 

Vaccine by end of the year

As for a vaccine timeline, Fauci told SCCM members, “We project that by the end of this year, namely November/December, we will know if we have a safe and effective vaccine and we are cautiously optimistic that we will be successful, based on promising data in the animal model as well as good immunological data that we see from the phase 1 and phase 2 trials.”

However, also on Friday, Fauci told MSNBC’s Andrea Mitchell that a sense of normalcy is not likely before the middle of next year.

“By the time you mobilize the distribution of the vaccinations, and you get the majority, or more, of the population vaccinated and protected, that’s likely not going to happen [until] the mid- or end of 2021,” he said.

According to the Centers for Disease Control and Prevention (CDC) case tracker, as of Thursday, COVID-19 had resulted in more than 190,000 deaths overall and more than 256,000 new cases in the United States in the past 7 days.

Fauci has warned that the next few months will be critical in the virus’ trajectory, with the double onslaught of COVID-19 and the flu season.

On Thursday, Fauci said, “We need to hunker down and get through this fall and winter because it’s not going to be easy.”

Fauci remains a top trusted source in COVID-19 information, poll numbers show.

A Kaiser Family Foundation poll released Thursday found that 68% of US adults had a fair amount or a great deal of trust that Fauci would provide reliable information on COVID-19, just slightly more that the 67% who said they trust the CDC information. About half (53%) say they trust Deborah Birx, MD, the coordinator for the White House Coronavirus Task Force, as a reliable source of information.

The poll also found that 54% of Americans said they would not get a COVID-19 vaccine if one was approved by the US Food and Drug Administration before the November election and was made available and free to all who wanted it.

Kaplan and Fauci report no relevant financial relationships.

This article first appeared on Medscape.com.

Many health care professionals are not following current, evidence-based guidelines to screen for and diagnose hypertension, and appear to have substantial gaps in knowledge, beliefs, and use of recommended practices, results from a large survey suggest.

“One surprising finding was that there was so much trust in the stethoscope, because the automated monitors are a better way to take blood pressure,” lead author Beverly Green, MD, of Kaiser Permanente Washington Health Research Institute, Seattle, said in an interview.

The results of the survey were presented Sept. 10 at the virtual joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

The U.S. Preventive Services Task Force (USPSTF) and the American Heart Association/American College of Cardiology recommend out-of-office blood pressure measurements – via ambulatory blood pressure monitoring (ABPM) or home BP monitoring – before making a new diagnosis of hypertension.

To gauge provider knowledge, beliefs, and practices related to BP diagnostic tests, the researchers surveyed 282 providers: 102 medical assistants (MA), 28 licensed practical nurses (LPNs), 33 registered nurses (RNs), 86 primary care physicians, and 33 advanced practitioners (APs).

More than three-quarters of providers (79%) felt that BP measured manually with a stethoscope and ABPM were “very or highly” accurate ways to measure BP when making a new diagnosis of hypertension.

Most did not think that automated clinic BPs, home BP, or kiosk BP measurements were very or highly accurate.

Nearly all providers surveyed (96%) reported that they “always or almost always” rely on clinic BP measurements when diagnosing hypertension, but the majority of physicians/APs would prefer using ABPM (61%) if available.

The problem with ABPM, said Dr. Green, is “it’s just not very available or convenient for patients, and a lot of providers think that patients won’t tolerate it.” Yet, without it, there is a risk for misclassification, she said.

Karen A. Griffin, MD, who chairs the AHA Council on Hypertension, said it became “customary to use clinic BP since ABPM was not previously reimbursed for the routine diagnosis of hypertension.

“Now that the payment for ABPM has been expanded, the number of machines at most institutions is not adequate for the need. Consequently, it will take some time to catch up with the current guidelines for diagnosing hypertension,” she said in an interview.

The provider survey by Dr. Green and colleagues also shows slow uptake of updated thresholds for high blood pressure.

Eighty-four percent of physicians/APs and 68% of MA/LPN/RNs said they used a clinic BP threshold of at least 140/90 mm Hg for making a new diagnosis of hypertension.

Only 3.5% and 9.0%, respectively, reported using the updated threshold of at least 130/80 mm Hg put forth in 2017.

Dr. Griffin said part of this stems from the fact that the survey began before the updated guidelines were released in 2017, “not to mention the fact that some societies have opposed the new threshold of 130/80 mm Hg.”

“I think, with time, the data on morbidity and mortality associated with the goal of 130/80 mm Hg will hopefully convince those who have not yet implemented these new guidelines that it is a safe and effective BP goal,” Dr. Griffin said.

This research had no specific funding. Dr. Green and Dr. Griffin have no relevant disclosures.
 

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

Many health care professionals are not following current, evidence-based guidelines to screen for and diagnose hypertension, and appear to have substantial gaps in knowledge, beliefs, and use of recommended practices, results from a large survey suggest.

“One surprising finding was that there was so much trust in the stethoscope, because the automated monitors are a better way to take blood pressure,” lead author Beverly Green, MD, of Kaiser Permanente Washington Health Research Institute, Seattle, said in an interview.

The results of the survey were presented Sept. 10 at the virtual joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

The U.S. Preventive Services Task Force (USPSTF) and the American Heart Association/American College of Cardiology recommend out-of-office blood pressure measurements – via ambulatory blood pressure monitoring (ABPM) or home BP monitoring – before making a new diagnosis of hypertension.

To gauge provider knowledge, beliefs, and practices related to BP diagnostic tests, the researchers surveyed 282 providers: 102 medical assistants (MA), 28 licensed practical nurses (LPNs), 33 registered nurses (RNs), 86 primary care physicians, and 33 advanced practitioners (APs).

More than three-quarters of providers (79%) felt that BP measured manually with a stethoscope and ABPM were “very or highly” accurate ways to measure BP when making a new diagnosis of hypertension.

Most did not think that automated clinic BPs, home BP, or kiosk BP measurements were very or highly accurate.

Nearly all providers surveyed (96%) reported that they “always or almost always” rely on clinic BP measurements when diagnosing hypertension, but the majority of physicians/APs would prefer using ABPM (61%) if available.

The problem with ABPM, said Dr. Green, is “it’s just not very available or convenient for patients, and a lot of providers think that patients won’t tolerate it.” Yet, without it, there is a risk for misclassification, she said.

Karen A. Griffin, MD, who chairs the AHA Council on Hypertension, said it became “customary to use clinic BP since ABPM was not previously reimbursed for the routine diagnosis of hypertension.

“Now that the payment for ABPM has been expanded, the number of machines at most institutions is not adequate for the need. Consequently, it will take some time to catch up with the current guidelines for diagnosing hypertension,” she said in an interview.

The provider survey by Dr. Green and colleagues also shows slow uptake of updated thresholds for high blood pressure.

Eighty-four percent of physicians/APs and 68% of MA/LPN/RNs said they used a clinic BP threshold of at least 140/90 mm Hg for making a new diagnosis of hypertension.

Only 3.5% and 9.0%, respectively, reported using the updated threshold of at least 130/80 mm Hg put forth in 2017.

Dr. Griffin said part of this stems from the fact that the survey began before the updated guidelines were released in 2017, “not to mention the fact that some societies have opposed the new threshold of 130/80 mm Hg.”

“I think, with time, the data on morbidity and mortality associated with the goal of 130/80 mm Hg will hopefully convince those who have not yet implemented these new guidelines that it is a safe and effective BP goal,” Dr. Griffin said.

This research had no specific funding. Dr. Green and Dr. Griffin have no relevant disclosures.
 

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

Many health care professionals are not following current, evidence-based guidelines to screen for and diagnose hypertension, and appear to have substantial gaps in knowledge, beliefs, and use of recommended practices, results from a large survey suggest.

“One surprising finding was that there was so much trust in the stethoscope, because the automated monitors are a better way to take blood pressure,” lead author Beverly Green, MD, of Kaiser Permanente Washington Health Research Institute, Seattle, said in an interview.

The results of the survey were presented Sept. 10 at the virtual joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

The U.S. Preventive Services Task Force (USPSTF) and the American Heart Association/American College of Cardiology recommend out-of-office blood pressure measurements – via ambulatory blood pressure monitoring (ABPM) or home BP monitoring – before making a new diagnosis of hypertension.

To gauge provider knowledge, beliefs, and practices related to BP diagnostic tests, the researchers surveyed 282 providers: 102 medical assistants (MA), 28 licensed practical nurses (LPNs), 33 registered nurses (RNs), 86 primary care physicians, and 33 advanced practitioners (APs).

More than three-quarters of providers (79%) felt that BP measured manually with a stethoscope and ABPM were “very or highly” accurate ways to measure BP when making a new diagnosis of hypertension.

Most did not think that automated clinic BPs, home BP, or kiosk BP measurements were very or highly accurate.

Nearly all providers surveyed (96%) reported that they “always or almost always” rely on clinic BP measurements when diagnosing hypertension, but the majority of physicians/APs would prefer using ABPM (61%) if available.

The problem with ABPM, said Dr. Green, is “it’s just not very available or convenient for patients, and a lot of providers think that patients won’t tolerate it.” Yet, without it, there is a risk for misclassification, she said.

Karen A. Griffin, MD, who chairs the AHA Council on Hypertension, said it became “customary to use clinic BP since ABPM was not previously reimbursed for the routine diagnosis of hypertension.

“Now that the payment for ABPM has been expanded, the number of machines at most institutions is not adequate for the need. Consequently, it will take some time to catch up with the current guidelines for diagnosing hypertension,” she said in an interview.

The provider survey by Dr. Green and colleagues also shows slow uptake of updated thresholds for high blood pressure.

Eighty-four percent of physicians/APs and 68% of MA/LPN/RNs said they used a clinic BP threshold of at least 140/90 mm Hg for making a new diagnosis of hypertension.

Only 3.5% and 9.0%, respectively, reported using the updated threshold of at least 130/80 mm Hg put forth in 2017.

Dr. Griffin said part of this stems from the fact that the survey began before the updated guidelines were released in 2017, “not to mention the fact that some societies have opposed the new threshold of 130/80 mm Hg.”

“I think, with time, the data on morbidity and mortality associated with the goal of 130/80 mm Hg will hopefully convince those who have not yet implemented these new guidelines that it is a safe and effective BP goal,” Dr. Griffin said.

This research had no specific funding. Dr. Green and Dr. Griffin have no relevant disclosures.
 

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

A few months ago, I published a short thought piece on the use of “sitters” with patients who were COVID-19 positive, or patients under investigation. In it, I recommended the use of telesitters for those who normally would warrant a human sitter, to decrease the discomfort of sitting in full personal protective equipment (PPE) (gown, mask, gloves, etc.) while monitoring a suicidal patient.

I received several queries, which I want to address here. In addition, I want to draw from my Army days in terms of the claustrophobia often experienced with PPE.

The first of the questions was about evidence-based practices. The second was about the discomfort of having sitters sit for many hours in the full gear.

I do not know of any evidence-based practices, but I hope we will develop them.

I agree that spending many hours in full PPE can be discomforting, which is why I wrote the essay.

As far as lessons learned from the Army time, I briefly learned how to wear a “gas mask” or Mission-Oriented Protective Posture (MOPP gear) while at Fort Bragg. We were run through the “gas chamber,” where sergeants released tear gas while we had the mask on. We were then asked to lift it up, and then tearing and sputtering, we could leave the small wooden building.

We wore the mask as part of our Army gear, usually on the right leg. After that, I mainly used the protective mask in its bag as a pillow when I was in the field.

Fast forward to August 1990. I arrived at Camp Casey, near the Korean demilitarized zone. Four days later, Saddam Hussein invaded Kuwait. The gas mask moved from a pillow to something we had to wear while doing 12-mile road marches in “full ruck.” In full ruck, you have your uniform on, with TA-50, knapsack, and weapon. No, I do not remember any more what TA-50 stands for, but essentially it is the webbing that holds your bullets and bandages.

Many could not tolerate it. They developed claustrophobia – sweating, air hunger, and panic. If stationed in the Gulf for Operation Desert Storm, they were evacuated home.

I wrote a couple of short articles on treatment of gas mask phobia.^1,2 I basically advised desensitization. Start by watching TV in it for 5 minutes. Graduate to ironing your uniform in the mask. Go then to shorter runs. Work up to the 12-mile road march.

In my second tour in Korea, we had exercises where we simulated being hit by nerve agents and had to operate the hospital for days at a time in partial or full PPE. It was tough but we did it, and felt more confident about surviving attacks from North Korea.

So back to the pandemic present. I have gotten more used to my constant wearing of a surgical mask. I get anxious when I see others with masks below their noses. I almost panic when others do not wear their masks at all, such as the lady today who was brushing her teeth in the shared ladies’ restroom.

The pandemic is not going away anytime soon, in my opinion. Furthermore, there are other viruses that are worse, such as Ebola. It is only a matter of time.

So, let us train with our PPE. If health care workers cannot tolerate them, use desensitization- and anxiety-reducing techniques to help them.

There are no easy answers here, in the time of the COVID pandemic. However, we owe it to ourselves, our patients, and society to do the best we can.

References

1. Ritchie EC. Milit Med. 1992 Feb;157(2):104-6.

2. Ritchie EC. Milit Med. 2001 Dec;166. Suppl. 2(1)83-4.
 

Dr. Ritchie is chair of psychiatry at Medstar Washington Hospital Center and professor of psychiatry at Georgetown University, Washington. She has no disclosures and can be reached at cpnews@mdedge.com.

A few months ago, I published a short thought piece on the use of “sitters” with patients who were COVID-19 positive, or patients under investigation. In it, I recommended the use of telesitters for those who normally would warrant a human sitter, to decrease the discomfort of sitting in full personal protective equipment (PPE) (gown, mask, gloves, etc.) while monitoring a suicidal patient.

I received several queries, which I want to address here. In addition, I want to draw from my Army days in terms of the claustrophobia often experienced with PPE.

The first of the questions was about evidence-based practices. The second was about the discomfort of having sitters sit for many hours in the full gear.

I do not know of any evidence-based practices, but I hope we will develop them.

I agree that spending many hours in full PPE can be discomforting, which is why I wrote the essay.

As far as lessons learned from the Army time, I briefly learned how to wear a “gas mask” or Mission-Oriented Protective Posture (MOPP gear) while at Fort Bragg. We were run through the “gas chamber,” where sergeants released tear gas while we had the mask on. We were then asked to lift it up, and then tearing and sputtering, we could leave the small wooden building.

We wore the mask as part of our Army gear, usually on the right leg. After that, I mainly used the protective mask in its bag as a pillow when I was in the field.

Fast forward to August 1990. I arrived at Camp Casey, near the Korean demilitarized zone. Four days later, Saddam Hussein invaded Kuwait. The gas mask moved from a pillow to something we had to wear while doing 12-mile road marches in “full ruck.” In full ruck, you have your uniform on, with TA-50, knapsack, and weapon. No, I do not remember any more what TA-50 stands for, but essentially it is the webbing that holds your bullets and bandages.

Many could not tolerate it. They developed claustrophobia – sweating, air hunger, and panic. If stationed in the Gulf for Operation Desert Storm, they were evacuated home.

I wrote a couple of short articles on treatment of gas mask phobia.^1,2 I basically advised desensitization. Start by watching TV in it for 5 minutes. Graduate to ironing your uniform in the mask. Go then to shorter runs. Work up to the 12-mile road march.

In my second tour in Korea, we had exercises where we simulated being hit by nerve agents and had to operate the hospital for days at a time in partial or full PPE. It was tough but we did it, and felt more confident about surviving attacks from North Korea.

So back to the pandemic present. I have gotten more used to my constant wearing of a surgical mask. I get anxious when I see others with masks below their noses. I almost panic when others do not wear their masks at all, such as the lady today who was brushing her teeth in the shared ladies’ restroom.

The pandemic is not going away anytime soon, in my opinion. Furthermore, there are other viruses that are worse, such as Ebola. It is only a matter of time.

So, let us train with our PPE. If health care workers cannot tolerate them, use desensitization- and anxiety-reducing techniques to help them.

There are no easy answers here, in the time of the COVID pandemic. However, we owe it to ourselves, our patients, and society to do the best we can.

References

1. Ritchie EC. Milit Med. 1992 Feb;157(2):104-6.

2. Ritchie EC. Milit Med. 2001 Dec;166. Suppl. 2(1)83-4.
 

Dr. Ritchie is chair of psychiatry at Medstar Washington Hospital Center and professor of psychiatry at Georgetown University, Washington. She has no disclosures and can be reached at cpnews@mdedge.com.

A few months ago, I published a short thought piece on the use of “sitters” with patients who were COVID-19 positive, or patients under investigation. In it, I recommended the use of telesitters for those who normally would warrant a human sitter, to decrease the discomfort of sitting in full personal protective equipment (PPE) (gown, mask, gloves, etc.) while monitoring a suicidal patient.

I received several queries, which I want to address here. In addition, I want to draw from my Army days in terms of the claustrophobia often experienced with PPE.

The first of the questions was about evidence-based practices. The second was about the discomfort of having sitters sit for many hours in the full gear.

I do not know of any evidence-based practices, but I hope we will develop them.

I agree that spending many hours in full PPE can be discomforting, which is why I wrote the essay.

As far as lessons learned from the Army time, I briefly learned how to wear a “gas mask” or Mission-Oriented Protective Posture (MOPP gear) while at Fort Bragg. We were run through the “gas chamber,” where sergeants released tear gas while we had the mask on. We were then asked to lift it up, and then tearing and sputtering, we could leave the small wooden building.

We wore the mask as part of our Army gear, usually on the right leg. After that, I mainly used the protective mask in its bag as a pillow when I was in the field.

Fast forward to August 1990. I arrived at Camp Casey, near the Korean demilitarized zone. Four days later, Saddam Hussein invaded Kuwait. The gas mask moved from a pillow to something we had to wear while doing 12-mile road marches in “full ruck.” In full ruck, you have your uniform on, with TA-50, knapsack, and weapon. No, I do not remember any more what TA-50 stands for, but essentially it is the webbing that holds your bullets and bandages.

Many could not tolerate it. They developed claustrophobia – sweating, air hunger, and panic. If stationed in the Gulf for Operation Desert Storm, they were evacuated home.

I wrote a couple of short articles on treatment of gas mask phobia.^1,2 I basically advised desensitization. Start by watching TV in it for 5 minutes. Graduate to ironing your uniform in the mask. Go then to shorter runs. Work up to the 12-mile road march.

In my second tour in Korea, we had exercises where we simulated being hit by nerve agents and had to operate the hospital for days at a time in partial or full PPE. It was tough but we did it, and felt more confident about surviving attacks from North Korea.

So back to the pandemic present. I have gotten more used to my constant wearing of a surgical mask. I get anxious when I see others with masks below their noses. I almost panic when others do not wear their masks at all, such as the lady today who was brushing her teeth in the shared ladies’ restroom.

The pandemic is not going away anytime soon, in my opinion. Furthermore, there are other viruses that are worse, such as Ebola. It is only a matter of time.

So, let us train with our PPE. If health care workers cannot tolerate them, use desensitization- and anxiety-reducing techniques to help them.

There are no easy answers here, in the time of the COVID pandemic. However, we owe it to ourselves, our patients, and society to do the best we can.

References

1. Ritchie EC. Milit Med. 1992 Feb;157(2):104-6.

2. Ritchie EC. Milit Med. 2001 Dec;166. Suppl. 2(1)83-4.
 

Dr. Ritchie is chair of psychiatry at Medstar Washington Hospital Center and professor of psychiatry at Georgetown University, Washington. She has no disclosures and can be reached at cpnews@mdedge.com.

It ain’t what you don’t know that gets you into trouble. It’s what you know for sure that just ain’t so. – Josh Billings
 

Some patients believe COVID-19 is a hoax. Many think there’s truth to the rumor that Bill Gates is behind it all and intends to use COVID vaccinations as a devious way to implant microchips in us. He will then, of course, use the new 5G towers to track us all (although what Gates will do with the information that I was shopping at a Trader Joe’s yesterday is yet unknown).

It’s easy to dismiss patients with these beliefs as nuts or dumb or both. They’re neither, they’re just human. Conspiracy theories have been shared from the first time two humans met. They are, after all, simply hypotheses to explain an experience that’s difficult to understand. Making up a story to explain things feels safer than living with the unknown, and so we do. Our natural tendency to be suspicious makes conspiracy hypotheses more salient and more likely to spread. The pandemic itself is exacerbating this problem: People are alone and afraid, and dependent on social media for connection. Add a compelling story about a nefarious robber baron plotting to exploit us and you’ve got the conditions for conspiracy theories to explode like wind-driven wildfires. Astonishingly, a Pew Research poll showed 36% of Americans surveyed who have heard something about it say the Bill Gates cabal theory is “probably” or “definitely” true.

That many patients fervently believe conspiracy theories poses several problems for us. First, when a vaccine does become available, some patients will refuse to be vaccinated. The consequences to their health and the health of the community are grave. Secondly, whenever patients have cause to distrust doctors, it makes our jobs more challenging. If they don’t trust us on vaccines, it can spread to not trusting us about wearing masks or sunscreens or taking statins. Lastly, it’s near impossible to have a friendly conversation with a patient carrying forth on why Bill Gates is not in jail or how I’m part of the medical-industrial complex enabling him. Sheesh.

It isn’t their fault. The underpinning of these beliefs can be understood as a cognitive bias. In this case, an idea that is easy to imagine or recall is believed to be true more than an idea that is complex and difficult. Understanding viral replication and R0 numbers or viral vectors and protein subunit vaccines is hard. Imagining a chip being injected into your arm is easy. And, as behavioral economist Daniel Kahneman opined, we humans possess an almost unlimited ability to ignore our ignorance. We physicians can help in a way that friends and family members can’t. Here are ways you can help patients who believe in conspiracy theories:

Approach this problem like any other infirmity, with compassion. No one wants to drink too much and knock out their teeth falling off a bike. It was a mistake. Similarly, when people are steeped in self-delusion, it’s not a misdeed, it’s a lapse. Be kind and respectful.

Meet them where they are. It might be helpful to state with sincerity: So you feel that there is a government plot to use COVID to track us? Have you considered that might not be true?

Have the conversation in private. Harder even than being wrong is being publicly wrong.

Try the Socratic method. (We’re pretty good at this from teaching students and residents.) Conspiracy-believing patients have the illusion of knowledge, yet, like students, it’s often easy to show them their gaps. Do so gently by leading them to discover for themselves.

Stop when you stall. You cannot change someone’s mind by dint of force. However, you surely can damage your relationship if you keep pushing them.

Don’t worry if you fail to break through; you might yet have moved them a bit. This might make it possible for them to discover the truth later. Or, you could simply switch to explain what holds up the ground we walk upon. There’s rumor we’re supported on the backs of turtles, all the way down. Maybe Bill Gates is feeding them.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

It ain’t what you don’t know that gets you into trouble. It’s what you know for sure that just ain’t so. – Josh Billings
 

Some patients believe COVID-19 is a hoax. Many think there’s truth to the rumor that Bill Gates is behind it all and intends to use COVID vaccinations as a devious way to implant microchips in us. He will then, of course, use the new 5G towers to track us all (although what Gates will do with the information that I was shopping at a Trader Joe’s yesterday is yet unknown).

It’s easy to dismiss patients with these beliefs as nuts or dumb or both. They’re neither, they’re just human. Conspiracy theories have been shared from the first time two humans met. They are, after all, simply hypotheses to explain an experience that’s difficult to understand. Making up a story to explain things feels safer than living with the unknown, and so we do. Our natural tendency to be suspicious makes conspiracy hypotheses more salient and more likely to spread. The pandemic itself is exacerbating this problem: People are alone and afraid, and dependent on social media for connection. Add a compelling story about a nefarious robber baron plotting to exploit us and you’ve got the conditions for conspiracy theories to explode like wind-driven wildfires. Astonishingly, a Pew Research poll showed 36% of Americans surveyed who have heard something about it say the Bill Gates cabal theory is “probably” or “definitely” true.

That many patients fervently believe conspiracy theories poses several problems for us. First, when a vaccine does become available, some patients will refuse to be vaccinated. The consequences to their health and the health of the community are grave. Secondly, whenever patients have cause to distrust doctors, it makes our jobs more challenging. If they don’t trust us on vaccines, it can spread to not trusting us about wearing masks or sunscreens or taking statins. Lastly, it’s near impossible to have a friendly conversation with a patient carrying forth on why Bill Gates is not in jail or how I’m part of the medical-industrial complex enabling him. Sheesh.

It isn’t their fault. The underpinning of these beliefs can be understood as a cognitive bias. In this case, an idea that is easy to imagine or recall is believed to be true more than an idea that is complex and difficult. Understanding viral replication and R0 numbers or viral vectors and protein subunit vaccines is hard. Imagining a chip being injected into your arm is easy. And, as behavioral economist Daniel Kahneman opined, we humans possess an almost unlimited ability to ignore our ignorance. We physicians can help in a way that friends and family members can’t. Here are ways you can help patients who believe in conspiracy theories:

Approach this problem like any other infirmity, with compassion. No one wants to drink too much and knock out their teeth falling off a bike. It was a mistake. Similarly, when people are steeped in self-delusion, it’s not a misdeed, it’s a lapse. Be kind and respectful.

Meet them where they are. It might be helpful to state with sincerity: So you feel that there is a government plot to use COVID to track us? Have you considered that might not be true?

Have the conversation in private. Harder even than being wrong is being publicly wrong.

Try the Socratic method. (We’re pretty good at this from teaching students and residents.) Conspiracy-believing patients have the illusion of knowledge, yet, like students, it’s often easy to show them their gaps. Do so gently by leading them to discover for themselves.

Stop when you stall. You cannot change someone’s mind by dint of force. However, you surely can damage your relationship if you keep pushing them.

Don’t worry if you fail to break through; you might yet have moved them a bit. This might make it possible for them to discover the truth later. Or, you could simply switch to explain what holds up the ground we walk upon. There’s rumor we’re supported on the backs of turtles, all the way down. Maybe Bill Gates is feeding them.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

It ain’t what you don’t know that gets you into trouble. It’s what you know for sure that just ain’t so. – Josh Billings
 

Some patients believe COVID-19 is a hoax. Many think there’s truth to the rumor that Bill Gates is behind it all and intends to use COVID vaccinations as a devious way to implant microchips in us. He will then, of course, use the new 5G towers to track us all (although what Gates will do with the information that I was shopping at a Trader Joe’s yesterday is yet unknown).

It’s easy to dismiss patients with these beliefs as nuts or dumb or both. They’re neither, they’re just human. Conspiracy theories have been shared from the first time two humans met. They are, after all, simply hypotheses to explain an experience that’s difficult to understand. Making up a story to explain things feels safer than living with the unknown, and so we do. Our natural tendency to be suspicious makes conspiracy hypotheses more salient and more likely to spread. The pandemic itself is exacerbating this problem: People are alone and afraid, and dependent on social media for connection. Add a compelling story about a nefarious robber baron plotting to exploit us and you’ve got the conditions for conspiracy theories to explode like wind-driven wildfires. Astonishingly, a Pew Research poll showed 36% of Americans surveyed who have heard something about it say the Bill Gates cabal theory is “probably” or “definitely” true.

That many patients fervently believe conspiracy theories poses several problems for us. First, when a vaccine does become available, some patients will refuse to be vaccinated. The consequences to their health and the health of the community are grave. Secondly, whenever patients have cause to distrust doctors, it makes our jobs more challenging. If they don’t trust us on vaccines, it can spread to not trusting us about wearing masks or sunscreens or taking statins. Lastly, it’s near impossible to have a friendly conversation with a patient carrying forth on why Bill Gates is not in jail or how I’m part of the medical-industrial complex enabling him. Sheesh.

It isn’t their fault. The underpinning of these beliefs can be understood as a cognitive bias. In this case, an idea that is easy to imagine or recall is believed to be true more than an idea that is complex and difficult. Understanding viral replication and R0 numbers or viral vectors and protein subunit vaccines is hard. Imagining a chip being injected into your arm is easy. And, as behavioral economist Daniel Kahneman opined, we humans possess an almost unlimited ability to ignore our ignorance. We physicians can help in a way that friends and family members can’t. Here are ways you can help patients who believe in conspiracy theories:

Approach this problem like any other infirmity, with compassion. No one wants to drink too much and knock out their teeth falling off a bike. It was a mistake. Similarly, when people are steeped in self-delusion, it’s not a misdeed, it’s a lapse. Be kind and respectful.

Meet them where they are. It might be helpful to state with sincerity: So you feel that there is a government plot to use COVID to track us? Have you considered that might not be true?

Have the conversation in private. Harder even than being wrong is being publicly wrong.

Try the Socratic method. (We’re pretty good at this from teaching students and residents.) Conspiracy-believing patients have the illusion of knowledge, yet, like students, it’s often easy to show them their gaps. Do so gently by leading them to discover for themselves.

Stop when you stall. You cannot change someone’s mind by dint of force. However, you surely can damage your relationship if you keep pushing them.

Don’t worry if you fail to break through; you might yet have moved them a bit. This might make it possible for them to discover the truth later. Or, you could simply switch to explain what holds up the ground we walk upon. There’s rumor we’re supported on the backs of turtles, all the way down. Maybe Bill Gates is feeding them.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

Continued use of tumor necrosis factor inhibitors or methotrexate is acceptable in most patients who acquire COVID-19, results of a recent cohort study suggest.

Among patients on tumor necrosis factor inhibitors (TNFi) or methotrexate who developed COVID-19, death and hospitalization rates were similar to matched COVID-19 patients not on those medications, according to authors of the multicenter research network study.

Reassuringly, likelihood of hospitalization and mortality were not significantly different between 214 patients with COVID-19 taking TNFi or methotrexate and 31,862 matched COVID-19 patients not on those medications, according to the investigators, whose findings were published recently in the Journal of the American Academy of Dermatology.

Zachary Zinn, MD, corresponding author on the study, said in an interview that the findings suggest these medicines can be safely continued in the majority of patients taking them during the COVID-19 pandemic.

“If you’re a prescribing physician who’s giving patients TNF inhibitors or methotrexate or both, I think you can comfortably tell your patients there is good data that these do not lead to worse outcomes if you get COVID-19,” said Dr. Zinn, associate professor in the department of dermatology at West Virginia University, Morgantown.

The findings from these researchers corroborate a growing body of evidence suggesting that immunosuppressive treatments can be continued in patients with dermatologic and rheumatic conditions.

In recent guidance from the National Psoriasis Foundation, released Sept. 4, an expert consensus panel cited 15 studies that they said suggested that treatments for psoriasis or psoriatic arthritis “do not meaningfully alter the risk of acquiring SARS-CoV-2 infection or having worse COVID-19 outcomes.”

That said, the data to date are mainly from small case series and registry studies based on spontaneously reported COVID-19 cases, which suggests a continued need for shared decision making. In addition, chronic systemic corticosteroids should be avoided for management of psoriatic arthritis, the guidance states, based on rheumatology and gastroenterology literature suggesting this treatment is linked to worse COVID-19 outcomes.

In the interview, Dr. Zinn noted that some previous studies of immunosuppressive treatments in patients who acquire COVID-19 have aggregated data on numerous classes of biologic medications, lessening the strength of data for each specific medication.

“By focusing specifically on TNF inhibitors and methotrexate, this study gives better guidance to prescribers of these medications,” he said.

To see whether TNFi or methotrexate increased risk of worsened COVID-19 outcomes, Dr. Zinn and coinvestigators evaluated data from TriNetX, a research network that includes approximately 53 million unique patient records, predominantly in the United States.

They identified 32,076 adult patients with COVID-19, of whom 214 had recent exposure to TNFi or methotrexate. The patients in the TNFi/methotrexate group were similar in age to those without exposure to those drugs, at 55.1 versus 53.2 years, respectively. However, patients in the drug exposure group were more frequently White, female, and had substantially more comorbidities, including diabetes and obesity, according to the investigators.

Nevertheless, the likelihood of hospitalization was not statistically different in the TNFi/methotrexate group versus the non-TNFi/methotrexate group, with a risk ratio of 0.91 (95% confidence interval, 0.68-1.22; P = .5260).

Likewise, the likelihood of death was not different between groups, with a RR of 0.87 (95% CI, 0.42-1.78; P = .6958). Looking at subgroups of patients exposed to TNFi or methotrexate only didn’t change the results, the investigators added.

Taken together, the findings argue against interruption of these treatments because of the fear of the possibly worse COVID-19 outcomes, the investigators concluded, although they emphasized the need for more research.

“Because the COVID-19 pandemic is ongoing, there is a desperate need for evidence-based data on biologic and immunomodulator exposure in the setting of COVID-19 infection,” they wrote.

Dr. Zinn and coauthors reported no conflicts of interest and no funding sources related to the study.

SOURCE: Zinn Z et al. J Am Acad Dermatol. 2020 Sep 11. doi: 10.1016/j.jaad.2020.09.009.

Continued use of tumor necrosis factor inhibitors or methotrexate is acceptable in most patients who acquire COVID-19, results of a recent cohort study suggest.

Among patients on tumor necrosis factor inhibitors (TNFi) or methotrexate who developed COVID-19, death and hospitalization rates were similar to matched COVID-19 patients not on those medications, according to authors of the multicenter research network study.

Reassuringly, likelihood of hospitalization and mortality were not significantly different between 214 patients with COVID-19 taking TNFi or methotrexate and 31,862 matched COVID-19 patients not on those medications, according to the investigators, whose findings were published recently in the Journal of the American Academy of Dermatology.

Zachary Zinn, MD, corresponding author on the study, said in an interview that the findings suggest these medicines can be safely continued in the majority of patients taking them during the COVID-19 pandemic.

“If you’re a prescribing physician who’s giving patients TNF inhibitors or methotrexate or both, I think you can comfortably tell your patients there is good data that these do not lead to worse outcomes if you get COVID-19,” said Dr. Zinn, associate professor in the department of dermatology at West Virginia University, Morgantown.

The findings from these researchers corroborate a growing body of evidence suggesting that immunosuppressive treatments can be continued in patients with dermatologic and rheumatic conditions.

In recent guidance from the National Psoriasis Foundation, released Sept. 4, an expert consensus panel cited 15 studies that they said suggested that treatments for psoriasis or psoriatic arthritis “do not meaningfully alter the risk of acquiring SARS-CoV-2 infection or having worse COVID-19 outcomes.”

That said, the data to date are mainly from small case series and registry studies based on spontaneously reported COVID-19 cases, which suggests a continued need for shared decision making. In addition, chronic systemic corticosteroids should be avoided for management of psoriatic arthritis, the guidance states, based on rheumatology and gastroenterology literature suggesting this treatment is linked to worse COVID-19 outcomes.

In the interview, Dr. Zinn noted that some previous studies of immunosuppressive treatments in patients who acquire COVID-19 have aggregated data on numerous classes of biologic medications, lessening the strength of data for each specific medication.

“By focusing specifically on TNF inhibitors and methotrexate, this study gives better guidance to prescribers of these medications,” he said.

To see whether TNFi or methotrexate increased risk of worsened COVID-19 outcomes, Dr. Zinn and coinvestigators evaluated data from TriNetX, a research network that includes approximately 53 million unique patient records, predominantly in the United States.

They identified 32,076 adult patients with COVID-19, of whom 214 had recent exposure to TNFi or methotrexate. The patients in the TNFi/methotrexate group were similar in age to those without exposure to those drugs, at 55.1 versus 53.2 years, respectively. However, patients in the drug exposure group were more frequently White, female, and had substantially more comorbidities, including diabetes and obesity, according to the investigators.

Nevertheless, the likelihood of hospitalization was not statistically different in the TNFi/methotrexate group versus the non-TNFi/methotrexate group, with a risk ratio of 0.91 (95% confidence interval, 0.68-1.22; P = .5260).

Likewise, the likelihood of death was not different between groups, with a RR of 0.87 (95% CI, 0.42-1.78; P = .6958). Looking at subgroups of patients exposed to TNFi or methotrexate only didn’t change the results, the investigators added.

Taken together, the findings argue against interruption of these treatments because of the fear of the possibly worse COVID-19 outcomes, the investigators concluded, although they emphasized the need for more research.

“Because the COVID-19 pandemic is ongoing, there is a desperate need for evidence-based data on biologic and immunomodulator exposure in the setting of COVID-19 infection,” they wrote.

Dr. Zinn and coauthors reported no conflicts of interest and no funding sources related to the study.

SOURCE: Zinn Z et al. J Am Acad Dermatol. 2020 Sep 11. doi: 10.1016/j.jaad.2020.09.009.

Continued use of tumor necrosis factor inhibitors or methotrexate is acceptable in most patients who acquire COVID-19, results of a recent cohort study suggest.

Among patients on tumor necrosis factor inhibitors (TNFi) or methotrexate who developed COVID-19, death and hospitalization rates were similar to matched COVID-19 patients not on those medications, according to authors of the multicenter research network study.

Reassuringly, likelihood of hospitalization and mortality were not significantly different between 214 patients with COVID-19 taking TNFi or methotrexate and 31,862 matched COVID-19 patients not on those medications, according to the investigators, whose findings were published recently in the Journal of the American Academy of Dermatology.

Zachary Zinn, MD, corresponding author on the study, said in an interview that the findings suggest these medicines can be safely continued in the majority of patients taking them during the COVID-19 pandemic.

“If you’re a prescribing physician who’s giving patients TNF inhibitors or methotrexate or both, I think you can comfortably tell your patients there is good data that these do not lead to worse outcomes if you get COVID-19,” said Dr. Zinn, associate professor in the department of dermatology at West Virginia University, Morgantown.

The findings from these researchers corroborate a growing body of evidence suggesting that immunosuppressive treatments can be continued in patients with dermatologic and rheumatic conditions.

In recent guidance from the National Psoriasis Foundation, released Sept. 4, an expert consensus panel cited 15 studies that they said suggested that treatments for psoriasis or psoriatic arthritis “do not meaningfully alter the risk of acquiring SARS-CoV-2 infection or having worse COVID-19 outcomes.”

That said, the data to date are mainly from small case series and registry studies based on spontaneously reported COVID-19 cases, which suggests a continued need for shared decision making. In addition, chronic systemic corticosteroids should be avoided for management of psoriatic arthritis, the guidance states, based on rheumatology and gastroenterology literature suggesting this treatment is linked to worse COVID-19 outcomes.

In the interview, Dr. Zinn noted that some previous studies of immunosuppressive treatments in patients who acquire COVID-19 have aggregated data on numerous classes of biologic medications, lessening the strength of data for each specific medication.

“By focusing specifically on TNF inhibitors and methotrexate, this study gives better guidance to prescribers of these medications,” he said.

To see whether TNFi or methotrexate increased risk of worsened COVID-19 outcomes, Dr. Zinn and coinvestigators evaluated data from TriNetX, a research network that includes approximately 53 million unique patient records, predominantly in the United States.

They identified 32,076 adult patients with COVID-19, of whom 214 had recent exposure to TNFi or methotrexate. The patients in the TNFi/methotrexate group were similar in age to those without exposure to those drugs, at 55.1 versus 53.2 years, respectively. However, patients in the drug exposure group were more frequently White, female, and had substantially more comorbidities, including diabetes and obesity, according to the investigators.

Nevertheless, the likelihood of hospitalization was not statistically different in the TNFi/methotrexate group versus the non-TNFi/methotrexate group, with a risk ratio of 0.91 (95% confidence interval, 0.68-1.22; P = .5260).

Likewise, the likelihood of death was not different between groups, with a RR of 0.87 (95% CI, 0.42-1.78; P = .6958). Looking at subgroups of patients exposed to TNFi or methotrexate only didn’t change the results, the investigators added.

Taken together, the findings argue against interruption of these treatments because of the fear of the possibly worse COVID-19 outcomes, the investigators concluded, although they emphasized the need for more research.

“Because the COVID-19 pandemic is ongoing, there is a desperate need for evidence-based data on biologic and immunomodulator exposure in the setting of COVID-19 infection,” they wrote.

Dr. Zinn and coauthors reported no conflicts of interest and no funding sources related to the study.

SOURCE: Zinn Z et al. J Am Acad Dermatol. 2020 Sep 11. doi: 10.1016/j.jaad.2020.09.009.

Obstructive sleep apnea (OSA) treatment with positive airway pressure (PAP) therapy was associated with a lower odds of incident Alzheimer’s disease and other dementia in a large retrospective cohort study of Medicare patients with the sleep disorder.

Courtesy ResMed

The study builds on research linking OSA to poor cognitive outcomes and dementia syndromes. With use of a 5% random sample of Medicare beneficiaries (more than 2.7 million) and their claims data, investigators identified approximately 53,000 who had an OSA diagnosis prior to 2011.

Of these Medicare beneficiaries, 78% with OSA were identified as “PAP-treated” based on having at least one durable medical equipment claim for PAP equipment. And of those treated, 74% were identified as “PAP adherent” based on having more than two PAP equipment claims separated by at least a month, said Galit Levi Dunietz, PhD, MPH, at the virtual annual meeting of the Associated Professional Sleep Societies.

Dr. Dunietz and her coinvestigators used logistic regression to examine the associations between PAP treatment and PAP treatment adherence, and incident ICD-9 diagnoses of Alzheimer’s disease (AD), mild cognitive impairment (MCI), and dementia not otherwise specified (DNOS) over the period 2011-2013.

After adjustments for potential confounders (age, sex, race, stroke, hypertension, cardiovascular disease, and depression), OSA treatment was associated with a significantly lower odds of a diagnosis of AD (odds ratio, 0.78; 95% confidence interval 0.69-0.89) or DNOS (OR, 0.69; 95% CI, 0.55-0.85), as well as nonsignificantly lower odds of MCI diagnosis (OR, 0.82; 95% CI, 0.66-1.02).

“People who are treated for OSA have a 22% reduced odds of being diagnosed with AD and a 31% reduced odds of getting DNOS,” said Dr. Dunietz, from the University of Michigan in Ann Arbor, in an interview after the meeting. “The 18% reduced odds of mild cognitive disorder is not really significant because the upper bound is 1.02, but we consider it approaching significance.”

Adherence to treatment was significantly associated with lower odds of AD, but not with significantly lower odds of DNOS or MCI, she said. OSA was confirmed by ICD-9 diagnosis codes plus the presence of relevant polysomnography current procedural terminology code.

All told, the findings “suggest that PAP therapy for OSA may lower short-term risk for dementia in older persons,” Dr. Dunietz and her co-nvestigators said in their poster presentation. “If a causal pathway exists between OSA and dementia, treatment of OSA may offer new opportunities to improve cognitive outcomes in older adults with OSA.”

Andrew W. Varga, MD, of the division of pulmonary, critical care, and sleep medicine at the Icahn School of Medicine at Mount Sinai and the Mount Sinai Integrative Sleep Center, both in New York, said that cognitive impairment is now a recognized clinical consequence of OSA and that OSA treatment could be a target for the prevention of cognitive impairment and Alzheimer’s disease in particular.

“I absolutely bring it up with patients in their 60s and 70s. I’m honest – I say, there seems to be more and more evidence for links between apnea and Alzheimer’s in particular. I tell them we don’t know 100% whether PAP reverses any of this, but it stands to reason that it does,” said Dr. Varga, who was asked to comment on the study and related research.

An analysis published several years ago in Neurology from the Alzheimer’s Disease Neuroimaging Initiative cohort found that patients with self-reported sleep apnea had a younger age of MCI or AD onset (about 10 years) and that patients who used continuous positive airway pressure had a delayed age of onset. “Those who had a subjective diagnosis of sleep apnea and who also reported using CPAP as treatment seemed to go in the opposite direction,” said Dr. Varga, a coauthor of that study. “They had an onset of AD that looked just like people who had no sleep apnea.”

While this study was limited by sleep apnea being self-reported – and by the lack of severity data – the newly reported study may be limited by the use of ICD codes and the fact that OSA is often entered into patient’s chart before diagnosis is confirmed through a sleep study, Dr. Varga said.

“The field is mature enough that we should be thinking of doing honest and rigorous clinical trials for sleep apnea with cognitive outcomes being a main measure of interest,” he said. “The issue we’re struggling with in the field is that such a trial would not be short.”

There are several theories for the link between OSA and cognitive impairment, he said, including disruptions in sleep architecture leading to increased production of amyloid and tau and/or decreased “clearance” of extracellular amyloid, neuronal sensitivity to hypoxia, and cardiovascular comorbidities.

Dr. Dunietz’s study was supported by The American Academy of Sleep Medicine Foundation. She reported having no disclosures. Dr. Varga said he has no relevant disclosures.

Obstructive sleep apnea (OSA) treatment with positive airway pressure (PAP) therapy was associated with a lower odds of incident Alzheimer’s disease and other dementia in a large retrospective cohort study of Medicare patients with the sleep disorder.

Courtesy ResMed

The study builds on research linking OSA to poor cognitive outcomes and dementia syndromes. With use of a 5% random sample of Medicare beneficiaries (more than 2.7 million) and their claims data, investigators identified approximately 53,000 who had an OSA diagnosis prior to 2011.

Of these Medicare beneficiaries, 78% with OSA were identified as “PAP-treated” based on having at least one durable medical equipment claim for PAP equipment. And of those treated, 74% were identified as “PAP adherent” based on having more than two PAP equipment claims separated by at least a month, said Galit Levi Dunietz, PhD, MPH, at the virtual annual meeting of the Associated Professional Sleep Societies.

Dr. Dunietz and her coinvestigators used logistic regression to examine the associations between PAP treatment and PAP treatment adherence, and incident ICD-9 diagnoses of Alzheimer’s disease (AD), mild cognitive impairment (MCI), and dementia not otherwise specified (DNOS) over the period 2011-2013.

After adjustments for potential confounders (age, sex, race, stroke, hypertension, cardiovascular disease, and depression), OSA treatment was associated with a significantly lower odds of a diagnosis of AD (odds ratio, 0.78; 95% confidence interval 0.69-0.89) or DNOS (OR, 0.69; 95% CI, 0.55-0.85), as well as nonsignificantly lower odds of MCI diagnosis (OR, 0.82; 95% CI, 0.66-1.02).

“People who are treated for OSA have a 22% reduced odds of being diagnosed with AD and a 31% reduced odds of getting DNOS,” said Dr. Dunietz, from the University of Michigan in Ann Arbor, in an interview after the meeting. “The 18% reduced odds of mild cognitive disorder is not really significant because the upper bound is 1.02, but we consider it approaching significance.”

Adherence to treatment was significantly associated with lower odds of AD, but not with significantly lower odds of DNOS or MCI, she said. OSA was confirmed by ICD-9 diagnosis codes plus the presence of relevant polysomnography current procedural terminology code.

All told, the findings “suggest that PAP therapy for OSA may lower short-term risk for dementia in older persons,” Dr. Dunietz and her co-nvestigators said in their poster presentation. “If a causal pathway exists between OSA and dementia, treatment of OSA may offer new opportunities to improve cognitive outcomes in older adults with OSA.”

Andrew W. Varga, MD, of the division of pulmonary, critical care, and sleep medicine at the Icahn School of Medicine at Mount Sinai and the Mount Sinai Integrative Sleep Center, both in New York, said that cognitive impairment is now a recognized clinical consequence of OSA and that OSA treatment could be a target for the prevention of cognitive impairment and Alzheimer’s disease in particular.

“I absolutely bring it up with patients in their 60s and 70s. I’m honest – I say, there seems to be more and more evidence for links between apnea and Alzheimer’s in particular. I tell them we don’t know 100% whether PAP reverses any of this, but it stands to reason that it does,” said Dr. Varga, who was asked to comment on the study and related research.

An analysis published several years ago in Neurology from the Alzheimer’s Disease Neuroimaging Initiative cohort found that patients with self-reported sleep apnea had a younger age of MCI or AD onset (about 10 years) and that patients who used continuous positive airway pressure had a delayed age of onset. “Those who had a subjective diagnosis of sleep apnea and who also reported using CPAP as treatment seemed to go in the opposite direction,” said Dr. Varga, a coauthor of that study. “They had an onset of AD that looked just like people who had no sleep apnea.”

While this study was limited by sleep apnea being self-reported – and by the lack of severity data – the newly reported study may be limited by the use of ICD codes and the fact that OSA is often entered into patient’s chart before diagnosis is confirmed through a sleep study, Dr. Varga said.

“The field is mature enough that we should be thinking of doing honest and rigorous clinical trials for sleep apnea with cognitive outcomes being a main measure of interest,” he said. “The issue we’re struggling with in the field is that such a trial would not be short.”

There are several theories for the link between OSA and cognitive impairment, he said, including disruptions in sleep architecture leading to increased production of amyloid and tau and/or decreased “clearance” of extracellular amyloid, neuronal sensitivity to hypoxia, and cardiovascular comorbidities.

Dr. Dunietz’s study was supported by The American Academy of Sleep Medicine Foundation. She reported having no disclosures. Dr. Varga said he has no relevant disclosures.

Obstructive sleep apnea (OSA) treatment with positive airway pressure (PAP) therapy was associated with a lower odds of incident Alzheimer’s disease and other dementia in a large retrospective cohort study of Medicare patients with the sleep disorder.

Courtesy ResMed

The study builds on research linking OSA to poor cognitive outcomes and dementia syndromes. With use of a 5% random sample of Medicare beneficiaries (more than 2.7 million) and their claims data, investigators identified approximately 53,000 who had an OSA diagnosis prior to 2011.

Of these Medicare beneficiaries, 78% with OSA were identified as “PAP-treated” based on having at least one durable medical equipment claim for PAP equipment. And of those treated, 74% were identified as “PAP adherent” based on having more than two PAP equipment claims separated by at least a month, said Galit Levi Dunietz, PhD, MPH, at the virtual annual meeting of the Associated Professional Sleep Societies.

Dr. Dunietz and her coinvestigators used logistic regression to examine the associations between PAP treatment and PAP treatment adherence, and incident ICD-9 diagnoses of Alzheimer’s disease (AD), mild cognitive impairment (MCI), and dementia not otherwise specified (DNOS) over the period 2011-2013.

After adjustments for potential confounders (age, sex, race, stroke, hypertension, cardiovascular disease, and depression), OSA treatment was associated with a significantly lower odds of a diagnosis of AD (odds ratio, 0.78; 95% confidence interval 0.69-0.89) or DNOS (OR, 0.69; 95% CI, 0.55-0.85), as well as nonsignificantly lower odds of MCI diagnosis (OR, 0.82; 95% CI, 0.66-1.02).

“People who are treated for OSA have a 22% reduced odds of being diagnosed with AD and a 31% reduced odds of getting DNOS,” said Dr. Dunietz, from the University of Michigan in Ann Arbor, in an interview after the meeting. “The 18% reduced odds of mild cognitive disorder is not really significant because the upper bound is 1.02, but we consider it approaching significance.”

Adherence to treatment was significantly associated with lower odds of AD, but not with significantly lower odds of DNOS or MCI, she said. OSA was confirmed by ICD-9 diagnosis codes plus the presence of relevant polysomnography current procedural terminology code.

All told, the findings “suggest that PAP therapy for OSA may lower short-term risk for dementia in older persons,” Dr. Dunietz and her co-nvestigators said in their poster presentation. “If a causal pathway exists between OSA and dementia, treatment of OSA may offer new opportunities to improve cognitive outcomes in older adults with OSA.”

Andrew W. Varga, MD, of the division of pulmonary, critical care, and sleep medicine at the Icahn School of Medicine at Mount Sinai and the Mount Sinai Integrative Sleep Center, both in New York, said that cognitive impairment is now a recognized clinical consequence of OSA and that OSA treatment could be a target for the prevention of cognitive impairment and Alzheimer’s disease in particular.

“I absolutely bring it up with patients in their 60s and 70s. I’m honest – I say, there seems to be more and more evidence for links between apnea and Alzheimer’s in particular. I tell them we don’t know 100% whether PAP reverses any of this, but it stands to reason that it does,” said Dr. Varga, who was asked to comment on the study and related research.

An analysis published several years ago in Neurology from the Alzheimer’s Disease Neuroimaging Initiative cohort found that patients with self-reported sleep apnea had a younger age of MCI or AD onset (about 10 years) and that patients who used continuous positive airway pressure had a delayed age of onset. “Those who had a subjective diagnosis of sleep apnea and who also reported using CPAP as treatment seemed to go in the opposite direction,” said Dr. Varga, a coauthor of that study. “They had an onset of AD that looked just like people who had no sleep apnea.”

While this study was limited by sleep apnea being self-reported – and by the lack of severity data – the newly reported study may be limited by the use of ICD codes and the fact that OSA is often entered into patient’s chart before diagnosis is confirmed through a sleep study, Dr. Varga said.

“The field is mature enough that we should be thinking of doing honest and rigorous clinical trials for sleep apnea with cognitive outcomes being a main measure of interest,” he said. “The issue we’re struggling with in the field is that such a trial would not be short.”

There are several theories for the link between OSA and cognitive impairment, he said, including disruptions in sleep architecture leading to increased production of amyloid and tau and/or decreased “clearance” of extracellular amyloid, neuronal sensitivity to hypoxia, and cardiovascular comorbidities.

Dr. Dunietz’s study was supported by The American Academy of Sleep Medicine Foundation. She reported having no disclosures. Dr. Varga said he has no relevant disclosures.

Responses from physicians in eight countries show profound effects from COVID-19 on their personal and professional lives, according to the results of a Medscape survey.

More than 7,500 physicians – nearly 5,000 in the United States, and others in Brazil, France, Germany, Mexico, Portugal, Spain, and the United Kingdom – responded to questions about their struggles to save patients and how the pandemic has changed their income and their lives at home and at work.

The pain was evident in this response from an emergency medicine physician in Spain: “It has been the worst time in my life ever, in both my personal and professional life.”

Conversely, some reported positive effects.

An internist in Brazil wrote: “I feel more proud of my career than ever before.”
 

One quarter of U.S. physicians considering earlier retirement

Physicians in the United States were asked what career changes, if any, they were considering in light of their experience with COVID-19. Although a little more than half (51%) said they were not planning any changes, 25% answered, “retiring earlier than previously planned,” and 12% answered, “a career change away from medicine.”

The number of physicians reporting an income drop was highest in Brazil (63% reported a drop), followed by the United States (62%), Mexico (56%), Portugal (49%), Germany (42%), France (41%), and Spain (31%). The question was not asked in the United Kingdom survey.

In the United States, the size of the drop has been substantial: 9% lost 76%-100% of their income; 14% lost 51%-75%; 28% lost 26%-50%; 33% lost 11%-25%; and 15% lost 1%-10%.

The U.S. specialists with the largest drop in income were ophthalmologists, who lost 51%, followed by allergists (46%), plastic surgeons (46%), and otolaryngologists (45%).

“I’m looking for a new profession due to economic impact,” an otolaryngologist in the United States said. “We are at risk while essentially using our private savings to keep our practice solvent.”

More than half of U.S. physicians (54%) have personally treated patients with COVID-19. Percentages were higher in France, Spain, and the United Kingdom (percentages ranged from 60%-68%).

The United States led all eight countries in treating patients with COVID-19 via telemedicine, at 26%. Germany had the lowest telemedicine percentage, at 10%.
 

Burnout intensifies

About two thirds of US physicians (64%) said that burnout had intensified during the crisis (70% of female physicians and 61% of male physicians said it had).

Many factors are feeding the burnout.

A critical care physician in the United States responded, “It is terrible to see people arriving at their rooms and assuming they were going to die soon; to see people saying goodbye to their families before dying or before being intubated.”

In all eight countries, a substantial percentage of physicians reported they “sometimes, often or always” treated patients with COVID-19 without the proper personal protective equipment. Spain had by far the largest percentage who answered that way (67%), followed by France (45%), Mexico (40%), the United Kingdom (34%), Brazil and Germany (28% each); and the United States and Portugal (23% each).

A U.S. rheumatologist wrote: “The fact that we were sent to take care of infectious patients without proper protection equipment made me feel we were betrayed in this fight.”

Sense of duty to volunteer to treat COVID-19 patients varied substantially among countries, from 69% who felt that way in Spain to 40% in Brazil. Half (50%) in the United States felt that way.

“Altruism must take second place where a real and present threat exists to my own personal existence,” one U.S. internist wrote.
 

Numbers personally infected

One fifth of physicians in Spain and the United Kingdom had personally been infected with the virus. Brazil, France, and Mexico had the next highest numbers, with 13%-15% of physicians infected; 5%-6% in the United States, Germany, and Portugal said they had been infected.

The percentage of physicians who reported that immediate family members had been infected ranged from 25% in Spain to 6% in Portugal. Among US physicians, 9% reported that family members had been diagnosed with COVID-19.

In the United States, 44% of respondents who had family living with them at home during the pandemic reported that relationships at home were more stressed because of stay-at-home guidelines and social distancing. Almost half (47%) said there had been no change, and 9% said relationships were less stressed.
 

Eating is coping mechanism of choice

Physicians were asked what they were doing more of during the pandemic, and food seemed to be the top source of comfort in all eight countries.

Loneliness reports differ across globe

Portugal had the highest percentage (51%) of physicians reporting increased loneliness. Next were Brazil (48%), the United States (46%), the United Kingdom (42%), France (41%), Spain and Mexico (40% each), and Germany (32%).

All eight countries lacked workplace activities to help physicians with grief. More than half (55%) of U.K. physicians reported having such activities available at their workplace, whereas only 25% of physicians in Germany did; 12%-24% of respondents across the countries were unsure about the offerings.

This article first appeared on Medscape.com.

Responses from physicians in eight countries show profound effects from COVID-19 on their personal and professional lives, according to the results of a Medscape survey.

More than 7,500 physicians – nearly 5,000 in the United States, and others in Brazil, France, Germany, Mexico, Portugal, Spain, and the United Kingdom – responded to questions about their struggles to save patients and how the pandemic has changed their income and their lives at home and at work.

The pain was evident in this response from an emergency medicine physician in Spain: “It has been the worst time in my life ever, in both my personal and professional life.”

Conversely, some reported positive effects.

An internist in Brazil wrote: “I feel more proud of my career than ever before.”
 

One quarter of U.S. physicians considering earlier retirement

Physicians in the United States were asked what career changes, if any, they were considering in light of their experience with COVID-19. Although a little more than half (51%) said they were not planning any changes, 25% answered, “retiring earlier than previously planned,” and 12% answered, “a career change away from medicine.”

The number of physicians reporting an income drop was highest in Brazil (63% reported a drop), followed by the United States (62%), Mexico (56%), Portugal (49%), Germany (42%), France (41%), and Spain (31%). The question was not asked in the United Kingdom survey.

In the United States, the size of the drop has been substantial: 9% lost 76%-100% of their income; 14% lost 51%-75%; 28% lost 26%-50%; 33% lost 11%-25%; and 15% lost 1%-10%.

The U.S. specialists with the largest drop in income were ophthalmologists, who lost 51%, followed by allergists (46%), plastic surgeons (46%), and otolaryngologists (45%).

“I’m looking for a new profession due to economic impact,” an otolaryngologist in the United States said. “We are at risk while essentially using our private savings to keep our practice solvent.”

More than half of U.S. physicians (54%) have personally treated patients with COVID-19. Percentages were higher in France, Spain, and the United Kingdom (percentages ranged from 60%-68%).

The United States led all eight countries in treating patients with COVID-19 via telemedicine, at 26%. Germany had the lowest telemedicine percentage, at 10%.
 

Burnout intensifies

About two thirds of US physicians (64%) said that burnout had intensified during the crisis (70% of female physicians and 61% of male physicians said it had).

Many factors are feeding the burnout.

A critical care physician in the United States responded, “It is terrible to see people arriving at their rooms and assuming they were going to die soon; to see people saying goodbye to their families before dying or before being intubated.”

In all eight countries, a substantial percentage of physicians reported they “sometimes, often or always” treated patients with COVID-19 without the proper personal protective equipment. Spain had by far the largest percentage who answered that way (67%), followed by France (45%), Mexico (40%), the United Kingdom (34%), Brazil and Germany (28% each); and the United States and Portugal (23% each).

A U.S. rheumatologist wrote: “The fact that we were sent to take care of infectious patients without proper protection equipment made me feel we were betrayed in this fight.”

Sense of duty to volunteer to treat COVID-19 patients varied substantially among countries, from 69% who felt that way in Spain to 40% in Brazil. Half (50%) in the United States felt that way.

“Altruism must take second place where a real and present threat exists to my own personal existence,” one U.S. internist wrote.
 

Numbers personally infected

One fifth of physicians in Spain and the United Kingdom had personally been infected with the virus. Brazil, France, and Mexico had the next highest numbers, with 13%-15% of physicians infected; 5%-6% in the United States, Germany, and Portugal said they had been infected.

The percentage of physicians who reported that immediate family members had been infected ranged from 25% in Spain to 6% in Portugal. Among US physicians, 9% reported that family members had been diagnosed with COVID-19.

In the United States, 44% of respondents who had family living with them at home during the pandemic reported that relationships at home were more stressed because of stay-at-home guidelines and social distancing. Almost half (47%) said there had been no change, and 9% said relationships were less stressed.
 

Eating is coping mechanism of choice

Physicians were asked what they were doing more of during the pandemic, and food seemed to be the top source of comfort in all eight countries.

Loneliness reports differ across globe

Portugal had the highest percentage (51%) of physicians reporting increased loneliness. Next were Brazil (48%), the United States (46%), the United Kingdom (42%), France (41%), Spain and Mexico (40% each), and Germany (32%).

All eight countries lacked workplace activities to help physicians with grief. More than half (55%) of U.K. physicians reported having such activities available at their workplace, whereas only 25% of physicians in Germany did; 12%-24% of respondents across the countries were unsure about the offerings.

This article first appeared on Medscape.com.

Responses from physicians in eight countries show profound effects from COVID-19 on their personal and professional lives, according to the results of a Medscape survey.

More than 7,500 physicians – nearly 5,000 in the United States, and others in Brazil, France, Germany, Mexico, Portugal, Spain, and the United Kingdom – responded to questions about their struggles to save patients and how the pandemic has changed their income and their lives at home and at work.

The pain was evident in this response from an emergency medicine physician in Spain: “It has been the worst time in my life ever, in both my personal and professional life.”

Conversely, some reported positive effects.

An internist in Brazil wrote: “I feel more proud of my career than ever before.”
 

One quarter of U.S. physicians considering earlier retirement

Physicians in the United States were asked what career changes, if any, they were considering in light of their experience with COVID-19. Although a little more than half (51%) said they were not planning any changes, 25% answered, “retiring earlier than previously planned,” and 12% answered, “a career change away from medicine.”

The number of physicians reporting an income drop was highest in Brazil (63% reported a drop), followed by the United States (62%), Mexico (56%), Portugal (49%), Germany (42%), France (41%), and Spain (31%). The question was not asked in the United Kingdom survey.

In the United States, the size of the drop has been substantial: 9% lost 76%-100% of their income; 14% lost 51%-75%; 28% lost 26%-50%; 33% lost 11%-25%; and 15% lost 1%-10%.

The U.S. specialists with the largest drop in income were ophthalmologists, who lost 51%, followed by allergists (46%), plastic surgeons (46%), and otolaryngologists (45%).

“I’m looking for a new profession due to economic impact,” an otolaryngologist in the United States said. “We are at risk while essentially using our private savings to keep our practice solvent.”

More than half of U.S. physicians (54%) have personally treated patients with COVID-19. Percentages were higher in France, Spain, and the United Kingdom (percentages ranged from 60%-68%).

The United States led all eight countries in treating patients with COVID-19 via telemedicine, at 26%. Germany had the lowest telemedicine percentage, at 10%.
 

Burnout intensifies

About two thirds of US physicians (64%) said that burnout had intensified during the crisis (70% of female physicians and 61% of male physicians said it had).

Many factors are feeding the burnout.

A critical care physician in the United States responded, “It is terrible to see people arriving at their rooms and assuming they were going to die soon; to see people saying goodbye to their families before dying or before being intubated.”

In all eight countries, a substantial percentage of physicians reported they “sometimes, often or always” treated patients with COVID-19 without the proper personal protective equipment. Spain had by far the largest percentage who answered that way (67%), followed by France (45%), Mexico (40%), the United Kingdom (34%), Brazil and Germany (28% each); and the United States and Portugal (23% each).

A U.S. rheumatologist wrote: “The fact that we were sent to take care of infectious patients without proper protection equipment made me feel we were betrayed in this fight.”

Sense of duty to volunteer to treat COVID-19 patients varied substantially among countries, from 69% who felt that way in Spain to 40% in Brazil. Half (50%) in the United States felt that way.

“Altruism must take second place where a real and present threat exists to my own personal existence,” one U.S. internist wrote.
 

Numbers personally infected

One fifth of physicians in Spain and the United Kingdom had personally been infected with the virus. Brazil, France, and Mexico had the next highest numbers, with 13%-15% of physicians infected; 5%-6% in the United States, Germany, and Portugal said they had been infected.

The percentage of physicians who reported that immediate family members had been infected ranged from 25% in Spain to 6% in Portugal. Among US physicians, 9% reported that family members had been diagnosed with COVID-19.

In the United States, 44% of respondents who had family living with them at home during the pandemic reported that relationships at home were more stressed because of stay-at-home guidelines and social distancing. Almost half (47%) said there had been no change, and 9% said relationships were less stressed.
 

Eating is coping mechanism of choice

Physicians were asked what they were doing more of during the pandemic, and food seemed to be the top source of comfort in all eight countries.

Loneliness reports differ across globe

Portugal had the highest percentage (51%) of physicians reporting increased loneliness. Next were Brazil (48%), the United States (46%), the United Kingdom (42%), France (41%), Spain and Mexico (40% each), and Germany (32%).

All eight countries lacked workplace activities to help physicians with grief. More than half (55%) of U.K. physicians reported having such activities available at their workplace, whereas only 25% of physicians in Germany did; 12%-24% of respondents across the countries were unsure about the offerings.

This article first appeared on Medscape.com.

For the first time, researchers detected active and prolonged infection of SARS-CoV-2 virus in the gastrointestinal (GI) tracts of people with confirmed COVID-19. Stool tests were positive among people with no GI symptoms, and in some cases up to 6 days after nasopharyngeal swabs yielded negative results.

The small pilot study suggests a quiescent but active infection in the gut. Stool testing revealed genomic evidence of active infection in 7 of the 15 participants tested in one of two hospitals in Hong Kong.

“We found active and prolonged SARS-CoV-2 infection in the stool of patients with COVID-19, even after recovery, suggesting that coronavirus could remain in the gut of asymptomatic carriers,” senior author Siew C. Ng, MBBS, PhD, told Medscape Medical News.

“Due to the potential threat of fecal-oral transmission, it is important to maintain long-term coronavirus and health surveillance,” said Ng, Associate Director of the Centre for Gut Microbiota Research at the Chinese University of Hong Kong (CUHK).

“Discharged patients and their caretakers should remain vigilant and observe strict personal and toileting hygiene,” she added.

The prospective, observational study was published online July 20 in Gut.
 

Ramping up COVID-19 testing

As a follow-up to these and other findings – including the testing of more than 2,000 stool samples in children and the needy arriving at Hong Kong airports starting March 29 – the same investigators are establishing a CUHK Coronavirus Testing Center.

As of Aug. 31, the detection rate in tested children was 0.28%. The Center plans to offer as many as 2,000 COVID-19 tests daily going forward to help identify asymptomatic carriers, the investigators announced in a Sept. 7 news release.

In contrast to nasopharyngeal sampling, stool specimens are “more convenient, safe and non-invasive to collect in the pediatric population,” professor Paul Chan, chairman of the Department of Microbiology, CU Medicine, said in the release. “This makes the stool test a better option for COVID-19 screening in babies, young children and those whose respiratory samples are difficult to collect.”

Even though previous researchers identified SARS-CoV-2 in the stool, the activity and infectivity of the virus in the gastrointestinal tract during and after COVID-19 respiratory positivity remained largely unknown.
 

Active infection detected in stool

This prospective study involved 15 people hospitalized with COVID-19 in March and April. Participants were a median 55 years old (range, 22-71 years) and all presented with respiratory symptoms. Only one patient had concurrent GI symptoms at admission. Median length of stay was 21 days.

Investigators collected fecal samples serially until discharge. They extracted viral DNA to test for transcriptional genetic evidence of active infection, which they detected in 7 of 15 patients. The patient with GI symptoms was not in this positive group.

The findings suggest a “quiescent but active GI infection,” the researchers note.

Three of the seven patients continued to test positive for active infection in their stool up to 6 days after respiratory clearance of SARS-CoV-2.
 

Microbiome matters

The investigators also extracted, amplified, and sequenced DNA from the stool samples. Their “metagenomic” profile revealed the type and amounts of bacterial strains in each patient’s gut microbiome.

Interestingly, bacterial strains differed between people with high SARS-CoV-2 infectivity versus participants with low to no evidence of active infection.

“Stool with high viral activity had higher abundance of pathogenic bacteria,” Ng said. In contrast, people with low or no infectivity had more beneficial bacterial strains, including bacteria that play critical roles in boosting host immunity.

Each patient’s microbiome composition changed during the course of the study. Whether the microbiome alters the course of COVID-19 or COVID-19 alters the composition of the microbiome requires further study, the authors note.

The U.S. Food and Drug Administration and officials in other countries have contacted the Hong Kong investigators for more details on their stool testing strategy, professor Francis K.L. Chan, dean of the faculty of medicine and director of the Centre for Gut Microbiota Research at CUHK, stated in the news release.

Further research into revealing the infectivity and pathogenesis of SARS-CoV-2 in the GI tract is warranted. The value of modulating the human gut microbiome in this patient population could be worthwhile to investigate as well, the researchers said.
 

Novel finding

“Some of it is not-so-new news and some is new,” David A. Johnson, MD, told Medscape Medical News when asked to comment on the study.

For example, previous researchers have detected SARS-CoV-2 virus in the stool. However, this study takes it a step further and shows that the virus present in stool can remain infectious on the basis of metagenomic signatures.

Furthermore, the virus can remain infectious in the gut even after a patient tests negative for COVID-19 through nasopharyngeal sampling – in this report up to 6 days later, said Johnson, professor of medicine, chief of gastroenterology, Eastern Virginia Medical School in Norfolk, Va.

The study carries important implications for people who currently test negative following active COVID-19 infection, he added. Centers for Disease Control and Prevention criteria clear a person as negative after two nasopharyngeal swabs at least 24 hours apart.

People in this category could believe they are no longer infectious and might return to a setting where they could infect others, Johnson said.

One potential means for spreading SARS-CoV-2 from the gut is from a toilet plume, as Johnson previously highlighted in a video report for Medscape Medical News.

The study authors disclosed no relevant financial relationships. Johnson serves as an adviser to WebMD/Medscape.
 

This article first appeared on Medscape.com.

For the first time, researchers detected active and prolonged infection of SARS-CoV-2 virus in the gastrointestinal (GI) tracts of people with confirmed COVID-19. Stool tests were positive among people with no GI symptoms, and in some cases up to 6 days after nasopharyngeal swabs yielded negative results.

The small pilot study suggests a quiescent but active infection in the gut. Stool testing revealed genomic evidence of active infection in 7 of the 15 participants tested in one of two hospitals in Hong Kong.

“We found active and prolonged SARS-CoV-2 infection in the stool of patients with COVID-19, even after recovery, suggesting that coronavirus could remain in the gut of asymptomatic carriers,” senior author Siew C. Ng, MBBS, PhD, told Medscape Medical News.

“Due to the potential threat of fecal-oral transmission, it is important to maintain long-term coronavirus and health surveillance,” said Ng, Associate Director of the Centre for Gut Microbiota Research at the Chinese University of Hong Kong (CUHK).

“Discharged patients and their caretakers should remain vigilant and observe strict personal and toileting hygiene,” she added.

The prospective, observational study was published online July 20 in Gut.
 

Ramping up COVID-19 testing

As a follow-up to these and other findings – including the testing of more than 2,000 stool samples in children and the needy arriving at Hong Kong airports starting March 29 – the same investigators are establishing a CUHK Coronavirus Testing Center.

As of Aug. 31, the detection rate in tested children was 0.28%. The Center plans to offer as many as 2,000 COVID-19 tests daily going forward to help identify asymptomatic carriers, the investigators announced in a Sept. 7 news release.

In contrast to nasopharyngeal sampling, stool specimens are “more convenient, safe and non-invasive to collect in the pediatric population,” professor Paul Chan, chairman of the Department of Microbiology, CU Medicine, said in the release. “This makes the stool test a better option for COVID-19 screening in babies, young children and those whose respiratory samples are difficult to collect.”

Even though previous researchers identified SARS-CoV-2 in the stool, the activity and infectivity of the virus in the gastrointestinal tract during and after COVID-19 respiratory positivity remained largely unknown.
 

Active infection detected in stool

This prospective study involved 15 people hospitalized with COVID-19 in March and April. Participants were a median 55 years old (range, 22-71 years) and all presented with respiratory symptoms. Only one patient had concurrent GI symptoms at admission. Median length of stay was 21 days.

Investigators collected fecal samples serially until discharge. They extracted viral DNA to test for transcriptional genetic evidence of active infection, which they detected in 7 of 15 patients. The patient with GI symptoms was not in this positive group.

The findings suggest a “quiescent but active GI infection,” the researchers note.

Three of the seven patients continued to test positive for active infection in their stool up to 6 days after respiratory clearance of SARS-CoV-2.
 

Microbiome matters

The investigators also extracted, amplified, and sequenced DNA from the stool samples. Their “metagenomic” profile revealed the type and amounts of bacterial strains in each patient’s gut microbiome.

Interestingly, bacterial strains differed between people with high SARS-CoV-2 infectivity versus participants with low to no evidence of active infection.

“Stool with high viral activity had higher abundance of pathogenic bacteria,” Ng said. In contrast, people with low or no infectivity had more beneficial bacterial strains, including bacteria that play critical roles in boosting host immunity.

Each patient’s microbiome composition changed during the course of the study. Whether the microbiome alters the course of COVID-19 or COVID-19 alters the composition of the microbiome requires further study, the authors note.

The U.S. Food and Drug Administration and officials in other countries have contacted the Hong Kong investigators for more details on their stool testing strategy, professor Francis K.L. Chan, dean of the faculty of medicine and director of the Centre for Gut Microbiota Research at CUHK, stated in the news release.

Further research into revealing the infectivity and pathogenesis of SARS-CoV-2 in the GI tract is warranted. The value of modulating the human gut microbiome in this patient population could be worthwhile to investigate as well, the researchers said.
 

Novel finding

“Some of it is not-so-new news and some is new,” David A. Johnson, MD, told Medscape Medical News when asked to comment on the study.

For example, previous researchers have detected SARS-CoV-2 virus in the stool. However, this study takes it a step further and shows that the virus present in stool can remain infectious on the basis of metagenomic signatures.

Furthermore, the virus can remain infectious in the gut even after a patient tests negative for COVID-19 through nasopharyngeal sampling – in this report up to 6 days later, said Johnson, professor of medicine, chief of gastroenterology, Eastern Virginia Medical School in Norfolk, Va.

The study carries important implications for people who currently test negative following active COVID-19 infection, he added. Centers for Disease Control and Prevention criteria clear a person as negative after two nasopharyngeal swabs at least 24 hours apart.

People in this category could believe they are no longer infectious and might return to a setting where they could infect others, Johnson said.

One potential means for spreading SARS-CoV-2 from the gut is from a toilet plume, as Johnson previously highlighted in a video report for Medscape Medical News.

The study authors disclosed no relevant financial relationships. Johnson serves as an adviser to WebMD/Medscape.
 

This article first appeared on Medscape.com.

For the first time, researchers detected active and prolonged infection of SARS-CoV-2 virus in the gastrointestinal (GI) tracts of people with confirmed COVID-19. Stool tests were positive among people with no GI symptoms, and in some cases up to 6 days after nasopharyngeal swabs yielded negative results.

The small pilot study suggests a quiescent but active infection in the gut. Stool testing revealed genomic evidence of active infection in 7 of the 15 participants tested in one of two hospitals in Hong Kong.

“We found active and prolonged SARS-CoV-2 infection in the stool of patients with COVID-19, even after recovery, suggesting that coronavirus could remain in the gut of asymptomatic carriers,” senior author Siew C. Ng, MBBS, PhD, told Medscape Medical News.

“Due to the potential threat of fecal-oral transmission, it is important to maintain long-term coronavirus and health surveillance,” said Ng, Associate Director of the Centre for Gut Microbiota Research at the Chinese University of Hong Kong (CUHK).

“Discharged patients and their caretakers should remain vigilant and observe strict personal and toileting hygiene,” she added.

The prospective, observational study was published online July 20 in Gut.
 

Ramping up COVID-19 testing

As a follow-up to these and other findings – including the testing of more than 2,000 stool samples in children and the needy arriving at Hong Kong airports starting March 29 – the same investigators are establishing a CUHK Coronavirus Testing Center.

As of Aug. 31, the detection rate in tested children was 0.28%. The Center plans to offer as many as 2,000 COVID-19 tests daily going forward to help identify asymptomatic carriers, the investigators announced in a Sept. 7 news release.

In contrast to nasopharyngeal sampling, stool specimens are “more convenient, safe and non-invasive to collect in the pediatric population,” professor Paul Chan, chairman of the Department of Microbiology, CU Medicine, said in the release. “This makes the stool test a better option for COVID-19 screening in babies, young children and those whose respiratory samples are difficult to collect.”

Even though previous researchers identified SARS-CoV-2 in the stool, the activity and infectivity of the virus in the gastrointestinal tract during and after COVID-19 respiratory positivity remained largely unknown.
 

Active infection detected in stool

This prospective study involved 15 people hospitalized with COVID-19 in March and April. Participants were a median 55 years old (range, 22-71 years) and all presented with respiratory symptoms. Only one patient had concurrent GI symptoms at admission. Median length of stay was 21 days.

Investigators collected fecal samples serially until discharge. They extracted viral DNA to test for transcriptional genetic evidence of active infection, which they detected in 7 of 15 patients. The patient with GI symptoms was not in this positive group.

The findings suggest a “quiescent but active GI infection,” the researchers note.

Three of the seven patients continued to test positive for active infection in their stool up to 6 days after respiratory clearance of SARS-CoV-2.
 

Microbiome matters

The investigators also extracted, amplified, and sequenced DNA from the stool samples. Their “metagenomic” profile revealed the type and amounts of bacterial strains in each patient’s gut microbiome.

Interestingly, bacterial strains differed between people with high SARS-CoV-2 infectivity versus participants with low to no evidence of active infection.

“Stool with high viral activity had higher abundance of pathogenic bacteria,” Ng said. In contrast, people with low or no infectivity had more beneficial bacterial strains, including bacteria that play critical roles in boosting host immunity.

Each patient’s microbiome composition changed during the course of the study. Whether the microbiome alters the course of COVID-19 or COVID-19 alters the composition of the microbiome requires further study, the authors note.

The U.S. Food and Drug Administration and officials in other countries have contacted the Hong Kong investigators for more details on their stool testing strategy, professor Francis K.L. Chan, dean of the faculty of medicine and director of the Centre for Gut Microbiota Research at CUHK, stated in the news release.

Further research into revealing the infectivity and pathogenesis of SARS-CoV-2 in the GI tract is warranted. The value of modulating the human gut microbiome in this patient population could be worthwhile to investigate as well, the researchers said.
 

Novel finding

“Some of it is not-so-new news and some is new,” David A. Johnson, MD, told Medscape Medical News when asked to comment on the study.

For example, previous researchers have detected SARS-CoV-2 virus in the stool. However, this study takes it a step further and shows that the virus present in stool can remain infectious on the basis of metagenomic signatures.

Furthermore, the virus can remain infectious in the gut even after a patient tests negative for COVID-19 through nasopharyngeal sampling – in this report up to 6 days later, said Johnson, professor of medicine, chief of gastroenterology, Eastern Virginia Medical School in Norfolk, Va.

The study carries important implications for people who currently test negative following active COVID-19 infection, he added. Centers for Disease Control and Prevention criteria clear a person as negative after two nasopharyngeal swabs at least 24 hours apart.

People in this category could believe they are no longer infectious and might return to a setting where they could infect others, Johnson said.

One potential means for spreading SARS-CoV-2 from the gut is from a toilet plume, as Johnson previously highlighted in a video report for Medscape Medical News.

The study authors disclosed no relevant financial relationships. Johnson serves as an adviser to WebMD/Medscape.
 

This article first appeared on Medscape.com.

The earlier the anti-inflammatory drug colchicine is initiated after a myocardial infarction (MI) the greater the benefit, a new COLCOT analysis suggests.

The parent trial was conducted in patients with a recent MI because of the intense inflammation present at that time, and added colchicine 0.5 mg daily to standard care within 30 days following MI.

As previously reported, colchicine significantly reduced the risk of the primary end point – a composite of cardiovascular (CV) death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring revascularization – by 23% compared with placebo.

This new analysis shows the risk was reduced by 48% in patients receiving colchicine within 3 days of an MI (4.3% vs. 8.3%; adjusted hazard ratio, 0.52; 95% confidence interval, 0.32-0.84, P = .007).

Risk of a secondary efficacy end point – CV death, resuscitated cardiac arrest, MI, or stroke – was reduced by 45% over an average follow up of 22.7 months (3.3% vs 6.1%; adjusted HR, 0.55; 95% CI, 0.32-0.95, P = .031).

“We believe that our results support an early, in-hospital initiation of adjunctive colchicine for post-MI prevention,” Nadia Bouabdallaoui, MD, Montreal Heart Institute, Quebec, Canada, said during an online session devoted to colchicine at the European Society of Cardiology Congress 2020.

Session moderator Massimo Imazio, MD, professor of cardiology at the University of Turin, Italy, said the improved outcomes suggest that earlier treatment is better – a finding that parallels his own experience using colchicine in patients with pericarditis.

“This substudy is very important because this is probably also the year in cardiovascular applications [that] early use of the drug could improve outcomes,” he said.

Positive data have been accumulating for colchicine from COLCOT, LoDoCo, and, most recently, the LoDoCo2 trial, even as another anti-inflammatory drug, methotrexate, flamed out as secondary prevention in the CIRT trial.

The new COLCOT substudy included 4,661 of the 4,745 original patients and examined treatment initiation using three strata: within 0-3 days (n = 1,193), 4-7 days (n = 720), and 8-30 days (n = 2,748). Patients who received treatment within 3 days were slightly younger, more likely to be smokers, and to have a shorter time from MI to randomization (2.1 days vs 5.1 days vs. 20.8 days, respectively).

In the subset receiving treatment within 3 days, those assigned to colchicine had the same number of cardiac deaths as those given placebo (2 vs. 2) but fewer resuscitated cardiac arrests (1 vs. 3), MIs (17 vs. 29), strokes (1 vs. 5), and urgent hospitalizations for angina requiring revascularization (6 vs. 17).

“A larger trial might have allowed for a better assessment of individual endpoints and subgroups,” observed Bouabdallaoui.

Although there is growing support for colchicine, experts caution that the drug many not be for everyone. In COLCOT, 1 in 10 patients were unable to tolerate the drug, largely because of gastrointestinal (GI) issues.
 

Pharmacogenomics substudy

A second COLCOT substudy aimed to identify genetic markers predictive of colchicine response and to gain insights into the mechanisms behind this response. It included 767 patients treated with colchicine and another 755 treated with placebo – or about one-third the patients in the original trial.

A genome-wide association study did not find a significant association for the primary CV endpoint, although a prespecified subgroup analysis in men identified an interesting region on chromosome 9 (variant: rs10811106), which just missed reaching genomewide significance, said Marie-Pierre Dubé, PhD, director of the Université de Montréal Beaulieu-Saucier Pharmacogenomics Centre at the Montreal Heart Institute.

In addition, the genomewide analysis found two significant regions for GI events: one on chromosome 6 (variant: rs6916345) and one on chromosome 10 (variant: rs74795203).

For each of the identified regions, the researchers then tested the effect of the allele in the placebo group and the interaction between the genetic variant and treatment with colchicine. For the chromosome 9 region in males, there was no effect in the placebo group and a significant interaction in the colchicine group.

For the significant GI event findings, there was a small effect for the chromosome 6 region in the placebo group and a very significant interaction with colchicine, Dubé said. Similarly, there was no effect for the chromosome 10 region in the placebo group and a significant interaction with colchicine.

Additional analyses in stratified patient populations showed that males with the protective allele (CC) for the chromosome 9 region represented 83% of the population. The primary CV endpoint occurred in 3.2% of these men treated with colchicine and 6.3% treated with placebo (HR, 0.46; 95% CI, 0.24 - 0.86).

For the gastrointestinal events, 25% of patients carried the risk allele (AA) for the chromosome 6 region and 36.9% of these had GI events when treated with colchicine versus 18.6% when treated with placebo (HR, 2.42; 95% CI, 1.57-3.72).

Similarly, 13% of individuals carried one or two copies of the risk allele (AG+GG) for the chromosome 10 region and the risk of GI events in these was nearly four times higher with colchicine (47.1% vs. 18.9%; HR, 3.98; 95% CI 2.24-7.07).

Functional genomic analyses of the identified regions were also performed and showed that the chromosome 9 locus overlaps with the SAXO1 gene, a stabilizer of axonemal microtubules 1.

“The leading variant at this locus (rs10811106 C allele) correlated with the expression of the HAUS6 gene, which is involved in microtubule generation from existing microtubules, and may interact with the effect of colchicine, which is known to inhibit microtubule formation,” observed Dubé. 

Also, the chromosome 6 locus associated with gastrointestinal events was colocalizing with the Crohn’s disease locus, adding further support for this region.

“The results support potential personalized approaches to inflammation reduction for cardiovascular prevention,” Dubé said.

This is a post hoc subgroup analysis, however, and replication is necessary, ideally in prospective randomized trials, she noted.

The substudy is important because it provides further insights into the link between colchicine and microtubule polymerization, affecting the activation of the inflammasome, session moderator Imazio said.

“Second, it is important because pharmacogenomics can help us to better understand the optimal responder to colchicine and colchicine resistance,” he said. “So it can be useful for personalized medicine, leading to the proper use of the drug for the proper patient.”

COLCOT was supported by the government of Quebec, the Canadian Institutes of Health Research, and philanthropic foundations. Bouabdallaoui has disclosed no relevant financial relationships. Dubé reported grants from the government of Quebec; personal fees from DalCor and GlaxoSmithKline; research support from AstraZeneca, Pfizer, Servier, Sanofi; and minor equity interest in DalCor. Dubé is also coauthor of patents on pharmacogenomics-guided CETP inhibition, and pharmacogenomics markers of response to colchicine.  

This article first appeared on Medscape.com.

The earlier the anti-inflammatory drug colchicine is initiated after a myocardial infarction (MI) the greater the benefit, a new COLCOT analysis suggests.

The parent trial was conducted in patients with a recent MI because of the intense inflammation present at that time, and added colchicine 0.5 mg daily to standard care within 30 days following MI.

As previously reported, colchicine significantly reduced the risk of the primary end point – a composite of cardiovascular (CV) death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring revascularization – by 23% compared with placebo.

This new analysis shows the risk was reduced by 48% in patients receiving colchicine within 3 days of an MI (4.3% vs. 8.3%; adjusted hazard ratio, 0.52; 95% confidence interval, 0.32-0.84, P = .007).

Risk of a secondary efficacy end point – CV death, resuscitated cardiac arrest, MI, or stroke – was reduced by 45% over an average follow up of 22.7 months (3.3% vs 6.1%; adjusted HR, 0.55; 95% CI, 0.32-0.95, P = .031).

“We believe that our results support an early, in-hospital initiation of adjunctive colchicine for post-MI prevention,” Nadia Bouabdallaoui, MD, Montreal Heart Institute, Quebec, Canada, said during an online session devoted to colchicine at the European Society of Cardiology Congress 2020.

Session moderator Massimo Imazio, MD, professor of cardiology at the University of Turin, Italy, said the improved outcomes suggest that earlier treatment is better – a finding that parallels his own experience using colchicine in patients with pericarditis.

“This substudy is very important because this is probably also the year in cardiovascular applications [that] early use of the drug could improve outcomes,” he said.

Positive data have been accumulating for colchicine from COLCOT, LoDoCo, and, most recently, the LoDoCo2 trial, even as another anti-inflammatory drug, methotrexate, flamed out as secondary prevention in the CIRT trial.

The new COLCOT substudy included 4,661 of the 4,745 original patients and examined treatment initiation using three strata: within 0-3 days (n = 1,193), 4-7 days (n = 720), and 8-30 days (n = 2,748). Patients who received treatment within 3 days were slightly younger, more likely to be smokers, and to have a shorter time from MI to randomization (2.1 days vs 5.1 days vs. 20.8 days, respectively).

In the subset receiving treatment within 3 days, those assigned to colchicine had the same number of cardiac deaths as those given placebo (2 vs. 2) but fewer resuscitated cardiac arrests (1 vs. 3), MIs (17 vs. 29), strokes (1 vs. 5), and urgent hospitalizations for angina requiring revascularization (6 vs. 17).

“A larger trial might have allowed for a better assessment of individual endpoints and subgroups,” observed Bouabdallaoui.

Although there is growing support for colchicine, experts caution that the drug many not be for everyone. In COLCOT, 1 in 10 patients were unable to tolerate the drug, largely because of gastrointestinal (GI) issues.
 

Pharmacogenomics substudy

A second COLCOT substudy aimed to identify genetic markers predictive of colchicine response and to gain insights into the mechanisms behind this response. It included 767 patients treated with colchicine and another 755 treated with placebo – or about one-third the patients in the original trial.

A genome-wide association study did not find a significant association for the primary CV endpoint, although a prespecified subgroup analysis in men identified an interesting region on chromosome 9 (variant: rs10811106), which just missed reaching genomewide significance, said Marie-Pierre Dubé, PhD, director of the Université de Montréal Beaulieu-Saucier Pharmacogenomics Centre at the Montreal Heart Institute.

In addition, the genomewide analysis found two significant regions for GI events: one on chromosome 6 (variant: rs6916345) and one on chromosome 10 (variant: rs74795203).

For each of the identified regions, the researchers then tested the effect of the allele in the placebo group and the interaction between the genetic variant and treatment with colchicine. For the chromosome 9 region in males, there was no effect in the placebo group and a significant interaction in the colchicine group.

For the significant GI event findings, there was a small effect for the chromosome 6 region in the placebo group and a very significant interaction with colchicine, Dubé said. Similarly, there was no effect for the chromosome 10 region in the placebo group and a significant interaction with colchicine.

Additional analyses in stratified patient populations showed that males with the protective allele (CC) for the chromosome 9 region represented 83% of the population. The primary CV endpoint occurred in 3.2% of these men treated with colchicine and 6.3% treated with placebo (HR, 0.46; 95% CI, 0.24 - 0.86).

For the gastrointestinal events, 25% of patients carried the risk allele (AA) for the chromosome 6 region and 36.9% of these had GI events when treated with colchicine versus 18.6% when treated with placebo (HR, 2.42; 95% CI, 1.57-3.72).

Similarly, 13% of individuals carried one or two copies of the risk allele (AG+GG) for the chromosome 10 region and the risk of GI events in these was nearly four times higher with colchicine (47.1% vs. 18.9%; HR, 3.98; 95% CI 2.24-7.07).

Functional genomic analyses of the identified regions were also performed and showed that the chromosome 9 locus overlaps with the SAXO1 gene, a stabilizer of axonemal microtubules 1.

“The leading variant at this locus (rs10811106 C allele) correlated with the expression of the HAUS6 gene, which is involved in microtubule generation from existing microtubules, and may interact with the effect of colchicine, which is known to inhibit microtubule formation,” observed Dubé. 

Also, the chromosome 6 locus associated with gastrointestinal events was colocalizing with the Crohn’s disease locus, adding further support for this region.

“The results support potential personalized approaches to inflammation reduction for cardiovascular prevention,” Dubé said.

This is a post hoc subgroup analysis, however, and replication is necessary, ideally in prospective randomized trials, she noted.

The substudy is important because it provides further insights into the link between colchicine and microtubule polymerization, affecting the activation of the inflammasome, session moderator Imazio said.

“Second, it is important because pharmacogenomics can help us to better understand the optimal responder to colchicine and colchicine resistance,” he said. “So it can be useful for personalized medicine, leading to the proper use of the drug for the proper patient.”

COLCOT was supported by the government of Quebec, the Canadian Institutes of Health Research, and philanthropic foundations. Bouabdallaoui has disclosed no relevant financial relationships. Dubé reported grants from the government of Quebec; personal fees from DalCor and GlaxoSmithKline; research support from AstraZeneca, Pfizer, Servier, Sanofi; and minor equity interest in DalCor. Dubé is also coauthor of patents on pharmacogenomics-guided CETP inhibition, and pharmacogenomics markers of response to colchicine.  

This article first appeared on Medscape.com.

The earlier the anti-inflammatory drug colchicine is initiated after a myocardial infarction (MI) the greater the benefit, a new COLCOT analysis suggests.

The parent trial was conducted in patients with a recent MI because of the intense inflammation present at that time, and added colchicine 0.5 mg daily to standard care within 30 days following MI.

As previously reported, colchicine significantly reduced the risk of the primary end point – a composite of cardiovascular (CV) death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring revascularization – by 23% compared with placebo.

This new analysis shows the risk was reduced by 48% in patients receiving colchicine within 3 days of an MI (4.3% vs. 8.3%; adjusted hazard ratio, 0.52; 95% confidence interval, 0.32-0.84, P = .007).

Risk of a secondary efficacy end point – CV death, resuscitated cardiac arrest, MI, or stroke – was reduced by 45% over an average follow up of 22.7 months (3.3% vs 6.1%; adjusted HR, 0.55; 95% CI, 0.32-0.95, P = .031).

“We believe that our results support an early, in-hospital initiation of adjunctive colchicine for post-MI prevention,” Nadia Bouabdallaoui, MD, Montreal Heart Institute, Quebec, Canada, said during an online session devoted to colchicine at the European Society of Cardiology Congress 2020.

Session moderator Massimo Imazio, MD, professor of cardiology at the University of Turin, Italy, said the improved outcomes suggest that earlier treatment is better – a finding that parallels his own experience using colchicine in patients with pericarditis.

“This substudy is very important because this is probably also the year in cardiovascular applications [that] early use of the drug could improve outcomes,” he said.

Positive data have been accumulating for colchicine from COLCOT, LoDoCo, and, most recently, the LoDoCo2 trial, even as another anti-inflammatory drug, methotrexate, flamed out as secondary prevention in the CIRT trial.

The new COLCOT substudy included 4,661 of the 4,745 original patients and examined treatment initiation using three strata: within 0-3 days (n = 1,193), 4-7 days (n = 720), and 8-30 days (n = 2,748). Patients who received treatment within 3 days were slightly younger, more likely to be smokers, and to have a shorter time from MI to randomization (2.1 days vs 5.1 days vs. 20.8 days, respectively).

In the subset receiving treatment within 3 days, those assigned to colchicine had the same number of cardiac deaths as those given placebo (2 vs. 2) but fewer resuscitated cardiac arrests (1 vs. 3), MIs (17 vs. 29), strokes (1 vs. 5), and urgent hospitalizations for angina requiring revascularization (6 vs. 17).

“A larger trial might have allowed for a better assessment of individual endpoints and subgroups,” observed Bouabdallaoui.

Although there is growing support for colchicine, experts caution that the drug many not be for everyone. In COLCOT, 1 in 10 patients were unable to tolerate the drug, largely because of gastrointestinal (GI) issues.
 

Pharmacogenomics substudy

A second COLCOT substudy aimed to identify genetic markers predictive of colchicine response and to gain insights into the mechanisms behind this response. It included 767 patients treated with colchicine and another 755 treated with placebo – or about one-third the patients in the original trial.

A genome-wide association study did not find a significant association for the primary CV endpoint, although a prespecified subgroup analysis in men identified an interesting region on chromosome 9 (variant: rs10811106), which just missed reaching genomewide significance, said Marie-Pierre Dubé, PhD, director of the Université de Montréal Beaulieu-Saucier Pharmacogenomics Centre at the Montreal Heart Institute.

In addition, the genomewide analysis found two significant regions for GI events: one on chromosome 6 (variant: rs6916345) and one on chromosome 10 (variant: rs74795203).

For each of the identified regions, the researchers then tested the effect of the allele in the placebo group and the interaction between the genetic variant and treatment with colchicine. For the chromosome 9 region in males, there was no effect in the placebo group and a significant interaction in the colchicine group.

For the significant GI event findings, there was a small effect for the chromosome 6 region in the placebo group and a very significant interaction with colchicine, Dubé said. Similarly, there was no effect for the chromosome 10 region in the placebo group and a significant interaction with colchicine.

Additional analyses in stratified patient populations showed that males with the protective allele (CC) for the chromosome 9 region represented 83% of the population. The primary CV endpoint occurred in 3.2% of these men treated with colchicine and 6.3% treated with placebo (HR, 0.46; 95% CI, 0.24 - 0.86).

For the gastrointestinal events, 25% of patients carried the risk allele (AA) for the chromosome 6 region and 36.9% of these had GI events when treated with colchicine versus 18.6% when treated with placebo (HR, 2.42; 95% CI, 1.57-3.72).

Similarly, 13% of individuals carried one or two copies of the risk allele (AG+GG) for the chromosome 10 region and the risk of GI events in these was nearly four times higher with colchicine (47.1% vs. 18.9%; HR, 3.98; 95% CI 2.24-7.07).

Functional genomic analyses of the identified regions were also performed and showed that the chromosome 9 locus overlaps with the SAXO1 gene, a stabilizer of axonemal microtubules 1.

“The leading variant at this locus (rs10811106 C allele) correlated with the expression of the HAUS6 gene, which is involved in microtubule generation from existing microtubules, and may interact with the effect of colchicine, which is known to inhibit microtubule formation,” observed Dubé. 

Also, the chromosome 6 locus associated with gastrointestinal events was colocalizing with the Crohn’s disease locus, adding further support for this region.

“The results support potential personalized approaches to inflammation reduction for cardiovascular prevention,” Dubé said.

This is a post hoc subgroup analysis, however, and replication is necessary, ideally in prospective randomized trials, she noted.

The substudy is important because it provides further insights into the link between colchicine and microtubule polymerization, affecting the activation of the inflammasome, session moderator Imazio said.

“Second, it is important because pharmacogenomics can help us to better understand the optimal responder to colchicine and colchicine resistance,” he said. “So it can be useful for personalized medicine, leading to the proper use of the drug for the proper patient.”

COLCOT was supported by the government of Quebec, the Canadian Institutes of Health Research, and philanthropic foundations. Bouabdallaoui has disclosed no relevant financial relationships. Dubé reported grants from the government of Quebec; personal fees from DalCor and GlaxoSmithKline; research support from AstraZeneca, Pfizer, Servier, Sanofi; and minor equity interest in DalCor. Dubé is also coauthor of patents on pharmacogenomics-guided CETP inhibition, and pharmacogenomics markers of response to colchicine.  

This article first appeared on Medscape.com.

The investigational drug masitinib (AB Science), which has a completely new mechanism of action for multiple sclerosis (MS), has shown a positive result in slowing disability in patients with primary progressive and secondary progressive forms of the disease and no signs of active inflammation in a phase 2b/3 study.

“This is the first time that we have seen significant activity in slowing disability in a population of nonactive primary progressive and secondary progressive MS,” lead investigator, Patrick Vermersch, MD, commented. “There are no drugs available for these patients, which make up the vast majority of progressive MS patients, so these results are impressive. They are definitely a big deal.”

Dr. Vermersch, who is professor of neurology at the University of Lille, France, presented the study at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020.

“Masitinib – a first-in-class tyrosine kinase inhibitor targeting the innate immune system via inhibition of mast cell and microglia/macrophage activity – may provide a new treatment option for primary progressive and nonactive secondary progressive MS,” he concluded.

This study, known as AB07002, demonstrated a sustained and significant benefit for masitinib at a dose of 4.5 mg/kg per day in Expanded Disability Status Scale (EDSS) score change over 2 years versus placebo, with a 37% reduction in 3-month confirmed disability progression. This change “is relevant from a medical standpoint,” Dr. Vermersch reported.

However, a second dosing schedule, in which the drug was titrated up to 6 mg/kg per day, did not show significant benefit. Dr. Vermersch said this was because of an unexpected improvement in EDSS score in the placebo group.   

In the 4.5-mg/kg group, the benefit was demonstrated across a broad population, with no difference with regard to age, duration of disease, or baseline disability. The benefits were similar in both primary and secondary MS phenotypes and were present irrespective of baseline active inflammation status.

Masitinib showed a safety profile “suitable for long-term administration in this population,” Dr. Vermersch said.  “Masitinib addresses the huge unmet need in progressive MS,” he said. “The drugs currently used in MS target B cells and T cells. They are immunomodulating drugs and are used for relapsing/remitting MS. But in progressive forms of the disease, there is a strong involvement of innate immunity, so to be effective we need drugs that target this part of the immune system.”

Innate immunity is a major part of the immune system in primates; it is related to the immune cells inside tissues and the CNS and is separate from adaptive peripheral immunity, he explained. 

Masitinib is a novel drug for MS in that it inhibits tyrosine kinase and blocks the activity of immune cells involved in the innate immune system – mainly microglia and mast cells. “Both of these types of cells are very involved in progressive MS. Masitinib has no action against T or B cells. It is a small molecule and penetrates the CNS,” Dr. Vermersch noted.

“This has opened up a whole new area of opportunity to develop treatments for progressive MS,” he added. 

“We showed a positive significant result in slowing disability in patients with nonactive progressive MS,” he said. “The term ‘nonactive’ is important. Some other drugs [ocrelizumab and siponimod] have shown some modest activity in slowing progressive forms of MS, but this is driven by patients with some degree of inflammatory activity at baseline. Our study excluded such patients.”  

The trial tested two different dosing schedules independently, each with its own placebo group. There were two subsets, each with 300 patients. The first subset was randomly assigned in a 2:1 ratio to daily masitinib at 4.5 mg/kg orally or placebo. The second subset was randomly assigned in a 2:1 ratio to daily masitinib titrated to 6 mg/kg or placebo.

The inclusion criteria were patients with primary progressive or secondary progressive MS without relapse (as measured by EDSS progression) within the previous 2 years.  “No patients were enrolled who had superimposed relapses during the previous 2 years,” Dr. Vermersch stressed.

Baseline EDSS score was 5.0, and patients had an average disease duration of 15 years. Mean age was 50 years.

The primary endpoint was change from baseline in absolute EDSS value, which was measured every 12 weeks throughout the study, averaged over the 2-year study period (mean change in EDSS score).

Results in the 4.5-mg/kg group showed a mean increase in EDSS score in the masitinib recipients of 0.001 versus 0.098 in the placebo group, giving a mean difference of –0.097 for masitinib (P = 0.025). The results were similar in patients with primary or secondary progressive MS. Sensitivity analysis based on ordinal EDSS change showed a significant 39% increased probability of having more improvements in EDSS or fewer worsening EDSS scores with masitinib (odds ratio, 0.61; P = 0.044). Other results showed that masitinib reduced the risk for first disability progression by 42% (hazard ratio, 0.58; P = 0.034) and the risk for confirmed (3-month) disability progression by 37% (hazard ratio, 0.63; P = 0.15).

Masitinib also showed a 98% reduction in the risk of reaching an EDSS score of 7, corresponding to disability severe enough that the patient is restricted to a wheelchair (hazard ratio, 0.02; P = 0.009). No patients in the masitinib group reached the endpoint of confirmed (3-month) EDSS score of 7, compared with four patients in the placebo group.

In terms of safety in the 4.5-mg/kg group, the most common adverse events were rash (1,5%) gastrointestinal (GI) disturbances (1%), neutropenia (1%), and edema (1%). “We had a couple of patients with skin reactions and neutropenia, but all adverse events were mild to moderate and very manageable,” Dr. Vermersch commented.  

He showed just one slide on the subset who were titrated up 6 mg/kg. “Numerically the change in EDSS was comparable in the 6-mg/kg–titrated group as it was in the 4.5-mg/kg group; however, the placebo arm of the 6-mg/kg subset unusually showed an improvement relative to baseline after 96 weeks. The placebo group of the 4.5-mg/kg cohort was consistent with the literature and expected worsening in EDSS score over 96 weeks,” Dr. Vermersch reported.

No new safety signal was observed in the 6-mg/kg cohort. Only the 4.5-mg/kg cohort will be pursued in further trials in MS.

Dr. Vermersch noted that masitinib is also being investigated in other indications and “there are thousands of patient-years of experience which show reassuring safety data.”

“There is some GI disturbances and skin reactions, but a very small percentage of patients discontinue treatment. If the drug is titrated slowly there are fewer adverse effects,” he said. “We will do that in the next study.”

A second confirmatory study is now being planned. The trial will enroll around 700 patients and is expected to recruit quickly because there is such a big unmet need, Dr. Vermersch added. 

Commenting on the findings, ACTRIMS president Jeffrey Cohen, MD, of the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic, Ohio, said this is “an interesting study from several perspectives.”

“Masitinib is a new drug for MS with a completely novel mechanism of action targeting the innate immune system”, he said. “The study had several innovative features in that it combined primary and secondary progressive MS patients and measured disability in a different way to what we are used to.”

“It did show a slowing of disability, which is great news as we do not have any drugs for these patients at the moment, so this is a very hopeful result,” Dr. Cohen said.

The study was supported by AB Science. Dr. Vermersch reports sitting on advisory boards for Biogen, Sanofi-Genzyme, Teva, Roche, Novartis, Celgene, and Merck KGaA.
 

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

The investigational drug masitinib (AB Science), which has a completely new mechanism of action for multiple sclerosis (MS), has shown a positive result in slowing disability in patients with primary progressive and secondary progressive forms of the disease and no signs of active inflammation in a phase 2b/3 study.

“This is the first time that we have seen significant activity in slowing disability in a population of nonactive primary progressive and secondary progressive MS,” lead investigator, Patrick Vermersch, MD, commented. “There are no drugs available for these patients, which make up the vast majority of progressive MS patients, so these results are impressive. They are definitely a big deal.”

Dr. Vermersch, who is professor of neurology at the University of Lille, France, presented the study at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020.

“Masitinib – a first-in-class tyrosine kinase inhibitor targeting the innate immune system via inhibition of mast cell and microglia/macrophage activity – may provide a new treatment option for primary progressive and nonactive secondary progressive MS,” he concluded.

This study, known as AB07002, demonstrated a sustained and significant benefit for masitinib at a dose of 4.5 mg/kg per day in Expanded Disability Status Scale (EDSS) score change over 2 years versus placebo, with a 37% reduction in 3-month confirmed disability progression. This change “is relevant from a medical standpoint,” Dr. Vermersch reported.

However, a second dosing schedule, in which the drug was titrated up to 6 mg/kg per day, did not show significant benefit. Dr. Vermersch said this was because of an unexpected improvement in EDSS score in the placebo group.   

In the 4.5-mg/kg group, the benefit was demonstrated across a broad population, with no difference with regard to age, duration of disease, or baseline disability. The benefits were similar in both primary and secondary MS phenotypes and were present irrespective of baseline active inflammation status.

Masitinib showed a safety profile “suitable for long-term administration in this population,” Dr. Vermersch said.  “Masitinib addresses the huge unmet need in progressive MS,” he said. “The drugs currently used in MS target B cells and T cells. They are immunomodulating drugs and are used for relapsing/remitting MS. But in progressive forms of the disease, there is a strong involvement of innate immunity, so to be effective we need drugs that target this part of the immune system.”

Innate immunity is a major part of the immune system in primates; it is related to the immune cells inside tissues and the CNS and is separate from adaptive peripheral immunity, he explained. 

Masitinib is a novel drug for MS in that it inhibits tyrosine kinase and blocks the activity of immune cells involved in the innate immune system – mainly microglia and mast cells. “Both of these types of cells are very involved in progressive MS. Masitinib has no action against T or B cells. It is a small molecule and penetrates the CNS,” Dr. Vermersch noted.

“This has opened up a whole new area of opportunity to develop treatments for progressive MS,” he added. 

“We showed a positive significant result in slowing disability in patients with nonactive progressive MS,” he said. “The term ‘nonactive’ is important. Some other drugs [ocrelizumab and siponimod] have shown some modest activity in slowing progressive forms of MS, but this is driven by patients with some degree of inflammatory activity at baseline. Our study excluded such patients.”  

The trial tested two different dosing schedules independently, each with its own placebo group. There were two subsets, each with 300 patients. The first subset was randomly assigned in a 2:1 ratio to daily masitinib at 4.5 mg/kg orally or placebo. The second subset was randomly assigned in a 2:1 ratio to daily masitinib titrated to 6 mg/kg or placebo.

The inclusion criteria were patients with primary progressive or secondary progressive MS without relapse (as measured by EDSS progression) within the previous 2 years.  “No patients were enrolled who had superimposed relapses during the previous 2 years,” Dr. Vermersch stressed.

Baseline EDSS score was 5.0, and patients had an average disease duration of 15 years. Mean age was 50 years.

The primary endpoint was change from baseline in absolute EDSS value, which was measured every 12 weeks throughout the study, averaged over the 2-year study period (mean change in EDSS score).

Results in the 4.5-mg/kg group showed a mean increase in EDSS score in the masitinib recipients of 0.001 versus 0.098 in the placebo group, giving a mean difference of –0.097 for masitinib (P = 0.025). The results were similar in patients with primary or secondary progressive MS. Sensitivity analysis based on ordinal EDSS change showed a significant 39% increased probability of having more improvements in EDSS or fewer worsening EDSS scores with masitinib (odds ratio, 0.61; P = 0.044). Other results showed that masitinib reduced the risk for first disability progression by 42% (hazard ratio, 0.58; P = 0.034) and the risk for confirmed (3-month) disability progression by 37% (hazard ratio, 0.63; P = 0.15).

Masitinib also showed a 98% reduction in the risk of reaching an EDSS score of 7, corresponding to disability severe enough that the patient is restricted to a wheelchair (hazard ratio, 0.02; P = 0.009). No patients in the masitinib group reached the endpoint of confirmed (3-month) EDSS score of 7, compared with four patients in the placebo group.

In terms of safety in the 4.5-mg/kg group, the most common adverse events were rash (1,5%) gastrointestinal (GI) disturbances (1%), neutropenia (1%), and edema (1%). “We had a couple of patients with skin reactions and neutropenia, but all adverse events were mild to moderate and very manageable,” Dr. Vermersch commented.  

He showed just one slide on the subset who were titrated up 6 mg/kg. “Numerically the change in EDSS was comparable in the 6-mg/kg–titrated group as it was in the 4.5-mg/kg group; however, the placebo arm of the 6-mg/kg subset unusually showed an improvement relative to baseline after 96 weeks. The placebo group of the 4.5-mg/kg cohort was consistent with the literature and expected worsening in EDSS score over 96 weeks,” Dr. Vermersch reported.

No new safety signal was observed in the 6-mg/kg cohort. Only the 4.5-mg/kg cohort will be pursued in further trials in MS.

Dr. Vermersch noted that masitinib is also being investigated in other indications and “there are thousands of patient-years of experience which show reassuring safety data.”

“There is some GI disturbances and skin reactions, but a very small percentage of patients discontinue treatment. If the drug is titrated slowly there are fewer adverse effects,” he said. “We will do that in the next study.”

A second confirmatory study is now being planned. The trial will enroll around 700 patients and is expected to recruit quickly because there is such a big unmet need, Dr. Vermersch added. 

Commenting on the findings, ACTRIMS president Jeffrey Cohen, MD, of the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic, Ohio, said this is “an interesting study from several perspectives.”

“Masitinib is a new drug for MS with a completely novel mechanism of action targeting the innate immune system”, he said. “The study had several innovative features in that it combined primary and secondary progressive MS patients and measured disability in a different way to what we are used to.”

“It did show a slowing of disability, which is great news as we do not have any drugs for these patients at the moment, so this is a very hopeful result,” Dr. Cohen said.

The study was supported by AB Science. Dr. Vermersch reports sitting on advisory boards for Biogen, Sanofi-Genzyme, Teva, Roche, Novartis, Celgene, and Merck KGaA.
 

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

The investigational drug masitinib (AB Science), which has a completely new mechanism of action for multiple sclerosis (MS), has shown a positive result in slowing disability in patients with primary progressive and secondary progressive forms of the disease and no signs of active inflammation in a phase 2b/3 study.

“This is the first time that we have seen significant activity in slowing disability in a population of nonactive primary progressive and secondary progressive MS,” lead investigator, Patrick Vermersch, MD, commented. “There are no drugs available for these patients, which make up the vast majority of progressive MS patients, so these results are impressive. They are definitely a big deal.”

Dr. Vermersch, who is professor of neurology at the University of Lille, France, presented the study at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020.

“Masitinib – a first-in-class tyrosine kinase inhibitor targeting the innate immune system via inhibition of mast cell and microglia/macrophage activity – may provide a new treatment option for primary progressive and nonactive secondary progressive MS,” he concluded.

This study, known as AB07002, demonstrated a sustained and significant benefit for masitinib at a dose of 4.5 mg/kg per day in Expanded Disability Status Scale (EDSS) score change over 2 years versus placebo, with a 37% reduction in 3-month confirmed disability progression. This change “is relevant from a medical standpoint,” Dr. Vermersch reported.

However, a second dosing schedule, in which the drug was titrated up to 6 mg/kg per day, did not show significant benefit. Dr. Vermersch said this was because of an unexpected improvement in EDSS score in the placebo group.   

In the 4.5-mg/kg group, the benefit was demonstrated across a broad population, with no difference with regard to age, duration of disease, or baseline disability. The benefits were similar in both primary and secondary MS phenotypes and were present irrespective of baseline active inflammation status.

Masitinib showed a safety profile “suitable for long-term administration in this population,” Dr. Vermersch said.  “Masitinib addresses the huge unmet need in progressive MS,” he said. “The drugs currently used in MS target B cells and T cells. They are immunomodulating drugs and are used for relapsing/remitting MS. But in progressive forms of the disease, there is a strong involvement of innate immunity, so to be effective we need drugs that target this part of the immune system.”

Innate immunity is a major part of the immune system in primates; it is related to the immune cells inside tissues and the CNS and is separate from adaptive peripheral immunity, he explained. 

Masitinib is a novel drug for MS in that it inhibits tyrosine kinase and blocks the activity of immune cells involved in the innate immune system – mainly microglia and mast cells. “Both of these types of cells are very involved in progressive MS. Masitinib has no action against T or B cells. It is a small molecule and penetrates the CNS,” Dr. Vermersch noted.

“This has opened up a whole new area of opportunity to develop treatments for progressive MS,” he added. 

“We showed a positive significant result in slowing disability in patients with nonactive progressive MS,” he said. “The term ‘nonactive’ is important. Some other drugs [ocrelizumab and siponimod] have shown some modest activity in slowing progressive forms of MS, but this is driven by patients with some degree of inflammatory activity at baseline. Our study excluded such patients.”  

The trial tested two different dosing schedules independently, each with its own placebo group. There were two subsets, each with 300 patients. The first subset was randomly assigned in a 2:1 ratio to daily masitinib at 4.5 mg/kg orally or placebo. The second subset was randomly assigned in a 2:1 ratio to daily masitinib titrated to 6 mg/kg or placebo.

The inclusion criteria were patients with primary progressive or secondary progressive MS without relapse (as measured by EDSS progression) within the previous 2 years.  “No patients were enrolled who had superimposed relapses during the previous 2 years,” Dr. Vermersch stressed.

Baseline EDSS score was 5.0, and patients had an average disease duration of 15 years. Mean age was 50 years.

The primary endpoint was change from baseline in absolute EDSS value, which was measured every 12 weeks throughout the study, averaged over the 2-year study period (mean change in EDSS score).

Results in the 4.5-mg/kg group showed a mean increase in EDSS score in the masitinib recipients of 0.001 versus 0.098 in the placebo group, giving a mean difference of –0.097 for masitinib (P = 0.025). The results were similar in patients with primary or secondary progressive MS. Sensitivity analysis based on ordinal EDSS change showed a significant 39% increased probability of having more improvements in EDSS or fewer worsening EDSS scores with masitinib (odds ratio, 0.61; P = 0.044). Other results showed that masitinib reduced the risk for first disability progression by 42% (hazard ratio, 0.58; P = 0.034) and the risk for confirmed (3-month) disability progression by 37% (hazard ratio, 0.63; P = 0.15).

Masitinib also showed a 98% reduction in the risk of reaching an EDSS score of 7, corresponding to disability severe enough that the patient is restricted to a wheelchair (hazard ratio, 0.02; P = 0.009). No patients in the masitinib group reached the endpoint of confirmed (3-month) EDSS score of 7, compared with four patients in the placebo group.

In terms of safety in the 4.5-mg/kg group, the most common adverse events were rash (1,5%) gastrointestinal (GI) disturbances (1%), neutropenia (1%), and edema (1%). “We had a couple of patients with skin reactions and neutropenia, but all adverse events were mild to moderate and very manageable,” Dr. Vermersch commented.  

He showed just one slide on the subset who were titrated up 6 mg/kg. “Numerically the change in EDSS was comparable in the 6-mg/kg–titrated group as it was in the 4.5-mg/kg group; however, the placebo arm of the 6-mg/kg subset unusually showed an improvement relative to baseline after 96 weeks. The placebo group of the 4.5-mg/kg cohort was consistent with the literature and expected worsening in EDSS score over 96 weeks,” Dr. Vermersch reported.

No new safety signal was observed in the 6-mg/kg cohort. Only the 4.5-mg/kg cohort will be pursued in further trials in MS.

Dr. Vermersch noted that masitinib is also being investigated in other indications and “there are thousands of patient-years of experience which show reassuring safety data.”

“There is some GI disturbances and skin reactions, but a very small percentage of patients discontinue treatment. If the drug is titrated slowly there are fewer adverse effects,” he said. “We will do that in the next study.”

A second confirmatory study is now being planned. The trial will enroll around 700 patients and is expected to recruit quickly because there is such a big unmet need, Dr. Vermersch added. 

Commenting on the findings, ACTRIMS president Jeffrey Cohen, MD, of the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic, Ohio, said this is “an interesting study from several perspectives.”

“Masitinib is a new drug for MS with a completely novel mechanism of action targeting the innate immune system”, he said. “The study had several innovative features in that it combined primary and secondary progressive MS patients and measured disability in a different way to what we are used to.”

“It did show a slowing of disability, which is great news as we do not have any drugs for these patients at the moment, so this is a very hopeful result,” Dr. Cohen said.

The study was supported by AB Science. Dr. Vermersch reports sitting on advisory boards for Biogen, Sanofi-Genzyme, Teva, Roche, Novartis, Celgene, and Merck KGaA.
 

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