Journal of Clinical Outcomes Management

Another coronavirus surge may be on the way in the United States as daily COVID-19 cases continue to plateau around 60,000, states begin to lift restrictions, and people embark on spring break trips this week, according to CNN.

Outbreaks will likely stem from the B.1.1.7 variant, which was first identified in the United Kingdom, and gain momentum during the next 6-14 weeks.

“Four weeks ago, the B.1.1.7 variant made up about 1%-4% of the virus that we were seeing in communities across the country. Today it’s up to 30%-40%,” Michael Osterholm, PhD, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, Minneapolis, told NBC’s Meet the Press on March 7.

Dr. Osterholm compared the current situation with the “eye of the hurricane,” where the skies appear clear but more storms are on the way. Across Europe, 27 countries are seeing significant B.1.1.7 case increases, and 10 are getting hit hard, he said.

“What we’ve seen in Europe, when we hit that 50% mark, you see cases surge,” he said. “So right now, we do have to keep America as safe as we can from this virus by not letting up on any of the public health measures we’ve taken.”

In January, the CDC warned that B.1.1.7 variant cases would increase in 2021 and become the dominant variant in the country by this month. The United States has now reported more than 3,000 cases across 46 states, according to the latest CDC tally updated on March 7. More than 600 cases have been found in Florida, followed by more than 400 in Michigan.

The CDC has said the tally doesn’t represent the total number of B.1.1.7 cases in the United States, only the ones that have been identified by analyzing samples through genomic sequencing.

“Where it has hit in the U.K. and now elsewhere in Europe, it has been catastrophic,” Celine Gounder, MD, an infectious disease specialist with New York University Langone Health, told CNN on March 7.

The variant is more transmissible than the original novel coronavirus, and the cases in the United States are “increasing exponentially,” she said.

“It has driven up rates of hospitalizations and deaths and it’s very difficult to control,” Dr. Gounder said.

Vaccination numbers aren’t yet high enough to stop the predicted surge, she added. The United States has shipped more than 116 million vaccine doses, according to the latest CDC update on March 7. Nearly 59 million people have received at least one dose, and 30.6 million people have received two vaccine doses. About 9% of the U.S. population has been fully vaccinated.

States shouldn’t ease restrictions until the vaccination numbers are much higher and daily COVID-19 cases fall below 10,000 – and maybe “considerably less than that,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, told CNN on March 4.

Several states have already begun to lift COVID-19 safety protocols, with Texas and Mississippi removing mask mandates last week. Businesses in Texas will be able to reopen at full capacity on March 10. For now, public health officials are urging Americans to continue to wear masks, avoid crowds, and follow social distancing guidelines as vaccines roll out across the country.

“This is sort of like we’ve been running this really long marathon, and we’re 100 yards from the finish line and we sit down and we give up,” Dr. Gounder told CNN on Sunday. ‘We’re almost there, we just need to give ourselves a bit more time to get a larger proportion of the population covered with vaccines.”

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

Another coronavirus surge may be on the way in the United States as daily COVID-19 cases continue to plateau around 60,000, states begin to lift restrictions, and people embark on spring break trips this week, according to CNN.

Outbreaks will likely stem from the B.1.1.7 variant, which was first identified in the United Kingdom, and gain momentum during the next 6-14 weeks.

“Four weeks ago, the B.1.1.7 variant made up about 1%-4% of the virus that we were seeing in communities across the country. Today it’s up to 30%-40%,” Michael Osterholm, PhD, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, Minneapolis, told NBC’s Meet the Press on March 7.

Dr. Osterholm compared the current situation with the “eye of the hurricane,” where the skies appear clear but more storms are on the way. Across Europe, 27 countries are seeing significant B.1.1.7 case increases, and 10 are getting hit hard, he said.

“What we’ve seen in Europe, when we hit that 50% mark, you see cases surge,” he said. “So right now, we do have to keep America as safe as we can from this virus by not letting up on any of the public health measures we’ve taken.”

In January, the CDC warned that B.1.1.7 variant cases would increase in 2021 and become the dominant variant in the country by this month. The United States has now reported more than 3,000 cases across 46 states, according to the latest CDC tally updated on March 7. More than 600 cases have been found in Florida, followed by more than 400 in Michigan.

The CDC has said the tally doesn’t represent the total number of B.1.1.7 cases in the United States, only the ones that have been identified by analyzing samples through genomic sequencing.

“Where it has hit in the U.K. and now elsewhere in Europe, it has been catastrophic,” Celine Gounder, MD, an infectious disease specialist with New York University Langone Health, told CNN on March 7.

The variant is more transmissible than the original novel coronavirus, and the cases in the United States are “increasing exponentially,” she said.

“It has driven up rates of hospitalizations and deaths and it’s very difficult to control,” Dr. Gounder said.

Vaccination numbers aren’t yet high enough to stop the predicted surge, she added. The United States has shipped more than 116 million vaccine doses, according to the latest CDC update on March 7. Nearly 59 million people have received at least one dose, and 30.6 million people have received two vaccine doses. About 9% of the U.S. population has been fully vaccinated.

States shouldn’t ease restrictions until the vaccination numbers are much higher and daily COVID-19 cases fall below 10,000 – and maybe “considerably less than that,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, told CNN on March 4.

Several states have already begun to lift COVID-19 safety protocols, with Texas and Mississippi removing mask mandates last week. Businesses in Texas will be able to reopen at full capacity on March 10. For now, public health officials are urging Americans to continue to wear masks, avoid crowds, and follow social distancing guidelines as vaccines roll out across the country.

“This is sort of like we’ve been running this really long marathon, and we’re 100 yards from the finish line and we sit down and we give up,” Dr. Gounder told CNN on Sunday. ‘We’re almost there, we just need to give ourselves a bit more time to get a larger proportion of the population covered with vaccines.”

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

Another coronavirus surge may be on the way in the United States as daily COVID-19 cases continue to plateau around 60,000, states begin to lift restrictions, and people embark on spring break trips this week, according to CNN.

Outbreaks will likely stem from the B.1.1.7 variant, which was first identified in the United Kingdom, and gain momentum during the next 6-14 weeks.

“Four weeks ago, the B.1.1.7 variant made up about 1%-4% of the virus that we were seeing in communities across the country. Today it’s up to 30%-40%,” Michael Osterholm, PhD, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, Minneapolis, told NBC’s Meet the Press on March 7.

Dr. Osterholm compared the current situation with the “eye of the hurricane,” where the skies appear clear but more storms are on the way. Across Europe, 27 countries are seeing significant B.1.1.7 case increases, and 10 are getting hit hard, he said.

“What we’ve seen in Europe, when we hit that 50% mark, you see cases surge,” he said. “So right now, we do have to keep America as safe as we can from this virus by not letting up on any of the public health measures we’ve taken.”

In January, the CDC warned that B.1.1.7 variant cases would increase in 2021 and become the dominant variant in the country by this month. The United States has now reported more than 3,000 cases across 46 states, according to the latest CDC tally updated on March 7. More than 600 cases have been found in Florida, followed by more than 400 in Michigan.

The CDC has said the tally doesn’t represent the total number of B.1.1.7 cases in the United States, only the ones that have been identified by analyzing samples through genomic sequencing.

“Where it has hit in the U.K. and now elsewhere in Europe, it has been catastrophic,” Celine Gounder, MD, an infectious disease specialist with New York University Langone Health, told CNN on March 7.

The variant is more transmissible than the original novel coronavirus, and the cases in the United States are “increasing exponentially,” she said.

“It has driven up rates of hospitalizations and deaths and it’s very difficult to control,” Dr. Gounder said.

Vaccination numbers aren’t yet high enough to stop the predicted surge, she added. The United States has shipped more than 116 million vaccine doses, according to the latest CDC update on March 7. Nearly 59 million people have received at least one dose, and 30.6 million people have received two vaccine doses. About 9% of the U.S. population has been fully vaccinated.

States shouldn’t ease restrictions until the vaccination numbers are much higher and daily COVID-19 cases fall below 10,000 – and maybe “considerably less than that,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, told CNN on March 4.

Several states have already begun to lift COVID-19 safety protocols, with Texas and Mississippi removing mask mandates last week. Businesses in Texas will be able to reopen at full capacity on March 10. For now, public health officials are urging Americans to continue to wear masks, avoid crowds, and follow social distancing guidelines as vaccines roll out across the country.

“This is sort of like we’ve been running this really long marathon, and we’re 100 yards from the finish line and we sit down and we give up,” Dr. Gounder told CNN on Sunday. ‘We’re almost there, we just need to give ourselves a bit more time to get a larger proportion of the population covered with vaccines.”

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

Direct oral anticoagulants (DOACs) are used in about 1% of patients undergoing surgical mechanical aortic and mitral valve replacement, but in up to 6% of surgical bioprosthetic valve replacements, according to registry data presented at CRT 2021.

In an analysis of the Society of Thoracic Surgery (STS) registry during 2014-2017, DOAC use increased steadily among those undergoing surgical bioprosthetic valve replacement, reaching a number that is potentially clinically significant, according to Ankur Kalra, MD, an interventional cardiologist at Akron General Hospital who has an academic appointment at the Cleveland Clinic.

There was no increase in the use of DOACs observed among patients undergoing mechanical valve replacement, “but even if the number is 1%, they should probably not be used at all until we accrue more data,” Dr. Kalra said.
 

DOACs discouraged in patients with mechanical or bioprosthetic valves

In Food and Drug Administration labeling, DOACs are contraindicated or not recommended. This can be traced to the randomized RE-ALIGN trial, which was stopped prematurely due to evidence of harm from a DOAC, according to Dr. Kalra.

In RE-ALIGN, which enrolled patients undergoing mechanical aortic or mitral valve replacement, dabigatran was associated not only with more bleeding events than warfarin, but also more thromboembolic events.

There are no randomized data comparing the factor Xa inhibitors rivaroxaban or apixaban to warfarin in heart valve surgery, but Dr. Kalra noted cautionary language is found in the labeling of both, “perhaps due to the RE-ALIGN data.”
 

Registry shows trends in prescribing

In the STS registry data, 193 (1.1%) of the 18,142 patients undergoing mechanical aortic valve surgery, 139 (1.0%) of the 13,942 patients undergoing mechanical mitral valve surgery, 5,625 (4.7%) of the 116,203 patients undergoing aortic bioprosthetic aortic valve surgery, and 2,180 (5.9%) of the 39,243 patients undergoing bioprosthetic mitral valve surgery were on a DOAC at discharge.

Among those receiving a mechanical value and placed on a DOAC, about two-thirds were on a factor Xa inhibitor rather than dabigatran. For those receiving a bioprosthetic value, the proportion was greater than 80%. Dr. Kalra speculated that the RE-ALIGN trial might be the reason factor Xa inhibitors were favored.

In both types of valves, whether mechanical or bioprosthetic, more comorbidities predicted a greater likelihood of receiving a DOAC rather than warfarin. For those receiving mechanical values, the comorbidities with a significant association with greater DOAC use included hypertension (P = .003), dyslipidemia (P = .02), arrhythmia (P < .001), and peripheral arterial disease (P < 0.001).

The same factors were significant for predicting increased likelihood of a DOAC following bioprosthetic valve replacement, but there were additional factors, including atrial fibrillation independent of other types of arrhythmias (P < .001), a factor not significant for mechanical valves, as well as diabetes (P < .001), cerebrovascular disease (P < .001), dialysis (P < .001), and endocarditis (P < .001).

“This is probably intuitive, but patients who were on a factor Xa inhibitor before their valve replacement were also more likely to be discharged on a factor Xa inhibitor,” Dr. Kalra said at the virtual meeting, sponsored by MedStar Heart & Vascular Institute.

The year-to-year increase in DOAC use among those undergoing bioprosthetic valve replacement over the study period, which was a significant trend, was not observed among those undergoing mechanical valve replacement. Rather, the 1% proportion remained stable over the study period.

“We wanted to look at outcomes, but we found that the STS database, which only includes data out to 30 days, is not structured for this type of analysis,” Dr. Kalra said. He was also concerned about the limitations of a comparison in which 1% of the sample was being compared to 99%.
 

Expert: One percent is ‘very small number’

David J. Cohen, MD, commented on the 1% figure, which was so low that a moderator questioned whether it could be due mostly to coding errors.

“This is a very, very small number so at some level it is reassuring that it is so low in the mechanical valves,” Dr. Cohen said. However, he was more circumspect about the larger number in bioprosthetic valves.

“I have always thought it was a bit strange there was a warning against using them in bioprosthetic valves, especially in the aortic position,” he said.

Direct oral anticoagulants (DOACs) are used in about 1% of patients undergoing surgical mechanical aortic and mitral valve replacement, but in up to 6% of surgical bioprosthetic valve replacements, according to registry data presented at CRT 2021.

In an analysis of the Society of Thoracic Surgery (STS) registry during 2014-2017, DOAC use increased steadily among those undergoing surgical bioprosthetic valve replacement, reaching a number that is potentially clinically significant, according to Ankur Kalra, MD, an interventional cardiologist at Akron General Hospital who has an academic appointment at the Cleveland Clinic.

There was no increase in the use of DOACs observed among patients undergoing mechanical valve replacement, “but even if the number is 1%, they should probably not be used at all until we accrue more data,” Dr. Kalra said.
 

DOACs discouraged in patients with mechanical or bioprosthetic valves

In Food and Drug Administration labeling, DOACs are contraindicated or not recommended. This can be traced to the randomized RE-ALIGN trial, which was stopped prematurely due to evidence of harm from a DOAC, according to Dr. Kalra.

In RE-ALIGN, which enrolled patients undergoing mechanical aortic or mitral valve replacement, dabigatran was associated not only with more bleeding events than warfarin, but also more thromboembolic events.

There are no randomized data comparing the factor Xa inhibitors rivaroxaban or apixaban to warfarin in heart valve surgery, but Dr. Kalra noted cautionary language is found in the labeling of both, “perhaps due to the RE-ALIGN data.”
 

Registry shows trends in prescribing

In the STS registry data, 193 (1.1%) of the 18,142 patients undergoing mechanical aortic valve surgery, 139 (1.0%) of the 13,942 patients undergoing mechanical mitral valve surgery, 5,625 (4.7%) of the 116,203 patients undergoing aortic bioprosthetic aortic valve surgery, and 2,180 (5.9%) of the 39,243 patients undergoing bioprosthetic mitral valve surgery were on a DOAC at discharge.

Among those receiving a mechanical value and placed on a DOAC, about two-thirds were on a factor Xa inhibitor rather than dabigatran. For those receiving a bioprosthetic value, the proportion was greater than 80%. Dr. Kalra speculated that the RE-ALIGN trial might be the reason factor Xa inhibitors were favored.

In both types of valves, whether mechanical or bioprosthetic, more comorbidities predicted a greater likelihood of receiving a DOAC rather than warfarin. For those receiving mechanical values, the comorbidities with a significant association with greater DOAC use included hypertension (P = .003), dyslipidemia (P = .02), arrhythmia (P < .001), and peripheral arterial disease (P < 0.001).

The same factors were significant for predicting increased likelihood of a DOAC following bioprosthetic valve replacement, but there were additional factors, including atrial fibrillation independent of other types of arrhythmias (P < .001), a factor not significant for mechanical valves, as well as diabetes (P < .001), cerebrovascular disease (P < .001), dialysis (P < .001), and endocarditis (P < .001).

“This is probably intuitive, but patients who were on a factor Xa inhibitor before their valve replacement were also more likely to be discharged on a factor Xa inhibitor,” Dr. Kalra said at the virtual meeting, sponsored by MedStar Heart & Vascular Institute.

The year-to-year increase in DOAC use among those undergoing bioprosthetic valve replacement over the study period, which was a significant trend, was not observed among those undergoing mechanical valve replacement. Rather, the 1% proportion remained stable over the study period.

“We wanted to look at outcomes, but we found that the STS database, which only includes data out to 30 days, is not structured for this type of analysis,” Dr. Kalra said. He was also concerned about the limitations of a comparison in which 1% of the sample was being compared to 99%.
 

Expert: One percent is ‘very small number’

David J. Cohen, MD, commented on the 1% figure, which was so low that a moderator questioned whether it could be due mostly to coding errors.

“This is a very, very small number so at some level it is reassuring that it is so low in the mechanical valves,” Dr. Cohen said. However, he was more circumspect about the larger number in bioprosthetic valves.

“I have always thought it was a bit strange there was a warning against using them in bioprosthetic valves, especially in the aortic position,” he said.

Direct oral anticoagulants (DOACs) are used in about 1% of patients undergoing surgical mechanical aortic and mitral valve replacement, but in up to 6% of surgical bioprosthetic valve replacements, according to registry data presented at CRT 2021.

In an analysis of the Society of Thoracic Surgery (STS) registry during 2014-2017, DOAC use increased steadily among those undergoing surgical bioprosthetic valve replacement, reaching a number that is potentially clinically significant, according to Ankur Kalra, MD, an interventional cardiologist at Akron General Hospital who has an academic appointment at the Cleveland Clinic.

There was no increase in the use of DOACs observed among patients undergoing mechanical valve replacement, “but even if the number is 1%, they should probably not be used at all until we accrue more data,” Dr. Kalra said.
 

DOACs discouraged in patients with mechanical or bioprosthetic valves

In Food and Drug Administration labeling, DOACs are contraindicated or not recommended. This can be traced to the randomized RE-ALIGN trial, which was stopped prematurely due to evidence of harm from a DOAC, according to Dr. Kalra.

In RE-ALIGN, which enrolled patients undergoing mechanical aortic or mitral valve replacement, dabigatran was associated not only with more bleeding events than warfarin, but also more thromboembolic events.

There are no randomized data comparing the factor Xa inhibitors rivaroxaban or apixaban to warfarin in heart valve surgery, but Dr. Kalra noted cautionary language is found in the labeling of both, “perhaps due to the RE-ALIGN data.”
 

Registry shows trends in prescribing

In the STS registry data, 193 (1.1%) of the 18,142 patients undergoing mechanical aortic valve surgery, 139 (1.0%) of the 13,942 patients undergoing mechanical mitral valve surgery, 5,625 (4.7%) of the 116,203 patients undergoing aortic bioprosthetic aortic valve surgery, and 2,180 (5.9%) of the 39,243 patients undergoing bioprosthetic mitral valve surgery were on a DOAC at discharge.

Among those receiving a mechanical value and placed on a DOAC, about two-thirds were on a factor Xa inhibitor rather than dabigatran. For those receiving a bioprosthetic value, the proportion was greater than 80%. Dr. Kalra speculated that the RE-ALIGN trial might be the reason factor Xa inhibitors were favored.

In both types of valves, whether mechanical or bioprosthetic, more comorbidities predicted a greater likelihood of receiving a DOAC rather than warfarin. For those receiving mechanical values, the comorbidities with a significant association with greater DOAC use included hypertension (P = .003), dyslipidemia (P = .02), arrhythmia (P < .001), and peripheral arterial disease (P < 0.001).

The same factors were significant for predicting increased likelihood of a DOAC following bioprosthetic valve replacement, but there were additional factors, including atrial fibrillation independent of other types of arrhythmias (P < .001), a factor not significant for mechanical valves, as well as diabetes (P < .001), cerebrovascular disease (P < .001), dialysis (P < .001), and endocarditis (P < .001).

“This is probably intuitive, but patients who were on a factor Xa inhibitor before their valve replacement were also more likely to be discharged on a factor Xa inhibitor,” Dr. Kalra said at the virtual meeting, sponsored by MedStar Heart & Vascular Institute.

The year-to-year increase in DOAC use among those undergoing bioprosthetic valve replacement over the study period, which was a significant trend, was not observed among those undergoing mechanical valve replacement. Rather, the 1% proportion remained stable over the study period.

“We wanted to look at outcomes, but we found that the STS database, which only includes data out to 30 days, is not structured for this type of analysis,” Dr. Kalra said. He was also concerned about the limitations of a comparison in which 1% of the sample was being compared to 99%.
 

Expert: One percent is ‘very small number’

David J. Cohen, MD, commented on the 1% figure, which was so low that a moderator questioned whether it could be due mostly to coding errors.

“This is a very, very small number so at some level it is reassuring that it is so low in the mechanical valves,” Dr. Cohen said. However, he was more circumspect about the larger number in bioprosthetic valves.

“I have always thought it was a bit strange there was a warning against using them in bioprosthetic valves, especially in the aortic position,” he said.

A single pill of the investigational drug molnupiravir taken twice a day for 5 days eliminated SARS-CoV-2 from the nasopharynx of 49 participants.

That led Carlos del Rio, MD, distinguished professor of medicine at Emory University, Atlanta, to suggest a future in which a drug like molnupiravir could be taken in the first few days of symptoms to prevent severe disease, similar to Tamiflu for influenza.

“I think it’s critically important,” he said of the data. Emory University was involved in the trial of molnupiravir but Dr. del Rio was not part of that team. “This drug offers the first antiviral oral drug that then could be used in an outpatient setting.”

Still, Dr. del Rio said it’s too soon to call this particular drug the breakthrough clinicians need to keep people out of the ICU. “It has the potential to be practice changing; it’s not practice changing at the moment.”

Wendy Painter, MD, of Ridgeback Biotherapeutics, who presented the data at the Conference on Retroviruses and Opportunistic Infections, agreed. While the data are promising, “We will need to see if people get better from actual illness” to assess the real value of the drug in clinical care.

“That’s a phase 3 objective we’ll need to prove,” she said in an interview.

Phase 2/3 efficacy and safety studies of the drug are now underway in hospitalized and nonhospitalized patients.

In a brief prerecorded presentation of the data, Dr. Painter laid out what researchers know so far: Preclinical studies suggest that molnupiravir is effective against a number of viruses, including coronaviruses and specifically SARS-CoV-2. It prevents a virus from replicating by inducing viral error catastrophe (Proc Natl Acad Sci U S A. 2002 Oct 15;99[21]:13374-6) – essentially overloading the virus with replication and mutation until the virus burns itself out and can’t produce replicable copies.

In this phase 2a, randomized, double-blind, controlled trial, researchers recruited 202 adults who were treated at an outpatient clinic with fever or other symptoms of a respiratory virus and confirmed SARS-CoV-2 infection by day 4. Participants were randomly assigned to three different groups: 200 mg of molnupiravir, 400 mg, or 800 mg. The 200-mg arm was matched 1:1 with a placebo-controlled group, and the other two groups had three participants in the active group for every one control.

Participants took the pills twice daily for 5 days, and then were followed for a total of 28 days to monitor for complications or adverse events. At days 3, 5, 7, 14, and 28, researchers also took nasopharyngeal swabs for polymerase chain reaction tests, to sequence the virus, and to grow cultures of SARS-CoV-2 to see if the virus that’s present is actually capable of infecting others.

Notably, the pills do not have to be refrigerated at any point in the process, alleviating the cold-chain challenges that have plagued vaccines.

“There’s an urgent need for an easily produced, transported, stored, and administered antiviral drug against SARS-CoV-2,” Dr. Painter said.

Of the 202 people recruited, 182 had swabs that could be evaluated, of which 78 showed infection at baseline. The results are based on labs of those 78 participants.

By day 3, 28% of patients in the placebo arm had SARS-CoV-2 in their nasopharynx, compared with 20.4% of patients receiving any dose of molnupiravir. But by day 5, none of the participants receiving the active drug had evidence of SARS-CoV-2 in their nasopharynx. In comparison, 24% of people in the placebo arm still had detectable virus.

Halfway through the treatment course, differences in the presence of infectious virus were already evident. By day 3 of the 5-day course, 36.4% of participants in the 200-mg group had detectable virus in the nasopharynx, compared with 21% in the 400-mg group and just 12.5% in the 800-mg group. And although the reduction in SARS-CoV-2 was noticeable in the 200-mg and the 400-mg arms, it was only statistically significant in the 800-mg arm.

In contrast, by the end of the 5 days in the placebo groups, infectious virus varied from 18.2% in the 200-mg placebo group to 30% in the 800-mg group. This points out the variability of the disease course of SARS-CoV-2.

“You just don’t know” which infections will lead to serious disease, Dr. Painter said in an interview. “And don’t you wish we did?”

Seven participants discontinued treatment, though only four experienced adverse events. Three of those discontinued the trial because of adverse events. The study is still blinded, so it’s unclear what those events were, but Dr. Painter said that they were not thought to be related to the study drug.

The bottom line, said Dr. Painter, was that people treated with molnupiravir had starkly different outcomes in lab measures during the study.

“An average of 10 days after symptom onset, 24% of placebo patients remained culture positive” for SARS-CoV-2 – meaning there wasn’t just virus in the nasopharynx, but it was capable of replicating, Dr. Painter said. “In contrast, no infectious virus could be recovered at study day 5 in any molnupiravir-treated patients.”

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

A single pill of the investigational drug molnupiravir taken twice a day for 5 days eliminated SARS-CoV-2 from the nasopharynx of 49 participants.

That led Carlos del Rio, MD, distinguished professor of medicine at Emory University, Atlanta, to suggest a future in which a drug like molnupiravir could be taken in the first few days of symptoms to prevent severe disease, similar to Tamiflu for influenza.

“I think it’s critically important,” he said of the data. Emory University was involved in the trial of molnupiravir but Dr. del Rio was not part of that team. “This drug offers the first antiviral oral drug that then could be used in an outpatient setting.”

Still, Dr. del Rio said it’s too soon to call this particular drug the breakthrough clinicians need to keep people out of the ICU. “It has the potential to be practice changing; it’s not practice changing at the moment.”

Wendy Painter, MD, of Ridgeback Biotherapeutics, who presented the data at the Conference on Retroviruses and Opportunistic Infections, agreed. While the data are promising, “We will need to see if people get better from actual illness” to assess the real value of the drug in clinical care.

“That’s a phase 3 objective we’ll need to prove,” she said in an interview.

Phase 2/3 efficacy and safety studies of the drug are now underway in hospitalized and nonhospitalized patients.

In a brief prerecorded presentation of the data, Dr. Painter laid out what researchers know so far: Preclinical studies suggest that molnupiravir is effective against a number of viruses, including coronaviruses and specifically SARS-CoV-2. It prevents a virus from replicating by inducing viral error catastrophe (Proc Natl Acad Sci U S A. 2002 Oct 15;99[21]:13374-6) – essentially overloading the virus with replication and mutation until the virus burns itself out and can’t produce replicable copies.

In this phase 2a, randomized, double-blind, controlled trial, researchers recruited 202 adults who were treated at an outpatient clinic with fever or other symptoms of a respiratory virus and confirmed SARS-CoV-2 infection by day 4. Participants were randomly assigned to three different groups: 200 mg of molnupiravir, 400 mg, or 800 mg. The 200-mg arm was matched 1:1 with a placebo-controlled group, and the other two groups had three participants in the active group for every one control.

Participants took the pills twice daily for 5 days, and then were followed for a total of 28 days to monitor for complications or adverse events. At days 3, 5, 7, 14, and 28, researchers also took nasopharyngeal swabs for polymerase chain reaction tests, to sequence the virus, and to grow cultures of SARS-CoV-2 to see if the virus that’s present is actually capable of infecting others.

Notably, the pills do not have to be refrigerated at any point in the process, alleviating the cold-chain challenges that have plagued vaccines.

“There’s an urgent need for an easily produced, transported, stored, and administered antiviral drug against SARS-CoV-2,” Dr. Painter said.

Of the 202 people recruited, 182 had swabs that could be evaluated, of which 78 showed infection at baseline. The results are based on labs of those 78 participants.

By day 3, 28% of patients in the placebo arm had SARS-CoV-2 in their nasopharynx, compared with 20.4% of patients receiving any dose of molnupiravir. But by day 5, none of the participants receiving the active drug had evidence of SARS-CoV-2 in their nasopharynx. In comparison, 24% of people in the placebo arm still had detectable virus.

Halfway through the treatment course, differences in the presence of infectious virus were already evident. By day 3 of the 5-day course, 36.4% of participants in the 200-mg group had detectable virus in the nasopharynx, compared with 21% in the 400-mg group and just 12.5% in the 800-mg group. And although the reduction in SARS-CoV-2 was noticeable in the 200-mg and the 400-mg arms, it was only statistically significant in the 800-mg arm.

In contrast, by the end of the 5 days in the placebo groups, infectious virus varied from 18.2% in the 200-mg placebo group to 30% in the 800-mg group. This points out the variability of the disease course of SARS-CoV-2.

“You just don’t know” which infections will lead to serious disease, Dr. Painter said in an interview. “And don’t you wish we did?”

Seven participants discontinued treatment, though only four experienced adverse events. Three of those discontinued the trial because of adverse events. The study is still blinded, so it’s unclear what those events were, but Dr. Painter said that they were not thought to be related to the study drug.

The bottom line, said Dr. Painter, was that people treated with molnupiravir had starkly different outcomes in lab measures during the study.

“An average of 10 days after symptom onset, 24% of placebo patients remained culture positive” for SARS-CoV-2 – meaning there wasn’t just virus in the nasopharynx, but it was capable of replicating, Dr. Painter said. “In contrast, no infectious virus could be recovered at study day 5 in any molnupiravir-treated patients.”

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

A single pill of the investigational drug molnupiravir taken twice a day for 5 days eliminated SARS-CoV-2 from the nasopharynx of 49 participants.

That led Carlos del Rio, MD, distinguished professor of medicine at Emory University, Atlanta, to suggest a future in which a drug like molnupiravir could be taken in the first few days of symptoms to prevent severe disease, similar to Tamiflu for influenza.

“I think it’s critically important,” he said of the data. Emory University was involved in the trial of molnupiravir but Dr. del Rio was not part of that team. “This drug offers the first antiviral oral drug that then could be used in an outpatient setting.”

Still, Dr. del Rio said it’s too soon to call this particular drug the breakthrough clinicians need to keep people out of the ICU. “It has the potential to be practice changing; it’s not practice changing at the moment.”

Wendy Painter, MD, of Ridgeback Biotherapeutics, who presented the data at the Conference on Retroviruses and Opportunistic Infections, agreed. While the data are promising, “We will need to see if people get better from actual illness” to assess the real value of the drug in clinical care.

“That’s a phase 3 objective we’ll need to prove,” she said in an interview.

Phase 2/3 efficacy and safety studies of the drug are now underway in hospitalized and nonhospitalized patients.

In a brief prerecorded presentation of the data, Dr. Painter laid out what researchers know so far: Preclinical studies suggest that molnupiravir is effective against a number of viruses, including coronaviruses and specifically SARS-CoV-2. It prevents a virus from replicating by inducing viral error catastrophe (Proc Natl Acad Sci U S A. 2002 Oct 15;99[21]:13374-6) – essentially overloading the virus with replication and mutation until the virus burns itself out and can’t produce replicable copies.

In this phase 2a, randomized, double-blind, controlled trial, researchers recruited 202 adults who were treated at an outpatient clinic with fever or other symptoms of a respiratory virus and confirmed SARS-CoV-2 infection by day 4. Participants were randomly assigned to three different groups: 200 mg of molnupiravir, 400 mg, or 800 mg. The 200-mg arm was matched 1:1 with a placebo-controlled group, and the other two groups had three participants in the active group for every one control.

Participants took the pills twice daily for 5 days, and then were followed for a total of 28 days to monitor for complications or adverse events. At days 3, 5, 7, 14, and 28, researchers also took nasopharyngeal swabs for polymerase chain reaction tests, to sequence the virus, and to grow cultures of SARS-CoV-2 to see if the virus that’s present is actually capable of infecting others.

Notably, the pills do not have to be refrigerated at any point in the process, alleviating the cold-chain challenges that have plagued vaccines.

“There’s an urgent need for an easily produced, transported, stored, and administered antiviral drug against SARS-CoV-2,” Dr. Painter said.

Of the 202 people recruited, 182 had swabs that could be evaluated, of which 78 showed infection at baseline. The results are based on labs of those 78 participants.

By day 3, 28% of patients in the placebo arm had SARS-CoV-2 in their nasopharynx, compared with 20.4% of patients receiving any dose of molnupiravir. But by day 5, none of the participants receiving the active drug had evidence of SARS-CoV-2 in their nasopharynx. In comparison, 24% of people in the placebo arm still had detectable virus.

Halfway through the treatment course, differences in the presence of infectious virus were already evident. By day 3 of the 5-day course, 36.4% of participants in the 200-mg group had detectable virus in the nasopharynx, compared with 21% in the 400-mg group and just 12.5% in the 800-mg group. And although the reduction in SARS-CoV-2 was noticeable in the 200-mg and the 400-mg arms, it was only statistically significant in the 800-mg arm.

In contrast, by the end of the 5 days in the placebo groups, infectious virus varied from 18.2% in the 200-mg placebo group to 30% in the 800-mg group. This points out the variability of the disease course of SARS-CoV-2.

“You just don’t know” which infections will lead to serious disease, Dr. Painter said in an interview. “And don’t you wish we did?”

Seven participants discontinued treatment, though only four experienced adverse events. Three of those discontinued the trial because of adverse events. The study is still blinded, so it’s unclear what those events were, but Dr. Painter said that they were not thought to be related to the study drug.

The bottom line, said Dr. Painter, was that people treated with molnupiravir had starkly different outcomes in lab measures during the study.

“An average of 10 days after symptom onset, 24% of placebo patients remained culture positive” for SARS-CoV-2 – meaning there wasn’t just virus in the nasopharynx, but it was capable of replicating, Dr. Painter said. “In contrast, no infectious virus could be recovered at study day 5 in any molnupiravir-treated patients.”

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

People who are fully vaccinated against COVID-19 can safely gather unmasked and inside with nonvulnerable people who are not yet immunized, according to long-awaited guidance released by the CDC.

“Today’s action represents an important first step. It is not our final destination,” CDC Director Rochelle Walensky, MD, said March 8 at a White House briefing. “As more people get vaccinated, levels of COVID-19 infection decline in communities, and as our understanding of COVID immunity improves, we look forward to updating these recommendations to the public.”

According to the new guidance, people who are at least 2 weeks out from their last dose can:

• Visit with other fully vaccinated people indoors without wearing masks or physical distancing.
• Visit with unvaccinated people from a single household who are at low risk for severe COVID-19 disease indoors without wearing masks or physical distancing
• Avoid quarantine and testing following exposure to someone if they remain asymptomatic.

However, there are still restrictions that will remain until further data are collected. Those who are fully vaccinated must still:

• Wear masks and physically distance in public settings and around people at high risk for severe disease.
• Wear masks and physically distance when visiting unvaccinated people from more than one household.
• Avoid medium- and large-sized gatherings.
• Avoid travel.

People considered at high risk for severe disease include older adults and those with cancer, chronic kidney disease, COPD, Down syndrome, heart disease, heart failure, a weakened immune system, obesity, sickle cell disease, and type 2 diabetes. The category also includes pregnant women and smokers.

“In public spaces, fully vaccinated people should continue to follow guidance to protect themselves and others, including wearing a well-fitted mask, physical distancing (at least 6 feet), avoiding crowds, avoiding poorly ventilated spaces, covering coughs and sneezes, washing hands often, and following any applicable workplace or school guidance,” the guidance says. “Fully vaccinated people should still watch for symptoms of COVID-19, especially following an exposure to someone with suspected or confirmed COVID-19.”

Respecting travel restrictions is still crucial, Dr. Walensky said, given past surges and variants that have emerged after periods of increased travel.

"We would like to give the opportunity for vaccinated grandparents to visit children and grandchildren who are healthy and local,” Dr. Walensky said.

But, she said, “It’s important to realize as we’re working through this that over 90% of the population is not yet vaccinated.”

For now, there are not enough data on transmission rates from those who are vaccinated to the rest of the public. However, Anthony Fauci, MD, said at a briefing last month that preliminary data are “pointing in a very favorable direction.”

Studies from Spain and Israel published last month showed the amount of viral load – or the amount of the COVID-19 virus in someone’s body – is significantly lower if someone gets infected after they’ve been vaccinated, compared with people who get infected and didn’t have the vaccine. Lower viral load means much lower chances of passing the virus to someone else, Dr. Fauci said.

“The science of COVID-19 is complex,” Dr. Walensky said, “and our understanding of it continues to evolve.”

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

People who are fully vaccinated against COVID-19 can safely gather unmasked and inside with nonvulnerable people who are not yet immunized, according to long-awaited guidance released by the CDC.

“Today’s action represents an important first step. It is not our final destination,” CDC Director Rochelle Walensky, MD, said March 8 at a White House briefing. “As more people get vaccinated, levels of COVID-19 infection decline in communities, and as our understanding of COVID immunity improves, we look forward to updating these recommendations to the public.”

According to the new guidance, people who are at least 2 weeks out from their last dose can:

• Visit with other fully vaccinated people indoors without wearing masks or physical distancing.
• Visit with unvaccinated people from a single household who are at low risk for severe COVID-19 disease indoors without wearing masks or physical distancing
• Avoid quarantine and testing following exposure to someone if they remain asymptomatic.

However, there are still restrictions that will remain until further data are collected. Those who are fully vaccinated must still:

• Wear masks and physically distance in public settings and around people at high risk for severe disease.
• Wear masks and physically distance when visiting unvaccinated people from more than one household.
• Avoid medium- and large-sized gatherings.
• Avoid travel.

People considered at high risk for severe disease include older adults and those with cancer, chronic kidney disease, COPD, Down syndrome, heart disease, heart failure, a weakened immune system, obesity, sickle cell disease, and type 2 diabetes. The category also includes pregnant women and smokers.

“In public spaces, fully vaccinated people should continue to follow guidance to protect themselves and others, including wearing a well-fitted mask, physical distancing (at least 6 feet), avoiding crowds, avoiding poorly ventilated spaces, covering coughs and sneezes, washing hands often, and following any applicable workplace or school guidance,” the guidance says. “Fully vaccinated people should still watch for symptoms of COVID-19, especially following an exposure to someone with suspected or confirmed COVID-19.”

Respecting travel restrictions is still crucial, Dr. Walensky said, given past surges and variants that have emerged after periods of increased travel.

"We would like to give the opportunity for vaccinated grandparents to visit children and grandchildren who are healthy and local,” Dr. Walensky said.

But, she said, “It’s important to realize as we’re working through this that over 90% of the population is not yet vaccinated.”

For now, there are not enough data on transmission rates from those who are vaccinated to the rest of the public. However, Anthony Fauci, MD, said at a briefing last month that preliminary data are “pointing in a very favorable direction.”

Studies from Spain and Israel published last month showed the amount of viral load – or the amount of the COVID-19 virus in someone’s body – is significantly lower if someone gets infected after they’ve been vaccinated, compared with people who get infected and didn’t have the vaccine. Lower viral load means much lower chances of passing the virus to someone else, Dr. Fauci said.

“The science of COVID-19 is complex,” Dr. Walensky said, “and our understanding of it continues to evolve.”

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

People who are fully vaccinated against COVID-19 can safely gather unmasked and inside with nonvulnerable people who are not yet immunized, according to long-awaited guidance released by the CDC.

“Today’s action represents an important first step. It is not our final destination,” CDC Director Rochelle Walensky, MD, said March 8 at a White House briefing. “As more people get vaccinated, levels of COVID-19 infection decline in communities, and as our understanding of COVID immunity improves, we look forward to updating these recommendations to the public.”

According to the new guidance, people who are at least 2 weeks out from their last dose can:

• Visit with other fully vaccinated people indoors without wearing masks or physical distancing.
• Visit with unvaccinated people from a single household who are at low risk for severe COVID-19 disease indoors without wearing masks or physical distancing
• Avoid quarantine and testing following exposure to someone if they remain asymptomatic.

However, there are still restrictions that will remain until further data are collected. Those who are fully vaccinated must still:

• Wear masks and physically distance in public settings and around people at high risk for severe disease.
• Wear masks and physically distance when visiting unvaccinated people from more than one household.
• Avoid medium- and large-sized gatherings.
• Avoid travel.

People considered at high risk for severe disease include older adults and those with cancer, chronic kidney disease, COPD, Down syndrome, heart disease, heart failure, a weakened immune system, obesity, sickle cell disease, and type 2 diabetes. The category also includes pregnant women and smokers.

“In public spaces, fully vaccinated people should continue to follow guidance to protect themselves and others, including wearing a well-fitted mask, physical distancing (at least 6 feet), avoiding crowds, avoiding poorly ventilated spaces, covering coughs and sneezes, washing hands often, and following any applicable workplace or school guidance,” the guidance says. “Fully vaccinated people should still watch for symptoms of COVID-19, especially following an exposure to someone with suspected or confirmed COVID-19.”

Respecting travel restrictions is still crucial, Dr. Walensky said, given past surges and variants that have emerged after periods of increased travel.

"We would like to give the opportunity for vaccinated grandparents to visit children and grandchildren who are healthy and local,” Dr. Walensky said.

But, she said, “It’s important to realize as we’re working through this that over 90% of the population is not yet vaccinated.”

For now, there are not enough data on transmission rates from those who are vaccinated to the rest of the public. However, Anthony Fauci, MD, said at a briefing last month that preliminary data are “pointing in a very favorable direction.”

Studies from Spain and Israel published last month showed the amount of viral load – or the amount of the COVID-19 virus in someone’s body – is significantly lower if someone gets infected after they’ve been vaccinated, compared with people who get infected and didn’t have the vaccine. Lower viral load means much lower chances of passing the virus to someone else, Dr. Fauci said.

“The science of COVID-19 is complex,” Dr. Walensky said, “and our understanding of it continues to evolve.”

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

The development and worsening of overlapping asthma and chronic obstructive pulmonary disease (COPD) can be affected by pollutants found in rural and urban environments, according to a recent presentation at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year.

“Urban-rural-occupational air pollutants or respiratory sensitizers impact asthma and the asthma-COPD overlap features,” Jill A. Poole, MD, division chief of allergy and immunology at the University of Nebraska Medical Center, Omaha, said in her presentation.

The Global Initiative for Asthma (GINA) first outlined a syndrome in 2015 described as “persistent airflow limitation with several features usually associated with asthma and several features usually associated with COPD” and called asthma-COPD overlap syndrome. In 2017, a joint American Thoracic Society/National Heart, Lung, and Blood Institute workshop outlined knowledge gaps about asthma-COPD overlap, noting it “does not represent a single discrete disease entity.”

“This is not a single disease and should be thought of as being heterogeneous and used as a descriptive label for patients commonly seen in clinical practice,” Dr. Poole said. “Both asthma and COPD definitions are not mutually exclusive because each disease includes several phenotypes with different underlining mechanisms.” An example of how asthma-COPD overlap might present is through a patient with allergic asthma who has a history of smoking who develops airflow obstruction that isn’t fully reversible, or a patient with COPD “with high reversible airflow, obstruction, type 2 inflammation, and perhaps the presence of peripheral blood eosinophils or sputum eosinophils.”

A patient’s interaction with urban, rural, and occupational environments may additionally impact their disease, Dr. Poole explained. “The environmental factors of an urban versus rural environment may not be necessarily mutually exclusive,” she said. “It’s also important to recognize occupational exposures that can be both seen in an urban or rural environment [can] contribute to asthma-COPD overlap.”

In a study of 6,040 men and women with asthma living in Canada, 630 (10.4%) had asthma-COPD overlap, with increased air pollution raising the likelihood of developing asthma-COPD overlap (odds ratio, 2.78; 95% confidence interval, 1.62-4.78). These people experienced later onset asthma, increased emergency department visits before a diagnosis of COPD, and increased mortality. Another study in Canada of women from Ontario in the Breast Cancer Screening Study found 1,705 of 4,051 women with asthma also had COPD. While air pollution did not increase the risk of developing asthma-COPD overlap, there was an association between body mass index, low level of education, living in a rural area, and smoking status.

Among farmers in rural areas, “it has been recognized that there is something called the asthma-like syndrome that’s been reported in adult farming communities,” Dr. Poole said, which includes “some degree of airflow obstruction and reversibility” that can be worsened by smoking and could be an overlap of asthma and COPD. Farmers can also experience asthma exacerbations while working, and “livestock farmers appear more at risk of developing [chronic bronchitis and/or COPD] than do the crop farmers,” she noted.

Occupational environments outside of agriculture exposure can cause incident asthma, with high-molecular-weight antigens such as flour cereal, animal dander, latex, psyllium, crab processing products, and enzymes as well as low-molecular-weight antigens such as isocyanates, woods, antibiotics, glues, epoxies colophony products, and dyes presenting a risk. In food processing, main allergen sources can include raw and processed animal and plant products, additives and preservatives, contaminants from microbes or insects, inhaled dust particles or aerosols, which can be “IgE mediated, mixed IgE-mediated and non-lgE mediated.”

While some studies have been conducted on the prevalence of work-related asthma and asthma-COPD overlap, “in general, the prevalence and clinical features have been scarcely investigated,” Dr. Poole said. One survey of 23,137 patients found 52.9% of adults with work-related asthma also had COPD, compared with 25.6% of participants whose asthma was not work related.

To prevent asthma-COPD overlap, Dr. Poole recommended tobacco cessation, reducing indoor biomass fuel use, medical surveillance programs such as preplacement questionnaires, and considering “reducing exposure to the respiratory sensitizers with ideally monitoring the levels to keep the levels below the permissible limits.”

Dr. Poole noted there is currently no unique treatment for asthma-COPD overlap, but it is “important to fully characterize and phenotype your individual patients, looking for eosinophilia or seeing if they have more neutrophil features and whether or not the allergy features are prevalent and can be treated,” she said. “[A]wareness is really required such that counseling is encouraged for prevention and or interventional strategies as we move forward.”

For patients with features of both asthma and COPD where there is a high likelihood of asthma, treat the disease as if it were asthma, Dr. Poole said, but clinicians should follow GINA GOLD COPD treatment recommendations, adding on long-acting beta-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) when needed, but avoiding LABAs and/or LAMAs without use of inhaled corticosteroids, and avoiding oral corticosteroids entirely. Clinicians should be reviewing the treatments of patients with asthma and COPD features “every 2-3 months to see how their response is to it, and what additional therapies could be used,” she said.

Dr. Poole reports receiving grant support from National Institute of Environmental Health Sciences, National Institute for Occupational Safety and Health, and the Central States Center for Agricultural Safety and Health at the University of Nebraska Medical Center.

The development and worsening of overlapping asthma and chronic obstructive pulmonary disease (COPD) can be affected by pollutants found in rural and urban environments, according to a recent presentation at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year.

“Urban-rural-occupational air pollutants or respiratory sensitizers impact asthma and the asthma-COPD overlap features,” Jill A. Poole, MD, division chief of allergy and immunology at the University of Nebraska Medical Center, Omaha, said in her presentation.

The Global Initiative for Asthma (GINA) first outlined a syndrome in 2015 described as “persistent airflow limitation with several features usually associated with asthma and several features usually associated with COPD” and called asthma-COPD overlap syndrome. In 2017, a joint American Thoracic Society/National Heart, Lung, and Blood Institute workshop outlined knowledge gaps about asthma-COPD overlap, noting it “does not represent a single discrete disease entity.”

“This is not a single disease and should be thought of as being heterogeneous and used as a descriptive label for patients commonly seen in clinical practice,” Dr. Poole said. “Both asthma and COPD definitions are not mutually exclusive because each disease includes several phenotypes with different underlining mechanisms.” An example of how asthma-COPD overlap might present is through a patient with allergic asthma who has a history of smoking who develops airflow obstruction that isn’t fully reversible, or a patient with COPD “with high reversible airflow, obstruction, type 2 inflammation, and perhaps the presence of peripheral blood eosinophils or sputum eosinophils.”

A patient’s interaction with urban, rural, and occupational environments may additionally impact their disease, Dr. Poole explained. “The environmental factors of an urban versus rural environment may not be necessarily mutually exclusive,” she said. “It’s also important to recognize occupational exposures that can be both seen in an urban or rural environment [can] contribute to asthma-COPD overlap.”

In a study of 6,040 men and women with asthma living in Canada, 630 (10.4%) had asthma-COPD overlap, with increased air pollution raising the likelihood of developing asthma-COPD overlap (odds ratio, 2.78; 95% confidence interval, 1.62-4.78). These people experienced later onset asthma, increased emergency department visits before a diagnosis of COPD, and increased mortality. Another study in Canada of women from Ontario in the Breast Cancer Screening Study found 1,705 of 4,051 women with asthma also had COPD. While air pollution did not increase the risk of developing asthma-COPD overlap, there was an association between body mass index, low level of education, living in a rural area, and smoking status.

Among farmers in rural areas, “it has been recognized that there is something called the asthma-like syndrome that’s been reported in adult farming communities,” Dr. Poole said, which includes “some degree of airflow obstruction and reversibility” that can be worsened by smoking and could be an overlap of asthma and COPD. Farmers can also experience asthma exacerbations while working, and “livestock farmers appear more at risk of developing [chronic bronchitis and/or COPD] than do the crop farmers,” she noted.

Occupational environments outside of agriculture exposure can cause incident asthma, with high-molecular-weight antigens such as flour cereal, animal dander, latex, psyllium, crab processing products, and enzymes as well as low-molecular-weight antigens such as isocyanates, woods, antibiotics, glues, epoxies colophony products, and dyes presenting a risk. In food processing, main allergen sources can include raw and processed animal and plant products, additives and preservatives, contaminants from microbes or insects, inhaled dust particles or aerosols, which can be “IgE mediated, mixed IgE-mediated and non-lgE mediated.”

While some studies have been conducted on the prevalence of work-related asthma and asthma-COPD overlap, “in general, the prevalence and clinical features have been scarcely investigated,” Dr. Poole said. One survey of 23,137 patients found 52.9% of adults with work-related asthma also had COPD, compared with 25.6% of participants whose asthma was not work related.

To prevent asthma-COPD overlap, Dr. Poole recommended tobacco cessation, reducing indoor biomass fuel use, medical surveillance programs such as preplacement questionnaires, and considering “reducing exposure to the respiratory sensitizers with ideally monitoring the levels to keep the levels below the permissible limits.”

Dr. Poole noted there is currently no unique treatment for asthma-COPD overlap, but it is “important to fully characterize and phenotype your individual patients, looking for eosinophilia or seeing if they have more neutrophil features and whether or not the allergy features are prevalent and can be treated,” she said. “[A]wareness is really required such that counseling is encouraged for prevention and or interventional strategies as we move forward.”

For patients with features of both asthma and COPD where there is a high likelihood of asthma, treat the disease as if it were asthma, Dr. Poole said, but clinicians should follow GINA GOLD COPD treatment recommendations, adding on long-acting beta-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) when needed, but avoiding LABAs and/or LAMAs without use of inhaled corticosteroids, and avoiding oral corticosteroids entirely. Clinicians should be reviewing the treatments of patients with asthma and COPD features “every 2-3 months to see how their response is to it, and what additional therapies could be used,” she said.

Dr. Poole reports receiving grant support from National Institute of Environmental Health Sciences, National Institute for Occupational Safety and Health, and the Central States Center for Agricultural Safety and Health at the University of Nebraska Medical Center.

The development and worsening of overlapping asthma and chronic obstructive pulmonary disease (COPD) can be affected by pollutants found in rural and urban environments, according to a recent presentation at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year.

“Urban-rural-occupational air pollutants or respiratory sensitizers impact asthma and the asthma-COPD overlap features,” Jill A. Poole, MD, division chief of allergy and immunology at the University of Nebraska Medical Center, Omaha, said in her presentation.

The Global Initiative for Asthma (GINA) first outlined a syndrome in 2015 described as “persistent airflow limitation with several features usually associated with asthma and several features usually associated with COPD” and called asthma-COPD overlap syndrome. In 2017, a joint American Thoracic Society/National Heart, Lung, and Blood Institute workshop outlined knowledge gaps about asthma-COPD overlap, noting it “does not represent a single discrete disease entity.”

“This is not a single disease and should be thought of as being heterogeneous and used as a descriptive label for patients commonly seen in clinical practice,” Dr. Poole said. “Both asthma and COPD definitions are not mutually exclusive because each disease includes several phenotypes with different underlining mechanisms.” An example of how asthma-COPD overlap might present is through a patient with allergic asthma who has a history of smoking who develops airflow obstruction that isn’t fully reversible, or a patient with COPD “with high reversible airflow, obstruction, type 2 inflammation, and perhaps the presence of peripheral blood eosinophils or sputum eosinophils.”

A patient’s interaction with urban, rural, and occupational environments may additionally impact their disease, Dr. Poole explained. “The environmental factors of an urban versus rural environment may not be necessarily mutually exclusive,” she said. “It’s also important to recognize occupational exposures that can be both seen in an urban or rural environment [can] contribute to asthma-COPD overlap.”

In a study of 6,040 men and women with asthma living in Canada, 630 (10.4%) had asthma-COPD overlap, with increased air pollution raising the likelihood of developing asthma-COPD overlap (odds ratio, 2.78; 95% confidence interval, 1.62-4.78). These people experienced later onset asthma, increased emergency department visits before a diagnosis of COPD, and increased mortality. Another study in Canada of women from Ontario in the Breast Cancer Screening Study found 1,705 of 4,051 women with asthma also had COPD. While air pollution did not increase the risk of developing asthma-COPD overlap, there was an association between body mass index, low level of education, living in a rural area, and smoking status.

Among farmers in rural areas, “it has been recognized that there is something called the asthma-like syndrome that’s been reported in adult farming communities,” Dr. Poole said, which includes “some degree of airflow obstruction and reversibility” that can be worsened by smoking and could be an overlap of asthma and COPD. Farmers can also experience asthma exacerbations while working, and “livestock farmers appear more at risk of developing [chronic bronchitis and/or COPD] than do the crop farmers,” she noted.

Occupational environments outside of agriculture exposure can cause incident asthma, with high-molecular-weight antigens such as flour cereal, animal dander, latex, psyllium, crab processing products, and enzymes as well as low-molecular-weight antigens such as isocyanates, woods, antibiotics, glues, epoxies colophony products, and dyes presenting a risk. In food processing, main allergen sources can include raw and processed animal and plant products, additives and preservatives, contaminants from microbes or insects, inhaled dust particles or aerosols, which can be “IgE mediated, mixed IgE-mediated and non-lgE mediated.”

While some studies have been conducted on the prevalence of work-related asthma and asthma-COPD overlap, “in general, the prevalence and clinical features have been scarcely investigated,” Dr. Poole said. One survey of 23,137 patients found 52.9% of adults with work-related asthma also had COPD, compared with 25.6% of participants whose asthma was not work related.

To prevent asthma-COPD overlap, Dr. Poole recommended tobacco cessation, reducing indoor biomass fuel use, medical surveillance programs such as preplacement questionnaires, and considering “reducing exposure to the respiratory sensitizers with ideally monitoring the levels to keep the levels below the permissible limits.”

Dr. Poole noted there is currently no unique treatment for asthma-COPD overlap, but it is “important to fully characterize and phenotype your individual patients, looking for eosinophilia or seeing if they have more neutrophil features and whether or not the allergy features are prevalent and can be treated,” she said. “[A]wareness is really required such that counseling is encouraged for prevention and or interventional strategies as we move forward.”

For patients with features of both asthma and COPD where there is a high likelihood of asthma, treat the disease as if it were asthma, Dr. Poole said, but clinicians should follow GINA GOLD COPD treatment recommendations, adding on long-acting beta-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) when needed, but avoiding LABAs and/or LAMAs without use of inhaled corticosteroids, and avoiding oral corticosteroids entirely. Clinicians should be reviewing the treatments of patients with asthma and COPD features “every 2-3 months to see how their response is to it, and what additional therapies could be used,” she said.

Dr. Poole reports receiving grant support from National Institute of Environmental Health Sciences, National Institute for Occupational Safety and Health, and the Central States Center for Agricultural Safety and Health at the University of Nebraska Medical Center.

On the advice of its independent data monitoring committee (DMC), the RECOVERY trial has stopped recruitment to the colchicine arm for lack of efficacy in patients hospitalized with COVID-19.

“The DMC saw no convincing evidence that further recruitment would provide conclusive proof of worthwhile mortality benefit either overall or in any prespecified subgroup,” the British investigators announced on March 5.

“The RECOVERY trial has already identified two anti-inflammatory drugs – dexamethasone and tocilizumab – that improve the chances of survival for patients with severe COVID-19. So, it is disappointing that colchicine, which is widely used to treat gout and other inflammatory conditions, has no effect in these patients,” cochief investigator Martin Landray, MBChB, PhD, said in a statement.

“We do large, randomized trials to establish whether a drug that seems promising in theory has real benefits for patients in practice. Unfortunately, colchicine is not one of those,” said Dr. Landry, University of Oxford (England).

The RECOVERY trial is evaluating a range of potential treatments for COVID-19 at 180 hospitals in the United Kingdom, Indonesia, and Nepal, and was designed with the expectation that drugs would be added or dropped as the evidence changes. Since November 2020, the trial has included an arm comparing colchicine with usual care alone.

As part of a routine meeting March 4, the DMC reviewed data from a preliminary analysis based on 2,178 deaths among 11,162 patients, 94% of whom were being treated with a corticosteroid such as dexamethasone.

The results showed no significant difference in the primary endpoint of 28-day mortality in patients randomized to colchicine versus usual care alone (20% vs. 19%; risk ratio, 1.02; 95% confidence interval, 0.94-1.11; P = .63).

Follow-up is ongoing and final results will be published as soon as possible, the investigators said. Thus far, there has been no convincing evidence of an effect of colchicine on clinical outcomes in hospitalized COVID-19 patients.

Recruitment will continue to all other treatment arms – aspirin, baricitinib, Regeneron’s antibody cocktail, and, in select hospitals, dimethyl fumarate – the investigators said.

Cochief investigator Peter Hornby, MD, PhD, also from the University of Oxford, noted that this has been the largest trial ever of colchicine. “Whilst we are disappointed that the overall result is negative, it is still important information for the future care of patients in the U.K. and worldwide.”

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

On the advice of its independent data monitoring committee (DMC), the RECOVERY trial has stopped recruitment to the colchicine arm for lack of efficacy in patients hospitalized with COVID-19.

“The DMC saw no convincing evidence that further recruitment would provide conclusive proof of worthwhile mortality benefit either overall or in any prespecified subgroup,” the British investigators announced on March 5.

“The RECOVERY trial has already identified two anti-inflammatory drugs – dexamethasone and tocilizumab – that improve the chances of survival for patients with severe COVID-19. So, it is disappointing that colchicine, which is widely used to treat gout and other inflammatory conditions, has no effect in these patients,” cochief investigator Martin Landray, MBChB, PhD, said in a statement.

“We do large, randomized trials to establish whether a drug that seems promising in theory has real benefits for patients in practice. Unfortunately, colchicine is not one of those,” said Dr. Landry, University of Oxford (England).

The RECOVERY trial is evaluating a range of potential treatments for COVID-19 at 180 hospitals in the United Kingdom, Indonesia, and Nepal, and was designed with the expectation that drugs would be added or dropped as the evidence changes. Since November 2020, the trial has included an arm comparing colchicine with usual care alone.

As part of a routine meeting March 4, the DMC reviewed data from a preliminary analysis based on 2,178 deaths among 11,162 patients, 94% of whom were being treated with a corticosteroid such as dexamethasone.

The results showed no significant difference in the primary endpoint of 28-day mortality in patients randomized to colchicine versus usual care alone (20% vs. 19%; risk ratio, 1.02; 95% confidence interval, 0.94-1.11; P = .63).

Follow-up is ongoing and final results will be published as soon as possible, the investigators said. Thus far, there has been no convincing evidence of an effect of colchicine on clinical outcomes in hospitalized COVID-19 patients.

Recruitment will continue to all other treatment arms – aspirin, baricitinib, Regeneron’s antibody cocktail, and, in select hospitals, dimethyl fumarate – the investigators said.

Cochief investigator Peter Hornby, MD, PhD, also from the University of Oxford, noted that this has been the largest trial ever of colchicine. “Whilst we are disappointed that the overall result is negative, it is still important information for the future care of patients in the U.K. and worldwide.”

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

On the advice of its independent data monitoring committee (DMC), the RECOVERY trial has stopped recruitment to the colchicine arm for lack of efficacy in patients hospitalized with COVID-19.

“The DMC saw no convincing evidence that further recruitment would provide conclusive proof of worthwhile mortality benefit either overall or in any prespecified subgroup,” the British investigators announced on March 5.

“The RECOVERY trial has already identified two anti-inflammatory drugs – dexamethasone and tocilizumab – that improve the chances of survival for patients with severe COVID-19. So, it is disappointing that colchicine, which is widely used to treat gout and other inflammatory conditions, has no effect in these patients,” cochief investigator Martin Landray, MBChB, PhD, said in a statement.

“We do large, randomized trials to establish whether a drug that seems promising in theory has real benefits for patients in practice. Unfortunately, colchicine is not one of those,” said Dr. Landry, University of Oxford (England).

The RECOVERY trial is evaluating a range of potential treatments for COVID-19 at 180 hospitals in the United Kingdom, Indonesia, and Nepal, and was designed with the expectation that drugs would be added or dropped as the evidence changes. Since November 2020, the trial has included an arm comparing colchicine with usual care alone.

As part of a routine meeting March 4, the DMC reviewed data from a preliminary analysis based on 2,178 deaths among 11,162 patients, 94% of whom were being treated with a corticosteroid such as dexamethasone.

The results showed no significant difference in the primary endpoint of 28-day mortality in patients randomized to colchicine versus usual care alone (20% vs. 19%; risk ratio, 1.02; 95% confidence interval, 0.94-1.11; P = .63).

Follow-up is ongoing and final results will be published as soon as possible, the investigators said. Thus far, there has been no convincing evidence of an effect of colchicine on clinical outcomes in hospitalized COVID-19 patients.

Recruitment will continue to all other treatment arms – aspirin, baricitinib, Regeneron’s antibody cocktail, and, in select hospitals, dimethyl fumarate – the investigators said.

Cochief investigator Peter Hornby, MD, PhD, also from the University of Oxford, noted that this has been the largest trial ever of colchicine. “Whilst we are disappointed that the overall result is negative, it is still important information for the future care of patients in the U.K. and worldwide.”

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

The terminology and classification scheme for heart failure (HF) is changing in ways that experts hope will directly impact patient outcomes.

In a new consensus statement, a multisociety group of experts proposed a new universal definition of heart failure and made substantial revisions to the way in which the disease is staged and classified.

The authors of the statement, led by writing committee chair and immediate past president of the Heart Failure Society of America Biykem Bozkurt, MD, PhD, hope their efforts will go far to improve standardization of terminology, but more importantly will facilitate better management of the disease in ways that keep pace with current knowledge and advances in the field.

“There is a great need for reframing and standardizing the terminology across societies and different stakeholders, and importantly for patients because a lot of the terminology we were using was understood by academicians, but were not being translated in important ways to ensure patients are being appropriately treated,” said Dr. Bozkurt, of Baylor College of Medicine, Houston.

The consensus statement was a group effort led by the HFSA, the Heart Failure Association of the European Society of Cardiology, and the Japanese Heart Failure Society, with endorsements from the Canadian Heart Failure Society, the Heart Failure Association of India, the Cardiac Society of Australia and New Zealand, and the Chinese Heart Failure Association.

The article was published March 1 in the Journal of Cardiac Failure and the European Journal of Heart Failure, authored by a writing committee of 38 individuals with domain expertise in HF, cardiomyopathy, and cardiovascular disease.

“This is a very thorough and very carefully written document that I think will be helpful for clinicians because they’ve tapped into important changes in the field that have occurred over the past 10 years and that now allow us to do more for patients than we could before,” Eugene Braunwald, MD, said in an interview.

A new universal definition

“[Heart failure] is a clinical syndrome with symptoms and or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion.”

This proposed definition, said the authors, is designed to be contemporary and simple “but conceptually comprehensive, with near universal applicability, prognostic and therapeutic viability, and acceptable sensitivity and specificity.”

Both left and right HF qualifies under this definition, said the authors, but conditions that result in marked volume overload, such as chronic kidney disease, which may present with signs and symptoms of HF, do not.

“Although some of these patients may have concomitant HF, these patients have a primary abnormality that may require a specific treatment beyond that for HF,” said the consensus statement authors.

For his part, Douglas L. Mann, MD, is happy to see what he considers a more accurate and practical definition for heart failure.

Proposed revised stages of the HF continuum

Overall, minimal changes have been made to the HF stages, with tweaks intended to enhance understanding and address the evolving role of biomarkers.

The authors proposed an approach to staging of HF:

• At-risk for HF (stage A), for patients at risk for HF but without current or prior symptoms or signs of HF and without structural or biomarkers evidence of heart disease.
• Pre-HF (stage B), for patients without current or prior symptoms or signs of HF, but evidence of structural heart disease or abnormal cardiac function, or elevated natriuretic peptide levels.
• HF (stage C), for patients with current or prior symptoms and/or signs of HF caused by a structural and/or functional cardiac abnormality.
• Advanced HF (stage D), for patients with severe symptoms and/or signs of HF at rest, recurrent hospitalizations despite guideline-directed management and therapy (GDMT), refractory or intolerant to GDMT, requiring advanced therapies such as consideration for transplant, mechanical circulatory support, or palliative care.

MDedge News

One notable change to the staging scheme is stage B, which the authors have reframed as “pre–heart failure.”

“Pre-cancer is a term widely understood and considered actionable and we wanted to tap into this successful messaging and embrace the pre–heart failure concept as something that is treatable and preventable,” said Dr. Bozkurt.

“We want patients and clinicians to understand that there are things we can do to prevent heart failure, strategies we didn’t have before, like SGLT2 inhibitors in patients with diabetes at risk for HF,” she added.

The revision also avoids the stigma of HF before the symptoms are manifest.

“Not calling it stage A and stage B heart failure you might say is semantics, but it’s important semantics,” said Dr. Braunwald. “When you’re talking to a patient or a relative and tell them they have stage A heart failure, it’s scares them unnecessarily. They don’t hear the stage A or B part, just the heart failure part.”
 

New classifications according to LVEF

And finally, in what some might consider the most obviously needed modification, the document proposes a new and revised classification of HF according to left ventricular ejection fraction (LVEF). Most agree on how to classify heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), but although the middle range has long been understood to be a clinically relevant, it has no proper name or clear delineation.

“For standardization across practice guidelines, to recognize clinical trajectories in HF, and to facilitate the recognition of different heart failure entities in a sensitive and specific manner that can guide therapy, we want to formalize the heart failure categories according to ejection fraction,” said Dr. Bozkurt.

To this end, the authors propose the following four classifications of EF:

• HF with reduced EF (HFrEF): LVEF of up to 40%.
• HF with mildly reduced EF (HFmrEF): LVEF of 41-49%.
• HF with preserved EF (HFpEF)HF with an LVEF of at least 50%.
• HF with improved EF (HFimpEF): HF with a baseline LVEF of 40% or less, an increase of at least 10 points from baseline LVEF, and a second measurement of LVEF of greater than 40%.

HFmrEF is usually a transition period, noted Dr. Bozkurt. “Patients with HF in this range may represent a population whose EF is likely to change, either increase or decrease over time and it’s important to be cognizant of that trajectory. Understanding where your patient is headed is crucial for prognosis and optimization of guideline-directed treatment,” she said.
 

Improved, not recovered, HF

The last classification of heart failure with improved ejection fraction (HFimpEF) represents an important change to the current classification scheme.

“We want to clarify what terms to use but also which not to use. For example, we don’t want people to use recovered heart failure or heart failure in remission, partly because we don’t want the medication to be stopped. We don’t want to give the false message that there has been full recovery,” said Dr. Bozkurt.

As seen in the TRED-HF trial, guideline-directed medical therapy should be continued in patients with HF with improved EF regardless of whether it has improved to a normal range of above 50% in subsequent measurements.

“This is a distinct group of people, and for a while the guidelines were lumping them in with HFpEF, which I think is totally wrong,” said Dr. Mann.

“I think it’s very important that we emphasize heart failure as a continuum, rather than a one-way street of [inevitable] progression. Because we do see improvements in ejection fraction and we do see that we can prevent heart failure if we do the right things, and this should be reflected in the terminology we use,” he added.

Dr. Bozkurt stressed that HFimpEF only applies if the EF improves to above 40%. A move from an EF of 10%-20% would still see the patient classified as having HFrEF, but a patient whose EF improved from, say, 30% to 45% would be classified as HFimpEF.

“The reason for this, again, is because a transition from, say an EF of 10%-20% does not change therapy, but a move upward over 40% might, especially regarding decisions for device therapies, so the trajectory as well as the absolute EF is important,” she added.

“Particularly in the early stages, people are responsive to therapy and it’s possible in some cases to reverse heart failure, so I think this change helps us understand when that’s happened,” said Dr. Braunwald.
 

One step toward universality

“The implementation of this terminology and nomenclature into practice will require a variety of tactics,” said Dr. Bozkurt. “For example, the current ICD 10 codes need to incorporate the at-risk and pre–heart failure categories, as well as the mid-range EF, preserved, and improved EF classifications, because the treatment differs between those three domains.”

In terms of how these proposed changes will be worked into practice guidelines, Dr. Bozkurt declined to comment on this to avoid any perception of conflict of interest as she is the cochair of the American College of Cardiology/American Heart Association HF guideline writing committee.

Dr. Braunwald and Dr. Antman suggest it may be premature to call the new terminology and classifications “universal.” In an interview, Dr. Braunwald lamented the absence of the World Heart Federation, the ACC, and the AHA as active participants in this effort and suggested this paper is only the first step of a multistep process that requires input from many stakeholders.

“It’s important that these organizations be involved, not just to bless it, but to contribute their expertise to the process,” he said.

For his part, Dr. Mann hopes these changes will gain widespread acceptance and clinical traction. “The problem sometimes with guidelines is that they’re so data driven that you just can’t come out and say the obvious, so making a position statement is a good first step. And they got good international representation on this, so I think these changes will be accepted in the next heart failure guidelines.”

To encourage further discussion and acceptance, Robert J. Mentz, MD, and Anuradha Lala, MD, editor-in-chief and deputy editor of the Journal of Cardiac Failure, respectively, announced a series of multidisciplinary perspective pieces to be published in the journal monthly, starting in May with editorials from Dr. Clyde W Yancy, MD, MSc, and Carolyn S.P. Lam, MBBS, PhD, both of whom were authors of the consensus statement.

Dr. Bozkurt reports being a consultant for Abbott, Amgen, Baxter, Bristol Myers Squibb, Liva Nova Relypsa/Vifor Pharma, Respicardia, and being on the registry steering committee for Sanofi-Aventis. Dr. Braunwald reports research grant support through Brigham and Women’s Hospital from AstraZeneca, Daiichi Sankyo, Merck, and Novartis; and consulting for Amgen, Boehringer-Ingelheim/Lilly, Cardurion, MyoKardia, Novo Nordisk, and Verve. Dr. Mann has been a consultant to Novartis, is on the steering committee for the PARADISE trial, and is on the scientific advisory board for MyoKardia/Bristol Myers Squibb.

The terminology and classification scheme for heart failure (HF) is changing in ways that experts hope will directly impact patient outcomes.

In a new consensus statement, a multisociety group of experts proposed a new universal definition of heart failure and made substantial revisions to the way in which the disease is staged and classified.

The authors of the statement, led by writing committee chair and immediate past president of the Heart Failure Society of America Biykem Bozkurt, MD, PhD, hope their efforts will go far to improve standardization of terminology, but more importantly will facilitate better management of the disease in ways that keep pace with current knowledge and advances in the field.

“There is a great need for reframing and standardizing the terminology across societies and different stakeholders, and importantly for patients because a lot of the terminology we were using was understood by academicians, but were not being translated in important ways to ensure patients are being appropriately treated,” said Dr. Bozkurt, of Baylor College of Medicine, Houston.

The consensus statement was a group effort led by the HFSA, the Heart Failure Association of the European Society of Cardiology, and the Japanese Heart Failure Society, with endorsements from the Canadian Heart Failure Society, the Heart Failure Association of India, the Cardiac Society of Australia and New Zealand, and the Chinese Heart Failure Association.

The article was published March 1 in the Journal of Cardiac Failure and the European Journal of Heart Failure, authored by a writing committee of 38 individuals with domain expertise in HF, cardiomyopathy, and cardiovascular disease.

“This is a very thorough and very carefully written document that I think will be helpful for clinicians because they’ve tapped into important changes in the field that have occurred over the past 10 years and that now allow us to do more for patients than we could before,” Eugene Braunwald, MD, said in an interview.

A new universal definition

“[Heart failure] is a clinical syndrome with symptoms and or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion.”

This proposed definition, said the authors, is designed to be contemporary and simple “but conceptually comprehensive, with near universal applicability, prognostic and therapeutic viability, and acceptable sensitivity and specificity.”

Both left and right HF qualifies under this definition, said the authors, but conditions that result in marked volume overload, such as chronic kidney disease, which may present with signs and symptoms of HF, do not.

“Although some of these patients may have concomitant HF, these patients have a primary abnormality that may require a specific treatment beyond that for HF,” said the consensus statement authors.

For his part, Douglas L. Mann, MD, is happy to see what he considers a more accurate and practical definition for heart failure.

Proposed revised stages of the HF continuum

Overall, minimal changes have been made to the HF stages, with tweaks intended to enhance understanding and address the evolving role of biomarkers.

The authors proposed an approach to staging of HF:

• At-risk for HF (stage A), for patients at risk for HF but without current or prior symptoms or signs of HF and without structural or biomarkers evidence of heart disease.
• Pre-HF (stage B), for patients without current or prior symptoms or signs of HF, but evidence of structural heart disease or abnormal cardiac function, or elevated natriuretic peptide levels.
• HF (stage C), for patients with current or prior symptoms and/or signs of HF caused by a structural and/or functional cardiac abnormality.
• Advanced HF (stage D), for patients with severe symptoms and/or signs of HF at rest, recurrent hospitalizations despite guideline-directed management and therapy (GDMT), refractory or intolerant to GDMT, requiring advanced therapies such as consideration for transplant, mechanical circulatory support, or palliative care.

MDedge News

One notable change to the staging scheme is stage B, which the authors have reframed as “pre–heart failure.”

“Pre-cancer is a term widely understood and considered actionable and we wanted to tap into this successful messaging and embrace the pre–heart failure concept as something that is treatable and preventable,” said Dr. Bozkurt.

“We want patients and clinicians to understand that there are things we can do to prevent heart failure, strategies we didn’t have before, like SGLT2 inhibitors in patients with diabetes at risk for HF,” she added.

The revision also avoids the stigma of HF before the symptoms are manifest.

“Not calling it stage A and stage B heart failure you might say is semantics, but it’s important semantics,” said Dr. Braunwald. “When you’re talking to a patient or a relative and tell them they have stage A heart failure, it’s scares them unnecessarily. They don’t hear the stage A or B part, just the heart failure part.”
 

New classifications according to LVEF

And finally, in what some might consider the most obviously needed modification, the document proposes a new and revised classification of HF according to left ventricular ejection fraction (LVEF). Most agree on how to classify heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), but although the middle range has long been understood to be a clinically relevant, it has no proper name or clear delineation.

“For standardization across practice guidelines, to recognize clinical trajectories in HF, and to facilitate the recognition of different heart failure entities in a sensitive and specific manner that can guide therapy, we want to formalize the heart failure categories according to ejection fraction,” said Dr. Bozkurt.

To this end, the authors propose the following four classifications of EF:

• HF with reduced EF (HFrEF): LVEF of up to 40%.
• HF with mildly reduced EF (HFmrEF): LVEF of 41-49%.
• HF with preserved EF (HFpEF)HF with an LVEF of at least 50%.
• HF with improved EF (HFimpEF): HF with a baseline LVEF of 40% or less, an increase of at least 10 points from baseline LVEF, and a second measurement of LVEF of greater than 40%.

HFmrEF is usually a transition period, noted Dr. Bozkurt. “Patients with HF in this range may represent a population whose EF is likely to change, either increase or decrease over time and it’s important to be cognizant of that trajectory. Understanding where your patient is headed is crucial for prognosis and optimization of guideline-directed treatment,” she said.
 

Improved, not recovered, HF

The last classification of heart failure with improved ejection fraction (HFimpEF) represents an important change to the current classification scheme.

“We want to clarify what terms to use but also which not to use. For example, we don’t want people to use recovered heart failure or heart failure in remission, partly because we don’t want the medication to be stopped. We don’t want to give the false message that there has been full recovery,” said Dr. Bozkurt.

As seen in the TRED-HF trial, guideline-directed medical therapy should be continued in patients with HF with improved EF regardless of whether it has improved to a normal range of above 50% in subsequent measurements.

“This is a distinct group of people, and for a while the guidelines were lumping them in with HFpEF, which I think is totally wrong,” said Dr. Mann.

“I think it’s very important that we emphasize heart failure as a continuum, rather than a one-way street of [inevitable] progression. Because we do see improvements in ejection fraction and we do see that we can prevent heart failure if we do the right things, and this should be reflected in the terminology we use,” he added.

Dr. Bozkurt stressed that HFimpEF only applies if the EF improves to above 40%. A move from an EF of 10%-20% would still see the patient classified as having HFrEF, but a patient whose EF improved from, say, 30% to 45% would be classified as HFimpEF.

“The reason for this, again, is because a transition from, say an EF of 10%-20% does not change therapy, but a move upward over 40% might, especially regarding decisions for device therapies, so the trajectory as well as the absolute EF is important,” she added.

“Particularly in the early stages, people are responsive to therapy and it’s possible in some cases to reverse heart failure, so I think this change helps us understand when that’s happened,” said Dr. Braunwald.
 

One step toward universality

“The implementation of this terminology and nomenclature into practice will require a variety of tactics,” said Dr. Bozkurt. “For example, the current ICD 10 codes need to incorporate the at-risk and pre–heart failure categories, as well as the mid-range EF, preserved, and improved EF classifications, because the treatment differs between those three domains.”

In terms of how these proposed changes will be worked into practice guidelines, Dr. Bozkurt declined to comment on this to avoid any perception of conflict of interest as she is the cochair of the American College of Cardiology/American Heart Association HF guideline writing committee.

Dr. Braunwald and Dr. Antman suggest it may be premature to call the new terminology and classifications “universal.” In an interview, Dr. Braunwald lamented the absence of the World Heart Federation, the ACC, and the AHA as active participants in this effort and suggested this paper is only the first step of a multistep process that requires input from many stakeholders.

“It’s important that these organizations be involved, not just to bless it, but to contribute their expertise to the process,” he said.

For his part, Dr. Mann hopes these changes will gain widespread acceptance and clinical traction. “The problem sometimes with guidelines is that they’re so data driven that you just can’t come out and say the obvious, so making a position statement is a good first step. And they got good international representation on this, so I think these changes will be accepted in the next heart failure guidelines.”

To encourage further discussion and acceptance, Robert J. Mentz, MD, and Anuradha Lala, MD, editor-in-chief and deputy editor of the Journal of Cardiac Failure, respectively, announced a series of multidisciplinary perspective pieces to be published in the journal monthly, starting in May with editorials from Dr. Clyde W Yancy, MD, MSc, and Carolyn S.P. Lam, MBBS, PhD, both of whom were authors of the consensus statement.

Dr. Bozkurt reports being a consultant for Abbott, Amgen, Baxter, Bristol Myers Squibb, Liva Nova Relypsa/Vifor Pharma, Respicardia, and being on the registry steering committee for Sanofi-Aventis. Dr. Braunwald reports research grant support through Brigham and Women’s Hospital from AstraZeneca, Daiichi Sankyo, Merck, and Novartis; and consulting for Amgen, Boehringer-Ingelheim/Lilly, Cardurion, MyoKardia, Novo Nordisk, and Verve. Dr. Mann has been a consultant to Novartis, is on the steering committee for the PARADISE trial, and is on the scientific advisory board for MyoKardia/Bristol Myers Squibb.

The terminology and classification scheme for heart failure (HF) is changing in ways that experts hope will directly impact patient outcomes.

In a new consensus statement, a multisociety group of experts proposed a new universal definition of heart failure and made substantial revisions to the way in which the disease is staged and classified.

The authors of the statement, led by writing committee chair and immediate past president of the Heart Failure Society of America Biykem Bozkurt, MD, PhD, hope their efforts will go far to improve standardization of terminology, but more importantly will facilitate better management of the disease in ways that keep pace with current knowledge and advances in the field.

“There is a great need for reframing and standardizing the terminology across societies and different stakeholders, and importantly for patients because a lot of the terminology we were using was understood by academicians, but were not being translated in important ways to ensure patients are being appropriately treated,” said Dr. Bozkurt, of Baylor College of Medicine, Houston.

The consensus statement was a group effort led by the HFSA, the Heart Failure Association of the European Society of Cardiology, and the Japanese Heart Failure Society, with endorsements from the Canadian Heart Failure Society, the Heart Failure Association of India, the Cardiac Society of Australia and New Zealand, and the Chinese Heart Failure Association.

The article was published March 1 in the Journal of Cardiac Failure and the European Journal of Heart Failure, authored by a writing committee of 38 individuals with domain expertise in HF, cardiomyopathy, and cardiovascular disease.

“This is a very thorough and very carefully written document that I think will be helpful for clinicians because they’ve tapped into important changes in the field that have occurred over the past 10 years and that now allow us to do more for patients than we could before,” Eugene Braunwald, MD, said in an interview.

A new universal definition

“[Heart failure] is a clinical syndrome with symptoms and or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion.”

This proposed definition, said the authors, is designed to be contemporary and simple “but conceptually comprehensive, with near universal applicability, prognostic and therapeutic viability, and acceptable sensitivity and specificity.”

Both left and right HF qualifies under this definition, said the authors, but conditions that result in marked volume overload, such as chronic kidney disease, which may present with signs and symptoms of HF, do not.

“Although some of these patients may have concomitant HF, these patients have a primary abnormality that may require a specific treatment beyond that for HF,” said the consensus statement authors.

For his part, Douglas L. Mann, MD, is happy to see what he considers a more accurate and practical definition for heart failure.

Proposed revised stages of the HF continuum

Overall, minimal changes have been made to the HF stages, with tweaks intended to enhance understanding and address the evolving role of biomarkers.

The authors proposed an approach to staging of HF:

• At-risk for HF (stage A), for patients at risk for HF but without current or prior symptoms or signs of HF and without structural or biomarkers evidence of heart disease.
• Pre-HF (stage B), for patients without current or prior symptoms or signs of HF, but evidence of structural heart disease or abnormal cardiac function, or elevated natriuretic peptide levels.
• HF (stage C), for patients with current or prior symptoms and/or signs of HF caused by a structural and/or functional cardiac abnormality.
• Advanced HF (stage D), for patients with severe symptoms and/or signs of HF at rest, recurrent hospitalizations despite guideline-directed management and therapy (GDMT), refractory or intolerant to GDMT, requiring advanced therapies such as consideration for transplant, mechanical circulatory support, or palliative care.

MDedge News

One notable change to the staging scheme is stage B, which the authors have reframed as “pre–heart failure.”

“Pre-cancer is a term widely understood and considered actionable and we wanted to tap into this successful messaging and embrace the pre–heart failure concept as something that is treatable and preventable,” said Dr. Bozkurt.

“We want patients and clinicians to understand that there are things we can do to prevent heart failure, strategies we didn’t have before, like SGLT2 inhibitors in patients with diabetes at risk for HF,” she added.

The revision also avoids the stigma of HF before the symptoms are manifest.

“Not calling it stage A and stage B heart failure you might say is semantics, but it’s important semantics,” said Dr. Braunwald. “When you’re talking to a patient or a relative and tell them they have stage A heart failure, it’s scares them unnecessarily. They don’t hear the stage A or B part, just the heart failure part.”
 

New classifications according to LVEF

And finally, in what some might consider the most obviously needed modification, the document proposes a new and revised classification of HF according to left ventricular ejection fraction (LVEF). Most agree on how to classify heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), but although the middle range has long been understood to be a clinically relevant, it has no proper name or clear delineation.

“For standardization across practice guidelines, to recognize clinical trajectories in HF, and to facilitate the recognition of different heart failure entities in a sensitive and specific manner that can guide therapy, we want to formalize the heart failure categories according to ejection fraction,” said Dr. Bozkurt.

To this end, the authors propose the following four classifications of EF:

• HF with reduced EF (HFrEF): LVEF of up to 40%.
• HF with mildly reduced EF (HFmrEF): LVEF of 41-49%.
• HF with preserved EF (HFpEF)HF with an LVEF of at least 50%.
• HF with improved EF (HFimpEF): HF with a baseline LVEF of 40% or less, an increase of at least 10 points from baseline LVEF, and a second measurement of LVEF of greater than 40%.

HFmrEF is usually a transition period, noted Dr. Bozkurt. “Patients with HF in this range may represent a population whose EF is likely to change, either increase or decrease over time and it’s important to be cognizant of that trajectory. Understanding where your patient is headed is crucial for prognosis and optimization of guideline-directed treatment,” she said.
 

Improved, not recovered, HF

The last classification of heart failure with improved ejection fraction (HFimpEF) represents an important change to the current classification scheme.

“We want to clarify what terms to use but also which not to use. For example, we don’t want people to use recovered heart failure or heart failure in remission, partly because we don’t want the medication to be stopped. We don’t want to give the false message that there has been full recovery,” said Dr. Bozkurt.

As seen in the TRED-HF trial, guideline-directed medical therapy should be continued in patients with HF with improved EF regardless of whether it has improved to a normal range of above 50% in subsequent measurements.

“This is a distinct group of people, and for a while the guidelines were lumping them in with HFpEF, which I think is totally wrong,” said Dr. Mann.

“I think it’s very important that we emphasize heart failure as a continuum, rather than a one-way street of [inevitable] progression. Because we do see improvements in ejection fraction and we do see that we can prevent heart failure if we do the right things, and this should be reflected in the terminology we use,” he added.

Dr. Bozkurt stressed that HFimpEF only applies if the EF improves to above 40%. A move from an EF of 10%-20% would still see the patient classified as having HFrEF, but a patient whose EF improved from, say, 30% to 45% would be classified as HFimpEF.

“The reason for this, again, is because a transition from, say an EF of 10%-20% does not change therapy, but a move upward over 40% might, especially regarding decisions for device therapies, so the trajectory as well as the absolute EF is important,” she added.

“Particularly in the early stages, people are responsive to therapy and it’s possible in some cases to reverse heart failure, so I think this change helps us understand when that’s happened,” said Dr. Braunwald.
 

One step toward universality

“The implementation of this terminology and nomenclature into practice will require a variety of tactics,” said Dr. Bozkurt. “For example, the current ICD 10 codes need to incorporate the at-risk and pre–heart failure categories, as well as the mid-range EF, preserved, and improved EF classifications, because the treatment differs between those three domains.”

In terms of how these proposed changes will be worked into practice guidelines, Dr. Bozkurt declined to comment on this to avoid any perception of conflict of interest as she is the cochair of the American College of Cardiology/American Heart Association HF guideline writing committee.

Dr. Braunwald and Dr. Antman suggest it may be premature to call the new terminology and classifications “universal.” In an interview, Dr. Braunwald lamented the absence of the World Heart Federation, the ACC, and the AHA as active participants in this effort and suggested this paper is only the first step of a multistep process that requires input from many stakeholders.

“It’s important that these organizations be involved, not just to bless it, but to contribute their expertise to the process,” he said.

For his part, Dr. Mann hopes these changes will gain widespread acceptance and clinical traction. “The problem sometimes with guidelines is that they’re so data driven that you just can’t come out and say the obvious, so making a position statement is a good first step. And they got good international representation on this, so I think these changes will be accepted in the next heart failure guidelines.”

To encourage further discussion and acceptance, Robert J. Mentz, MD, and Anuradha Lala, MD, editor-in-chief and deputy editor of the Journal of Cardiac Failure, respectively, announced a series of multidisciplinary perspective pieces to be published in the journal monthly, starting in May with editorials from Dr. Clyde W Yancy, MD, MSc, and Carolyn S.P. Lam, MBBS, PhD, both of whom were authors of the consensus statement.

Dr. Bozkurt reports being a consultant for Abbott, Amgen, Baxter, Bristol Myers Squibb, Liva Nova Relypsa/Vifor Pharma, Respicardia, and being on the registry steering committee for Sanofi-Aventis. Dr. Braunwald reports research grant support through Brigham and Women’s Hospital from AstraZeneca, Daiichi Sankyo, Merck, and Novartis; and consulting for Amgen, Boehringer-Ingelheim/Lilly, Cardurion, MyoKardia, Novo Nordisk, and Verve. Dr. Mann has been a consultant to Novartis, is on the steering committee for the PARADISE trial, and is on the scientific advisory board for MyoKardia/Bristol Myers Squibb.

The numbers are in to back up two policies designed to restrict the spread of the COVID-19 pandemic.

Researchers at the Centers for Disease Control and Prevention) found that when states lifted restrictions on dining on premises at restaurants, rates of daily COVID-19 cases jumped 41-100 days later. COVID-19-related deaths also increased significantly after 60 days.

On the other hand, the same report demonstrates that state mask mandates slowed the spread of SARS-CoV-2 within a few weeks.

The study was published online March 5 in the CDC Morbidity and Mortality Weekly Report.

The investigators did not distinguish between outdoor and indoor restaurant dining. But they did compare COVID-19 case and death rates before and after most states banned restaurants from serving patrons on-premises in March and April 2020.

They found, for example, that COVID-19 daily cases increased by 0.9% at 41-60 days after on-premise dining was permitted. Similarly, rates jumped by 1.2% at 61-80 days, and 1.1% at 81-100 days after the restaurant restrictions were lifted. 

The differences were statistically significant, with P values of .02, <.01, and .04, respectively.

COVID-19–related death rates did not increase significantly at first – but did jump 2.2% between 61 and 80 days after the return of on-premises dining, for example. Deaths also increased by 3% at 81-100 days.

Both these differences were statistically significant (P < .01).

This is not the first report where the CDC announced reservations about in-person dining. In September 2020, CDC investigators implicated the inability to wear a mask while eating and drinking as likely contributing to the heightened risk.
 

Masks make a difference

The CDC report also provided more evidence to back mask-wearing policies for public spaces. Between March 1 and Dec. 31, 2020, 74% of U.S. counties issued mask mandates.

Investigators found that these policies had a more immediate effect, reducing daily COVID-19 cases by 0.5% in the first 20 days. Mask mandates likewise were linked to daily cases dropping 1.1% between 21 and 40 days, 1.5% between 41 and 60 days, 1.7% between 61 and 80 days, and 1.8% between 81 and 100 days.

These decreases in daily COVID-19 cases were statistically significant (P < .01) compared with a reference period before March 1, 2020.

The CDC also linked mask mandates to lower mortality. For example, these state policies were associated with 0.7% fewer deaths at 1-20 days post implementation. The effect increased thereafter – 1.0% drop at 21-40 days, 1.4% decrease at 41-60 days, 1.6% drop between 61 and 80 days, and 1.9% fewer deaths between 81 and 100 days.

The decrease in deaths was statistically significant at 1-20 days after the mask mandate (P = .03), as well as during the other periods (each P < .01) compared with the reference period.

CDC Director Rochelle Walensky, MD, reacted to the new findings at a White House press briefing. She cited how increases in COVID-19 cases and death rates “slowed significantly within 20 days of putting mask mandates into place. This is why I’m asking you to double down on prevention measures.

“We have seen this movie before,” Dr. Walensky added. “When prevention measures like mask-wearing mandates are lifted, cases go up.”

Recently, multiple states have announced plans to roll back restrictions related to the pandemic, including mask mandates, which prompted warnings from some public health officials.

These are not the first CDC data to show that mask mandates make a difference.

In February 2021, for example, the agency pointed out that state-wide mask mandates reduced COVID-19 hospitalizations by 5.5% among adults 18-64 years old within 3 weeks of implementation.

Restrictions regarding on-premises restaurant dining and implementation of state-wide mask mandates are two tactics within a more comprehensive CDC strategy to reduce the spread of SARS-CoV-2. The researchers note that “such efforts are increasingly important given the emergence of highly transmissible SARS-CoV-2 variants in the United States.”

The researchers have disclosed no relevant financial relationships.

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

The numbers are in to back up two policies designed to restrict the spread of the COVID-19 pandemic.

Researchers at the Centers for Disease Control and Prevention) found that when states lifted restrictions on dining on premises at restaurants, rates of daily COVID-19 cases jumped 41-100 days later. COVID-19-related deaths also increased significantly after 60 days.

On the other hand, the same report demonstrates that state mask mandates slowed the spread of SARS-CoV-2 within a few weeks.

The study was published online March 5 in the CDC Morbidity and Mortality Weekly Report.

The investigators did not distinguish between outdoor and indoor restaurant dining. But they did compare COVID-19 case and death rates before and after most states banned restaurants from serving patrons on-premises in March and April 2020.

They found, for example, that COVID-19 daily cases increased by 0.9% at 41-60 days after on-premise dining was permitted. Similarly, rates jumped by 1.2% at 61-80 days, and 1.1% at 81-100 days after the restaurant restrictions were lifted. 

The differences were statistically significant, with P values of .02, <.01, and .04, respectively.

COVID-19–related death rates did not increase significantly at first – but did jump 2.2% between 61 and 80 days after the return of on-premises dining, for example. Deaths also increased by 3% at 81-100 days.

Both these differences were statistically significant (P < .01).

This is not the first report where the CDC announced reservations about in-person dining. In September 2020, CDC investigators implicated the inability to wear a mask while eating and drinking as likely contributing to the heightened risk.
 

Masks make a difference

The CDC report also provided more evidence to back mask-wearing policies for public spaces. Between March 1 and Dec. 31, 2020, 74% of U.S. counties issued mask mandates.

Investigators found that these policies had a more immediate effect, reducing daily COVID-19 cases by 0.5% in the first 20 days. Mask mandates likewise were linked to daily cases dropping 1.1% between 21 and 40 days, 1.5% between 41 and 60 days, 1.7% between 61 and 80 days, and 1.8% between 81 and 100 days.

These decreases in daily COVID-19 cases were statistically significant (P < .01) compared with a reference period before March 1, 2020.

The CDC also linked mask mandates to lower mortality. For example, these state policies were associated with 0.7% fewer deaths at 1-20 days post implementation. The effect increased thereafter – 1.0% drop at 21-40 days, 1.4% decrease at 41-60 days, 1.6% drop between 61 and 80 days, and 1.9% fewer deaths between 81 and 100 days.

The decrease in deaths was statistically significant at 1-20 days after the mask mandate (P = .03), as well as during the other periods (each P < .01) compared with the reference period.

CDC Director Rochelle Walensky, MD, reacted to the new findings at a White House press briefing. She cited how increases in COVID-19 cases and death rates “slowed significantly within 20 days of putting mask mandates into place. This is why I’m asking you to double down on prevention measures.

“We have seen this movie before,” Dr. Walensky added. “When prevention measures like mask-wearing mandates are lifted, cases go up.”

Recently, multiple states have announced plans to roll back restrictions related to the pandemic, including mask mandates, which prompted warnings from some public health officials.

These are not the first CDC data to show that mask mandates make a difference.

In February 2021, for example, the agency pointed out that state-wide mask mandates reduced COVID-19 hospitalizations by 5.5% among adults 18-64 years old within 3 weeks of implementation.

Restrictions regarding on-premises restaurant dining and implementation of state-wide mask mandates are two tactics within a more comprehensive CDC strategy to reduce the spread of SARS-CoV-2. The researchers note that “such efforts are increasingly important given the emergence of highly transmissible SARS-CoV-2 variants in the United States.”

The researchers have disclosed no relevant financial relationships.

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

The numbers are in to back up two policies designed to restrict the spread of the COVID-19 pandemic.

Researchers at the Centers for Disease Control and Prevention) found that when states lifted restrictions on dining on premises at restaurants, rates of daily COVID-19 cases jumped 41-100 days later. COVID-19-related deaths also increased significantly after 60 days.

On the other hand, the same report demonstrates that state mask mandates slowed the spread of SARS-CoV-2 within a few weeks.

The study was published online March 5 in the CDC Morbidity and Mortality Weekly Report.

The investigators did not distinguish between outdoor and indoor restaurant dining. But they did compare COVID-19 case and death rates before and after most states banned restaurants from serving patrons on-premises in March and April 2020.

They found, for example, that COVID-19 daily cases increased by 0.9% at 41-60 days after on-premise dining was permitted. Similarly, rates jumped by 1.2% at 61-80 days, and 1.1% at 81-100 days after the restaurant restrictions were lifted. 

The differences were statistically significant, with P values of .02, <.01, and .04, respectively.

COVID-19–related death rates did not increase significantly at first – but did jump 2.2% between 61 and 80 days after the return of on-premises dining, for example. Deaths also increased by 3% at 81-100 days.

Both these differences were statistically significant (P < .01).

This is not the first report where the CDC announced reservations about in-person dining. In September 2020, CDC investigators implicated the inability to wear a mask while eating and drinking as likely contributing to the heightened risk.
 

Masks make a difference

The CDC report also provided more evidence to back mask-wearing policies for public spaces. Between March 1 and Dec. 31, 2020, 74% of U.S. counties issued mask mandates.

Investigators found that these policies had a more immediate effect, reducing daily COVID-19 cases by 0.5% in the first 20 days. Mask mandates likewise were linked to daily cases dropping 1.1% between 21 and 40 days, 1.5% between 41 and 60 days, 1.7% between 61 and 80 days, and 1.8% between 81 and 100 days.

These decreases in daily COVID-19 cases were statistically significant (P < .01) compared with a reference period before March 1, 2020.

The CDC also linked mask mandates to lower mortality. For example, these state policies were associated with 0.7% fewer deaths at 1-20 days post implementation. The effect increased thereafter – 1.0% drop at 21-40 days, 1.4% decrease at 41-60 days, 1.6% drop between 61 and 80 days, and 1.9% fewer deaths between 81 and 100 days.

The decrease in deaths was statistically significant at 1-20 days after the mask mandate (P = .03), as well as during the other periods (each P < .01) compared with the reference period.

CDC Director Rochelle Walensky, MD, reacted to the new findings at a White House press briefing. She cited how increases in COVID-19 cases and death rates “slowed significantly within 20 days of putting mask mandates into place. This is why I’m asking you to double down on prevention measures.

“We have seen this movie before,” Dr. Walensky added. “When prevention measures like mask-wearing mandates are lifted, cases go up.”

Recently, multiple states have announced plans to roll back restrictions related to the pandemic, including mask mandates, which prompted warnings from some public health officials.

These are not the first CDC data to show that mask mandates make a difference.

In February 2021, for example, the agency pointed out that state-wide mask mandates reduced COVID-19 hospitalizations by 5.5% among adults 18-64 years old within 3 weeks of implementation.

Restrictions regarding on-premises restaurant dining and implementation of state-wide mask mandates are two tactics within a more comprehensive CDC strategy to reduce the spread of SARS-CoV-2. The researchers note that “such efforts are increasingly important given the emergence of highly transmissible SARS-CoV-2 variants in the United States.”

The researchers have disclosed no relevant financial relationships.

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

The Food and Drug Administration has approved subcutaneously-injected tocilizumab (Actemra) to reduce the rate of pulmonary function decline in systemic sclerosis–associated interstitial lung disease (SSc-ILD) patients, according to a press release from manufacturer Genentech.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

Tocilizumab is the first biologic to be approved by the agency for adults with SSc-ILD, a rare and potentially life-threatening condition that may affect up to 80% of SSc patients and lead to lung inflammation and scarring.

The approval was based primarily on data from a phase 3 randomized, double-blind, placebo-controlled clinical trial (the focuSSced trial) that included 212 adults with SSc. Although that study failed to meet its primary endpoint of change from baseline to 48 weeks in the modified Rodnan Skin Score, the researchers observed a significantly reduced lung function decline as measured by forced vital capacity (FVC) and percent predicted forced vital capacity (ppFVC) among tocilizumab-treated patients, compared with those who received placebo. A total of 68 patients (65%) in the tocilizumab group and 68 patients (64%) in the placebo group had SSc-ILD at baseline.

In a subgroup analysis, patients taking tocilizumab had a smaller decline in mean ppFVC, compared with placebo patients (0.07% vs. –6.4%; mean difference, 6.47%), and a smaller decline in FVC (mean change –14 mL vs. –255 mL with placebo; mean difference, 241 mL).

The mean change from baseline to week 48 in modified Rodnan Skin Score was –5.88 for patients on tocilizumab and –3.77 with placebo.

Safety data were similar between tocilizumab and placebo groups through 48 weeks, and similar for patients with and without SSc-ILD. In general, tocilizumab side effects include increased susceptibility to infections, and serious side effects may include stomach tears, hepatotoxicity, and increased risk of cancer and hepatitis B, according to the prescribing information. However, the most common side effects are upper respiratory tract infections, headache, hypertension, and injection-site reactions.

Tocilizumab, an interleukin-6 receptor antagonist, is already approved for the treatment of adult patients with moderately to severely active rheumatoid arthritis, as well as for adult patients with giant cell arteritis; patients aged 2 years and older with active polyarticular juvenile idiopathic arthritis or active systemic juvenile idiopathic arthritis; and adults and pediatric patients 2 years of age and older with chimeric antigen receptor T-cell–induced severe or life-threatening cytokine release syndrome.

Prescribing information is available here.

The Food and Drug Administration has approved subcutaneously-injected tocilizumab (Actemra) to reduce the rate of pulmonary function decline in systemic sclerosis–associated interstitial lung disease (SSc-ILD) patients, according to a press release from manufacturer Genentech.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

Tocilizumab is the first biologic to be approved by the agency for adults with SSc-ILD, a rare and potentially life-threatening condition that may affect up to 80% of SSc patients and lead to lung inflammation and scarring.

The approval was based primarily on data from a phase 3 randomized, double-blind, placebo-controlled clinical trial (the focuSSced trial) that included 212 adults with SSc. Although that study failed to meet its primary endpoint of change from baseline to 48 weeks in the modified Rodnan Skin Score, the researchers observed a significantly reduced lung function decline as measured by forced vital capacity (FVC) and percent predicted forced vital capacity (ppFVC) among tocilizumab-treated patients, compared with those who received placebo. A total of 68 patients (65%) in the tocilizumab group and 68 patients (64%) in the placebo group had SSc-ILD at baseline.

In a subgroup analysis, patients taking tocilizumab had a smaller decline in mean ppFVC, compared with placebo patients (0.07% vs. –6.4%; mean difference, 6.47%), and a smaller decline in FVC (mean change –14 mL vs. –255 mL with placebo; mean difference, 241 mL).

The mean change from baseline to week 48 in modified Rodnan Skin Score was –5.88 for patients on tocilizumab and –3.77 with placebo.

Safety data were similar between tocilizumab and placebo groups through 48 weeks, and similar for patients with and without SSc-ILD. In general, tocilizumab side effects include increased susceptibility to infections, and serious side effects may include stomach tears, hepatotoxicity, and increased risk of cancer and hepatitis B, according to the prescribing information. However, the most common side effects are upper respiratory tract infections, headache, hypertension, and injection-site reactions.

Tocilizumab, an interleukin-6 receptor antagonist, is already approved for the treatment of adult patients with moderately to severely active rheumatoid arthritis, as well as for adult patients with giant cell arteritis; patients aged 2 years and older with active polyarticular juvenile idiopathic arthritis or active systemic juvenile idiopathic arthritis; and adults and pediatric patients 2 years of age and older with chimeric antigen receptor T-cell–induced severe or life-threatening cytokine release syndrome.

Prescribing information is available here.

The Food and Drug Administration has approved subcutaneously-injected tocilizumab (Actemra) to reduce the rate of pulmonary function decline in systemic sclerosis–associated interstitial lung disease (SSc-ILD) patients, according to a press release from manufacturer Genentech.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

Tocilizumab is the first biologic to be approved by the agency for adults with SSc-ILD, a rare and potentially life-threatening condition that may affect up to 80% of SSc patients and lead to lung inflammation and scarring.

The approval was based primarily on data from a phase 3 randomized, double-blind, placebo-controlled clinical trial (the focuSSced trial) that included 212 adults with SSc. Although that study failed to meet its primary endpoint of change from baseline to 48 weeks in the modified Rodnan Skin Score, the researchers observed a significantly reduced lung function decline as measured by forced vital capacity (FVC) and percent predicted forced vital capacity (ppFVC) among tocilizumab-treated patients, compared with those who received placebo. A total of 68 patients (65%) in the tocilizumab group and 68 patients (64%) in the placebo group had SSc-ILD at baseline.

In a subgroup analysis, patients taking tocilizumab had a smaller decline in mean ppFVC, compared with placebo patients (0.07% vs. –6.4%; mean difference, 6.47%), and a smaller decline in FVC (mean change –14 mL vs. –255 mL with placebo; mean difference, 241 mL).

The mean change from baseline to week 48 in modified Rodnan Skin Score was –5.88 for patients on tocilizumab and –3.77 with placebo.

Safety data were similar between tocilizumab and placebo groups through 48 weeks, and similar for patients with and without SSc-ILD. In general, tocilizumab side effects include increased susceptibility to infections, and serious side effects may include stomach tears, hepatotoxicity, and increased risk of cancer and hepatitis B, according to the prescribing information. However, the most common side effects are upper respiratory tract infections, headache, hypertension, and injection-site reactions.

Tocilizumab, an interleukin-6 receptor antagonist, is already approved for the treatment of adult patients with moderately to severely active rheumatoid arthritis, as well as for adult patients with giant cell arteritis; patients aged 2 years and older with active polyarticular juvenile idiopathic arthritis or active systemic juvenile idiopathic arthritis; and adults and pediatric patients 2 years of age and older with chimeric antigen receptor T-cell–induced severe or life-threatening cytokine release syndrome.

Prescribing information is available here.

COVID-19 vaccines are considered safe for patients with multiple sclerosis (MS), a neurologist told colleagues, but those who are on disease-modifying therapy (DMT) – or about to begin it – should be cautious about the timing of their shots.

“There’s no reason to think any of the three authorized vaccines are in any way more dangerous in people with MS, or in the context of MS DMTs. It’s only a question of whether certain DMTs will influence the degree of benefit you get from the vaccine,” said Amit Bar-Or, MD, director of the Center for Neuroinflammation and Neurotherapeutics, chief of the multiple sclerosis division, and Melissa and Paul Anderson President’s Distinguished Professor at the University of Pennsylvania, Philadelphia. He spoke at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, and he also answered questions in a follow-up interview.

“The merits of being protected by the COVID-19 vaccines far outweigh any risks that one would consider associated with vaccines and individuals with MS,” said Dr. Bar-Or. “And there’s reason to think that the RNA vaccines may even be safer than prior, more traditional vaccines. They are nonlive, noninactivated vaccines, and there is no risk in terms of interacting with MS.”

Where do DMTs fit in? In an interview, Hesham Abboud, MD, PhD, of University Hospitals of Cleveland and Case Western Reserve University, also in Cleveland, said there’s reason for caution regarding DMTs that deplete immune cells or entrap them in the lymph nodes. “What is not clearly known is the effect of the fumarates, which do not act through cell depletion but can occasionally deplete immune cells as a side effect. These likely have no negative effect on vaccine efficacy in patients with normal immune cell count but may have a negative effect in those with significant immune cell reduction. Luckily, significant immune cell reduction is rare in patients taking fumarates.”

In addition, he said, “interferons and natalizumab are generally thought to have no impact on vaccine efficacy while glatiramer acetate and teriflunomide are thought to have no or only little impact on vaccines. Most of these concepts are derived from studies of non–COVID-19 vaccines.”

Dr. Bar-Or highlighted specific DMTs. Teriflunomide (Aubagio) “has a relatively mild effect on the immune system and is not thought to be particularly immune suppressive or deplete immune cells,” Dr. Bar-Or said, as shown in a 2015 study he led (Neurol Neuroimmunol Neuroinflamm. 2015 Feb 12;2[2]:e70). In contrast, a 2020 study, also led by Dr. Bar-Or, showed that nonlive vaccinations given after treatment with ocrelizumab (Ocrevus) – an anti-CD20 monoclonal antibody – are “attenuated, compared with untreated or interferon-beta–treated patients, but they can still be expected to be protective.”

Dr. Bar-Or pointed to National MS Society guidelines about the timing of the Pfizer and Moderna mRNA vaccines for patients with MS who are on DMT. In patients with stable MS, the society recommends no adjustments in timing for patients starting or remaining on several DMTs. The list includes teriflunomide, glatiramer acetate (Copaxone), and dimethyl fumarate, among others.

Patients shouldn’t start fingolimod (Gilenya), siponimod (Mayzent), or ozanimod (Zeposia) until 4 weeks or more after their second vaccine dose, the guidelines suggest. Vaccine doses are recommended 3-5 days after the final dose of high-dose steroids. And there are more complicated recommendations regarding a number of other DMTs – ocrelizumab, ofatumumab (Kesimpta), alemtuzumab (Lemtrada), cladribine (Mavenclad), and rituximab (Rituxan).

Dr. Bar-Or cautioned that the guidelines are an imperfect “first pass” and are being updated.

He added that the guidelines are not set in stone: “Scheduling is not always possible in terms of adjusting the vaccine timing. Patients in general are recommended to take the vaccine when it becomes available, as it may be more important for them to get the vaccine than to try to time the vaccine relative to the DMT.”

Guidance regarding the newly authorized Johnson & Johnson vaccine is expected soon, said neurologist Barbara Giesser, MD, of Pacific Neuroscience Institute in Santa Monica, Calif., in an interview. As for her advice to patients, she said that, “in general, I am recommending that patients get [vaccinated] as soon as it is available to them with adjustment of timing of some DMTs as may be appropriate.”

Dr. Bar-Or has received consulting fees and/or grant support from – or participated as a speaker in events sponsored by – Accure, Atara Biotherapeutics, Biogen, Bristol-Myer Squibb/Celgene/Receptos, GlaxoSmithKline, Gossamer, Janssen/Actelion, Medimmune, Merck/EMD Serono, Novartis, Roche/Genentech, and Sanofi-Genzyme. He also receives research funding from various organizations and agencies. Dr. Abboud reported receiving consulting fees from Biogen, Genentech, Bristol-Myer Squibb, Alexion, and Viela Bio. He receives research support from Novartis, Bristol-Myer Squibb, Genentech, and Sanofi-Genzyme. Dr. Giesser reports no disclosures.
 

COVID-19 vaccines are considered safe for patients with multiple sclerosis (MS), a neurologist told colleagues, but those who are on disease-modifying therapy (DMT) – or about to begin it – should be cautious about the timing of their shots.

“There’s no reason to think any of the three authorized vaccines are in any way more dangerous in people with MS, or in the context of MS DMTs. It’s only a question of whether certain DMTs will influence the degree of benefit you get from the vaccine,” said Amit Bar-Or, MD, director of the Center for Neuroinflammation and Neurotherapeutics, chief of the multiple sclerosis division, and Melissa and Paul Anderson President’s Distinguished Professor at the University of Pennsylvania, Philadelphia. He spoke at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, and he also answered questions in a follow-up interview.

“The merits of being protected by the COVID-19 vaccines far outweigh any risks that one would consider associated with vaccines and individuals with MS,” said Dr. Bar-Or. “And there’s reason to think that the RNA vaccines may even be safer than prior, more traditional vaccines. They are nonlive, noninactivated vaccines, and there is no risk in terms of interacting with MS.”

Where do DMTs fit in? In an interview, Hesham Abboud, MD, PhD, of University Hospitals of Cleveland and Case Western Reserve University, also in Cleveland, said there’s reason for caution regarding DMTs that deplete immune cells or entrap them in the lymph nodes. “What is not clearly known is the effect of the fumarates, which do not act through cell depletion but can occasionally deplete immune cells as a side effect. These likely have no negative effect on vaccine efficacy in patients with normal immune cell count but may have a negative effect in those with significant immune cell reduction. Luckily, significant immune cell reduction is rare in patients taking fumarates.”

In addition, he said, “interferons and natalizumab are generally thought to have no impact on vaccine efficacy while glatiramer acetate and teriflunomide are thought to have no or only little impact on vaccines. Most of these concepts are derived from studies of non–COVID-19 vaccines.”

Dr. Bar-Or highlighted specific DMTs. Teriflunomide (Aubagio) “has a relatively mild effect on the immune system and is not thought to be particularly immune suppressive or deplete immune cells,” Dr. Bar-Or said, as shown in a 2015 study he led (Neurol Neuroimmunol Neuroinflamm. 2015 Feb 12;2[2]:e70). In contrast, a 2020 study, also led by Dr. Bar-Or, showed that nonlive vaccinations given after treatment with ocrelizumab (Ocrevus) – an anti-CD20 monoclonal antibody – are “attenuated, compared with untreated or interferon-beta–treated patients, but they can still be expected to be protective.”

Dr. Bar-Or pointed to National MS Society guidelines about the timing of the Pfizer and Moderna mRNA vaccines for patients with MS who are on DMT. In patients with stable MS, the society recommends no adjustments in timing for patients starting or remaining on several DMTs. The list includes teriflunomide, glatiramer acetate (Copaxone), and dimethyl fumarate, among others.

Patients shouldn’t start fingolimod (Gilenya), siponimod (Mayzent), or ozanimod (Zeposia) until 4 weeks or more after their second vaccine dose, the guidelines suggest. Vaccine doses are recommended 3-5 days after the final dose of high-dose steroids. And there are more complicated recommendations regarding a number of other DMTs – ocrelizumab, ofatumumab (Kesimpta), alemtuzumab (Lemtrada), cladribine (Mavenclad), and rituximab (Rituxan).

Dr. Bar-Or cautioned that the guidelines are an imperfect “first pass” and are being updated.

He added that the guidelines are not set in stone: “Scheduling is not always possible in terms of adjusting the vaccine timing. Patients in general are recommended to take the vaccine when it becomes available, as it may be more important for them to get the vaccine than to try to time the vaccine relative to the DMT.”

Guidance regarding the newly authorized Johnson & Johnson vaccine is expected soon, said neurologist Barbara Giesser, MD, of Pacific Neuroscience Institute in Santa Monica, Calif., in an interview. As for her advice to patients, she said that, “in general, I am recommending that patients get [vaccinated] as soon as it is available to them with adjustment of timing of some DMTs as may be appropriate.”

Dr. Bar-Or has received consulting fees and/or grant support from – or participated as a speaker in events sponsored by – Accure, Atara Biotherapeutics, Biogen, Bristol-Myer Squibb/Celgene/Receptos, GlaxoSmithKline, Gossamer, Janssen/Actelion, Medimmune, Merck/EMD Serono, Novartis, Roche/Genentech, and Sanofi-Genzyme. He also receives research funding from various organizations and agencies. Dr. Abboud reported receiving consulting fees from Biogen, Genentech, Bristol-Myer Squibb, Alexion, and Viela Bio. He receives research support from Novartis, Bristol-Myer Squibb, Genentech, and Sanofi-Genzyme. Dr. Giesser reports no disclosures.
 

COVID-19 vaccines are considered safe for patients with multiple sclerosis (MS), a neurologist told colleagues, but those who are on disease-modifying therapy (DMT) – or about to begin it – should be cautious about the timing of their shots.

“There’s no reason to think any of the three authorized vaccines are in any way more dangerous in people with MS, or in the context of MS DMTs. It’s only a question of whether certain DMTs will influence the degree of benefit you get from the vaccine,” said Amit Bar-Or, MD, director of the Center for Neuroinflammation and Neurotherapeutics, chief of the multiple sclerosis division, and Melissa and Paul Anderson President’s Distinguished Professor at the University of Pennsylvania, Philadelphia. He spoke at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, and he also answered questions in a follow-up interview.

“The merits of being protected by the COVID-19 vaccines far outweigh any risks that one would consider associated with vaccines and individuals with MS,” said Dr. Bar-Or. “And there’s reason to think that the RNA vaccines may even be safer than prior, more traditional vaccines. They are nonlive, noninactivated vaccines, and there is no risk in terms of interacting with MS.”

Where do DMTs fit in? In an interview, Hesham Abboud, MD, PhD, of University Hospitals of Cleveland and Case Western Reserve University, also in Cleveland, said there’s reason for caution regarding DMTs that deplete immune cells or entrap them in the lymph nodes. “What is not clearly known is the effect of the fumarates, which do not act through cell depletion but can occasionally deplete immune cells as a side effect. These likely have no negative effect on vaccine efficacy in patients with normal immune cell count but may have a negative effect in those with significant immune cell reduction. Luckily, significant immune cell reduction is rare in patients taking fumarates.”

In addition, he said, “interferons and natalizumab are generally thought to have no impact on vaccine efficacy while glatiramer acetate and teriflunomide are thought to have no or only little impact on vaccines. Most of these concepts are derived from studies of non–COVID-19 vaccines.”

Dr. Bar-Or highlighted specific DMTs. Teriflunomide (Aubagio) “has a relatively mild effect on the immune system and is not thought to be particularly immune suppressive or deplete immune cells,” Dr. Bar-Or said, as shown in a 2015 study he led (Neurol Neuroimmunol Neuroinflamm. 2015 Feb 12;2[2]:e70). In contrast, a 2020 study, also led by Dr. Bar-Or, showed that nonlive vaccinations given after treatment with ocrelizumab (Ocrevus) – an anti-CD20 monoclonal antibody – are “attenuated, compared with untreated or interferon-beta–treated patients, but they can still be expected to be protective.”

Dr. Bar-Or pointed to National MS Society guidelines about the timing of the Pfizer and Moderna mRNA vaccines for patients with MS who are on DMT. In patients with stable MS, the society recommends no adjustments in timing for patients starting or remaining on several DMTs. The list includes teriflunomide, glatiramer acetate (Copaxone), and dimethyl fumarate, among others.

Patients shouldn’t start fingolimod (Gilenya), siponimod (Mayzent), or ozanimod (Zeposia) until 4 weeks or more after their second vaccine dose, the guidelines suggest. Vaccine doses are recommended 3-5 days after the final dose of high-dose steroids. And there are more complicated recommendations regarding a number of other DMTs – ocrelizumab, ofatumumab (Kesimpta), alemtuzumab (Lemtrada), cladribine (Mavenclad), and rituximab (Rituxan).

Dr. Bar-Or cautioned that the guidelines are an imperfect “first pass” and are being updated.

He added that the guidelines are not set in stone: “Scheduling is not always possible in terms of adjusting the vaccine timing. Patients in general are recommended to take the vaccine when it becomes available, as it may be more important for them to get the vaccine than to try to time the vaccine relative to the DMT.”

Guidance regarding the newly authorized Johnson & Johnson vaccine is expected soon, said neurologist Barbara Giesser, MD, of Pacific Neuroscience Institute in Santa Monica, Calif., in an interview. As for her advice to patients, she said that, “in general, I am recommending that patients get [vaccinated] as soon as it is available to them with adjustment of timing of some DMTs as may be appropriate.”

Dr. Bar-Or has received consulting fees and/or grant support from – or participated as a speaker in events sponsored by – Accure, Atara Biotherapeutics, Biogen, Bristol-Myer Squibb/Celgene/Receptos, GlaxoSmithKline, Gossamer, Janssen/Actelion, Medimmune, Merck/EMD Serono, Novartis, Roche/Genentech, and Sanofi-Genzyme. He also receives research funding from various organizations and agencies. Dr. Abboud reported receiving consulting fees from Biogen, Genentech, Bristol-Myer Squibb, Alexion, and Viela Bio. He receives research support from Novartis, Bristol-Myer Squibb, Genentech, and Sanofi-Genzyme. Dr. Giesser reports no disclosures.