CHEST Physician

Moderna’s COVID-19 vaccine — the second now cleared for emergency use in the United States — was endorsed by the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) on December 19.

The panel voted 11-0, with three recusals, to recommend use of Moderna’s vaccine for people aged 18 years and older, while seeking more information on risk for anaphylaxis. This vote followed the December 18th decision by the US Food and Drug Administration (FDA) to grant emergency use authorization (EUA) for the vaccine, known as mRNA-1273.

On December 11, the FDA granted the first US emergency clearance for a COVID-19 vaccine to the Pfizer-BioNTech product. ACIP met the following day and voted to endorse the use of that vaccine, with a vote of 11-0 and three recusals. The Pfizer-BioNTech COVID-19 vaccine is recommended for use in people aged 16 years and older.

Moderna’s vaccine is expected to help curb the pandemic, with clinical trial data showing a 94.1% efficacy rate. But there’s also concerns about side effects noted in testing of both vaccines and in the early rollout of the Pfizer vaccine, particularly anaphylaxis.

“There are likely going to be lots of bumps in the road” with the introduction of the COVID-19 vaccines, but these are being disclosed to the public in a way that is “fair and transparent,” said ACIP member Beth P. Bell, MD, MPH.

“Our systems so far appear to be doing what they are supposed to do” in terms of determining risks from the COVID-19 vaccine, added Bell, who is a clinical professor in the department of global health at the University of Washington’s School of Public Health in Seattle. The Moderna EUA  “represents progress towards ending this horrific pandemic,” she said.

In a new forecast released this week, the CDC projects that the number of newly reported COVID-19 deaths will likely increase over the next 4 weeks, with 15,800 to 27,700 new deaths likely to be reported in the week ending January 9, 2021. That could bring the total number of COVID-19 deaths in the United States to between 357,000 and 391,000 by this date, according to the agency.

ACIP panelist Lynn Bahta, RN, MPH, CPH, said she had been “eager” to have the panel proceed with its endorsement of the Moderna vaccine, “especially in light of the fact that we are seeing an average 2600 deaths a day.”

Having two COVID-19 vaccines available might help slow down the pandemic, “despite the fact that we still have a lot to learn both about the disease and the vaccine,” said Bahta, who is an immunization consultant with the Minnesota Department of Health in Saint Paul.

ACIP members encouraged Moderna officials who presented at the meeting to continue studies for potential complications associated with the vaccine when given to women who are pregnant or breastfeeding.

Panelists also pressed for more data on the risk for Bell’s palsy, which the FDA staff also had noted in the agency’s review of Moderna’s vaccine. Moderna has reported four cases from a pivotal study, one in the placebo group and three among study participants who received the company’s vaccine. These cases occurred between 15 and 33 days after vaccination, and are all resolved or resolving, according to Moderna.

There was also a question raised about how many doses of vaccine might be squeezed out of a vial. CDC will explore this topic further at its meeting on COVID-19 vaccines December 20, said Nancy Messonnier, MD, director of the agency’s National Center for Immunization and Respiratory Diseases, at the Saturday meeting.

“In this time of public health crisis, none of us would want to squander a single dose of a vaccine that’s potentially lifesaving,” CDC’s Messonnier said. “We’re going to plan to have a short discussion of that issue tomorrow.”

Messonnier also responded to a comment made during the meeting about cases where people who received COVID-19 vaccine were unaware of the CDC’s V-safe tool.

V-safe is a smartphone-based tool that uses text messaging and web surveys to help people keep in touch with the medical community after getting the COVID-19 vaccine and is seen as a way to help spot side effects. Messonnier asked that people listening to the webcast of the ACIP meeting help spread the word about the CDC’s V-safe tool.

“Our perception, based on the number of people who have enrolled in V-safe, is that the message is getting out to many places, but even one site that doesn’t have this information is something that we want to try to correct,” she said.

Anaphylaxis concerns

The chief concern for ACIP members and CDC staff about COVID-19 vaccines appeared to be reports of allergic reactions. Thomas Clark, MD, MPH, a CDC staff member, told the ACIP panel that, as of December 18, the agency had identified six cases of anaphylaxis following administration of the Pfizer-BioNTech vaccine that met a certain standard, known as the Brighton Collaboration criteria.

Additional case reports have been reviewed and determined not to be anaphylaxis, Clark said. All suspect cases were identified through processes such as the federal Vaccine Adverse Event Reporting System (VAERS), he said.

People who experience anaphylaxis following COVID-19 vaccination should not receive additional doses of the shot, Clark said in his presentation to ACIP. Members of the panel asked Clark whether there have been any discernible patterns to these cases, such as geographic clusters.

Clark replied that it was “early” in the process to make reports, with investigations still ongoing. He did note that the people who had anaphylaxis following vaccination had received their doses from more than one production lot, with multiple lots having been distributed.

“You folks may have seen in the news a couple of cases from Alaska, but we’ve had reports from other jurisdictions so there’s no obvious clustering geographically,” Clark said.

Another CDC staff member, Sarah Mbaeyi, MD, MPH, noted in her presentation that there should be an observation period of 30 minutes following COVID-19 vaccination for anyone with a history of anaphylaxis for any reason, and of at least 15 minutes for other recipients.

Disclosure of ingredients used in the COVID-19 vaccines might help people with an allergy assess these products, the representative for the American Medical Association, Sandra Fryhofer, MD, told ACIP. As such, she thanked CDC’s Mbaeyi for including a breakout of ingredients in her presentation to the panel. Fryhofer encouraged Moderna officials to be as transparent as possible in disclosing the ingredients of the company’s COVID-19 vaccine.

“That might be important because I think it’s very essential that we figure out what might be triggering these anaphylactic reactions, because that is definitely going to affect the vaccine implementation,” Fryhofer said.

The three ACIP members who had conflicts that prevented their voting were Robert L. Atmar, MD, who said at the Saturday meeting he had participated in COVID-19 trials, including research on the Moderna vaccine; Sharon E. Frey, MD, who said at the Saturday meeting that she had been involved with research on COVID-19 vaccines, including Moderna’s; and Paul Hunter, MD, who said he has received a grant from Pfizer for pneumococcal vaccines.

The other panel members have reported no relevant financial relationships.

This article first appeared on Medscape.com.

Moderna’s COVID-19 vaccine — the second now cleared for emergency use in the United States — was endorsed by the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) on December 19.

The panel voted 11-0, with three recusals, to recommend use of Moderna’s vaccine for people aged 18 years and older, while seeking more information on risk for anaphylaxis. This vote followed the December 18th decision by the US Food and Drug Administration (FDA) to grant emergency use authorization (EUA) for the vaccine, known as mRNA-1273.

On December 11, the FDA granted the first US emergency clearance for a COVID-19 vaccine to the Pfizer-BioNTech product. ACIP met the following day and voted to endorse the use of that vaccine, with a vote of 11-0 and three recusals. The Pfizer-BioNTech COVID-19 vaccine is recommended for use in people aged 16 years and older.

Moderna’s vaccine is expected to help curb the pandemic, with clinical trial data showing a 94.1% efficacy rate. But there’s also concerns about side effects noted in testing of both vaccines and in the early rollout of the Pfizer vaccine, particularly anaphylaxis.

“There are likely going to be lots of bumps in the road” with the introduction of the COVID-19 vaccines, but these are being disclosed to the public in a way that is “fair and transparent,” said ACIP member Beth P. Bell, MD, MPH.

“Our systems so far appear to be doing what they are supposed to do” in terms of determining risks from the COVID-19 vaccine, added Bell, who is a clinical professor in the department of global health at the University of Washington’s School of Public Health in Seattle. The Moderna EUA  “represents progress towards ending this horrific pandemic,” she said.

In a new forecast released this week, the CDC projects that the number of newly reported COVID-19 deaths will likely increase over the next 4 weeks, with 15,800 to 27,700 new deaths likely to be reported in the week ending January 9, 2021. That could bring the total number of COVID-19 deaths in the United States to between 357,000 and 391,000 by this date, according to the agency.

ACIP panelist Lynn Bahta, RN, MPH, CPH, said she had been “eager” to have the panel proceed with its endorsement of the Moderna vaccine, “especially in light of the fact that we are seeing an average 2600 deaths a day.”

Having two COVID-19 vaccines available might help slow down the pandemic, “despite the fact that we still have a lot to learn both about the disease and the vaccine,” said Bahta, who is an immunization consultant with the Minnesota Department of Health in Saint Paul.

ACIP members encouraged Moderna officials who presented at the meeting to continue studies for potential complications associated with the vaccine when given to women who are pregnant or breastfeeding.

Panelists also pressed for more data on the risk for Bell’s palsy, which the FDA staff also had noted in the agency’s review of Moderna’s vaccine. Moderna has reported four cases from a pivotal study, one in the placebo group and three among study participants who received the company’s vaccine. These cases occurred between 15 and 33 days after vaccination, and are all resolved or resolving, according to Moderna.

There was also a question raised about how many doses of vaccine might be squeezed out of a vial. CDC will explore this topic further at its meeting on COVID-19 vaccines December 20, said Nancy Messonnier, MD, director of the agency’s National Center for Immunization and Respiratory Diseases, at the Saturday meeting.

“In this time of public health crisis, none of us would want to squander a single dose of a vaccine that’s potentially lifesaving,” CDC’s Messonnier said. “We’re going to plan to have a short discussion of that issue tomorrow.”

Messonnier also responded to a comment made during the meeting about cases where people who received COVID-19 vaccine were unaware of the CDC’s V-safe tool.

V-safe is a smartphone-based tool that uses text messaging and web surveys to help people keep in touch with the medical community after getting the COVID-19 vaccine and is seen as a way to help spot side effects. Messonnier asked that people listening to the webcast of the ACIP meeting help spread the word about the CDC’s V-safe tool.

“Our perception, based on the number of people who have enrolled in V-safe, is that the message is getting out to many places, but even one site that doesn’t have this information is something that we want to try to correct,” she said.

Anaphylaxis concerns

The chief concern for ACIP members and CDC staff about COVID-19 vaccines appeared to be reports of allergic reactions. Thomas Clark, MD, MPH, a CDC staff member, told the ACIP panel that, as of December 18, the agency had identified six cases of anaphylaxis following administration of the Pfizer-BioNTech vaccine that met a certain standard, known as the Brighton Collaboration criteria.

Additional case reports have been reviewed and determined not to be anaphylaxis, Clark said. All suspect cases were identified through processes such as the federal Vaccine Adverse Event Reporting System (VAERS), he said.

People who experience anaphylaxis following COVID-19 vaccination should not receive additional doses of the shot, Clark said in his presentation to ACIP. Members of the panel asked Clark whether there have been any discernible patterns to these cases, such as geographic clusters.

Clark replied that it was “early” in the process to make reports, with investigations still ongoing. He did note that the people who had anaphylaxis following vaccination had received their doses from more than one production lot, with multiple lots having been distributed.

“You folks may have seen in the news a couple of cases from Alaska, but we’ve had reports from other jurisdictions so there’s no obvious clustering geographically,” Clark said.

Another CDC staff member, Sarah Mbaeyi, MD, MPH, noted in her presentation that there should be an observation period of 30 minutes following COVID-19 vaccination for anyone with a history of anaphylaxis for any reason, and of at least 15 minutes for other recipients.

Disclosure of ingredients used in the COVID-19 vaccines might help people with an allergy assess these products, the representative for the American Medical Association, Sandra Fryhofer, MD, told ACIP. As such, she thanked CDC’s Mbaeyi for including a breakout of ingredients in her presentation to the panel. Fryhofer encouraged Moderna officials to be as transparent as possible in disclosing the ingredients of the company’s COVID-19 vaccine.

“That might be important because I think it’s very essential that we figure out what might be triggering these anaphylactic reactions, because that is definitely going to affect the vaccine implementation,” Fryhofer said.

The three ACIP members who had conflicts that prevented their voting were Robert L. Atmar, MD, who said at the Saturday meeting he had participated in COVID-19 trials, including research on the Moderna vaccine; Sharon E. Frey, MD, who said at the Saturday meeting that she had been involved with research on COVID-19 vaccines, including Moderna’s; and Paul Hunter, MD, who said he has received a grant from Pfizer for pneumococcal vaccines.

The other panel members have reported no relevant financial relationships.

This article first appeared on Medscape.com.

Moderna’s COVID-19 vaccine — the second now cleared for emergency use in the United States — was endorsed by the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) on December 19.

The panel voted 11-0, with three recusals, to recommend use of Moderna’s vaccine for people aged 18 years and older, while seeking more information on risk for anaphylaxis. This vote followed the December 18th decision by the US Food and Drug Administration (FDA) to grant emergency use authorization (EUA) for the vaccine, known as mRNA-1273.

On December 11, the FDA granted the first US emergency clearance for a COVID-19 vaccine to the Pfizer-BioNTech product. ACIP met the following day and voted to endorse the use of that vaccine, with a vote of 11-0 and three recusals. The Pfizer-BioNTech COVID-19 vaccine is recommended for use in people aged 16 years and older.

Moderna’s vaccine is expected to help curb the pandemic, with clinical trial data showing a 94.1% efficacy rate. But there’s also concerns about side effects noted in testing of both vaccines and in the early rollout of the Pfizer vaccine, particularly anaphylaxis.

“There are likely going to be lots of bumps in the road” with the introduction of the COVID-19 vaccines, but these are being disclosed to the public in a way that is “fair and transparent,” said ACIP member Beth P. Bell, MD, MPH.

“Our systems so far appear to be doing what they are supposed to do” in terms of determining risks from the COVID-19 vaccine, added Bell, who is a clinical professor in the department of global health at the University of Washington’s School of Public Health in Seattle. The Moderna EUA  “represents progress towards ending this horrific pandemic,” she said.

In a new forecast released this week, the CDC projects that the number of newly reported COVID-19 deaths will likely increase over the next 4 weeks, with 15,800 to 27,700 new deaths likely to be reported in the week ending January 9, 2021. That could bring the total number of COVID-19 deaths in the United States to between 357,000 and 391,000 by this date, according to the agency.

ACIP panelist Lynn Bahta, RN, MPH, CPH, said she had been “eager” to have the panel proceed with its endorsement of the Moderna vaccine, “especially in light of the fact that we are seeing an average 2600 deaths a day.”

Having two COVID-19 vaccines available might help slow down the pandemic, “despite the fact that we still have a lot to learn both about the disease and the vaccine,” said Bahta, who is an immunization consultant with the Minnesota Department of Health in Saint Paul.

ACIP members encouraged Moderna officials who presented at the meeting to continue studies for potential complications associated with the vaccine when given to women who are pregnant or breastfeeding.

Panelists also pressed for more data on the risk for Bell’s palsy, which the FDA staff also had noted in the agency’s review of Moderna’s vaccine. Moderna has reported four cases from a pivotal study, one in the placebo group and three among study participants who received the company’s vaccine. These cases occurred between 15 and 33 days after vaccination, and are all resolved or resolving, according to Moderna.

There was also a question raised about how many doses of vaccine might be squeezed out of a vial. CDC will explore this topic further at its meeting on COVID-19 vaccines December 20, said Nancy Messonnier, MD, director of the agency’s National Center for Immunization and Respiratory Diseases, at the Saturday meeting.

“In this time of public health crisis, none of us would want to squander a single dose of a vaccine that’s potentially lifesaving,” CDC’s Messonnier said. “We’re going to plan to have a short discussion of that issue tomorrow.”

Messonnier also responded to a comment made during the meeting about cases where people who received COVID-19 vaccine were unaware of the CDC’s V-safe tool.

V-safe is a smartphone-based tool that uses text messaging and web surveys to help people keep in touch with the medical community after getting the COVID-19 vaccine and is seen as a way to help spot side effects. Messonnier asked that people listening to the webcast of the ACIP meeting help spread the word about the CDC’s V-safe tool.

“Our perception, based on the number of people who have enrolled in V-safe, is that the message is getting out to many places, but even one site that doesn’t have this information is something that we want to try to correct,” she said.

Anaphylaxis concerns

The chief concern for ACIP members and CDC staff about COVID-19 vaccines appeared to be reports of allergic reactions. Thomas Clark, MD, MPH, a CDC staff member, told the ACIP panel that, as of December 18, the agency had identified six cases of anaphylaxis following administration of the Pfizer-BioNTech vaccine that met a certain standard, known as the Brighton Collaboration criteria.

Additional case reports have been reviewed and determined not to be anaphylaxis, Clark said. All suspect cases were identified through processes such as the federal Vaccine Adverse Event Reporting System (VAERS), he said.

People who experience anaphylaxis following COVID-19 vaccination should not receive additional doses of the shot, Clark said in his presentation to ACIP. Members of the panel asked Clark whether there have been any discernible patterns to these cases, such as geographic clusters.

Clark replied that it was “early” in the process to make reports, with investigations still ongoing. He did note that the people who had anaphylaxis following vaccination had received their doses from more than one production lot, with multiple lots having been distributed.

“You folks may have seen in the news a couple of cases from Alaska, but we’ve had reports from other jurisdictions so there’s no obvious clustering geographically,” Clark said.

Another CDC staff member, Sarah Mbaeyi, MD, MPH, noted in her presentation that there should be an observation period of 30 minutes following COVID-19 vaccination for anyone with a history of anaphylaxis for any reason, and of at least 15 minutes for other recipients.

Disclosure of ingredients used in the COVID-19 vaccines might help people with an allergy assess these products, the representative for the American Medical Association, Sandra Fryhofer, MD, told ACIP. As such, she thanked CDC’s Mbaeyi for including a breakout of ingredients in her presentation to the panel. Fryhofer encouraged Moderna officials to be as transparent as possible in disclosing the ingredients of the company’s COVID-19 vaccine.

“That might be important because I think it’s very essential that we figure out what might be triggering these anaphylactic reactions, because that is definitely going to affect the vaccine implementation,” Fryhofer said.

The three ACIP members who had conflicts that prevented their voting were Robert L. Atmar, MD, who said at the Saturday meeting he had participated in COVID-19 trials, including research on the Moderna vaccine; Sharon E. Frey, MD, who said at the Saturday meeting that she had been involved with research on COVID-19 vaccines, including Moderna’s; and Paul Hunter, MD, who said he has received a grant from Pfizer for pneumococcal vaccines.

The other panel members have reported no relevant financial relationships.

This article first appeared on Medscape.com.

As expected, the US Food and Drug Administration granted Moderna an emergency use authorization (EUA) for its messenger RNA COVID-19 vaccine December 18. The vaccine becomes the second authorized for emergency use in the United States, and will likely increase the number of vaccine doses available in the coming days.

There is one final step — the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices will need to recommend its use, as it did 2 days after the Pfizer/BioNTech mRNA vaccine received its EUA on December 10.

The EUA for the Moderna vaccine is “a major milestone in trying to contain this pandemic,” Hana Mohammed El Sahly, MD, told Medscape Medical News.

Scaling up distribution of the two vaccine products will come next. She notes that even under less emergent conditions, making sure people who need a vaccine receive it can be hard. “I hope the media attention around this will make more people aware that there are vaccines that might help them,” said El Sahly, chair of the FDA Vaccines and Related Biological Products Advisory Committee (VRBPAC).

The EUA for the Moderna vaccine follows a review by the independent VRBPAC members on December 17, which voted 20-0 with one abstention to recommend the EUA. The vaccine is authorized for use in people 18 and older.


Emergency approval of a second COVID-19 vaccine “is great — we need all the tools we can to fight this pandemic,” Stephen Schrantz, MD, infectious disease specialist and assistant professor of medicine at the University of Chicago, told Medscape Medical News. “The early data coming from Moderna looks good, and I agree with the FDA that an EUA is indicated.

“It’s incumbent upon all us healthcare professionals to put ourselves out there as supporting this vaccine and supporting people getting it,” Schrantz continued. “We want to make sure people who are on the fence understand this is a safe vaccine that has been vetted appropriately through the FDA and through phase 3 clinical trials.”

“I know the critical role physicians play as vaccine influencers,” AMA President Susan Bailey, MD, said during a December 14 webinar for journalists reporting on COVID-19 vaccines. “We have to continue to do what physicians have always done: review the evidence and trust the science. Lives are at stake.” The webinar was cosponsored by the AMA and the Poynter Institute.

Ramping up healthcare provider immunizations

“I am very excited to see the FDA’s positive review of the Moderna vaccine. We have been waiting to have another vaccine we can use for healthcare workers and staff, and now we have it,” Aneesh Mehta, MD, of Emory University School of Medicine in Atlanta, Georgia, told Medscape Medical News.

“We had been hoping for a vaccine with a 70% or 80% efficacy, and to see two vaccines now with greater than 90% efficacy is remarkable,” he added.

The efficacy levels associated with both mRNA vaccines “did exceed expectations for sure — this is not what we built the studies around. It was surprising in the good sense of the word,” said El Sahly, who is also associate professor of molecular virology and microbiology at Baylor College of Medicine in Houston, Texas.

Unanswered questions remain

Schrantz likewise said the high efficacy rate was important but not all that is needed. “[W]hat we know about this vaccine is it is very effective at preventing disease. We don’t have any understanding at this time whether or not these vaccines prevent infection and transmissibility.”

Bailey said, “The jury is still out on whether or not you can still transmit the virus after you’ve had the vaccine. Hopefully not, but we don’t really know that for sure.”

“It’s risky to think that once you get the shot in your arm everything goes back to normal. It doesn’t,” Bailey added.

Another unknown is the duration of protection following immunization. The Pfizer and Moderna products “have similar constructs, seem to have a reasonable safety profile, and excellent short-term efficacy,” El Sahly said. She cautioned, however, that long-term efficacy still needs to be determined.

Whether any rare adverse events will emerge in the long run is another question. Answers could come over time from the ongoing phase 3 trials, as well as from post-EUA surveillance among vaccine recipients.  

“Our work is not done after issuing an EUA,” FDA Commissioner Stephen Hahn, MD, said in a JAMA webinar on December 14. The FDA is closely monitoring for any adverse event rates above the normal background incidence. “We are going to be transparent about it if we are seeing anything that is not at base level.”

“The key is to be humble, keep your eyes open and know that once the vaccine is out there, there may be things we learn that we don’t know now. That is true for virtually any medical innovation,” Paul Offit, MD, director of The Vaccine Education Center at Children’s Hospital of Philadelphia and a member of the FDA VRBPAC, said during the AMA/Poynter Institute webinar.

During the same webinar, an attendee asked about prioritizing immunization for spouses and family members of healthcare workers. “My husband wants to know that too,” replied Patricia A. Stinchfield, APRN, CNP, pediatric nurse practitioner in infectious diseases at Children’s Minnesota, St. Paul.

“It is true we should be thinking about our healthcare workers’ family members. But at this point in time we just don’t have the supplies to address it that way,” said Stinchfield, who is also the president-elect of the National Foundation for Infectious Diseases.

Advantages beyond the numbers?

“The major advantage of having two vaccines is sheer volume,” Mehta said. An additional advantage of more than one product is the potential to offer an option when a specific vaccine is contraindicated. “We could offer someone a different vaccine…similar to what we do with the influenza vaccine.”

“The more the merrier in terms of having more vaccine products,” Schrantz said. Despite differences in shipping, storage, minimum age requirements, and dosing intervals, the Pfizer and Moderna vaccines are very similar, he said. “Really the only difference between these two vaccines is the proprietary lipid nanoparticle — the delivery vehicle if you will.”

Both vaccines “appear very similar in their capacity to protect against disease, to protect [people in] various racial and ethnic backgrounds, and in their capacity to protect against severe disease,” Offit said.

In terms of vaccines in the development pipeline, “We don’t know but we might start to see a difference with the Johnson & Johnson vaccine or the Janssen vaccine, which are single dose. They might confer some advantages, but we are waiting on the safety and efficacy data,” Schrantz said.

As a two-dose vaccine, the AstraZeneca product does not offer an advantage on the dosing strategy, “but it is easier to transport than the mRNA vaccines,” he said. Some concerns with the initial data on the AstraZeneca vaccine will likely need to be addressed before the company applies for an EUA, Schrantz added.

“That is an important question,” El Sahly said. The ongoing studies should provide more data from participants of all ages and ethnic backgrounds that “will allow us to make a determination as to whether there is any difference between these two vaccines.

She added that the Pfizer and Moderna vaccines seem comparable from the early data. “We’ll see if this stands in the long run.”

Future outlook

Now that the FDA approved emergency use of two COVID-19 vaccines, “we need each state to quickly implement their plans to get the vaccines into the hands of providers who need to give the vaccines,” Mehta said. “We are seeing very effective rollout in multiple regions of the country. And we hope to see that continue as we get more vaccines from manufacturers over the coming months.”

“Within a year of identifying the sequence of this virus we have two large clinical vaccine trials that show efficacy,” Offit said. “That was an amazing technologic accomplishment, but now comes the hard part. Mass producing this vaccine, getting it out there, making sure everybody who most benefits gets it, is going to be really, really hard.”

“But I’m optimistic,” Offit said. “If we can do this by next Thanksgiving, we’re going to see a dramatic drop in the number of cases, hospitalizations and deaths, and we can get our lives back together again.”

“My greatest hope is that a year from now we look back and realize we did something really amazing together,” Bailey said, “and we have a feeling of accomplishment and appreciation for all the hard work that has been done.”

Mehta shared the important message he shares when walking around the hospital: “While these vaccines are coming and they are very promising, we need to continue to remember the 3 Ws: wearing a mask, washing your hands, and watching your distance,” he said.

“With the combination of those 3Ws and those vaccines, we will hopefully come through this COVID pandemic.”

El Sahly receives funding through the NIH for her research, including her role as co-chair of the Moderna vaccine phase 3 clinical trial. Schrantz is a site investigator for the Moderna and Janssen vaccine trials. Mehta also receives funding through the NIH. None of these experts had any relevant financial disclosures.

This article first appeared on Medscape.com.

As expected, the US Food and Drug Administration granted Moderna an emergency use authorization (EUA) for its messenger RNA COVID-19 vaccine December 18. The vaccine becomes the second authorized for emergency use in the United States, and will likely increase the number of vaccine doses available in the coming days.

There is one final step — the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices will need to recommend its use, as it did 2 days after the Pfizer/BioNTech mRNA vaccine received its EUA on December 10.

The EUA for the Moderna vaccine is “a major milestone in trying to contain this pandemic,” Hana Mohammed El Sahly, MD, told Medscape Medical News.

Scaling up distribution of the two vaccine products will come next. She notes that even under less emergent conditions, making sure people who need a vaccine receive it can be hard. “I hope the media attention around this will make more people aware that there are vaccines that might help them,” said El Sahly, chair of the FDA Vaccines and Related Biological Products Advisory Committee (VRBPAC).

The EUA for the Moderna vaccine follows a review by the independent VRBPAC members on December 17, which voted 20-0 with one abstention to recommend the EUA. The vaccine is authorized for use in people 18 and older.


Emergency approval of a second COVID-19 vaccine “is great — we need all the tools we can to fight this pandemic,” Stephen Schrantz, MD, infectious disease specialist and assistant professor of medicine at the University of Chicago, told Medscape Medical News. “The early data coming from Moderna looks good, and I agree with the FDA that an EUA is indicated.

“It’s incumbent upon all us healthcare professionals to put ourselves out there as supporting this vaccine and supporting people getting it,” Schrantz continued. “We want to make sure people who are on the fence understand this is a safe vaccine that has been vetted appropriately through the FDA and through phase 3 clinical trials.”

“I know the critical role physicians play as vaccine influencers,” AMA President Susan Bailey, MD, said during a December 14 webinar for journalists reporting on COVID-19 vaccines. “We have to continue to do what physicians have always done: review the evidence and trust the science. Lives are at stake.” The webinar was cosponsored by the AMA and the Poynter Institute.

Ramping up healthcare provider immunizations

“I am very excited to see the FDA’s positive review of the Moderna vaccine. We have been waiting to have another vaccine we can use for healthcare workers and staff, and now we have it,” Aneesh Mehta, MD, of Emory University School of Medicine in Atlanta, Georgia, told Medscape Medical News.

“We had been hoping for a vaccine with a 70% or 80% efficacy, and to see two vaccines now with greater than 90% efficacy is remarkable,” he added.

The efficacy levels associated with both mRNA vaccines “did exceed expectations for sure — this is not what we built the studies around. It was surprising in the good sense of the word,” said El Sahly, who is also associate professor of molecular virology and microbiology at Baylor College of Medicine in Houston, Texas.

Unanswered questions remain

Schrantz likewise said the high efficacy rate was important but not all that is needed. “[W]hat we know about this vaccine is it is very effective at preventing disease. We don’t have any understanding at this time whether or not these vaccines prevent infection and transmissibility.”

Bailey said, “The jury is still out on whether or not you can still transmit the virus after you’ve had the vaccine. Hopefully not, but we don’t really know that for sure.”

“It’s risky to think that once you get the shot in your arm everything goes back to normal. It doesn’t,” Bailey added.

Another unknown is the duration of protection following immunization. The Pfizer and Moderna products “have similar constructs, seem to have a reasonable safety profile, and excellent short-term efficacy,” El Sahly said. She cautioned, however, that long-term efficacy still needs to be determined.

Whether any rare adverse events will emerge in the long run is another question. Answers could come over time from the ongoing phase 3 trials, as well as from post-EUA surveillance among vaccine recipients.  

“Our work is not done after issuing an EUA,” FDA Commissioner Stephen Hahn, MD, said in a JAMA webinar on December 14. The FDA is closely monitoring for any adverse event rates above the normal background incidence. “We are going to be transparent about it if we are seeing anything that is not at base level.”

“The key is to be humble, keep your eyes open and know that once the vaccine is out there, there may be things we learn that we don’t know now. That is true for virtually any medical innovation,” Paul Offit, MD, director of The Vaccine Education Center at Children’s Hospital of Philadelphia and a member of the FDA VRBPAC, said during the AMA/Poynter Institute webinar.

During the same webinar, an attendee asked about prioritizing immunization for spouses and family members of healthcare workers. “My husband wants to know that too,” replied Patricia A. Stinchfield, APRN, CNP, pediatric nurse practitioner in infectious diseases at Children’s Minnesota, St. Paul.

“It is true we should be thinking about our healthcare workers’ family members. But at this point in time we just don’t have the supplies to address it that way,” said Stinchfield, who is also the president-elect of the National Foundation for Infectious Diseases.

Advantages beyond the numbers?

“The major advantage of having two vaccines is sheer volume,” Mehta said. An additional advantage of more than one product is the potential to offer an option when a specific vaccine is contraindicated. “We could offer someone a different vaccine…similar to what we do with the influenza vaccine.”

“The more the merrier in terms of having more vaccine products,” Schrantz said. Despite differences in shipping, storage, minimum age requirements, and dosing intervals, the Pfizer and Moderna vaccines are very similar, he said. “Really the only difference between these two vaccines is the proprietary lipid nanoparticle — the delivery vehicle if you will.”

Both vaccines “appear very similar in their capacity to protect against disease, to protect [people in] various racial and ethnic backgrounds, and in their capacity to protect against severe disease,” Offit said.

In terms of vaccines in the development pipeline, “We don’t know but we might start to see a difference with the Johnson & Johnson vaccine or the Janssen vaccine, which are single dose. They might confer some advantages, but we are waiting on the safety and efficacy data,” Schrantz said.

As a two-dose vaccine, the AstraZeneca product does not offer an advantage on the dosing strategy, “but it is easier to transport than the mRNA vaccines,” he said. Some concerns with the initial data on the AstraZeneca vaccine will likely need to be addressed before the company applies for an EUA, Schrantz added.

“That is an important question,” El Sahly said. The ongoing studies should provide more data from participants of all ages and ethnic backgrounds that “will allow us to make a determination as to whether there is any difference between these two vaccines.

She added that the Pfizer and Moderna vaccines seem comparable from the early data. “We’ll see if this stands in the long run.”

Future outlook

Now that the FDA approved emergency use of two COVID-19 vaccines, “we need each state to quickly implement their plans to get the vaccines into the hands of providers who need to give the vaccines,” Mehta said. “We are seeing very effective rollout in multiple regions of the country. And we hope to see that continue as we get more vaccines from manufacturers over the coming months.”

“Within a year of identifying the sequence of this virus we have two large clinical vaccine trials that show efficacy,” Offit said. “That was an amazing technologic accomplishment, but now comes the hard part. Mass producing this vaccine, getting it out there, making sure everybody who most benefits gets it, is going to be really, really hard.”

“But I’m optimistic,” Offit said. “If we can do this by next Thanksgiving, we’re going to see a dramatic drop in the number of cases, hospitalizations and deaths, and we can get our lives back together again.”

“My greatest hope is that a year from now we look back and realize we did something really amazing together,” Bailey said, “and we have a feeling of accomplishment and appreciation for all the hard work that has been done.”

Mehta shared the important message he shares when walking around the hospital: “While these vaccines are coming and they are very promising, we need to continue to remember the 3 Ws: wearing a mask, washing your hands, and watching your distance,” he said.

“With the combination of those 3Ws and those vaccines, we will hopefully come through this COVID pandemic.”

El Sahly receives funding through the NIH for her research, including her role as co-chair of the Moderna vaccine phase 3 clinical trial. Schrantz is a site investigator for the Moderna and Janssen vaccine trials. Mehta also receives funding through the NIH. None of these experts had any relevant financial disclosures.

This article first appeared on Medscape.com.

As expected, the US Food and Drug Administration granted Moderna an emergency use authorization (EUA) for its messenger RNA COVID-19 vaccine December 18. The vaccine becomes the second authorized for emergency use in the United States, and will likely increase the number of vaccine doses available in the coming days.

There is one final step — the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices will need to recommend its use, as it did 2 days after the Pfizer/BioNTech mRNA vaccine received its EUA on December 10.

The EUA for the Moderna vaccine is “a major milestone in trying to contain this pandemic,” Hana Mohammed El Sahly, MD, told Medscape Medical News.

Scaling up distribution of the two vaccine products will come next. She notes that even under less emergent conditions, making sure people who need a vaccine receive it can be hard. “I hope the media attention around this will make more people aware that there are vaccines that might help them,” said El Sahly, chair of the FDA Vaccines and Related Biological Products Advisory Committee (VRBPAC).

The EUA for the Moderna vaccine follows a review by the independent VRBPAC members on December 17, which voted 20-0 with one abstention to recommend the EUA. The vaccine is authorized for use in people 18 and older.


Emergency approval of a second COVID-19 vaccine “is great — we need all the tools we can to fight this pandemic,” Stephen Schrantz, MD, infectious disease specialist and assistant professor of medicine at the University of Chicago, told Medscape Medical News. “The early data coming from Moderna looks good, and I agree with the FDA that an EUA is indicated.

“It’s incumbent upon all us healthcare professionals to put ourselves out there as supporting this vaccine and supporting people getting it,” Schrantz continued. “We want to make sure people who are on the fence understand this is a safe vaccine that has been vetted appropriately through the FDA and through phase 3 clinical trials.”

“I know the critical role physicians play as vaccine influencers,” AMA President Susan Bailey, MD, said during a December 14 webinar for journalists reporting on COVID-19 vaccines. “We have to continue to do what physicians have always done: review the evidence and trust the science. Lives are at stake.” The webinar was cosponsored by the AMA and the Poynter Institute.

Ramping up healthcare provider immunizations

“I am very excited to see the FDA’s positive review of the Moderna vaccine. We have been waiting to have another vaccine we can use for healthcare workers and staff, and now we have it,” Aneesh Mehta, MD, of Emory University School of Medicine in Atlanta, Georgia, told Medscape Medical News.

“We had been hoping for a vaccine with a 70% or 80% efficacy, and to see two vaccines now with greater than 90% efficacy is remarkable,” he added.

The efficacy levels associated with both mRNA vaccines “did exceed expectations for sure — this is not what we built the studies around. It was surprising in the good sense of the word,” said El Sahly, who is also associate professor of molecular virology and microbiology at Baylor College of Medicine in Houston, Texas.

Unanswered questions remain

Schrantz likewise said the high efficacy rate was important but not all that is needed. “[W]hat we know about this vaccine is it is very effective at preventing disease. We don’t have any understanding at this time whether or not these vaccines prevent infection and transmissibility.”

Bailey said, “The jury is still out on whether or not you can still transmit the virus after you’ve had the vaccine. Hopefully not, but we don’t really know that for sure.”

“It’s risky to think that once you get the shot in your arm everything goes back to normal. It doesn’t,” Bailey added.

Another unknown is the duration of protection following immunization. The Pfizer and Moderna products “have similar constructs, seem to have a reasonable safety profile, and excellent short-term efficacy,” El Sahly said. She cautioned, however, that long-term efficacy still needs to be determined.

Whether any rare adverse events will emerge in the long run is another question. Answers could come over time from the ongoing phase 3 trials, as well as from post-EUA surveillance among vaccine recipients.  

“Our work is not done after issuing an EUA,” FDA Commissioner Stephen Hahn, MD, said in a JAMA webinar on December 14. The FDA is closely monitoring for any adverse event rates above the normal background incidence. “We are going to be transparent about it if we are seeing anything that is not at base level.”

“The key is to be humble, keep your eyes open and know that once the vaccine is out there, there may be things we learn that we don’t know now. That is true for virtually any medical innovation,” Paul Offit, MD, director of The Vaccine Education Center at Children’s Hospital of Philadelphia and a member of the FDA VRBPAC, said during the AMA/Poynter Institute webinar.

During the same webinar, an attendee asked about prioritizing immunization for spouses and family members of healthcare workers. “My husband wants to know that too,” replied Patricia A. Stinchfield, APRN, CNP, pediatric nurse practitioner in infectious diseases at Children’s Minnesota, St. Paul.

“It is true we should be thinking about our healthcare workers’ family members. But at this point in time we just don’t have the supplies to address it that way,” said Stinchfield, who is also the president-elect of the National Foundation for Infectious Diseases.

Advantages beyond the numbers?

“The major advantage of having two vaccines is sheer volume,” Mehta said. An additional advantage of more than one product is the potential to offer an option when a specific vaccine is contraindicated. “We could offer someone a different vaccine…similar to what we do with the influenza vaccine.”

“The more the merrier in terms of having more vaccine products,” Schrantz said. Despite differences in shipping, storage, minimum age requirements, and dosing intervals, the Pfizer and Moderna vaccines are very similar, he said. “Really the only difference between these two vaccines is the proprietary lipid nanoparticle — the delivery vehicle if you will.”

Both vaccines “appear very similar in their capacity to protect against disease, to protect [people in] various racial and ethnic backgrounds, and in their capacity to protect against severe disease,” Offit said.

In terms of vaccines in the development pipeline, “We don’t know but we might start to see a difference with the Johnson & Johnson vaccine or the Janssen vaccine, which are single dose. They might confer some advantages, but we are waiting on the safety and efficacy data,” Schrantz said.

As a two-dose vaccine, the AstraZeneca product does not offer an advantage on the dosing strategy, “but it is easier to transport than the mRNA vaccines,” he said. Some concerns with the initial data on the AstraZeneca vaccine will likely need to be addressed before the company applies for an EUA, Schrantz added.

“That is an important question,” El Sahly said. The ongoing studies should provide more data from participants of all ages and ethnic backgrounds that “will allow us to make a determination as to whether there is any difference between these two vaccines.

She added that the Pfizer and Moderna vaccines seem comparable from the early data. “We’ll see if this stands in the long run.”

Future outlook

Now that the FDA approved emergency use of two COVID-19 vaccines, “we need each state to quickly implement their plans to get the vaccines into the hands of providers who need to give the vaccines,” Mehta said. “We are seeing very effective rollout in multiple regions of the country. And we hope to see that continue as we get more vaccines from manufacturers over the coming months.”

“Within a year of identifying the sequence of this virus we have two large clinical vaccine trials that show efficacy,” Offit said. “That was an amazing technologic accomplishment, but now comes the hard part. Mass producing this vaccine, getting it out there, making sure everybody who most benefits gets it, is going to be really, really hard.”

“But I’m optimistic,” Offit said. “If we can do this by next Thanksgiving, we’re going to see a dramatic drop in the number of cases, hospitalizations and deaths, and we can get our lives back together again.”

“My greatest hope is that a year from now we look back and realize we did something really amazing together,” Bailey said, “and we have a feeling of accomplishment and appreciation for all the hard work that has been done.”

Mehta shared the important message he shares when walking around the hospital: “While these vaccines are coming and they are very promising, we need to continue to remember the 3 Ws: wearing a mask, washing your hands, and watching your distance,” he said.

“With the combination of those 3Ws and those vaccines, we will hopefully come through this COVID pandemic.”

El Sahly receives funding through the NIH for her research, including her role as co-chair of the Moderna vaccine phase 3 clinical trial. Schrantz is a site investigator for the Moderna and Janssen vaccine trials. Mehta also receives funding through the NIH. None of these experts had any relevant financial disclosures.

This article first appeared on Medscape.com.

The Pfizer COVID-19 vaccine was shown to be highly effective in a large trial, but clinicians will be waiting and watching for reactions and adverse events in their vaccinated patients.

A two-dose regimen of the BNT162b2 mRNA COVID-19 vaccine was found to be safe and 95% effective in preventing SARS-CoV-2 infection in persons aged 16 years and older, according to an ongoing phase 2/3 trial. Pfizer and BioNTech published safety and efficacy results from the landmark global phase 1/2/3 trial of their COVID-19 vaccine candidate in the New England Journal of Medicine .

“We previously reported phase 1 safety and immunogenicity results from clinical trials of the vaccine candidate BNT162b2,” lead author Fernando P. Polack, MD, of Vanderbilt University, Nashville, Tenn., and colleagues wrote. “This data set and [present] trial results are the basis for an application for emergency-use authorization,” they explained.
 

The BNT162b2 vaccine trial

Among 43,448 individuals aged 16 years and older, the efficacy, safety, and immunogenicity of the BNT162b2 vaccine candidate was evaluated in a continuous phase 1/2/3 study. Participants were randomly assigned (1:1) to receive two injections of either 30 mcg of BNT162b2 (n = 21,720) or saline placebo (n = 21,728) administered intramuscularly 21 days apart. The safety evaluation, where subjects were monitored 30 minutes post vaccination for acute reactions, was observer blinded.

Eligibility criteria included healthy individuals or those with stable chronic medical conditions, including viral hepatitis B and C, as well as human immunodeficiency virus. Persons with a diagnosis of an immunocompromising condition, those receiving immunosuppressive therapy, and individuals with a medical history of COVID-19 were excluded.

The first primary endpoint was efficacy of BNT162b2 against laboratory-confirmed COVID-19 with onset at least 7 days following the second dose. The primary safety endpoint was local and systemic reactions occurring within 7 days post injection of BNT162b2 or placebo.
 

Safety

“At the data cutoff date of Oct. 9, a total of 37,706 participants had a median of at least 2 months of safety data available after the second dose and contributed to the main safety data set,” the authors wrote.

Among these participants, 83% were White, 28% were Hispanic or Latinx, and 9% were Black or African American; 49% of subjects were female and the median age was 52 years, with 42% over aged 55 years.

Overall, BNT162b2 had a favorable safety profile. Mild to moderate pain at the injection site within 7 days after the injection was the most frequently reported local reaction (<1% across all age groups reported severe pain). Most local reactions resolved within 1-2 days and no grade 4 reactions were reported.

The investigators reported: “Fever (temperature, ≥38° C) was reported after the second dose by 16% of younger vaccine recipients and by 11% of older recipients. Only 0.2% of vaccine recipients and 0.1% of placebo recipients reported fever (temperature, 38.9-40° C) after the first dose, as compared with 0.8% and 0.1%, respectively, after the second dose.”

BNT162b2 recipients had more injection-site pain than those receiving the placebo. After the first and second doses, younger recipients (under 55 years) had more pain at the injection site (83 vs. 14 and 78 vs. 12 events, respectively), redness (5 vs. 1 and 6 vs. 1), and swelling (6 vs. 0 and 6 vs. 0), compared with placebo recipients.

The same trend was observed for patients aged over 55 years, with vaccine recipients reporting more pain at the injection site (71 vs. 9 and 66 vs. 8 events, respectively), redness (5 vs. 1 and 7 vs. 1), and swelling (7 vs. 1 and 7 vs. 1) than placebo recipients.

Pain was less common overall among vaccine recipients aged over 55 years (71% reported pain after the first dose; 66% post second dose) than among younger vaccine recipients (83% post first dose; 78% post second dose).

The most common systemic events following the second dose were fatigue and headache, which occurred in 59% and 52% of younger vaccine recipients and 51% and 39% of older vaccine recipients, respectively. But fatigue and headache were also reported by participants in the placebo group (23% and 24%, respectively, post second dose, among younger vaccine recipients; 17% and 14% among older recipients).

The incidence of serious adverse events was low and similar in the vaccine (0.6%) and placebo (0.5%) arms. Severe systemic events occurred in 2% or less of vaccine recipients following either dose, except for fatigue (3.8%) and headache (2.0%) post second dose. No deaths were considered to be vaccine or placebo related.

“The safety appears comparable to other vaccines, but the relatively short period of observation, 2 months, and the relatively small number of subjects who have received the vaccine (less than 30,000), compared to the hundreds of millions likely to ultimately receive the vaccine, precludes conclusions regarding the potential for rare long term adverse effects,” David L. Bowton, MD, FCCP, a pulmonologist and professor emeritus of critical care anesthesiology at Wake Forest University, Winston-Salem, N.C., said in an interview. “Clinicians should be aware of the risk of anaphylactic reactions and discuss it with their patients [who have] a history of these reactions.”
 

Efficacy

Among 36,523 subjects without evidence of existing or prior COVID-19 infection, 8 cases of COVID-19 with onset at least 7 days after the second dose were seen among vaccine recipients and 162 among placebo recipients, corresponding to 95.0% vaccine efficacy (95% credible interval, 90.3%-97.6%).

“Supplemental analyses indicated that vaccine efficacy among subgroups defined by age, sex, race, ethnicity, obesity, and presence of a coexisting condition was generally consistent with that observed in the overall population,” the authors wrote.

Between the first and second doses, 39 cases of COVID-19 were observed among BNT162b2 recipients and 82 cases among placebo recipients, corresponding to 52% vaccine efficacy during the 21-day interval (95% CI, 29.5%-68.4%) suggesting early protection may begin as soon as 12 days after the first injection.

“This is an incredible achievement given that an effective vaccine has never been developed and approved for use in such a short timeframe,” Dr. Bowton explained. “That the vaccine is highly effective in reducing the incidence of symptomatic COVID-19 seems incontrovertible.”

“This vaccine has shockingly amazing efficacy and is well tolerated, and the results are beyond even optimistic projections,” Douglas S. Paauw, MD, of the University of Washington, Seattle, said in an interview.
 

Questions remain

“It is not yet known if the vaccine prevents asymptomatic infections, with their attendant risk of contagion, as rates of seroconversion of trial participants against betacoronavirus nucleoproteins not included in the vaccine has not been reported,” Dr. Bowton commented.

“Common questions our patients will ask us remain unanswered for now, [including] how long will the protection last, is it safe in pregnant women, and does it prevent asymptomatic infection,” Dr. Paauw explained. “We do not know everything about longer term side effects, but the benefits of this vaccine appear to outweigh the risks of the vaccine.”

The researchers noted these and other limitations in their report, acknowledging that longer follow-up is needed to evaluate long-term safety of the vaccine.

This study was supported by BioNTech and Pfizer. Several authors disclosed financial relationships with Pfizer and other pharmaceutical companies outside the submitted work. Dr. Bowton and Dr. Paauw had no conflicts to disclose.

SOURCE: Polack FP et al. N Engl J Med. 2020 Dec 10. doi: 10.1056/NEJMoa2034577
 

The Pfizer COVID-19 vaccine was shown to be highly effective in a large trial, but clinicians will be waiting and watching for reactions and adverse events in their vaccinated patients.

A two-dose regimen of the BNT162b2 mRNA COVID-19 vaccine was found to be safe and 95% effective in preventing SARS-CoV-2 infection in persons aged 16 years and older, according to an ongoing phase 2/3 trial. Pfizer and BioNTech published safety and efficacy results from the landmark global phase 1/2/3 trial of their COVID-19 vaccine candidate in the New England Journal of Medicine .

“We previously reported phase 1 safety and immunogenicity results from clinical trials of the vaccine candidate BNT162b2,” lead author Fernando P. Polack, MD, of Vanderbilt University, Nashville, Tenn., and colleagues wrote. “This data set and [present] trial results are the basis for an application for emergency-use authorization,” they explained.
 

The BNT162b2 vaccine trial

Among 43,448 individuals aged 16 years and older, the efficacy, safety, and immunogenicity of the BNT162b2 vaccine candidate was evaluated in a continuous phase 1/2/3 study. Participants were randomly assigned (1:1) to receive two injections of either 30 mcg of BNT162b2 (n = 21,720) or saline placebo (n = 21,728) administered intramuscularly 21 days apart. The safety evaluation, where subjects were monitored 30 minutes post vaccination for acute reactions, was observer blinded.

Eligibility criteria included healthy individuals or those with stable chronic medical conditions, including viral hepatitis B and C, as well as human immunodeficiency virus. Persons with a diagnosis of an immunocompromising condition, those receiving immunosuppressive therapy, and individuals with a medical history of COVID-19 were excluded.

The first primary endpoint was efficacy of BNT162b2 against laboratory-confirmed COVID-19 with onset at least 7 days following the second dose. The primary safety endpoint was local and systemic reactions occurring within 7 days post injection of BNT162b2 or placebo.
 

Safety

“At the data cutoff date of Oct. 9, a total of 37,706 participants had a median of at least 2 months of safety data available after the second dose and contributed to the main safety data set,” the authors wrote.

Among these participants, 83% were White, 28% were Hispanic or Latinx, and 9% were Black or African American; 49% of subjects were female and the median age was 52 years, with 42% over aged 55 years.

Overall, BNT162b2 had a favorable safety profile. Mild to moderate pain at the injection site within 7 days after the injection was the most frequently reported local reaction (<1% across all age groups reported severe pain). Most local reactions resolved within 1-2 days and no grade 4 reactions were reported.

The investigators reported: “Fever (temperature, ≥38° C) was reported after the second dose by 16% of younger vaccine recipients and by 11% of older recipients. Only 0.2% of vaccine recipients and 0.1% of placebo recipients reported fever (temperature, 38.9-40° C) after the first dose, as compared with 0.8% and 0.1%, respectively, after the second dose.”

BNT162b2 recipients had more injection-site pain than those receiving the placebo. After the first and second doses, younger recipients (under 55 years) had more pain at the injection site (83 vs. 14 and 78 vs. 12 events, respectively), redness (5 vs. 1 and 6 vs. 1), and swelling (6 vs. 0 and 6 vs. 0), compared with placebo recipients.

The same trend was observed for patients aged over 55 years, with vaccine recipients reporting more pain at the injection site (71 vs. 9 and 66 vs. 8 events, respectively), redness (5 vs. 1 and 7 vs. 1), and swelling (7 vs. 1 and 7 vs. 1) than placebo recipients.

Pain was less common overall among vaccine recipients aged over 55 years (71% reported pain after the first dose; 66% post second dose) than among younger vaccine recipients (83% post first dose; 78% post second dose).

The most common systemic events following the second dose were fatigue and headache, which occurred in 59% and 52% of younger vaccine recipients and 51% and 39% of older vaccine recipients, respectively. But fatigue and headache were also reported by participants in the placebo group (23% and 24%, respectively, post second dose, among younger vaccine recipients; 17% and 14% among older recipients).

The incidence of serious adverse events was low and similar in the vaccine (0.6%) and placebo (0.5%) arms. Severe systemic events occurred in 2% or less of vaccine recipients following either dose, except for fatigue (3.8%) and headache (2.0%) post second dose. No deaths were considered to be vaccine or placebo related.

“The safety appears comparable to other vaccines, but the relatively short period of observation, 2 months, and the relatively small number of subjects who have received the vaccine (less than 30,000), compared to the hundreds of millions likely to ultimately receive the vaccine, precludes conclusions regarding the potential for rare long term adverse effects,” David L. Bowton, MD, FCCP, a pulmonologist and professor emeritus of critical care anesthesiology at Wake Forest University, Winston-Salem, N.C., said in an interview. “Clinicians should be aware of the risk of anaphylactic reactions and discuss it with their patients [who have] a history of these reactions.”
 

Efficacy

Among 36,523 subjects without evidence of existing or prior COVID-19 infection, 8 cases of COVID-19 with onset at least 7 days after the second dose were seen among vaccine recipients and 162 among placebo recipients, corresponding to 95.0% vaccine efficacy (95% credible interval, 90.3%-97.6%).

“Supplemental analyses indicated that vaccine efficacy among subgroups defined by age, sex, race, ethnicity, obesity, and presence of a coexisting condition was generally consistent with that observed in the overall population,” the authors wrote.

Between the first and second doses, 39 cases of COVID-19 were observed among BNT162b2 recipients and 82 cases among placebo recipients, corresponding to 52% vaccine efficacy during the 21-day interval (95% CI, 29.5%-68.4%) suggesting early protection may begin as soon as 12 days after the first injection.

“This is an incredible achievement given that an effective vaccine has never been developed and approved for use in such a short timeframe,” Dr. Bowton explained. “That the vaccine is highly effective in reducing the incidence of symptomatic COVID-19 seems incontrovertible.”

“This vaccine has shockingly amazing efficacy and is well tolerated, and the results are beyond even optimistic projections,” Douglas S. Paauw, MD, of the University of Washington, Seattle, said in an interview.
 

Questions remain

“It is not yet known if the vaccine prevents asymptomatic infections, with their attendant risk of contagion, as rates of seroconversion of trial participants against betacoronavirus nucleoproteins not included in the vaccine has not been reported,” Dr. Bowton commented.

“Common questions our patients will ask us remain unanswered for now, [including] how long will the protection last, is it safe in pregnant women, and does it prevent asymptomatic infection,” Dr. Paauw explained. “We do not know everything about longer term side effects, but the benefits of this vaccine appear to outweigh the risks of the vaccine.”

The researchers noted these and other limitations in their report, acknowledging that longer follow-up is needed to evaluate long-term safety of the vaccine.

This study was supported by BioNTech and Pfizer. Several authors disclosed financial relationships with Pfizer and other pharmaceutical companies outside the submitted work. Dr. Bowton and Dr. Paauw had no conflicts to disclose.

SOURCE: Polack FP et al. N Engl J Med. 2020 Dec 10. doi: 10.1056/NEJMoa2034577
 

The Pfizer COVID-19 vaccine was shown to be highly effective in a large trial, but clinicians will be waiting and watching for reactions and adverse events in their vaccinated patients.

A two-dose regimen of the BNT162b2 mRNA COVID-19 vaccine was found to be safe and 95% effective in preventing SARS-CoV-2 infection in persons aged 16 years and older, according to an ongoing phase 2/3 trial. Pfizer and BioNTech published safety and efficacy results from the landmark global phase 1/2/3 trial of their COVID-19 vaccine candidate in the New England Journal of Medicine .

“We previously reported phase 1 safety and immunogenicity results from clinical trials of the vaccine candidate BNT162b2,” lead author Fernando P. Polack, MD, of Vanderbilt University, Nashville, Tenn., and colleagues wrote. “This data set and [present] trial results are the basis for an application for emergency-use authorization,” they explained.
 

The BNT162b2 vaccine trial

Among 43,448 individuals aged 16 years and older, the efficacy, safety, and immunogenicity of the BNT162b2 vaccine candidate was evaluated in a continuous phase 1/2/3 study. Participants were randomly assigned (1:1) to receive two injections of either 30 mcg of BNT162b2 (n = 21,720) or saline placebo (n = 21,728) administered intramuscularly 21 days apart. The safety evaluation, where subjects were monitored 30 minutes post vaccination for acute reactions, was observer blinded.

Eligibility criteria included healthy individuals or those with stable chronic medical conditions, including viral hepatitis B and C, as well as human immunodeficiency virus. Persons with a diagnosis of an immunocompromising condition, those receiving immunosuppressive therapy, and individuals with a medical history of COVID-19 were excluded.

The first primary endpoint was efficacy of BNT162b2 against laboratory-confirmed COVID-19 with onset at least 7 days following the second dose. The primary safety endpoint was local and systemic reactions occurring within 7 days post injection of BNT162b2 or placebo.
 

Safety

“At the data cutoff date of Oct. 9, a total of 37,706 participants had a median of at least 2 months of safety data available after the second dose and contributed to the main safety data set,” the authors wrote.

Among these participants, 83% were White, 28% were Hispanic or Latinx, and 9% were Black or African American; 49% of subjects were female and the median age was 52 years, with 42% over aged 55 years.

Overall, BNT162b2 had a favorable safety profile. Mild to moderate pain at the injection site within 7 days after the injection was the most frequently reported local reaction (<1% across all age groups reported severe pain). Most local reactions resolved within 1-2 days and no grade 4 reactions were reported.

The investigators reported: “Fever (temperature, ≥38° C) was reported after the second dose by 16% of younger vaccine recipients and by 11% of older recipients. Only 0.2% of vaccine recipients and 0.1% of placebo recipients reported fever (temperature, 38.9-40° C) after the first dose, as compared with 0.8% and 0.1%, respectively, after the second dose.”

BNT162b2 recipients had more injection-site pain than those receiving the placebo. After the first and second doses, younger recipients (under 55 years) had more pain at the injection site (83 vs. 14 and 78 vs. 12 events, respectively), redness (5 vs. 1 and 6 vs. 1), and swelling (6 vs. 0 and 6 vs. 0), compared with placebo recipients.

The same trend was observed for patients aged over 55 years, with vaccine recipients reporting more pain at the injection site (71 vs. 9 and 66 vs. 8 events, respectively), redness (5 vs. 1 and 7 vs. 1), and swelling (7 vs. 1 and 7 vs. 1) than placebo recipients.

Pain was less common overall among vaccine recipients aged over 55 years (71% reported pain after the first dose; 66% post second dose) than among younger vaccine recipients (83% post first dose; 78% post second dose).

The most common systemic events following the second dose were fatigue and headache, which occurred in 59% and 52% of younger vaccine recipients and 51% and 39% of older vaccine recipients, respectively. But fatigue and headache were also reported by participants in the placebo group (23% and 24%, respectively, post second dose, among younger vaccine recipients; 17% and 14% among older recipients).

The incidence of serious adverse events was low and similar in the vaccine (0.6%) and placebo (0.5%) arms. Severe systemic events occurred in 2% or less of vaccine recipients following either dose, except for fatigue (3.8%) and headache (2.0%) post second dose. No deaths were considered to be vaccine or placebo related.

“The safety appears comparable to other vaccines, but the relatively short period of observation, 2 months, and the relatively small number of subjects who have received the vaccine (less than 30,000), compared to the hundreds of millions likely to ultimately receive the vaccine, precludes conclusions regarding the potential for rare long term adverse effects,” David L. Bowton, MD, FCCP, a pulmonologist and professor emeritus of critical care anesthesiology at Wake Forest University, Winston-Salem, N.C., said in an interview. “Clinicians should be aware of the risk of anaphylactic reactions and discuss it with their patients [who have] a history of these reactions.”
 

Efficacy

Among 36,523 subjects without evidence of existing or prior COVID-19 infection, 8 cases of COVID-19 with onset at least 7 days after the second dose were seen among vaccine recipients and 162 among placebo recipients, corresponding to 95.0% vaccine efficacy (95% credible interval, 90.3%-97.6%).

“Supplemental analyses indicated that vaccine efficacy among subgroups defined by age, sex, race, ethnicity, obesity, and presence of a coexisting condition was generally consistent with that observed in the overall population,” the authors wrote.

Between the first and second doses, 39 cases of COVID-19 were observed among BNT162b2 recipients and 82 cases among placebo recipients, corresponding to 52% vaccine efficacy during the 21-day interval (95% CI, 29.5%-68.4%) suggesting early protection may begin as soon as 12 days after the first injection.

“This is an incredible achievement given that an effective vaccine has never been developed and approved for use in such a short timeframe,” Dr. Bowton explained. “That the vaccine is highly effective in reducing the incidence of symptomatic COVID-19 seems incontrovertible.”

“This vaccine has shockingly amazing efficacy and is well tolerated, and the results are beyond even optimistic projections,” Douglas S. Paauw, MD, of the University of Washington, Seattle, said in an interview.
 

Questions remain

“It is not yet known if the vaccine prevents asymptomatic infections, with their attendant risk of contagion, as rates of seroconversion of trial participants against betacoronavirus nucleoproteins not included in the vaccine has not been reported,” Dr. Bowton commented.

“Common questions our patients will ask us remain unanswered for now, [including] how long will the protection last, is it safe in pregnant women, and does it prevent asymptomatic infection,” Dr. Paauw explained. “We do not know everything about longer term side effects, but the benefits of this vaccine appear to outweigh the risks of the vaccine.”

The researchers noted these and other limitations in their report, acknowledging that longer follow-up is needed to evaluate long-term safety of the vaccine.

This study was supported by BioNTech and Pfizer. Several authors disclosed financial relationships with Pfizer and other pharmaceutical companies outside the submitted work. Dr. Bowton and Dr. Paauw had no conflicts to disclose.

SOURCE: Polack FP et al. N Engl J Med. 2020 Dec 10. doi: 10.1056/NEJMoa2034577
 

A Food and Drug Administration advisory committee lit a long-standing fuse, recommending that evidence from the controversial TOPCAT trial can be used to support a new indication for spironolactone.

The generic aldosterone blocker is already approved for the treatment of heart failure with reduced ejection fraction (HFrEF). 

Hopes that it could be the first therapy to show improved outcomes in HF with preserved EF (HFpEF) were dashed in 2013 when TOPCAT failed to show a significant benefit over placebo for the primary endpoint of cardiovascular (CV) death, HF hospitalization, or aborted cardiac arrest.

Regional differences in the data, however, aroused concerns about the findings early on. Patients enrolled in Russia and the Republic of Georgia were younger, less likely to qualify on the basis of elevated natriuretic peptide levels, and had more evidence of ischemic heart disease than those in the Americas.

Event rates were also substantially lower in Russia/Georgia than in the Americas and in previous HFpEF trials, suggesting that many of these patients may not have had heart failure, the trialists argued.

In the Americas, results for the primary endpoint favor spironolactone over placebo (10.4 vs. 12.6 events per 100 patient-years; P = .026), whereas the rate in Russia/Georgia was much lower than in the Americas and slightly favors placebo (2.5 vs. 2.3 events/100 patient-years).

Medication noncompliance also may have been more common in Russia/Georgia based on pharmacodynamic studies and a 2017 analysis showing undetectable levels of canrenone, an active metabolite of spironolactone, in 30% of Russian versus 3% of North American patients who reported using the drug at 1 year.

TOPCAT investigator Marc Pfeffer, MD, PhD, from Brigham and Women’s Hospital and Harvard Medical School, Boston, said no trial is without flaws but that the observations represent serious misconduct. “Really we’re talking about a cancer, a cancer that has clear margins. The margins are Russia, Georgia that warrant censoring their data.”

The FDA’s own review of the National Institutes of Health–sponsored study, however, showed no significant interaction between treatment and region (P = .12) and “insufficient evidence to conclude the two regions are different enough such that overall results should not be considered,” said FDA statistician Ququan Liu, MD, MS.

She cautioned against removing data from a whole region that constituted almost half the study population and said it would set a precedent on what is considered substantial evidence for approval.

Several advisors concurred but, ultimately, the Cardiovascular and Renal Drugs Advisory Committee voted 8 to 4, with 1 abstention, that TOPCAT provides “sufficient evidence to support any indication.”

The same committee voted yesterday in support of an expanded role for sacubitril/valsartan (Entresto, Novartis) in select patients with HFpEF. In casting a “no” vote, panelist Steven E. Nissen, MD, from the Cleveland Clinic, said that decisions made by the panel set precedent.

Catherine Hackett

“If the pharmaceutical industry came to us with a study like this and said the P value was .14 but we think a bunch of our sites weren’t very good and so we’re going to throw those data out and just look at the sites we like, the FDA would not have even brought that before us,” he said. “I cannot hold other sponsors, including our own government, to a different standard.”

Dr. Nissen argued that the primary endpoint failed by a significant margin (P = .138), the study was marginally powered, there was a troubling amount of missing data in the two regions, and spironolactone is also not without side effects. “Poor study conduct cannot be an excuse for a result we don’t like.”

Panel chair Julia B. Lewis, MD, from Vanderbilt University Medical Center in Nashville, Tenn., said she would love to support a cheap, generic drug to keep HF patients out of the hospital but was troubled by the egregious conduct of the trial and concerns about cherry-picking results. “My heart says this would be a great place for us to go but I can’t say that my head thinks this is an acceptable body of data.”

Several panelists, however, highlighted the benefits with spironolactone over placebo in the Americas including an 18% reduction in hospitalization for HF (21% vs. 25%; hazard ratio, 0.82; P = .04) and a 25% reduction in cumulative HF hospitalizations (361 vs. 438 events; incidence rate ratio, 0.75; P = .024).

There was also a reduction in CV mortality with spironolactone (11% vs. 14%; HR, 0.74; P = .027) – something, it was noted, not observed during the prior day’s proceeding on sacubitril/valsartan.

Panelist Christopher M. O’Connor, MD, from Inova Heart and Vascular Institute in Falls Church, Va., and Duke University, Durham, N.C., said he voted “yes” because of the totality of the information and that the investigators provided “compelling evidence” with or without the Russia/Georgia cohort on the efficacy on HF hospitalization reduction. “I think this is the augmented sweet spot of this data set.”

C. Michael Gibson, MD, said his decision to vote yes was not based on analyses that excluded half the patients but rather on the totality of the evidence, particularly the benefit on cumulative HF hospitalizations and in those with an EF lower than 56%.

Several panelists and members of the public cited for treatments among patients with HFpEF. Edward K. Kasper, MD, from Johns Hopkins University, Baltimore, said he found both sides of the argument persuasive but that he already uses spironolactone in this setting. “Somehow I’ve become convinced that this drug worked, so I voted yes.”

Dr. Kasper said the FDA may ultimately find there isn’t an indication for spironolactone in HFpEF but that it will likely move from a IIb to IIa recommendation in the next iteration of the American College of Cardiology guidelines.

Paul Ridker, MD, MPH, from Brigham and Women’s Hospital and Harvard Medical School, said he shared concerns about the precedent of dropping half the data, “even though, in this case, I believe half the data is wrong.”

Dr. Ridker noted that he would have been comfortable using the secondary endpoint of HF reduction as an indication in patients with mildly reduced EF but abstained because that data was not presented today, although it may be available from TOPCAT and the RALES trial.

The panel took up other nonvoting questions, including what additional data would be needed to augment support for approval. Suggestions ranged from additional analyses to a new trial, with TOPCAT serving as “pilot data,” but no recommendation was made.

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

A Food and Drug Administration advisory committee lit a long-standing fuse, recommending that evidence from the controversial TOPCAT trial can be used to support a new indication for spironolactone.

The generic aldosterone blocker is already approved for the treatment of heart failure with reduced ejection fraction (HFrEF). 

Hopes that it could be the first therapy to show improved outcomes in HF with preserved EF (HFpEF) were dashed in 2013 when TOPCAT failed to show a significant benefit over placebo for the primary endpoint of cardiovascular (CV) death, HF hospitalization, or aborted cardiac arrest.

Regional differences in the data, however, aroused concerns about the findings early on. Patients enrolled in Russia and the Republic of Georgia were younger, less likely to qualify on the basis of elevated natriuretic peptide levels, and had more evidence of ischemic heart disease than those in the Americas.

Event rates were also substantially lower in Russia/Georgia than in the Americas and in previous HFpEF trials, suggesting that many of these patients may not have had heart failure, the trialists argued.

In the Americas, results for the primary endpoint favor spironolactone over placebo (10.4 vs. 12.6 events per 100 patient-years; P = .026), whereas the rate in Russia/Georgia was much lower than in the Americas and slightly favors placebo (2.5 vs. 2.3 events/100 patient-years).

Medication noncompliance also may have been more common in Russia/Georgia based on pharmacodynamic studies and a 2017 analysis showing undetectable levels of canrenone, an active metabolite of spironolactone, in 30% of Russian versus 3% of North American patients who reported using the drug at 1 year.

TOPCAT investigator Marc Pfeffer, MD, PhD, from Brigham and Women’s Hospital and Harvard Medical School, Boston, said no trial is without flaws but that the observations represent serious misconduct. “Really we’re talking about a cancer, a cancer that has clear margins. The margins are Russia, Georgia that warrant censoring their data.”

The FDA’s own review of the National Institutes of Health–sponsored study, however, showed no significant interaction between treatment and region (P = .12) and “insufficient evidence to conclude the two regions are different enough such that overall results should not be considered,” said FDA statistician Ququan Liu, MD, MS.

She cautioned against removing data from a whole region that constituted almost half the study population and said it would set a precedent on what is considered substantial evidence for approval.

Several advisors concurred but, ultimately, the Cardiovascular and Renal Drugs Advisory Committee voted 8 to 4, with 1 abstention, that TOPCAT provides “sufficient evidence to support any indication.”

The same committee voted yesterday in support of an expanded role for sacubitril/valsartan (Entresto, Novartis) in select patients with HFpEF. In casting a “no” vote, panelist Steven E. Nissen, MD, from the Cleveland Clinic, said that decisions made by the panel set precedent.

Catherine Hackett

“If the pharmaceutical industry came to us with a study like this and said the P value was .14 but we think a bunch of our sites weren’t very good and so we’re going to throw those data out and just look at the sites we like, the FDA would not have even brought that before us,” he said. “I cannot hold other sponsors, including our own government, to a different standard.”

Dr. Nissen argued that the primary endpoint failed by a significant margin (P = .138), the study was marginally powered, there was a troubling amount of missing data in the two regions, and spironolactone is also not without side effects. “Poor study conduct cannot be an excuse for a result we don’t like.”

Panel chair Julia B. Lewis, MD, from Vanderbilt University Medical Center in Nashville, Tenn., said she would love to support a cheap, generic drug to keep HF patients out of the hospital but was troubled by the egregious conduct of the trial and concerns about cherry-picking results. “My heart says this would be a great place for us to go but I can’t say that my head thinks this is an acceptable body of data.”

Several panelists, however, highlighted the benefits with spironolactone over placebo in the Americas including an 18% reduction in hospitalization for HF (21% vs. 25%; hazard ratio, 0.82; P = .04) and a 25% reduction in cumulative HF hospitalizations (361 vs. 438 events; incidence rate ratio, 0.75; P = .024).

There was also a reduction in CV mortality with spironolactone (11% vs. 14%; HR, 0.74; P = .027) – something, it was noted, not observed during the prior day’s proceeding on sacubitril/valsartan.

Panelist Christopher M. O’Connor, MD, from Inova Heart and Vascular Institute in Falls Church, Va., and Duke University, Durham, N.C., said he voted “yes” because of the totality of the information and that the investigators provided “compelling evidence” with or without the Russia/Georgia cohort on the efficacy on HF hospitalization reduction. “I think this is the augmented sweet spot of this data set.”

C. Michael Gibson, MD, said his decision to vote yes was not based on analyses that excluded half the patients but rather on the totality of the evidence, particularly the benefit on cumulative HF hospitalizations and in those with an EF lower than 56%.

Several panelists and members of the public cited for treatments among patients with HFpEF. Edward K. Kasper, MD, from Johns Hopkins University, Baltimore, said he found both sides of the argument persuasive but that he already uses spironolactone in this setting. “Somehow I’ve become convinced that this drug worked, so I voted yes.”

Dr. Kasper said the FDA may ultimately find there isn’t an indication for spironolactone in HFpEF but that it will likely move from a IIb to IIa recommendation in the next iteration of the American College of Cardiology guidelines.

Paul Ridker, MD, MPH, from Brigham and Women’s Hospital and Harvard Medical School, said he shared concerns about the precedent of dropping half the data, “even though, in this case, I believe half the data is wrong.”

Dr. Ridker noted that he would have been comfortable using the secondary endpoint of HF reduction as an indication in patients with mildly reduced EF but abstained because that data was not presented today, although it may be available from TOPCAT and the RALES trial.

The panel took up other nonvoting questions, including what additional data would be needed to augment support for approval. Suggestions ranged from additional analyses to a new trial, with TOPCAT serving as “pilot data,” but no recommendation was made.

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

A Food and Drug Administration advisory committee lit a long-standing fuse, recommending that evidence from the controversial TOPCAT trial can be used to support a new indication for spironolactone.

The generic aldosterone blocker is already approved for the treatment of heart failure with reduced ejection fraction (HFrEF). 

Hopes that it could be the first therapy to show improved outcomes in HF with preserved EF (HFpEF) were dashed in 2013 when TOPCAT failed to show a significant benefit over placebo for the primary endpoint of cardiovascular (CV) death, HF hospitalization, or aborted cardiac arrest.

Regional differences in the data, however, aroused concerns about the findings early on. Patients enrolled in Russia and the Republic of Georgia were younger, less likely to qualify on the basis of elevated natriuretic peptide levels, and had more evidence of ischemic heart disease than those in the Americas.

Event rates were also substantially lower in Russia/Georgia than in the Americas and in previous HFpEF trials, suggesting that many of these patients may not have had heart failure, the trialists argued.

In the Americas, results for the primary endpoint favor spironolactone over placebo (10.4 vs. 12.6 events per 100 patient-years; P = .026), whereas the rate in Russia/Georgia was much lower than in the Americas and slightly favors placebo (2.5 vs. 2.3 events/100 patient-years).

Medication noncompliance also may have been more common in Russia/Georgia based on pharmacodynamic studies and a 2017 analysis showing undetectable levels of canrenone, an active metabolite of spironolactone, in 30% of Russian versus 3% of North American patients who reported using the drug at 1 year.

TOPCAT investigator Marc Pfeffer, MD, PhD, from Brigham and Women’s Hospital and Harvard Medical School, Boston, said no trial is without flaws but that the observations represent serious misconduct. “Really we’re talking about a cancer, a cancer that has clear margins. The margins are Russia, Georgia that warrant censoring their data.”

The FDA’s own review of the National Institutes of Health–sponsored study, however, showed no significant interaction between treatment and region (P = .12) and “insufficient evidence to conclude the two regions are different enough such that overall results should not be considered,” said FDA statistician Ququan Liu, MD, MS.

She cautioned against removing data from a whole region that constituted almost half the study population and said it would set a precedent on what is considered substantial evidence for approval.

Several advisors concurred but, ultimately, the Cardiovascular and Renal Drugs Advisory Committee voted 8 to 4, with 1 abstention, that TOPCAT provides “sufficient evidence to support any indication.”

The same committee voted yesterday in support of an expanded role for sacubitril/valsartan (Entresto, Novartis) in select patients with HFpEF. In casting a “no” vote, panelist Steven E. Nissen, MD, from the Cleveland Clinic, said that decisions made by the panel set precedent.

Catherine Hackett

“If the pharmaceutical industry came to us with a study like this and said the P value was .14 but we think a bunch of our sites weren’t very good and so we’re going to throw those data out and just look at the sites we like, the FDA would not have even brought that before us,” he said. “I cannot hold other sponsors, including our own government, to a different standard.”

Dr. Nissen argued that the primary endpoint failed by a significant margin (P = .138), the study was marginally powered, there was a troubling amount of missing data in the two regions, and spironolactone is also not without side effects. “Poor study conduct cannot be an excuse for a result we don’t like.”

Panel chair Julia B. Lewis, MD, from Vanderbilt University Medical Center in Nashville, Tenn., said she would love to support a cheap, generic drug to keep HF patients out of the hospital but was troubled by the egregious conduct of the trial and concerns about cherry-picking results. “My heart says this would be a great place for us to go but I can’t say that my head thinks this is an acceptable body of data.”

Several panelists, however, highlighted the benefits with spironolactone over placebo in the Americas including an 18% reduction in hospitalization for HF (21% vs. 25%; hazard ratio, 0.82; P = .04) and a 25% reduction in cumulative HF hospitalizations (361 vs. 438 events; incidence rate ratio, 0.75; P = .024).

There was also a reduction in CV mortality with spironolactone (11% vs. 14%; HR, 0.74; P = .027) – something, it was noted, not observed during the prior day’s proceeding on sacubitril/valsartan.

Panelist Christopher M. O’Connor, MD, from Inova Heart and Vascular Institute in Falls Church, Va., and Duke University, Durham, N.C., said he voted “yes” because of the totality of the information and that the investigators provided “compelling evidence” with or without the Russia/Georgia cohort on the efficacy on HF hospitalization reduction. “I think this is the augmented sweet spot of this data set.”

C. Michael Gibson, MD, said his decision to vote yes was not based on analyses that excluded half the patients but rather on the totality of the evidence, particularly the benefit on cumulative HF hospitalizations and in those with an EF lower than 56%.

Several panelists and members of the public cited for treatments among patients with HFpEF. Edward K. Kasper, MD, from Johns Hopkins University, Baltimore, said he found both sides of the argument persuasive but that he already uses spironolactone in this setting. “Somehow I’ve become convinced that this drug worked, so I voted yes.”

Dr. Kasper said the FDA may ultimately find there isn’t an indication for spironolactone in HFpEF but that it will likely move from a IIb to IIa recommendation in the next iteration of the American College of Cardiology guidelines.

Paul Ridker, MD, MPH, from Brigham and Women’s Hospital and Harvard Medical School, said he shared concerns about the precedent of dropping half the data, “even though, in this case, I believe half the data is wrong.”

Dr. Ridker noted that he would have been comfortable using the secondary endpoint of HF reduction as an indication in patients with mildly reduced EF but abstained because that data was not presented today, although it may be available from TOPCAT and the RALES trial.

The panel took up other nonvoting questions, including what additional data would be needed to augment support for approval. Suggestions ranged from additional analyses to a new trial, with TOPCAT serving as “pilot data,” but no recommendation was made.

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

The 16 million–plus people in the United States, and 72 million worldwide, who have been infected with COVID-19 – and survived – are likely asking themselves the same questions: Am I immune now? Is it over or do I have to brace myself for the possibility of a reinfection? Moreover, could the second time potentially be worse than the first?

I was diagnosed with COVID in March of this year. After spending 10 days in the hospital, and one night in the ICU, it took another 2 months for the air-hunger, headaches, and fatigue to completely resolve. Compared with many other unfortunate victims, I did all right – and I am very grateful for the care I received.

Now, as the surge in cases takes new life, I will be on the front lines taking care of patients. Having had an eventful personal encounter with the virus, I now have a unique vantage point and remain fully committed to paying my fortunate circumstances forward. Although I can’t help but have the same question faced by millions of others: Am I safe now?

It is no surprise that studies have shown health care workers comprising 6% of COVID hospital admissions, with one-third of these admissions being nurses. Recently, we heard that over 900 health care workers at Mayo Clinic had acquired the infection in the first 2 weeks of the ongoing second COVID surge. Are these frontline workers protected? Can they return to work with no fear of a rerun? Or, for that matter, anyone who has been afflicted by COVID – are they now forever immune?

There are no clear answers here. But to understand this a little, let’s quickly revisit some basic principles of immunity.
 

Innate and adaptive immunity

Simply put, there are two forms of immunity: innate and adaptive. Innate immunity encompasses our body’s natural protective mechanisms that come into play almost immediately. This enables recognition of the virus and activates an immediate antiviral defense and attempt at removal of the infective agent. This, however, does not always do the job. Accordingly, a couple weeks after the initial exposure to the pathogen, adaptive immunity is invoked. Circulating white blood cells within our body recognize the virus and set off an immune response, involving the activation of T and B cells that actively attack the infective agent. It is this T- and B-cell–mediated immunity that should protect one against a second infection with the same agent.

What about herd immunity?

Herd immunity is defined as essentially yielding to the virus and letting it spread naturally in order to develop community-wide immunity. By consequence of a large proportion of the population becoming immune after exposure to the disease, person-to-person spread can potentially be mitigated. This does not confer immunity to the virus at the individual level; rather, it reduces the risk of vulnerable people coming in contact with the pathogen.

Unfortunately, depending on herd immunity as a way to deal with COVID-19 has not worked well, even in well-contained countries like Sweden, where a disproportionate number of their most vulnerable populations have died. It is self-evident that containment strategies with vaccination may be our best way forward to achieve herd immunity. Not surrendering to the virus.
 

Am I safe from reinfection?

In all honesty, we’re not entirely sure. But it is important to recognize a few points when considering your relative safety.

• The immune system is far from perfect. Not everyone has a robust immune response. And in those who do, the immune response can wane over time, potentially allowing for reinfection. While rare, there have already been some clearly documented reinfections, four that have been confirmed and published; two patients (in Nevada and Ecuador) actually fared worse the second time around.
• The virus can mutate and escape detection by the immune system. One could still be susceptible to reinfection from a different strain. (At least, this remains the case with the influenza virus.) There is some evidence that SARS-CoV-2 does not mutate rapidly, and hence this may not be a problem. But we don’t know for certain, at least as of yet.
• Even a vigorous immune response can be overwhelmed by the virus. It is unclear whether the relative length of time and the amount of virus exposure could undermine a previously primed immune system.

A prior infection and a consequent healthy immunity may help you combat a reinfection but it does not prevent you from harboring or carrying the virus. You may be asymptomatic, but you can still be a carrier and spread the infection. I am a strong advocate for limiting your exposure to others no matter your previous exposure status, in order to limit the spread of the virus.
 

So, what should I do?

I guess the answer is that you can’t be too careful. Not everyone has had their antibody levels tested, and even if positive, it is unclear how well that affords protection. It is best to presume that you are vulnerable for a reinfection and that you can still carry and spread the virus. This may be the safest approach until we actually achieve herd immunity through vaccination.

Even then, for a period of time, there will remain a sense of uncertainty. So, containment strategies inclusive of distancing and masking will and should remain a way of life at least until mid-2021, when we will be in a better position to reassess the landscape.

The surge is back. As I repay my debt and get back to the front line, I will continue to mask up and practice distancing. I am taking no chances of getting reinfected or being an asymptomatic carrier.

I had COVID, I also have antibodies, and I will be taking the vaccine. I implore you all to do the same.

Jag Singh is a physician, scientist, and professor at Harvard. He is passionate about social issues, leadership, digital health, and medical innovations. You can follow him on Twitter @JagSinghMD.

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

The 16 million–plus people in the United States, and 72 million worldwide, who have been infected with COVID-19 – and survived – are likely asking themselves the same questions: Am I immune now? Is it over or do I have to brace myself for the possibility of a reinfection? Moreover, could the second time potentially be worse than the first?

I was diagnosed with COVID in March of this year. After spending 10 days in the hospital, and one night in the ICU, it took another 2 months for the air-hunger, headaches, and fatigue to completely resolve. Compared with many other unfortunate victims, I did all right – and I am very grateful for the care I received.

Now, as the surge in cases takes new life, I will be on the front lines taking care of patients. Having had an eventful personal encounter with the virus, I now have a unique vantage point and remain fully committed to paying my fortunate circumstances forward. Although I can’t help but have the same question faced by millions of others: Am I safe now?

It is no surprise that studies have shown health care workers comprising 6% of COVID hospital admissions, with one-third of these admissions being nurses. Recently, we heard that over 900 health care workers at Mayo Clinic had acquired the infection in the first 2 weeks of the ongoing second COVID surge. Are these frontline workers protected? Can they return to work with no fear of a rerun? Or, for that matter, anyone who has been afflicted by COVID – are they now forever immune?

There are no clear answers here. But to understand this a little, let’s quickly revisit some basic principles of immunity.
 

Innate and adaptive immunity

Simply put, there are two forms of immunity: innate and adaptive. Innate immunity encompasses our body’s natural protective mechanisms that come into play almost immediately. This enables recognition of the virus and activates an immediate antiviral defense and attempt at removal of the infective agent. This, however, does not always do the job. Accordingly, a couple weeks after the initial exposure to the pathogen, adaptive immunity is invoked. Circulating white blood cells within our body recognize the virus and set off an immune response, involving the activation of T and B cells that actively attack the infective agent. It is this T- and B-cell–mediated immunity that should protect one against a second infection with the same agent.

What about herd immunity?

Herd immunity is defined as essentially yielding to the virus and letting it spread naturally in order to develop community-wide immunity. By consequence of a large proportion of the population becoming immune after exposure to the disease, person-to-person spread can potentially be mitigated. This does not confer immunity to the virus at the individual level; rather, it reduces the risk of vulnerable people coming in contact with the pathogen.

Unfortunately, depending on herd immunity as a way to deal with COVID-19 has not worked well, even in well-contained countries like Sweden, where a disproportionate number of their most vulnerable populations have died. It is self-evident that containment strategies with vaccination may be our best way forward to achieve herd immunity. Not surrendering to the virus.
 

Am I safe from reinfection?

In all honesty, we’re not entirely sure. But it is important to recognize a few points when considering your relative safety.

• The immune system is far from perfect. Not everyone has a robust immune response. And in those who do, the immune response can wane over time, potentially allowing for reinfection. While rare, there have already been some clearly documented reinfections, four that have been confirmed and published; two patients (in Nevada and Ecuador) actually fared worse the second time around.
• The virus can mutate and escape detection by the immune system. One could still be susceptible to reinfection from a different strain. (At least, this remains the case with the influenza virus.) There is some evidence that SARS-CoV-2 does not mutate rapidly, and hence this may not be a problem. But we don’t know for certain, at least as of yet.
• Even a vigorous immune response can be overwhelmed by the virus. It is unclear whether the relative length of time and the amount of virus exposure could undermine a previously primed immune system.

A prior infection and a consequent healthy immunity may help you combat a reinfection but it does not prevent you from harboring or carrying the virus. You may be asymptomatic, but you can still be a carrier and spread the infection. I am a strong advocate for limiting your exposure to others no matter your previous exposure status, in order to limit the spread of the virus.
 

So, what should I do?

I guess the answer is that you can’t be too careful. Not everyone has had their antibody levels tested, and even if positive, it is unclear how well that affords protection. It is best to presume that you are vulnerable for a reinfection and that you can still carry and spread the virus. This may be the safest approach until we actually achieve herd immunity through vaccination.

Even then, for a period of time, there will remain a sense of uncertainty. So, containment strategies inclusive of distancing and masking will and should remain a way of life at least until mid-2021, when we will be in a better position to reassess the landscape.

The surge is back. As I repay my debt and get back to the front line, I will continue to mask up and practice distancing. I am taking no chances of getting reinfected or being an asymptomatic carrier.

I had COVID, I also have antibodies, and I will be taking the vaccine. I implore you all to do the same.

Jag Singh is a physician, scientist, and professor at Harvard. He is passionate about social issues, leadership, digital health, and medical innovations. You can follow him on Twitter @JagSinghMD.

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

The 16 million–plus people in the United States, and 72 million worldwide, who have been infected with COVID-19 – and survived – are likely asking themselves the same questions: Am I immune now? Is it over or do I have to brace myself for the possibility of a reinfection? Moreover, could the second time potentially be worse than the first?

I was diagnosed with COVID in March of this year. After spending 10 days in the hospital, and one night in the ICU, it took another 2 months for the air-hunger, headaches, and fatigue to completely resolve. Compared with many other unfortunate victims, I did all right – and I am very grateful for the care I received.

Now, as the surge in cases takes new life, I will be on the front lines taking care of patients. Having had an eventful personal encounter with the virus, I now have a unique vantage point and remain fully committed to paying my fortunate circumstances forward. Although I can’t help but have the same question faced by millions of others: Am I safe now?

It is no surprise that studies have shown health care workers comprising 6% of COVID hospital admissions, with one-third of these admissions being nurses. Recently, we heard that over 900 health care workers at Mayo Clinic had acquired the infection in the first 2 weeks of the ongoing second COVID surge. Are these frontline workers protected? Can they return to work with no fear of a rerun? Or, for that matter, anyone who has been afflicted by COVID – are they now forever immune?

There are no clear answers here. But to understand this a little, let’s quickly revisit some basic principles of immunity.
 

Innate and adaptive immunity

Simply put, there are two forms of immunity: innate and adaptive. Innate immunity encompasses our body’s natural protective mechanisms that come into play almost immediately. This enables recognition of the virus and activates an immediate antiviral defense and attempt at removal of the infective agent. This, however, does not always do the job. Accordingly, a couple weeks after the initial exposure to the pathogen, adaptive immunity is invoked. Circulating white blood cells within our body recognize the virus and set off an immune response, involving the activation of T and B cells that actively attack the infective agent. It is this T- and B-cell–mediated immunity that should protect one against a second infection with the same agent.

What about herd immunity?

Herd immunity is defined as essentially yielding to the virus and letting it spread naturally in order to develop community-wide immunity. By consequence of a large proportion of the population becoming immune after exposure to the disease, person-to-person spread can potentially be mitigated. This does not confer immunity to the virus at the individual level; rather, it reduces the risk of vulnerable people coming in contact with the pathogen.

Unfortunately, depending on herd immunity as a way to deal with COVID-19 has not worked well, even in well-contained countries like Sweden, where a disproportionate number of their most vulnerable populations have died. It is self-evident that containment strategies with vaccination may be our best way forward to achieve herd immunity. Not surrendering to the virus.
 

Am I safe from reinfection?

In all honesty, we’re not entirely sure. But it is important to recognize a few points when considering your relative safety.

• The immune system is far from perfect. Not everyone has a robust immune response. And in those who do, the immune response can wane over time, potentially allowing for reinfection. While rare, there have already been some clearly documented reinfections, four that have been confirmed and published; two patients (in Nevada and Ecuador) actually fared worse the second time around.
• The virus can mutate and escape detection by the immune system. One could still be susceptible to reinfection from a different strain. (At least, this remains the case with the influenza virus.) There is some evidence that SARS-CoV-2 does not mutate rapidly, and hence this may not be a problem. But we don’t know for certain, at least as of yet.
• Even a vigorous immune response can be overwhelmed by the virus. It is unclear whether the relative length of time and the amount of virus exposure could undermine a previously primed immune system.

A prior infection and a consequent healthy immunity may help you combat a reinfection but it does not prevent you from harboring or carrying the virus. You may be asymptomatic, but you can still be a carrier and spread the infection. I am a strong advocate for limiting your exposure to others no matter your previous exposure status, in order to limit the spread of the virus.
 

So, what should I do?

I guess the answer is that you can’t be too careful. Not everyone has had their antibody levels tested, and even if positive, it is unclear how well that affords protection. It is best to presume that you are vulnerable for a reinfection and that you can still carry and spread the virus. This may be the safest approach until we actually achieve herd immunity through vaccination.

Even then, for a period of time, there will remain a sense of uncertainty. So, containment strategies inclusive of distancing and masking will and should remain a way of life at least until mid-2021, when we will be in a better position to reassess the landscape.

The surge is back. As I repay my debt and get back to the front line, I will continue to mask up and practice distancing. I am taking no chances of getting reinfected or being an asymptomatic carrier.

I had COVID, I also have antibodies, and I will be taking the vaccine. I implore you all to do the same.

Jag Singh is a physician, scientist, and professor at Harvard. He is passionate about social issues, leadership, digital health, and medical innovations. You can follow him on Twitter @JagSinghMD.

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

Levels of nicotine and marijuana vaping among adolescents remain elevated but did not increase significantly in the past year, data from the annual Monitoring the Future survey show.

The 2020 survey included responses from 11,821 individuals in 112 schools across the United States from Feb. 11, 2020, to March 14, 2020, at which time data collection ended prematurely because of the COVID-19 pandemic. The results represent approximately 25% of the usual data collection.

A key positive finding in this year’s survey was the relatively stable levels of nicotine vaping from 2019 to 2020, following a trend of notably increased use annually since vaping was added to the survey in 2017.

During the years 2017-2019, the percentage of teens who reported vaping nicotine in the past 12 months increased from 7.5% to 16.5% among 8th graders, from 15.8% to 30.7% among 10th graders, and from 18.8% to 35.3% among 12th graders. However, in 2020, the percentages of teens who reported past-year nicotine vaping were relatively steady at 16.6%, 30.7%, and 34.5%, for 8th-, 10th-, and 12th-grade students, respectively. In addition, reports of daily or near-daily nicotine vaping (defined as 20 occasions in the past 30 days) decreased significantly, from 6.8% to 3.6% among 10th graders and from 11.6% to 5.3% among 12th graders.

“The rapid rise of teen nicotine vaping in recent years has been unprecedented and deeply concerning since we know that nicotine is highly addictive and can be delivered at high doses by vaping devices, which may also contain other toxic chemicals that may be harmful when inhaled,” said Nora D. Volkow, MD, director of the National Institute on Drug Abuse in a press release accompanying the release of the findings. “It is encouraging to see a leveling off of this trend though the rates still remain very high.”

Reports of past-year marijuana vaping remained similar to 2019 levels after a twofold increase in the past 2 years, according to the survey. In early 2020, 8.1%, 19.1%, and 22.1% of 8th, 10th, and 12th graders reported past-year use. However, daily marijuana vaping decreased by more than half from 2019, to 1.1% among 10th graders and 1.5% among 12th graders.

Past-year use of the JUUL devices specifically also declined among older teens, from 28.7% in 2019 to 20% in 2020 among 10th graders and from 28.4% in 2019 to 22.7% in 2020 among 12th graders.

Other trends this year included the increased past-year use of amphetamines, inhalants, and cough medicines among 8th graders, and relatively low reported use among 12th graders of LSD (3.9%), synthetic cannabinoids (2.4%), cocaine (2.9%), ecstasy (1.8%), methamphetamine (1.4%), and heroin (0.3%).

The findings were published in JAMA Pediatrics.

 

Early data show progress

“The MTF survey is the most referenced and reliable longitudinal study reporting current use of tobacco, drugs, and alcohol among young people,” said Mark S. Gold, MD, of Washington University, St. Louis, in an interview.

“The new data, collected before data collection stopped prematurely due to the COVID-19 pandemic, suggests that some progress is being made in slowing the increase in substance use among these, the most vulnerable,” he said.

“The best news was that nicotine vaping decreased significantly after its meteoric increase over the past few years,” Dr. Gold emphasized. “Past-year vaping of marijuana remained steady at alarming levels in 2020, with 8.1% of 8th graders, 19.1% of 10th graders, and 22.1% of 12th graders reporting past-year use, following a two-fold increase over the past 2 years.” The use of all forms of marijuana, including smoking and vaping, did not significantly change in any of the three grades for lifetime use, past 12-month use, past 30-day use, and daily use from 2019 to 2020.

“Teen alcohol use has not significantly changed over the past 5 years,” and cigarette smoking in the last 30 days did not significantly change from 2019 to 2020, said Dr. Gold. However, “as with adults, psychostimulant use is increasing. Past year nonmedical use of amphetamines among 8th graders increased, from 3.5% in 2017 to 5.3% in 2020.”
 

COVID-era limitations

“The data suggest that pre-COVID pandemic vaping, smoking cigarettes, marijuana, and alcohol use had stabilized,” Dr. Gold said. “However, it is very difficult to predict what the COVID era data will show as many young people are at home, on the streets, and unsupervised; while adult substance misuse, substance use disorders, and overdoses are increasing. Drug supplies and access have increased for alcohol, cannabis, vaping, and tobacco as have supply synthetics like methamphetamine and fentanyl.”

In addition, “access to evaluation, intervention, and treatment have been curtailed during the pandemic,” Dr. Gold said. “The loss of peer role models, daily routine, and teacher or other adult supervision and interventions may interact with increasing despair, social isolation, depression, and anxiety in ways that are unknown. “It will not be clear until the next survey if perceived dangerousness has changed in ways that can protect these 8th, 10th, and 12th graders and increase the numbers of never users or current nonusers.”

The Monitoring the Future survey is conducted each year by the University of Michigan’s Institute for Social Research, Ann Arbor, and supported by NIDA, part of the National Institutes of Health. Dr. Gold had no relevant financial conflicts to disclose.

Levels of nicotine and marijuana vaping among adolescents remain elevated but did not increase significantly in the past year, data from the annual Monitoring the Future survey show.

The 2020 survey included responses from 11,821 individuals in 112 schools across the United States from Feb. 11, 2020, to March 14, 2020, at which time data collection ended prematurely because of the COVID-19 pandemic. The results represent approximately 25% of the usual data collection.

A key positive finding in this year’s survey was the relatively stable levels of nicotine vaping from 2019 to 2020, following a trend of notably increased use annually since vaping was added to the survey in 2017.

During the years 2017-2019, the percentage of teens who reported vaping nicotine in the past 12 months increased from 7.5% to 16.5% among 8th graders, from 15.8% to 30.7% among 10th graders, and from 18.8% to 35.3% among 12th graders. However, in 2020, the percentages of teens who reported past-year nicotine vaping were relatively steady at 16.6%, 30.7%, and 34.5%, for 8th-, 10th-, and 12th-grade students, respectively. In addition, reports of daily or near-daily nicotine vaping (defined as 20 occasions in the past 30 days) decreased significantly, from 6.8% to 3.6% among 10th graders and from 11.6% to 5.3% among 12th graders.

“The rapid rise of teen nicotine vaping in recent years has been unprecedented and deeply concerning since we know that nicotine is highly addictive and can be delivered at high doses by vaping devices, which may also contain other toxic chemicals that may be harmful when inhaled,” said Nora D. Volkow, MD, director of the National Institute on Drug Abuse in a press release accompanying the release of the findings. “It is encouraging to see a leveling off of this trend though the rates still remain very high.”

Reports of past-year marijuana vaping remained similar to 2019 levels after a twofold increase in the past 2 years, according to the survey. In early 2020, 8.1%, 19.1%, and 22.1% of 8th, 10th, and 12th graders reported past-year use. However, daily marijuana vaping decreased by more than half from 2019, to 1.1% among 10th graders and 1.5% among 12th graders.

Past-year use of the JUUL devices specifically also declined among older teens, from 28.7% in 2019 to 20% in 2020 among 10th graders and from 28.4% in 2019 to 22.7% in 2020 among 12th graders.

Other trends this year included the increased past-year use of amphetamines, inhalants, and cough medicines among 8th graders, and relatively low reported use among 12th graders of LSD (3.9%), synthetic cannabinoids (2.4%), cocaine (2.9%), ecstasy (1.8%), methamphetamine (1.4%), and heroin (0.3%).

The findings were published in JAMA Pediatrics.

 

Early data show progress

“The MTF survey is the most referenced and reliable longitudinal study reporting current use of tobacco, drugs, and alcohol among young people,” said Mark S. Gold, MD, of Washington University, St. Louis, in an interview.

“The new data, collected before data collection stopped prematurely due to the COVID-19 pandemic, suggests that some progress is being made in slowing the increase in substance use among these, the most vulnerable,” he said.

“The best news was that nicotine vaping decreased significantly after its meteoric increase over the past few years,” Dr. Gold emphasized. “Past-year vaping of marijuana remained steady at alarming levels in 2020, with 8.1% of 8th graders, 19.1% of 10th graders, and 22.1% of 12th graders reporting past-year use, following a two-fold increase over the past 2 years.” The use of all forms of marijuana, including smoking and vaping, did not significantly change in any of the three grades for lifetime use, past 12-month use, past 30-day use, and daily use from 2019 to 2020.

“Teen alcohol use has not significantly changed over the past 5 years,” and cigarette smoking in the last 30 days did not significantly change from 2019 to 2020, said Dr. Gold. However, “as with adults, psychostimulant use is increasing. Past year nonmedical use of amphetamines among 8th graders increased, from 3.5% in 2017 to 5.3% in 2020.”
 

COVID-era limitations

“The data suggest that pre-COVID pandemic vaping, smoking cigarettes, marijuana, and alcohol use had stabilized,” Dr. Gold said. “However, it is very difficult to predict what the COVID era data will show as many young people are at home, on the streets, and unsupervised; while adult substance misuse, substance use disorders, and overdoses are increasing. Drug supplies and access have increased for alcohol, cannabis, vaping, and tobacco as have supply synthetics like methamphetamine and fentanyl.”

In addition, “access to evaluation, intervention, and treatment have been curtailed during the pandemic,” Dr. Gold said. “The loss of peer role models, daily routine, and teacher or other adult supervision and interventions may interact with increasing despair, social isolation, depression, and anxiety in ways that are unknown. “It will not be clear until the next survey if perceived dangerousness has changed in ways that can protect these 8th, 10th, and 12th graders and increase the numbers of never users or current nonusers.”

The Monitoring the Future survey is conducted each year by the University of Michigan’s Institute for Social Research, Ann Arbor, and supported by NIDA, part of the National Institutes of Health. Dr. Gold had no relevant financial conflicts to disclose.

Levels of nicotine and marijuana vaping among adolescents remain elevated but did not increase significantly in the past year, data from the annual Monitoring the Future survey show.

The 2020 survey included responses from 11,821 individuals in 112 schools across the United States from Feb. 11, 2020, to March 14, 2020, at which time data collection ended prematurely because of the COVID-19 pandemic. The results represent approximately 25% of the usual data collection.

A key positive finding in this year’s survey was the relatively stable levels of nicotine vaping from 2019 to 2020, following a trend of notably increased use annually since vaping was added to the survey in 2017.

During the years 2017-2019, the percentage of teens who reported vaping nicotine in the past 12 months increased from 7.5% to 16.5% among 8th graders, from 15.8% to 30.7% among 10th graders, and from 18.8% to 35.3% among 12th graders. However, in 2020, the percentages of teens who reported past-year nicotine vaping were relatively steady at 16.6%, 30.7%, and 34.5%, for 8th-, 10th-, and 12th-grade students, respectively. In addition, reports of daily or near-daily nicotine vaping (defined as 20 occasions in the past 30 days) decreased significantly, from 6.8% to 3.6% among 10th graders and from 11.6% to 5.3% among 12th graders.

“The rapid rise of teen nicotine vaping in recent years has been unprecedented and deeply concerning since we know that nicotine is highly addictive and can be delivered at high doses by vaping devices, which may also contain other toxic chemicals that may be harmful when inhaled,” said Nora D. Volkow, MD, director of the National Institute on Drug Abuse in a press release accompanying the release of the findings. “It is encouraging to see a leveling off of this trend though the rates still remain very high.”

Reports of past-year marijuana vaping remained similar to 2019 levels after a twofold increase in the past 2 years, according to the survey. In early 2020, 8.1%, 19.1%, and 22.1% of 8th, 10th, and 12th graders reported past-year use. However, daily marijuana vaping decreased by more than half from 2019, to 1.1% among 10th graders and 1.5% among 12th graders.

Past-year use of the JUUL devices specifically also declined among older teens, from 28.7% in 2019 to 20% in 2020 among 10th graders and from 28.4% in 2019 to 22.7% in 2020 among 12th graders.

Other trends this year included the increased past-year use of amphetamines, inhalants, and cough medicines among 8th graders, and relatively low reported use among 12th graders of LSD (3.9%), synthetic cannabinoids (2.4%), cocaine (2.9%), ecstasy (1.8%), methamphetamine (1.4%), and heroin (0.3%).

The findings were published in JAMA Pediatrics.

 

Early data show progress

“The MTF survey is the most referenced and reliable longitudinal study reporting current use of tobacco, drugs, and alcohol among young people,” said Mark S. Gold, MD, of Washington University, St. Louis, in an interview.

“The new data, collected before data collection stopped prematurely due to the COVID-19 pandemic, suggests that some progress is being made in slowing the increase in substance use among these, the most vulnerable,” he said.

“The best news was that nicotine vaping decreased significantly after its meteoric increase over the past few years,” Dr. Gold emphasized. “Past-year vaping of marijuana remained steady at alarming levels in 2020, with 8.1% of 8th graders, 19.1% of 10th graders, and 22.1% of 12th graders reporting past-year use, following a two-fold increase over the past 2 years.” The use of all forms of marijuana, including smoking and vaping, did not significantly change in any of the three grades for lifetime use, past 12-month use, past 30-day use, and daily use from 2019 to 2020.

“Teen alcohol use has not significantly changed over the past 5 years,” and cigarette smoking in the last 30 days did not significantly change from 2019 to 2020, said Dr. Gold. However, “as with adults, psychostimulant use is increasing. Past year nonmedical use of amphetamines among 8th graders increased, from 3.5% in 2017 to 5.3% in 2020.”
 

COVID-era limitations

“The data suggest that pre-COVID pandemic vaping, smoking cigarettes, marijuana, and alcohol use had stabilized,” Dr. Gold said. “However, it is very difficult to predict what the COVID era data will show as many young people are at home, on the streets, and unsupervised; while adult substance misuse, substance use disorders, and overdoses are increasing. Drug supplies and access have increased for alcohol, cannabis, vaping, and tobacco as have supply synthetics like methamphetamine and fentanyl.”

In addition, “access to evaluation, intervention, and treatment have been curtailed during the pandemic,” Dr. Gold said. “The loss of peer role models, daily routine, and teacher or other adult supervision and interventions may interact with increasing despair, social isolation, depression, and anxiety in ways that are unknown. “It will not be clear until the next survey if perceived dangerousness has changed in ways that can protect these 8th, 10th, and 12th graders and increase the numbers of never users or current nonusers.”

The Monitoring the Future survey is conducted each year by the University of Michigan’s Institute for Social Research, Ann Arbor, and supported by NIDA, part of the National Institutes of Health. Dr. Gold had no relevant financial conflicts to disclose.

Sleep medications for older patients who report sleep problems may not be the best treatment given growing evidence of the link between these medications and the risk of incident dementia.

Adults aged 65 years and older who used sleep medications 5-7 days a week demonstrated a 30% increased risk of dementia, compared with those who did not use sleep medications, findings from a prospective study of 6,373 individuals show.

Adults aged 65 and older report a higher burden of sleep problems than other age groups, but major medical associations discourage the use of sleep medications by older adults because of growing evidence of a link between sleep medication use and cognitive decline, wrote Rebecca Robbins, MD, of Brigham and Women’s Hospital, Boston, and colleagues. However, data on this association among adults in the United States are limited, they said.

In a study published in Sleep Medicine, the researchers surveyed 6,373 adults aged 65 years and older who were enrolled in the nationally representative National Health and Aging Trends Study (NHATS). The majority of the participants were non-Hispanic White (71%), 59% were women, and 21% ranged in age from 70 to 74 years.

Participants responded to questions about routine sleep medication use. Routine was defined as “most nights” or “every night.” The data were collected for an 8-year period from 2011 to 2018. The study began in 2011, with a core interview administered annually.

Approximately 15% of the study population reported routine use of sleep medications. Overall, routine use of sleep medication was significantly associated with risk of incident dementia (hazard ratio, 1.30; P < .01) after controlling for multiple variables including age, sex, education level, and chronic conditions.

Dementia screening was conducted by participants rating their memory and then performing a memory-related activity (immediate and delayed 10-word recall) and other exercises to assess executive function and orientation. A separate eight-item informant screener was performed for patient proxies. The researcher noted, “Sensitivity of the NHATS probable dementia screening measure has been determined in previous research to be 66%, and specificity is 87%, with respect to a clinical dementia diagnosis.”

The study findings were limited by several factors including the use of self-reports, the lack of data on type or dose of sleep medication, and lack of data on the indication for the prescription, the researchers noted.

“Also, sleep medication use leads to worse performance on cognitive testing, such as the questionnaires used to screen for dementia in this study, and therefore could have resulted in a false diagnosis of dementia,” they added.

However, the results were strengthened by the large, nationally representative study population and support the need for quality geriatric care, the researchers said.

“Our findings provide further support and evidence that sleep medications are all too commonly administered, yet associated with greater risk for incident dementia, and that the U.S. health care system is in need of creative solutions for addressing poor sleep among older individuals,” they concluded.
 

Implications and alternatives

The study is important as the number of aging Americans increases, said Carolyn M. D’Ambrosio, MD, FCCP, of Brigham and Women’s Hospital and Harvard Medical School, Boston, in an interview. “In the elderly, inability to fall asleep or stay asleep are common issues that are brought to a health care provider,” she said. Dr. D’Ambrosio said she was not surprised by the study findings “as elderly patients often have sleep issues and sometimes a well-meaning health care provider gives them sleep medication to help. We have known that some of these sleep medications such as benzodiazepines affect cognitive performance,” she said.

Dr. D’Ambrosio said she avoids prescribing sleep medications for older adults if possible. “A deep dive into sleep habits, environment, and other things that disrupt sleep often gets to the problem rather than just masking it with a sleep medication,” she noted. Alternatives to improve sleep in older adults include exercise, exposure to bright light during the day, and good healthy sleep habits, all of which contribute to improved sleep in the elderly, said Dr. D’Ambrosio. She also recommends screening older adults for other issues that affect sleep, such as chronic pain.

The current study highlighted the association between sleep medication use and dementia, but it does not show causation, Dr. D’Ambrosio said. “So much more needs to be done to determine whether the sleep medications are causing worsening cognitive function long term, or if the dementia is starting but not yet diagnosed and the sleep medication is given but not the cause of the dementia, she noted.
 

Research gaps and treatment strategies

Older adults experiencing sleep difficulties may try various medications including pharmacologics (e.g., benzodiazepines), over-the-counter agents, such as diphenhydramine or doxylamine preparations, and/or herbal and nutritional supplements such as valerian or melatonin, said Mary Jo S. Farmer, MD, FCCP, of the University of Massachusetts Medical School–Baystate, Springfield, in an interview. “However, sleep medications, particularly benzodiazepines, are strongly discouraged by major medical associations including the American Geriatrics Society in part because of the growing evidence that use of sleep medications is associated with cognitive impairment and decline,” she said.

The current study results contribute to previous work demonstrating that both pharmacologic and nonpharmacologic sleep medication, although commonly administered, is associated with subsequent adverse outcomes in older adults, Dr. Farmer said. This association sets the stage for creative and different solutions for addressing poor sleep among older adults, such as behavioral treatments including cognitive-behavioral therapy, she noted.

Dr. Farmer said, “Areas for future research include exploring the causal link between prescription and/or over-the-counter sleep medication use and incident dementia in a randomized controlled trial,” she added.

“Another interesting opportunity for future research is to explore the indications for sleep medications among older adults since it has been shown in the general population that sleep difficulties represent only 12% of the indication for sleep medication prescriptions,” Dr. Farmer noted. “Future research could examine the strength of the underlying motivation to use sleep medication even in light of suggested long-term effects, and the effectiveness of other measures to avoid or minimize sleep difficulties,” she said.

“My experience is that the majority of ambulatory patients recently seen in sleep clinic want to avoid long-term use of sleep medications and will ask what other measures can be tried to consistently achieve a good night’s sleep without medication use,” Dr. Farmer said. “If medications are used, patients would rather try melatonin than a benzodiazepine. Many patients who come to sleep clinic with sleep medications already prescribed and are subsequently found to have sleep apnea and/or restless legs find that they no longer need sleep medication when these other medical conditions are appropriately diagnosed and managed,” she explained. “Finally, many patients tell me they feel less energetic upon awakening, almost feel hung over, and express being less sharp cognitively when taking pharmacologic sleep medication, whether for short or long periods of time, and therefore they want to avoid continuing with sleep medication use,” she said.

Dr. Farmer’s strategy for developing alternatives to sleep medications in older adults includes taking a careful history, including a complete list of medical problems, review of medications, and a thorough sleep history including usual time of sleep onset, awake time, and the frequency of daytime naps. “Tips for improving the quality of nighttime sleep may include adequately treating pain and other medical conditions such as heartburn, sleep apnea, and restless legs, creating a soothing environment to promote sleep by eliminating noise and bright lights, avoiding stimulant medications and substances such as caffeine and nicotine before bedtime, avoiding excessive amounts of alcohol, avoiding diuretics before bedtime, encouraging physical activity during the day, spending time in the sunlight as much as possible to help regulate the sleep cycle, limiting daytime naps, and establishing a regular sleep schedule,” she said.

The study was supported by National Institutes of Health awards K01HL150339, U54MD000538, K07AG052685, R01AG056531, R01AG056031. Lead author Dr. Robbins had no financial conflicts to disclose. Dr. D’Ambrosio disclosed serving as a section editor for sleep medicine for Dynamed and owning a patent on a circadian programming device. Dr. Farmer had no disclosures.

SOURCE: Robbins R et al. Sleep Med. 2020 Nov 11. doi: 10.1016/j.sleep.2020.11.004.

Sleep medications for older patients who report sleep problems may not be the best treatment given growing evidence of the link between these medications and the risk of incident dementia.

Adults aged 65 years and older who used sleep medications 5-7 days a week demonstrated a 30% increased risk of dementia, compared with those who did not use sleep medications, findings from a prospective study of 6,373 individuals show.

Adults aged 65 and older report a higher burden of sleep problems than other age groups, but major medical associations discourage the use of sleep medications by older adults because of growing evidence of a link between sleep medication use and cognitive decline, wrote Rebecca Robbins, MD, of Brigham and Women’s Hospital, Boston, and colleagues. However, data on this association among adults in the United States are limited, they said.

In a study published in Sleep Medicine, the researchers surveyed 6,373 adults aged 65 years and older who were enrolled in the nationally representative National Health and Aging Trends Study (NHATS). The majority of the participants were non-Hispanic White (71%), 59% were women, and 21% ranged in age from 70 to 74 years.

Participants responded to questions about routine sleep medication use. Routine was defined as “most nights” or “every night.” The data were collected for an 8-year period from 2011 to 2018. The study began in 2011, with a core interview administered annually.

Approximately 15% of the study population reported routine use of sleep medications. Overall, routine use of sleep medication was significantly associated with risk of incident dementia (hazard ratio, 1.30; P < .01) after controlling for multiple variables including age, sex, education level, and chronic conditions.

Dementia screening was conducted by participants rating their memory and then performing a memory-related activity (immediate and delayed 10-word recall) and other exercises to assess executive function and orientation. A separate eight-item informant screener was performed for patient proxies. The researcher noted, “Sensitivity of the NHATS probable dementia screening measure has been determined in previous research to be 66%, and specificity is 87%, with respect to a clinical dementia diagnosis.”

The study findings were limited by several factors including the use of self-reports, the lack of data on type or dose of sleep medication, and lack of data on the indication for the prescription, the researchers noted.

“Also, sleep medication use leads to worse performance on cognitive testing, such as the questionnaires used to screen for dementia in this study, and therefore could have resulted in a false diagnosis of dementia,” they added.

However, the results were strengthened by the large, nationally representative study population and support the need for quality geriatric care, the researchers said.

“Our findings provide further support and evidence that sleep medications are all too commonly administered, yet associated with greater risk for incident dementia, and that the U.S. health care system is in need of creative solutions for addressing poor sleep among older individuals,” they concluded.
 

Implications and alternatives

The study is important as the number of aging Americans increases, said Carolyn M. D’Ambrosio, MD, FCCP, of Brigham and Women’s Hospital and Harvard Medical School, Boston, in an interview. “In the elderly, inability to fall asleep or stay asleep are common issues that are brought to a health care provider,” she said. Dr. D’Ambrosio said she was not surprised by the study findings “as elderly patients often have sleep issues and sometimes a well-meaning health care provider gives them sleep medication to help. We have known that some of these sleep medications such as benzodiazepines affect cognitive performance,” she said.

Dr. D’Ambrosio said she avoids prescribing sleep medications for older adults if possible. “A deep dive into sleep habits, environment, and other things that disrupt sleep often gets to the problem rather than just masking it with a sleep medication,” she noted. Alternatives to improve sleep in older adults include exercise, exposure to bright light during the day, and good healthy sleep habits, all of which contribute to improved sleep in the elderly, said Dr. D’Ambrosio. She also recommends screening older adults for other issues that affect sleep, such as chronic pain.

The current study highlighted the association between sleep medication use and dementia, but it does not show causation, Dr. D’Ambrosio said. “So much more needs to be done to determine whether the sleep medications are causing worsening cognitive function long term, or if the dementia is starting but not yet diagnosed and the sleep medication is given but not the cause of the dementia, she noted.
 

Research gaps and treatment strategies

Older adults experiencing sleep difficulties may try various medications including pharmacologics (e.g., benzodiazepines), over-the-counter agents, such as diphenhydramine or doxylamine preparations, and/or herbal and nutritional supplements such as valerian or melatonin, said Mary Jo S. Farmer, MD, FCCP, of the University of Massachusetts Medical School–Baystate, Springfield, in an interview. “However, sleep medications, particularly benzodiazepines, are strongly discouraged by major medical associations including the American Geriatrics Society in part because of the growing evidence that use of sleep medications is associated with cognitive impairment and decline,” she said.

The current study results contribute to previous work demonstrating that both pharmacologic and nonpharmacologic sleep medication, although commonly administered, is associated with subsequent adverse outcomes in older adults, Dr. Farmer said. This association sets the stage for creative and different solutions for addressing poor sleep among older adults, such as behavioral treatments including cognitive-behavioral therapy, she noted.

Dr. Farmer said, “Areas for future research include exploring the causal link between prescription and/or over-the-counter sleep medication use and incident dementia in a randomized controlled trial,” she added.

“Another interesting opportunity for future research is to explore the indications for sleep medications among older adults since it has been shown in the general population that sleep difficulties represent only 12% of the indication for sleep medication prescriptions,” Dr. Farmer noted. “Future research could examine the strength of the underlying motivation to use sleep medication even in light of suggested long-term effects, and the effectiveness of other measures to avoid or minimize sleep difficulties,” she said.

“My experience is that the majority of ambulatory patients recently seen in sleep clinic want to avoid long-term use of sleep medications and will ask what other measures can be tried to consistently achieve a good night’s sleep without medication use,” Dr. Farmer said. “If medications are used, patients would rather try melatonin than a benzodiazepine. Many patients who come to sleep clinic with sleep medications already prescribed and are subsequently found to have sleep apnea and/or restless legs find that they no longer need sleep medication when these other medical conditions are appropriately diagnosed and managed,” she explained. “Finally, many patients tell me they feel less energetic upon awakening, almost feel hung over, and express being less sharp cognitively when taking pharmacologic sleep medication, whether for short or long periods of time, and therefore they want to avoid continuing with sleep medication use,” she said.

Dr. Farmer’s strategy for developing alternatives to sleep medications in older adults includes taking a careful history, including a complete list of medical problems, review of medications, and a thorough sleep history including usual time of sleep onset, awake time, and the frequency of daytime naps. “Tips for improving the quality of nighttime sleep may include adequately treating pain and other medical conditions such as heartburn, sleep apnea, and restless legs, creating a soothing environment to promote sleep by eliminating noise and bright lights, avoiding stimulant medications and substances such as caffeine and nicotine before bedtime, avoiding excessive amounts of alcohol, avoiding diuretics before bedtime, encouraging physical activity during the day, spending time in the sunlight as much as possible to help regulate the sleep cycle, limiting daytime naps, and establishing a regular sleep schedule,” she said.

The study was supported by National Institutes of Health awards K01HL150339, U54MD000538, K07AG052685, R01AG056531, R01AG056031. Lead author Dr. Robbins had no financial conflicts to disclose. Dr. D’Ambrosio disclosed serving as a section editor for sleep medicine for Dynamed and owning a patent on a circadian programming device. Dr. Farmer had no disclosures.

SOURCE: Robbins R et al. Sleep Med. 2020 Nov 11. doi: 10.1016/j.sleep.2020.11.004.

Sleep medications for older patients who report sleep problems may not be the best treatment given growing evidence of the link between these medications and the risk of incident dementia.

Adults aged 65 years and older who used sleep medications 5-7 days a week demonstrated a 30% increased risk of dementia, compared with those who did not use sleep medications, findings from a prospective study of 6,373 individuals show.

Adults aged 65 and older report a higher burden of sleep problems than other age groups, but major medical associations discourage the use of sleep medications by older adults because of growing evidence of a link between sleep medication use and cognitive decline, wrote Rebecca Robbins, MD, of Brigham and Women’s Hospital, Boston, and colleagues. However, data on this association among adults in the United States are limited, they said.

In a study published in Sleep Medicine, the researchers surveyed 6,373 adults aged 65 years and older who were enrolled in the nationally representative National Health and Aging Trends Study (NHATS). The majority of the participants were non-Hispanic White (71%), 59% were women, and 21% ranged in age from 70 to 74 years.

Participants responded to questions about routine sleep medication use. Routine was defined as “most nights” or “every night.” The data were collected for an 8-year period from 2011 to 2018. The study began in 2011, with a core interview administered annually.

Approximately 15% of the study population reported routine use of sleep medications. Overall, routine use of sleep medication was significantly associated with risk of incident dementia (hazard ratio, 1.30; P < .01) after controlling for multiple variables including age, sex, education level, and chronic conditions.

Dementia screening was conducted by participants rating their memory and then performing a memory-related activity (immediate and delayed 10-word recall) and other exercises to assess executive function and orientation. A separate eight-item informant screener was performed for patient proxies. The researcher noted, “Sensitivity of the NHATS probable dementia screening measure has been determined in previous research to be 66%, and specificity is 87%, with respect to a clinical dementia diagnosis.”

The study findings were limited by several factors including the use of self-reports, the lack of data on type or dose of sleep medication, and lack of data on the indication for the prescription, the researchers noted.

“Also, sleep medication use leads to worse performance on cognitive testing, such as the questionnaires used to screen for dementia in this study, and therefore could have resulted in a false diagnosis of dementia,” they added.

However, the results were strengthened by the large, nationally representative study population and support the need for quality geriatric care, the researchers said.

“Our findings provide further support and evidence that sleep medications are all too commonly administered, yet associated with greater risk for incident dementia, and that the U.S. health care system is in need of creative solutions for addressing poor sleep among older individuals,” they concluded.
 

Implications and alternatives

The study is important as the number of aging Americans increases, said Carolyn M. D’Ambrosio, MD, FCCP, of Brigham and Women’s Hospital and Harvard Medical School, Boston, in an interview. “In the elderly, inability to fall asleep or stay asleep are common issues that are brought to a health care provider,” she said. Dr. D’Ambrosio said she was not surprised by the study findings “as elderly patients often have sleep issues and sometimes a well-meaning health care provider gives them sleep medication to help. We have known that some of these sleep medications such as benzodiazepines affect cognitive performance,” she said.

Dr. D’Ambrosio said she avoids prescribing sleep medications for older adults if possible. “A deep dive into sleep habits, environment, and other things that disrupt sleep often gets to the problem rather than just masking it with a sleep medication,” she noted. Alternatives to improve sleep in older adults include exercise, exposure to bright light during the day, and good healthy sleep habits, all of which contribute to improved sleep in the elderly, said Dr. D’Ambrosio. She also recommends screening older adults for other issues that affect sleep, such as chronic pain.

The current study highlighted the association between sleep medication use and dementia, but it does not show causation, Dr. D’Ambrosio said. “So much more needs to be done to determine whether the sleep medications are causing worsening cognitive function long term, or if the dementia is starting but not yet diagnosed and the sleep medication is given but not the cause of the dementia, she noted.
 

Research gaps and treatment strategies

Older adults experiencing sleep difficulties may try various medications including pharmacologics (e.g., benzodiazepines), over-the-counter agents, such as diphenhydramine or doxylamine preparations, and/or herbal and nutritional supplements such as valerian or melatonin, said Mary Jo S. Farmer, MD, FCCP, of the University of Massachusetts Medical School–Baystate, Springfield, in an interview. “However, sleep medications, particularly benzodiazepines, are strongly discouraged by major medical associations including the American Geriatrics Society in part because of the growing evidence that use of sleep medications is associated with cognitive impairment and decline,” she said.

The current study results contribute to previous work demonstrating that both pharmacologic and nonpharmacologic sleep medication, although commonly administered, is associated with subsequent adverse outcomes in older adults, Dr. Farmer said. This association sets the stage for creative and different solutions for addressing poor sleep among older adults, such as behavioral treatments including cognitive-behavioral therapy, she noted.

Dr. Farmer said, “Areas for future research include exploring the causal link between prescription and/or over-the-counter sleep medication use and incident dementia in a randomized controlled trial,” she added.

“Another interesting opportunity for future research is to explore the indications for sleep medications among older adults since it has been shown in the general population that sleep difficulties represent only 12% of the indication for sleep medication prescriptions,” Dr. Farmer noted. “Future research could examine the strength of the underlying motivation to use sleep medication even in light of suggested long-term effects, and the effectiveness of other measures to avoid or minimize sleep difficulties,” she said.

“My experience is that the majority of ambulatory patients recently seen in sleep clinic want to avoid long-term use of sleep medications and will ask what other measures can be tried to consistently achieve a good night’s sleep without medication use,” Dr. Farmer said. “If medications are used, patients would rather try melatonin than a benzodiazepine. Many patients who come to sleep clinic with sleep medications already prescribed and are subsequently found to have sleep apnea and/or restless legs find that they no longer need sleep medication when these other medical conditions are appropriately diagnosed and managed,” she explained. “Finally, many patients tell me they feel less energetic upon awakening, almost feel hung over, and express being less sharp cognitively when taking pharmacologic sleep medication, whether for short or long periods of time, and therefore they want to avoid continuing with sleep medication use,” she said.

Dr. Farmer’s strategy for developing alternatives to sleep medications in older adults includes taking a careful history, including a complete list of medical problems, review of medications, and a thorough sleep history including usual time of sleep onset, awake time, and the frequency of daytime naps. “Tips for improving the quality of nighttime sleep may include adequately treating pain and other medical conditions such as heartburn, sleep apnea, and restless legs, creating a soothing environment to promote sleep by eliminating noise and bright lights, avoiding stimulant medications and substances such as caffeine and nicotine before bedtime, avoiding excessive amounts of alcohol, avoiding diuretics before bedtime, encouraging physical activity during the day, spending time in the sunlight as much as possible to help regulate the sleep cycle, limiting daytime naps, and establishing a regular sleep schedule,” she said.

The study was supported by National Institutes of Health awards K01HL150339, U54MD000538, K07AG052685, R01AG056531, R01AG056031. Lead author Dr. Robbins had no financial conflicts to disclose. Dr. D’Ambrosio disclosed serving as a section editor for sleep medicine for Dynamed and owning a patent on a circadian programming device. Dr. Farmer had no disclosures.

SOURCE: Robbins R et al. Sleep Med. 2020 Nov 11. doi: 10.1016/j.sleep.2020.11.004.

Federal advisers on December 17 overwhelmingly recommended an emergency clearance to Moderna Inc’s COVID-19 vaccine, while noting concerns about potential allergic reactions and the challenges of continuing testing of this medicine.

The US Food and Drug Administration (FDA) put Moderna’s application before its Vaccines and Related Biological Products Advisory Committee. The panel voted 20-0 on this question: “Based on the totality of scientific evidence available, do the benefits of the Moderna COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?” There was one abstention.

The FDA is not bound to act on the recommendations of its advisers, but the agency usually takes the panel’s advice. The FDA cleared the similar Pfizer-BioNTech vaccine on December 11 through an emergency use authorization (EUA), following a positive vote for the product at a December 10 advisory committee meeting. In this case, the FDA staff appeared to be pushing for a broad endorsement of the Moderna vaccine, for which the agency appears likely to soon also grant an EUA.

Marion Gruber, PhD, director of the Office of Vaccines Research and Review at FDA’s Center for Biologics Evaluation and Research, earlier rebuffed attempts by some of the panelists to alter the voting question. Some panelists wanted to make tweaks, including a rephrasing to underscore the limited nature of an EUA, compared with a more complete approval through the biologics license application (BLA) process.

FDA panelist Michael Kurilla, MD, PhD, of the National Institutes of Health was the only panelist to abstain from voting. He said he was uncomfortable with the phrasing of the question.

“In the midst of a pandemic and with limited vaccine supply available, a blanket statement for individuals 18 years and older is just too broad,” he said. “I’m not convinced that for all of those age groups the benefits do actually outweigh the risks.”

In general, though, there was strong support for Moderna’s vaccine. FDA panelist James Hildreth Sr, MD, PhD, of Meharry Medical College in Nashville, Tennessee spoke of the “remarkable achievement” seen in having two vaccines ready for clearance by December for a virus that only emerged as a threat this year.

Study data indicate the primary efficacy endpoint demonstrated vaccine efficacy (VE) of 94.1% (95% CI, 89.3% - 96.8%) for the Moderna vaccine, with 11 COVID-19 cases in the vaccine group and 185 COVID-19 cases in the placebo group, the FDA staff noted during the meeting.

The advisers and FDA staff also honed in on several key issues with COVID-19 vaccines, including the challenge of having people in the placebo groups of studies seek to get cleared vaccines. Also of concern to the panel were early reports of allergic reactions seen with the Pfizer product.

Doran L. Fink, MD, PhD, an FDA official who has been closely involved with the COVID-19 vaccines, told the panel that two healthcare workers in Alaska had allergic reactions minutes after receiving the Pfizer vaccine, one of which was a case of anaphylactic reaction that resulted in hospitalization.

In the United Kingdom, there were two cases reported of notable allergic reactions, leading regulators there to issue a warning that people who have a history of significant allergic reactions should not currently receive the Pfizer-BioNTech vaccine.

The people involved in these incidents have recovered or are recovering, Fink said. But the FDA expects there will be additional reports of allergic reactions to COVID-19 vaccines.

“These cases underscores the need to remain vigilant during the early phase of the vaccination campaign,” Fink said. “To this end, FDA is working with Pfizer to further revise factsheets and prescribing information for their vaccine to draw attention to CDC guidelines for post- vaccination monitoring and management of immediate allergic reactions.”

mRNA vaccines in the lead

An FDA emergency clearance for Moderna’s product would be another vote of confidence in a new approach to making vaccines. Both the Pfizer-BioNTech and Moderna vaccines provide the immune system with a kind of blueprint in the form of genetic material, mRNA. The mRNA sets the stage for the synthesis of the signature spike protein that the SARS-CoV-2 virus uses to attach to and infect human cells.

In a December 15 commentary for this news organization Michael E. Pichichero, MD, wrote that the “revolutionary aspect of mRNA vaccines is the speed at which they can be designed and produced.”

“This is why they lead the pack among the SARS-CoV-2 vaccine candidates and why the National Institute of Allergy and Infectious Diseases provided financial, technical, and/or clinical support. Indeed, once the amino acid sequence of a protein can be determined (a relatively easy task these days) it’s straightforward to synthesize mRNA in the lab — and it can be done incredibly fast,” he wrote.

The FDA allowed one waiver for panelist James K. Hildreth in connection with his personal relationship to a trial participant and his university’s participation in vaccine testing.

This article first appeared on Medscape.com.

Federal advisers on December 17 overwhelmingly recommended an emergency clearance to Moderna Inc’s COVID-19 vaccine, while noting concerns about potential allergic reactions and the challenges of continuing testing of this medicine.

The US Food and Drug Administration (FDA) put Moderna’s application before its Vaccines and Related Biological Products Advisory Committee. The panel voted 20-0 on this question: “Based on the totality of scientific evidence available, do the benefits of the Moderna COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?” There was one abstention.

The FDA is not bound to act on the recommendations of its advisers, but the agency usually takes the panel’s advice. The FDA cleared the similar Pfizer-BioNTech vaccine on December 11 through an emergency use authorization (EUA), following a positive vote for the product at a December 10 advisory committee meeting. In this case, the FDA staff appeared to be pushing for a broad endorsement of the Moderna vaccine, for which the agency appears likely to soon also grant an EUA.

Marion Gruber, PhD, director of the Office of Vaccines Research and Review at FDA’s Center for Biologics Evaluation and Research, earlier rebuffed attempts by some of the panelists to alter the voting question. Some panelists wanted to make tweaks, including a rephrasing to underscore the limited nature of an EUA, compared with a more complete approval through the biologics license application (BLA) process.

FDA panelist Michael Kurilla, MD, PhD, of the National Institutes of Health was the only panelist to abstain from voting. He said he was uncomfortable with the phrasing of the question.

“In the midst of a pandemic and with limited vaccine supply available, a blanket statement for individuals 18 years and older is just too broad,” he said. “I’m not convinced that for all of those age groups the benefits do actually outweigh the risks.”

In general, though, there was strong support for Moderna’s vaccine. FDA panelist James Hildreth Sr, MD, PhD, of Meharry Medical College in Nashville, Tennessee spoke of the “remarkable achievement” seen in having two vaccines ready for clearance by December for a virus that only emerged as a threat this year.

Study data indicate the primary efficacy endpoint demonstrated vaccine efficacy (VE) of 94.1% (95% CI, 89.3% - 96.8%) for the Moderna vaccine, with 11 COVID-19 cases in the vaccine group and 185 COVID-19 cases in the placebo group, the FDA staff noted during the meeting.

The advisers and FDA staff also honed in on several key issues with COVID-19 vaccines, including the challenge of having people in the placebo groups of studies seek to get cleared vaccines. Also of concern to the panel were early reports of allergic reactions seen with the Pfizer product.

Doran L. Fink, MD, PhD, an FDA official who has been closely involved with the COVID-19 vaccines, told the panel that two healthcare workers in Alaska had allergic reactions minutes after receiving the Pfizer vaccine, one of which was a case of anaphylactic reaction that resulted in hospitalization.

In the United Kingdom, there were two cases reported of notable allergic reactions, leading regulators there to issue a warning that people who have a history of significant allergic reactions should not currently receive the Pfizer-BioNTech vaccine.

The people involved in these incidents have recovered or are recovering, Fink said. But the FDA expects there will be additional reports of allergic reactions to COVID-19 vaccines.

“These cases underscores the need to remain vigilant during the early phase of the vaccination campaign,” Fink said. “To this end, FDA is working with Pfizer to further revise factsheets and prescribing information for their vaccine to draw attention to CDC guidelines for post- vaccination monitoring and management of immediate allergic reactions.”

mRNA vaccines in the lead

An FDA emergency clearance for Moderna’s product would be another vote of confidence in a new approach to making vaccines. Both the Pfizer-BioNTech and Moderna vaccines provide the immune system with a kind of blueprint in the form of genetic material, mRNA. The mRNA sets the stage for the synthesis of the signature spike protein that the SARS-CoV-2 virus uses to attach to and infect human cells.

In a December 15 commentary for this news organization Michael E. Pichichero, MD, wrote that the “revolutionary aspect of mRNA vaccines is the speed at which they can be designed and produced.”

“This is why they lead the pack among the SARS-CoV-2 vaccine candidates and why the National Institute of Allergy and Infectious Diseases provided financial, technical, and/or clinical support. Indeed, once the amino acid sequence of a protein can be determined (a relatively easy task these days) it’s straightforward to synthesize mRNA in the lab — and it can be done incredibly fast,” he wrote.

The FDA allowed one waiver for panelist James K. Hildreth in connection with his personal relationship to a trial participant and his university’s participation in vaccine testing.

This article first appeared on Medscape.com.

Federal advisers on December 17 overwhelmingly recommended an emergency clearance to Moderna Inc’s COVID-19 vaccine, while noting concerns about potential allergic reactions and the challenges of continuing testing of this medicine.

The US Food and Drug Administration (FDA) put Moderna’s application before its Vaccines and Related Biological Products Advisory Committee. The panel voted 20-0 on this question: “Based on the totality of scientific evidence available, do the benefits of the Moderna COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?” There was one abstention.

The FDA is not bound to act on the recommendations of its advisers, but the agency usually takes the panel’s advice. The FDA cleared the similar Pfizer-BioNTech vaccine on December 11 through an emergency use authorization (EUA), following a positive vote for the product at a December 10 advisory committee meeting. In this case, the FDA staff appeared to be pushing for a broad endorsement of the Moderna vaccine, for which the agency appears likely to soon also grant an EUA.

Marion Gruber, PhD, director of the Office of Vaccines Research and Review at FDA’s Center for Biologics Evaluation and Research, earlier rebuffed attempts by some of the panelists to alter the voting question. Some panelists wanted to make tweaks, including a rephrasing to underscore the limited nature of an EUA, compared with a more complete approval through the biologics license application (BLA) process.

FDA panelist Michael Kurilla, MD, PhD, of the National Institutes of Health was the only panelist to abstain from voting. He said he was uncomfortable with the phrasing of the question.

“In the midst of a pandemic and with limited vaccine supply available, a blanket statement for individuals 18 years and older is just too broad,” he said. “I’m not convinced that for all of those age groups the benefits do actually outweigh the risks.”

In general, though, there was strong support for Moderna’s vaccine. FDA panelist James Hildreth Sr, MD, PhD, of Meharry Medical College in Nashville, Tennessee spoke of the “remarkable achievement” seen in having two vaccines ready for clearance by December for a virus that only emerged as a threat this year.

Study data indicate the primary efficacy endpoint demonstrated vaccine efficacy (VE) of 94.1% (95% CI, 89.3% - 96.8%) for the Moderna vaccine, with 11 COVID-19 cases in the vaccine group and 185 COVID-19 cases in the placebo group, the FDA staff noted during the meeting.

The advisers and FDA staff also honed in on several key issues with COVID-19 vaccines, including the challenge of having people in the placebo groups of studies seek to get cleared vaccines. Also of concern to the panel were early reports of allergic reactions seen with the Pfizer product.

Doran L. Fink, MD, PhD, an FDA official who has been closely involved with the COVID-19 vaccines, told the panel that two healthcare workers in Alaska had allergic reactions minutes after receiving the Pfizer vaccine, one of which was a case of anaphylactic reaction that resulted in hospitalization.

In the United Kingdom, there were two cases reported of notable allergic reactions, leading regulators there to issue a warning that people who have a history of significant allergic reactions should not currently receive the Pfizer-BioNTech vaccine.

The people involved in these incidents have recovered or are recovering, Fink said. But the FDA expects there will be additional reports of allergic reactions to COVID-19 vaccines.

“These cases underscores the need to remain vigilant during the early phase of the vaccination campaign,” Fink said. “To this end, FDA is working with Pfizer to further revise factsheets and prescribing information for their vaccine to draw attention to CDC guidelines for post- vaccination monitoring and management of immediate allergic reactions.”

mRNA vaccines in the lead

An FDA emergency clearance for Moderna’s product would be another vote of confidence in a new approach to making vaccines. Both the Pfizer-BioNTech and Moderna vaccines provide the immune system with a kind of blueprint in the form of genetic material, mRNA. The mRNA sets the stage for the synthesis of the signature spike protein that the SARS-CoV-2 virus uses to attach to and infect human cells.

In a December 15 commentary for this news organization Michael E. Pichichero, MD, wrote that the “revolutionary aspect of mRNA vaccines is the speed at which they can be designed and produced.”

“This is why they lead the pack among the SARS-CoV-2 vaccine candidates and why the National Institute of Allergy and Infectious Diseases provided financial, technical, and/or clinical support. Indeed, once the amino acid sequence of a protein can be determined (a relatively easy task these days) it’s straightforward to synthesize mRNA in the lab — and it can be done incredibly fast,” he wrote.

The FDA allowed one waiver for panelist James K. Hildreth in connection with his personal relationship to a trial participant and his university’s participation in vaccine testing.

This article first appeared on Medscape.com.

If the initial success of the Pfizer-BioNTech rollout continues, and emergency use authorization (EAU) is granted to Moderna and Johnson & Johnson vaccines in development, Operation Warp Speed officials expect to have 300 million doses of COVID-19 vaccines to distribute across the United States between now and March 31.

The initial rollout remains on track, said Alex Azar, US Department of Health and Human Services (HHS) secretary, during a media briefing today. “We continue to have good news to report. As of today, shipments of vaccine will have been delivered to every delivery site identified by public health jurisdictions for our first wave of shipments.”

Anomalies in shipments to California and Alabama arose when temperature monitors showed the Pfizer vaccine dropped lower than the recommended -80 ºC (-112 °F). These vaccine trays remained on delivery trucks and were returned to Pfizer for prompt replacement, said Operation Warp Speed Chief Operating Officer Gen. Gustave F. Perna.

Azar estimated another 2 million doses of the Pfizer vaccine will be available next week. “And if the Moderna vaccine is authorized by the FDA in the coming days, we have allocated nearly 5.9 million doses of that product.”

The Moderna vaccine data released this week look promising, said Moncef Slaoui, PhD, Operation Warp Speed chief scientific adviser. “In the short term, I expect the protection to be quite significant.”

The findings in the first 2 weeks after the first dose show up to 65% protection, he said, and predicted the second-dose efficacy data will be coming in the next few weeks.

Enrollment in the phase 3 Johnson & Johnson trial with nearly 44,000 participants is expected to end December 17. Initial efficacy results are anticipated by early January, with more complete efficacy numbers by late January, Slaoui said.

The AstraZeneca COVID-19 vaccine trial also is underway with enrollment continuing. “We expect accruement to end in late December or early next year, with first results expected probably in February,” Slaoui said.
 

Antibody treatments underutilized

The media briefing also addressed COVID-19 therapeutics. Azar reported low uptake of available antibody therapies. “I want to remind Americans that there are two authorized antibody treatments that Operation Warp Speed has supported. They can help prevent hospitalization in those patients with the highest risk for severe disease.”

The higher-risk group includes those who are 65 and older and people with comorbid conditions that put them at increased risk for COVID-19 hospitalization.

The federal government allocated more than 330,000 doses of these treatments and many states have product available, Azar said.

Slaoui agreed, saying there is a “disappointing level of usage of monoclonal antibody therapy in hospitals. We look forward to that improving.”
 

Up to 3 billion vaccine doses possible

“We now have more than 900 million doses of the vaccine we have contracted delivery for,” Azar said. The government has options to increase that to a total of 3 billion doses.

In addition to the 100 million Pfizer vaccine doses and 100 million Moderna doses already ordered, the government just took an option for another 100 million Moderna doses for the second quarter of 2021. Operation Warp Speed officials are negotiating with Pfizer for additional product as well.

Azar added that there are 100 million doses of the Johnson & Johnson vaccine in active production and expects AstraZeneca can provide 300 million doses of their product.

With the possibility of three or more vaccine products and with 330 million Americans, minus the 70 million or so children under age 16, “we believe we will actually have surplus supplies,” Azar said. Plans are to take the US surplus vaccine and surplus manufacturing capacity “and use that for the benefit of the world community.”

This article first appeared on Medscape.com.

If the initial success of the Pfizer-BioNTech rollout continues, and emergency use authorization (EAU) is granted to Moderna and Johnson & Johnson vaccines in development, Operation Warp Speed officials expect to have 300 million doses of COVID-19 vaccines to distribute across the United States between now and March 31.

The initial rollout remains on track, said Alex Azar, US Department of Health and Human Services (HHS) secretary, during a media briefing today. “We continue to have good news to report. As of today, shipments of vaccine will have been delivered to every delivery site identified by public health jurisdictions for our first wave of shipments.”

Anomalies in shipments to California and Alabama arose when temperature monitors showed the Pfizer vaccine dropped lower than the recommended -80 ºC (-112 °F). These vaccine trays remained on delivery trucks and were returned to Pfizer for prompt replacement, said Operation Warp Speed Chief Operating Officer Gen. Gustave F. Perna.

Azar estimated another 2 million doses of the Pfizer vaccine will be available next week. “And if the Moderna vaccine is authorized by the FDA in the coming days, we have allocated nearly 5.9 million doses of that product.”

The Moderna vaccine data released this week look promising, said Moncef Slaoui, PhD, Operation Warp Speed chief scientific adviser. “In the short term, I expect the protection to be quite significant.”

The findings in the first 2 weeks after the first dose show up to 65% protection, he said, and predicted the second-dose efficacy data will be coming in the next few weeks.

Enrollment in the phase 3 Johnson & Johnson trial with nearly 44,000 participants is expected to end December 17. Initial efficacy results are anticipated by early January, with more complete efficacy numbers by late January, Slaoui said.

The AstraZeneca COVID-19 vaccine trial also is underway with enrollment continuing. “We expect accruement to end in late December or early next year, with first results expected probably in February,” Slaoui said.
 

Antibody treatments underutilized

The media briefing also addressed COVID-19 therapeutics. Azar reported low uptake of available antibody therapies. “I want to remind Americans that there are two authorized antibody treatments that Operation Warp Speed has supported. They can help prevent hospitalization in those patients with the highest risk for severe disease.”

The higher-risk group includes those who are 65 and older and people with comorbid conditions that put them at increased risk for COVID-19 hospitalization.

The federal government allocated more than 330,000 doses of these treatments and many states have product available, Azar said.

Slaoui agreed, saying there is a “disappointing level of usage of monoclonal antibody therapy in hospitals. We look forward to that improving.”
 

Up to 3 billion vaccine doses possible

“We now have more than 900 million doses of the vaccine we have contracted delivery for,” Azar said. The government has options to increase that to a total of 3 billion doses.

In addition to the 100 million Pfizer vaccine doses and 100 million Moderna doses already ordered, the government just took an option for another 100 million Moderna doses for the second quarter of 2021. Operation Warp Speed officials are negotiating with Pfizer for additional product as well.

Azar added that there are 100 million doses of the Johnson & Johnson vaccine in active production and expects AstraZeneca can provide 300 million doses of their product.

With the possibility of three or more vaccine products and with 330 million Americans, minus the 70 million or so children under age 16, “we believe we will actually have surplus supplies,” Azar said. Plans are to take the US surplus vaccine and surplus manufacturing capacity “and use that for the benefit of the world community.”

This article first appeared on Medscape.com.

If the initial success of the Pfizer-BioNTech rollout continues, and emergency use authorization (EAU) is granted to Moderna and Johnson & Johnson vaccines in development, Operation Warp Speed officials expect to have 300 million doses of COVID-19 vaccines to distribute across the United States between now and March 31.

The initial rollout remains on track, said Alex Azar, US Department of Health and Human Services (HHS) secretary, during a media briefing today. “We continue to have good news to report. As of today, shipments of vaccine will have been delivered to every delivery site identified by public health jurisdictions for our first wave of shipments.”

Anomalies in shipments to California and Alabama arose when temperature monitors showed the Pfizer vaccine dropped lower than the recommended -80 ºC (-112 °F). These vaccine trays remained on delivery trucks and were returned to Pfizer for prompt replacement, said Operation Warp Speed Chief Operating Officer Gen. Gustave F. Perna.

Azar estimated another 2 million doses of the Pfizer vaccine will be available next week. “And if the Moderna vaccine is authorized by the FDA in the coming days, we have allocated nearly 5.9 million doses of that product.”

The Moderna vaccine data released this week look promising, said Moncef Slaoui, PhD, Operation Warp Speed chief scientific adviser. “In the short term, I expect the protection to be quite significant.”

The findings in the first 2 weeks after the first dose show up to 65% protection, he said, and predicted the second-dose efficacy data will be coming in the next few weeks.

Enrollment in the phase 3 Johnson & Johnson trial with nearly 44,000 participants is expected to end December 17. Initial efficacy results are anticipated by early January, with more complete efficacy numbers by late January, Slaoui said.

The AstraZeneca COVID-19 vaccine trial also is underway with enrollment continuing. “We expect accruement to end in late December or early next year, with first results expected probably in February,” Slaoui said.
 

Antibody treatments underutilized

The media briefing also addressed COVID-19 therapeutics. Azar reported low uptake of available antibody therapies. “I want to remind Americans that there are two authorized antibody treatments that Operation Warp Speed has supported. They can help prevent hospitalization in those patients with the highest risk for severe disease.”

The higher-risk group includes those who are 65 and older and people with comorbid conditions that put them at increased risk for COVID-19 hospitalization.

The federal government allocated more than 330,000 doses of these treatments and many states have product available, Azar said.

Slaoui agreed, saying there is a “disappointing level of usage of monoclonal antibody therapy in hospitals. We look forward to that improving.”
 

Up to 3 billion vaccine doses possible

“We now have more than 900 million doses of the vaccine we have contracted delivery for,” Azar said. The government has options to increase that to a total of 3 billion doses.

In addition to the 100 million Pfizer vaccine doses and 100 million Moderna doses already ordered, the government just took an option for another 100 million Moderna doses for the second quarter of 2021. Operation Warp Speed officials are negotiating with Pfizer for additional product as well.

Azar added that there are 100 million doses of the Johnson & Johnson vaccine in active production and expects AstraZeneca can provide 300 million doses of their product.

With the possibility of three or more vaccine products and with 330 million Americans, minus the 70 million or so children under age 16, “we believe we will actually have surplus supplies,” Azar said. Plans are to take the US surplus vaccine and surplus manufacturing capacity “and use that for the benefit of the world community.”

This article first appeared on Medscape.com.

COVID-19 became a leading cause of death in the United States in 2020, particularly for people over age 35, according to a new report published in JAMA on Thursday.

Adults over age 45 were more likely to die from COVID-19 than car crashes, respiratory diseases, drug overdoses, and suicide. And those over age 55 faced even higher rates of dying because of the coronavirus.

“The current exponential increase in COVID-19 is reaching a calamitous scale in the U.S.,” the authors wrote. “Putting these numbers in perspective may be difficult.”

Population health researchers at Virginia Commonwealth University put COVID-19 deaths into context by comparing this year’s numbers to the leading causes of death for March through October 2018, sorting by age.

By October 2020, COVID-19 had become the third leading cause of death overall for those between the ages of 45 and 84 years, following after heart disease and cancer. For those over age 85, COVID-19 was the second leading cause of death, surpassing cancer and following behind heart disease.

For people aged 35-44 years, COVID-19 surpassed car crashes and respiratory diseases and was slightly lower than suicide, heart disease, and cancer. For those under age 35, drug overdoses, suicide, and car crashes remained the leading causes of death.

Importantly, the authors wrote, death rates for the two leading causes – heart disease and cancer – are about 1,700 and 1,600 per day, respectively. COVID-19 deaths have surpassed these numbers individually throughout December and, on Wednesday, beat them combined. More than 3,400 deaths were reported, according to the COVID Tracking Project, marking an all-time high that continues to increase. Hospitalizations were also at a new high, with more than 113,000 COVID-19 patients in hospitals across the country, and another 232,000 new cases were reported.

“With COVID-19 mortality rates now exceeding these thresholds, this infectious disease has become deadlier than heart disease and cancer,” the authors wrote. “Its lethality may increase further as transmission increases with holiday travel and gatherings and with the intensified indoor exposure that winter brings.”

The reported number of COVID-19 deaths is likely a 20% underestimate, they wrote, attributable to delays in reporting and an increase in non–COVID-19 deaths that were undetected and untreated because of pandemic-related disruptions. Since the coronavirus is communicable and spreads easily, COVID-19 deaths are particularly unique and worrying, they said.

“Individuals who die from homicide or cancer do not transmit the risk of morbidity and mortality to those nearby,” they wrote. “Every COVID-19 death signals the possibility of more deaths among close contacts.”

The fall surge in cases and deaths is widespread nationally, as compared to the spring, with hot spots on both coasts and in rural areas, according to an accompanying editorial in JAMA from public health researchers at the Harvard T.H. Chan School of Public Health, Boston. People of color have faced twice the death rate as well, with one in 875 Black people and one in 925 Indigenous people dying from COVID-19, as compared with one in 1,625 White people.

“The year 2020 ends with COVID-19 massively surging, as it was in the spring, to be the leading cause of death,” they wrote. “The accelerating numbers of deaths fall far short of fully capturing each devastating human story: Every death represents untold loss for countless families.”

Vaccines offer hope, they said, but won’t prevent the upcoming increase in COVID-19 hospitalizations and deaths this winter. In 2021, containing the pandemic will require national coordination, resources to help overwhelmed health care workers, new support for state and local public health officials, a stimulus package for schools and businesses, and financial aid for people on the brink of eviction. The country needs federal coordination of testing, contact tracing, personal protective equipment, travel precautions, and a face mask mandate, they wrote.

“Ending this crisis will require not only further advances in treatment but also unprecedented commitment to all aspects of prevention, vaccination, and public health,” they wrote. “Only by doing so can future years see this illness revert back to the unfamiliar and unknown condition it once was.”

This article first appeared on WebMD.com.

COVID-19 became a leading cause of death in the United States in 2020, particularly for people over age 35, according to a new report published in JAMA on Thursday.

Adults over age 45 were more likely to die from COVID-19 than car crashes, respiratory diseases, drug overdoses, and suicide. And those over age 55 faced even higher rates of dying because of the coronavirus.

“The current exponential increase in COVID-19 is reaching a calamitous scale in the U.S.,” the authors wrote. “Putting these numbers in perspective may be difficult.”

Population health researchers at Virginia Commonwealth University put COVID-19 deaths into context by comparing this year’s numbers to the leading causes of death for March through October 2018, sorting by age.

By October 2020, COVID-19 had become the third leading cause of death overall for those between the ages of 45 and 84 years, following after heart disease and cancer. For those over age 85, COVID-19 was the second leading cause of death, surpassing cancer and following behind heart disease.

For people aged 35-44 years, COVID-19 surpassed car crashes and respiratory diseases and was slightly lower than suicide, heart disease, and cancer. For those under age 35, drug overdoses, suicide, and car crashes remained the leading causes of death.

Importantly, the authors wrote, death rates for the two leading causes – heart disease and cancer – are about 1,700 and 1,600 per day, respectively. COVID-19 deaths have surpassed these numbers individually throughout December and, on Wednesday, beat them combined. More than 3,400 deaths were reported, according to the COVID Tracking Project, marking an all-time high that continues to increase. Hospitalizations were also at a new high, with more than 113,000 COVID-19 patients in hospitals across the country, and another 232,000 new cases were reported.

“With COVID-19 mortality rates now exceeding these thresholds, this infectious disease has become deadlier than heart disease and cancer,” the authors wrote. “Its lethality may increase further as transmission increases with holiday travel and gatherings and with the intensified indoor exposure that winter brings.”

The reported number of COVID-19 deaths is likely a 20% underestimate, they wrote, attributable to delays in reporting and an increase in non–COVID-19 deaths that were undetected and untreated because of pandemic-related disruptions. Since the coronavirus is communicable and spreads easily, COVID-19 deaths are particularly unique and worrying, they said.

“Individuals who die from homicide or cancer do not transmit the risk of morbidity and mortality to those nearby,” they wrote. “Every COVID-19 death signals the possibility of more deaths among close contacts.”

The fall surge in cases and deaths is widespread nationally, as compared to the spring, with hot spots on both coasts and in rural areas, according to an accompanying editorial in JAMA from public health researchers at the Harvard T.H. Chan School of Public Health, Boston. People of color have faced twice the death rate as well, with one in 875 Black people and one in 925 Indigenous people dying from COVID-19, as compared with one in 1,625 White people.

“The year 2020 ends with COVID-19 massively surging, as it was in the spring, to be the leading cause of death,” they wrote. “The accelerating numbers of deaths fall far short of fully capturing each devastating human story: Every death represents untold loss for countless families.”

Vaccines offer hope, they said, but won’t prevent the upcoming increase in COVID-19 hospitalizations and deaths this winter. In 2021, containing the pandemic will require national coordination, resources to help overwhelmed health care workers, new support for state and local public health officials, a stimulus package for schools and businesses, and financial aid for people on the brink of eviction. The country needs federal coordination of testing, contact tracing, personal protective equipment, travel precautions, and a face mask mandate, they wrote.

“Ending this crisis will require not only further advances in treatment but also unprecedented commitment to all aspects of prevention, vaccination, and public health,” they wrote. “Only by doing so can future years see this illness revert back to the unfamiliar and unknown condition it once was.”

This article first appeared on WebMD.com.

COVID-19 became a leading cause of death in the United States in 2020, particularly for people over age 35, according to a new report published in JAMA on Thursday.

Adults over age 45 were more likely to die from COVID-19 than car crashes, respiratory diseases, drug overdoses, and suicide. And those over age 55 faced even higher rates of dying because of the coronavirus.

“The current exponential increase in COVID-19 is reaching a calamitous scale in the U.S.,” the authors wrote. “Putting these numbers in perspective may be difficult.”

Population health researchers at Virginia Commonwealth University put COVID-19 deaths into context by comparing this year’s numbers to the leading causes of death for March through October 2018, sorting by age.

By October 2020, COVID-19 had become the third leading cause of death overall for those between the ages of 45 and 84 years, following after heart disease and cancer. For those over age 85, COVID-19 was the second leading cause of death, surpassing cancer and following behind heart disease.

For people aged 35-44 years, COVID-19 surpassed car crashes and respiratory diseases and was slightly lower than suicide, heart disease, and cancer. For those under age 35, drug overdoses, suicide, and car crashes remained the leading causes of death.

Importantly, the authors wrote, death rates for the two leading causes – heart disease and cancer – are about 1,700 and 1,600 per day, respectively. COVID-19 deaths have surpassed these numbers individually throughout December and, on Wednesday, beat them combined. More than 3,400 deaths were reported, according to the COVID Tracking Project, marking an all-time high that continues to increase. Hospitalizations were also at a new high, with more than 113,000 COVID-19 patients in hospitals across the country, and another 232,000 new cases were reported.

“With COVID-19 mortality rates now exceeding these thresholds, this infectious disease has become deadlier than heart disease and cancer,” the authors wrote. “Its lethality may increase further as transmission increases with holiday travel and gatherings and with the intensified indoor exposure that winter brings.”

The reported number of COVID-19 deaths is likely a 20% underestimate, they wrote, attributable to delays in reporting and an increase in non–COVID-19 deaths that were undetected and untreated because of pandemic-related disruptions. Since the coronavirus is communicable and spreads easily, COVID-19 deaths are particularly unique and worrying, they said.

“Individuals who die from homicide or cancer do not transmit the risk of morbidity and mortality to those nearby,” they wrote. “Every COVID-19 death signals the possibility of more deaths among close contacts.”

The fall surge in cases and deaths is widespread nationally, as compared to the spring, with hot spots on both coasts and in rural areas, according to an accompanying editorial in JAMA from public health researchers at the Harvard T.H. Chan School of Public Health, Boston. People of color have faced twice the death rate as well, with one in 875 Black people and one in 925 Indigenous people dying from COVID-19, as compared with one in 1,625 White people.

“The year 2020 ends with COVID-19 massively surging, as it was in the spring, to be the leading cause of death,” they wrote. “The accelerating numbers of deaths fall far short of fully capturing each devastating human story: Every death represents untold loss for countless families.”

Vaccines offer hope, they said, but won’t prevent the upcoming increase in COVID-19 hospitalizations and deaths this winter. In 2021, containing the pandemic will require national coordination, resources to help overwhelmed health care workers, new support for state and local public health officials, a stimulus package for schools and businesses, and financial aid for people on the brink of eviction. The country needs federal coordination of testing, contact tracing, personal protective equipment, travel precautions, and a face mask mandate, they wrote.

“Ending this crisis will require not only further advances in treatment but also unprecedented commitment to all aspects of prevention, vaccination, and public health,” they wrote. “Only by doing so can future years see this illness revert back to the unfamiliar and unknown condition it once was.”

This article first appeared on WebMD.com.