MDedge Cardiology

Infection with the SARS-CoV-2 virus may provide some immunity for at least 5 months, interim results from a study has found.

The first report from the Sarscov2 Immunity & Reinfection Evaluation (SIREN) study suggested that antibodies from people who had recovered from COVID-19 gave at least 83% protection against reinfection compared with people who had not had the disease before.

However, Public Health England (PHE) researchers said some people with antibodies may still be able to carry and transmit the SARS-CoV-2 virus.

‘Strongly encouraged’

Susan Hopkins, PhD, senior medical advisor at PHE, who is leading the study, said the overall findings were good news. She told a briefing hosted by the Science Media Centre: “I am strongly encouraged that people have immunity that is lasting much more than the few months that was speculated before the summer.”

She added: “It allows people to feel that their prior infection will protect them from future infections but at the same time it is not complete protection, and therefore they still need to be careful when they are out and about.”

PHE scientists said they would continue to assess whether protection might last longer than 5 months.

Eleanor Riley, PhD, professor of immunology and infectious disease at the University of Edinburgh, said the report suggested that “natural infection provides short-term protection against COVID-19 that is very similar to that conferred by vaccination.”

Simon Clarke, PhD, associate professor in cellular microbiology at the University of Reading, said: “The concerning finding is that some people who have COVID antibodies appear to still be able to carry the coronavirus and could spread it to others. This means that the vast majority of the population will either need to have natural immunity or have been immunised for us to fully lift restrictions on our lives.”

The analysis took place before the new variant of SARS-CoV-2 became widespread in the UK. The PHE scientists said that further work was underway to establish whether and to what extent antibodies also provide protection from the VOC202012/01 variant.

Healthcare Workers

The SIREN preprint analysed data from 20,787 health care workers from 102 NHS trusts who had undergone antibody and PCR testing from June 18 to November 9, 2020.

Of those, 6614 tested positive for COVID-19 antibodies.

Of the 44 potential reinfections identified, two were designated ‘probable’ and 42 ‘possible’, based on available evidence.

Both of the two individuals classified as probable reinfections reported having experienced COVID-19 symptoms during the first wave of the pandemic but were not tested at the time. Both reported that their symptoms were less severe the second time.

None of the 44 potential reinfection cases were PCR tested during the first wave, but all tested positive for COVID-19 antibodies at the time they were recruited to the study.

Tom Wingfield, PhD, senior clinical lecturer at the Liverpool School of Tropical Medicine, said that given the high risk of SARS-CoV-2 infection for frontline NHS staff, it was “vital that we do all that we can to understand, predict, and prevent risk of SARS-CoV-2 amongst healthcare workers”.

The study will continue to follow participants for 12 months to explore how long any immunity may last, the effectiveness of vaccines, and to what extent people with immunity are able to carry and transmit the virus.

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

Infection with the SARS-CoV-2 virus may provide some immunity for at least 5 months, interim results from a study has found.

The first report from the Sarscov2 Immunity & Reinfection Evaluation (SIREN) study suggested that antibodies from people who had recovered from COVID-19 gave at least 83% protection against reinfection compared with people who had not had the disease before.

However, Public Health England (PHE) researchers said some people with antibodies may still be able to carry and transmit the SARS-CoV-2 virus.

‘Strongly encouraged’

Susan Hopkins, PhD, senior medical advisor at PHE, who is leading the study, said the overall findings were good news. She told a briefing hosted by the Science Media Centre: “I am strongly encouraged that people have immunity that is lasting much more than the few months that was speculated before the summer.”

She added: “It allows people to feel that their prior infection will protect them from future infections but at the same time it is not complete protection, and therefore they still need to be careful when they are out and about.”

PHE scientists said they would continue to assess whether protection might last longer than 5 months.

Eleanor Riley, PhD, professor of immunology and infectious disease at the University of Edinburgh, said the report suggested that “natural infection provides short-term protection against COVID-19 that is very similar to that conferred by vaccination.”

Simon Clarke, PhD, associate professor in cellular microbiology at the University of Reading, said: “The concerning finding is that some people who have COVID antibodies appear to still be able to carry the coronavirus and could spread it to others. This means that the vast majority of the population will either need to have natural immunity or have been immunised for us to fully lift restrictions on our lives.”

The analysis took place before the new variant of SARS-CoV-2 became widespread in the UK. The PHE scientists said that further work was underway to establish whether and to what extent antibodies also provide protection from the VOC202012/01 variant.

Healthcare Workers

The SIREN preprint analysed data from 20,787 health care workers from 102 NHS trusts who had undergone antibody and PCR testing from June 18 to November 9, 2020.

Of those, 6614 tested positive for COVID-19 antibodies.

Of the 44 potential reinfections identified, two were designated ‘probable’ and 42 ‘possible’, based on available evidence.

Both of the two individuals classified as probable reinfections reported having experienced COVID-19 symptoms during the first wave of the pandemic but were not tested at the time. Both reported that their symptoms were less severe the second time.

None of the 44 potential reinfection cases were PCR tested during the first wave, but all tested positive for COVID-19 antibodies at the time they were recruited to the study.

Tom Wingfield, PhD, senior clinical lecturer at the Liverpool School of Tropical Medicine, said that given the high risk of SARS-CoV-2 infection for frontline NHS staff, it was “vital that we do all that we can to understand, predict, and prevent risk of SARS-CoV-2 amongst healthcare workers”.

The study will continue to follow participants for 12 months to explore how long any immunity may last, the effectiveness of vaccines, and to what extent people with immunity are able to carry and transmit the virus.

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

Infection with the SARS-CoV-2 virus may provide some immunity for at least 5 months, interim results from a study has found.

The first report from the Sarscov2 Immunity & Reinfection Evaluation (SIREN) study suggested that antibodies from people who had recovered from COVID-19 gave at least 83% protection against reinfection compared with people who had not had the disease before.

However, Public Health England (PHE) researchers said some people with antibodies may still be able to carry and transmit the SARS-CoV-2 virus.

‘Strongly encouraged’

Susan Hopkins, PhD, senior medical advisor at PHE, who is leading the study, said the overall findings were good news. She told a briefing hosted by the Science Media Centre: “I am strongly encouraged that people have immunity that is lasting much more than the few months that was speculated before the summer.”

She added: “It allows people to feel that their prior infection will protect them from future infections but at the same time it is not complete protection, and therefore they still need to be careful when they are out and about.”

PHE scientists said they would continue to assess whether protection might last longer than 5 months.

Eleanor Riley, PhD, professor of immunology and infectious disease at the University of Edinburgh, said the report suggested that “natural infection provides short-term protection against COVID-19 that is very similar to that conferred by vaccination.”

Simon Clarke, PhD, associate professor in cellular microbiology at the University of Reading, said: “The concerning finding is that some people who have COVID antibodies appear to still be able to carry the coronavirus and could spread it to others. This means that the vast majority of the population will either need to have natural immunity or have been immunised for us to fully lift restrictions on our lives.”

The analysis took place before the new variant of SARS-CoV-2 became widespread in the UK. The PHE scientists said that further work was underway to establish whether and to what extent antibodies also provide protection from the VOC202012/01 variant.

Healthcare Workers

The SIREN preprint analysed data from 20,787 health care workers from 102 NHS trusts who had undergone antibody and PCR testing from June 18 to November 9, 2020.

Of those, 6614 tested positive for COVID-19 antibodies.

Of the 44 potential reinfections identified, two were designated ‘probable’ and 42 ‘possible’, based on available evidence.

Both of the two individuals classified as probable reinfections reported having experienced COVID-19 symptoms during the first wave of the pandemic but were not tested at the time. Both reported that their symptoms were less severe the second time.

None of the 44 potential reinfection cases were PCR tested during the first wave, but all tested positive for COVID-19 antibodies at the time they were recruited to the study.

Tom Wingfield, PhD, senior clinical lecturer at the Liverpool School of Tropical Medicine, said that given the high risk of SARS-CoV-2 infection for frontline NHS staff, it was “vital that we do all that we can to understand, predict, and prevent risk of SARS-CoV-2 amongst healthcare workers”.

The study will continue to follow participants for 12 months to explore how long any immunity may last, the effectiveness of vaccines, and to what extent people with immunity are able to carry and transmit the virus.

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

Left-handed cardiology trainees face unique challenges when it comes to learning how to perform common procedures, according to a new report.

About 10% of the world’s population is left-handed, and rates of left-handedness among medical students and practicing physicians is believed to be similar.

“Extrapolating this to 3,017 active general cardiovascular fellowship positions and 339 interventional cardiology fellowship positions for the year 2018-2019, it is estimated there are more than 300 LH [left-handed] trainees in U.S. cardiovascular fellowship programs at any given time. Despite this, any standard clinical setting is designed to be convenient for RH [right-handed] providers, thereby creating a variable amount of impediment for LH trainees,” wrote Prashant Patel, MD, and Mandira Patel, DO, from University of California, Riverside.

“With about 10% prevalence, left-handedness is far more common, including among cardiology trainees, than most people realize. Most of the procedural set-up is designed for the right-hand majority, and it may cause a variable amount of impediment for the left-handed trainees. It is very important for the academic cardiology community to recognize this,” Dr. Prashant Patel said in an interview.

The findings were published in the Jan.5 issue of the Journal of the American College of Cardiology.

Dr. Prashant Patel, who is left-handed, said he was prompted to look into the issue because of his own experience.

“In my first procedural rotation several years ago, I noticed that I was positioning myself somewhat differently than my attendings due to my preference for using my left hand for fine motor control,” he said. “I started looking up existing literature to see what other left-handed cardiologists have done in the past, but realized that nothing along this line was published.

“I started discussions with my colleagues and superiors and found that our small cardiology fellowship program contains about 20%-40% of left-handed trainees at any given time, and we felt it was important to elaborate on this,” he added.

Practice makes perfect, and repeated practice eventually leads to automation of motor procedures, but the learning curve may be more protracted for left-handed trainees. “Acquisition of procedural skills is a function of time and repetition. Eventually, most practicing left-handed cardiologists see that as a nonissue and do not even realize they may have gone through a differential learning curve based on their hand dominance,” Dr. Prashant Patel noted.

“South-paw” cardiology trainees face their first challenge in the examination room.

Physicians typically examine patients from the right-hand side of the bed. The majority of clinic offices are set up for the right-handed provider, with the examining table placed with the head of the bed distal from the door and the left side of the bed aligned in close proximity to the wall, leaving examination on the right side of the patient as the only option. In the hospital setting, monitors and intravenous poles are usually placed on the patient’s left-hand side of the bed.

“This practice, more than anything else, is born out of tradition. The same clinical examination can potentially be performed with the same accuracy and efficacy from the left-hand side,” said Dr. Prashant Patel.

In the echocardiography lab, some facilities perform transthoracic echocardiography from the right side of the patient, thereby requiring the operator to get the right scanning hand over and across the patient.

“This is ergonomically disadvantageous, as one has to sit on the table, reach over the patient, and twist the torso. Scanning from the left side of the patient is ergonomically superior in preventing back injuries and may be advantageous for the left-handed person as the probe is held in the dominant hand,” noted Dr. Prashant Patel.

In the cath lab, the difficulty for left-handed cardiologists starts with establishing arterial or venous access.

“The two most frequently used arterial-access sites are right radial and right femoral. Both of them pose unique challenges in terms of positioning for most left-handed trainees in the early part of their training. The right arm is kept adducted and externally rotated in a standard setup, which is difficult to access for a left-handed operator, and would require the operator to use their nondominant right hand awkwardly to gain access,” he said.

A solution could be to reposition the patient’s arm using a radial board into abduction of the arm at about 45 degrees, with external rotation.

“This creates room for the left-handed operator to stand caudal to the patient’s arm and approach the radial access site conveniently using their dominant hand,” Dr. Prashant Patel suggested.

For the femoral approach, the left-handed operator could stand left of the patient and either get left femoral access or reach out across to the right groin of the patient and obtain access in this manner, or alternatively, the operator could resort to using their right hand to gain right femoral access.

“The large size of the femoral vessels allows even the strongly left-handed operators to get accustomed to using their nondominant hand with practice. This may be preferable to switching to the left side,” he said.

There are also some advantages to being left-handed, Dr. Prashant Patel said.

This is true “especially in the cath lab, for example, establishing antegrade right femoral access for peripheral interventions,” he noted. “Having a left-handed operator can also come in handy when two operators need to simultaneously and quickly work on both groins, as is often the case in complex coronary or structural interventions. Left-handed operators are also at ease obtaining left radial access, which has been shown to have certain advantages over right radial access.”

“We hope to raise awareness among the academic cardiology community about left-handedness,” Dr. Prashant Patel added. “We hope that acknowledgment, support, and minor modifications in work flow will allow a lot of young trainees in the early part of their career to stay on course and realize their full potential in this procedural specialty.”
 

An insightful paper

“This paper by Dr. Prashant Patel and Dr. Mandira Patel is most insightful about the unique challenges and occasional opportunities for the left-handed cardiologist,” wrote Simon Kendall, MBBS, president of the Society for Cardiothoracic Surgery Great Britain and Ireland, London, in an accompanying response.

“As a left-handed cardiac surgeon, I am embarrassed not to have considered such significant issues for my cardiology colleagues: the edict of examining a patient from the right side, performing echocardiography with the right hand, and the complex arena of catheter laboratory that is designed around the right-handed majority. Before reading this paper, I had not appreciated that for my whole career I have had to use my less-favored right hand when inserting a balloon pump,” Dr. Kendall wrote.

“Dr. Patel and Dr. Patel have written very sensible conclusions, such as that left-handedness should be acknowledged and adapted for and the training environment has to help access the specific tips and tricks from others, as shared in cardiac surgery, for instance. They rightly describe this as not a binary phenomenon and that there is a spectrum of laterality, so that some left-handers will adapt with ease and others will need more time and patience to learn the necessary skills,” he wrote. “We are fortunate to live in an era of increasing awareness and tolerance. Left-handedness is one small example of such progress.”

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

Left-handed cardiology trainees face unique challenges when it comes to learning how to perform common procedures, according to a new report.

About 10% of the world’s population is left-handed, and rates of left-handedness among medical students and practicing physicians is believed to be similar.

“Extrapolating this to 3,017 active general cardiovascular fellowship positions and 339 interventional cardiology fellowship positions for the year 2018-2019, it is estimated there are more than 300 LH [left-handed] trainees in U.S. cardiovascular fellowship programs at any given time. Despite this, any standard clinical setting is designed to be convenient for RH [right-handed] providers, thereby creating a variable amount of impediment for LH trainees,” wrote Prashant Patel, MD, and Mandira Patel, DO, from University of California, Riverside.

“With about 10% prevalence, left-handedness is far more common, including among cardiology trainees, than most people realize. Most of the procedural set-up is designed for the right-hand majority, and it may cause a variable amount of impediment for the left-handed trainees. It is very important for the academic cardiology community to recognize this,” Dr. Prashant Patel said in an interview.

The findings were published in the Jan.5 issue of the Journal of the American College of Cardiology.

Dr. Prashant Patel, who is left-handed, said he was prompted to look into the issue because of his own experience.

“In my first procedural rotation several years ago, I noticed that I was positioning myself somewhat differently than my attendings due to my preference for using my left hand for fine motor control,” he said. “I started looking up existing literature to see what other left-handed cardiologists have done in the past, but realized that nothing along this line was published.

“I started discussions with my colleagues and superiors and found that our small cardiology fellowship program contains about 20%-40% of left-handed trainees at any given time, and we felt it was important to elaborate on this,” he added.

Practice makes perfect, and repeated practice eventually leads to automation of motor procedures, but the learning curve may be more protracted for left-handed trainees. “Acquisition of procedural skills is a function of time and repetition. Eventually, most practicing left-handed cardiologists see that as a nonissue and do not even realize they may have gone through a differential learning curve based on their hand dominance,” Dr. Prashant Patel noted.

“South-paw” cardiology trainees face their first challenge in the examination room.

Physicians typically examine patients from the right-hand side of the bed. The majority of clinic offices are set up for the right-handed provider, with the examining table placed with the head of the bed distal from the door and the left side of the bed aligned in close proximity to the wall, leaving examination on the right side of the patient as the only option. In the hospital setting, monitors and intravenous poles are usually placed on the patient’s left-hand side of the bed.

“This practice, more than anything else, is born out of tradition. The same clinical examination can potentially be performed with the same accuracy and efficacy from the left-hand side,” said Dr. Prashant Patel.

In the echocardiography lab, some facilities perform transthoracic echocardiography from the right side of the patient, thereby requiring the operator to get the right scanning hand over and across the patient.

“This is ergonomically disadvantageous, as one has to sit on the table, reach over the patient, and twist the torso. Scanning from the left side of the patient is ergonomically superior in preventing back injuries and may be advantageous for the left-handed person as the probe is held in the dominant hand,” noted Dr. Prashant Patel.

In the cath lab, the difficulty for left-handed cardiologists starts with establishing arterial or venous access.

“The two most frequently used arterial-access sites are right radial and right femoral. Both of them pose unique challenges in terms of positioning for most left-handed trainees in the early part of their training. The right arm is kept adducted and externally rotated in a standard setup, which is difficult to access for a left-handed operator, and would require the operator to use their nondominant right hand awkwardly to gain access,” he said.

A solution could be to reposition the patient’s arm using a radial board into abduction of the arm at about 45 degrees, with external rotation.

“This creates room for the left-handed operator to stand caudal to the patient’s arm and approach the radial access site conveniently using their dominant hand,” Dr. Prashant Patel suggested.

For the femoral approach, the left-handed operator could stand left of the patient and either get left femoral access or reach out across to the right groin of the patient and obtain access in this manner, or alternatively, the operator could resort to using their right hand to gain right femoral access.

“The large size of the femoral vessels allows even the strongly left-handed operators to get accustomed to using their nondominant hand with practice. This may be preferable to switching to the left side,” he said.

There are also some advantages to being left-handed, Dr. Prashant Patel said.

This is true “especially in the cath lab, for example, establishing antegrade right femoral access for peripheral interventions,” he noted. “Having a left-handed operator can also come in handy when two operators need to simultaneously and quickly work on both groins, as is often the case in complex coronary or structural interventions. Left-handed operators are also at ease obtaining left radial access, which has been shown to have certain advantages over right radial access.”

“We hope to raise awareness among the academic cardiology community about left-handedness,” Dr. Prashant Patel added. “We hope that acknowledgment, support, and minor modifications in work flow will allow a lot of young trainees in the early part of their career to stay on course and realize their full potential in this procedural specialty.”
 

An insightful paper

“This paper by Dr. Prashant Patel and Dr. Mandira Patel is most insightful about the unique challenges and occasional opportunities for the left-handed cardiologist,” wrote Simon Kendall, MBBS, president of the Society for Cardiothoracic Surgery Great Britain and Ireland, London, in an accompanying response.

“As a left-handed cardiac surgeon, I am embarrassed not to have considered such significant issues for my cardiology colleagues: the edict of examining a patient from the right side, performing echocardiography with the right hand, and the complex arena of catheter laboratory that is designed around the right-handed majority. Before reading this paper, I had not appreciated that for my whole career I have had to use my less-favored right hand when inserting a balloon pump,” Dr. Kendall wrote.

“Dr. Patel and Dr. Patel have written very sensible conclusions, such as that left-handedness should be acknowledged and adapted for and the training environment has to help access the specific tips and tricks from others, as shared in cardiac surgery, for instance. They rightly describe this as not a binary phenomenon and that there is a spectrum of laterality, so that some left-handers will adapt with ease and others will need more time and patience to learn the necessary skills,” he wrote. “We are fortunate to live in an era of increasing awareness and tolerance. Left-handedness is one small example of such progress.”

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

Left-handed cardiology trainees face unique challenges when it comes to learning how to perform common procedures, according to a new report.

About 10% of the world’s population is left-handed, and rates of left-handedness among medical students and practicing physicians is believed to be similar.

“Extrapolating this to 3,017 active general cardiovascular fellowship positions and 339 interventional cardiology fellowship positions for the year 2018-2019, it is estimated there are more than 300 LH [left-handed] trainees in U.S. cardiovascular fellowship programs at any given time. Despite this, any standard clinical setting is designed to be convenient for RH [right-handed] providers, thereby creating a variable amount of impediment for LH trainees,” wrote Prashant Patel, MD, and Mandira Patel, DO, from University of California, Riverside.

“With about 10% prevalence, left-handedness is far more common, including among cardiology trainees, than most people realize. Most of the procedural set-up is designed for the right-hand majority, and it may cause a variable amount of impediment for the left-handed trainees. It is very important for the academic cardiology community to recognize this,” Dr. Prashant Patel said in an interview.

The findings were published in the Jan.5 issue of the Journal of the American College of Cardiology.

Dr. Prashant Patel, who is left-handed, said he was prompted to look into the issue because of his own experience.

“In my first procedural rotation several years ago, I noticed that I was positioning myself somewhat differently than my attendings due to my preference for using my left hand for fine motor control,” he said. “I started looking up existing literature to see what other left-handed cardiologists have done in the past, but realized that nothing along this line was published.

“I started discussions with my colleagues and superiors and found that our small cardiology fellowship program contains about 20%-40% of left-handed trainees at any given time, and we felt it was important to elaborate on this,” he added.

Practice makes perfect, and repeated practice eventually leads to automation of motor procedures, but the learning curve may be more protracted for left-handed trainees. “Acquisition of procedural skills is a function of time and repetition. Eventually, most practicing left-handed cardiologists see that as a nonissue and do not even realize they may have gone through a differential learning curve based on their hand dominance,” Dr. Prashant Patel noted.

“South-paw” cardiology trainees face their first challenge in the examination room.

Physicians typically examine patients from the right-hand side of the bed. The majority of clinic offices are set up for the right-handed provider, with the examining table placed with the head of the bed distal from the door and the left side of the bed aligned in close proximity to the wall, leaving examination on the right side of the patient as the only option. In the hospital setting, monitors and intravenous poles are usually placed on the patient’s left-hand side of the bed.

“This practice, more than anything else, is born out of tradition. The same clinical examination can potentially be performed with the same accuracy and efficacy from the left-hand side,” said Dr. Prashant Patel.

In the echocardiography lab, some facilities perform transthoracic echocardiography from the right side of the patient, thereby requiring the operator to get the right scanning hand over and across the patient.

“This is ergonomically disadvantageous, as one has to sit on the table, reach over the patient, and twist the torso. Scanning from the left side of the patient is ergonomically superior in preventing back injuries and may be advantageous for the left-handed person as the probe is held in the dominant hand,” noted Dr. Prashant Patel.

In the cath lab, the difficulty for left-handed cardiologists starts with establishing arterial or venous access.

“The two most frequently used arterial-access sites are right radial and right femoral. Both of them pose unique challenges in terms of positioning for most left-handed trainees in the early part of their training. The right arm is kept adducted and externally rotated in a standard setup, which is difficult to access for a left-handed operator, and would require the operator to use their nondominant right hand awkwardly to gain access,” he said.

A solution could be to reposition the patient’s arm using a radial board into abduction of the arm at about 45 degrees, with external rotation.

“This creates room for the left-handed operator to stand caudal to the patient’s arm and approach the radial access site conveniently using their dominant hand,” Dr. Prashant Patel suggested.

For the femoral approach, the left-handed operator could stand left of the patient and either get left femoral access or reach out across to the right groin of the patient and obtain access in this manner, or alternatively, the operator could resort to using their right hand to gain right femoral access.

“The large size of the femoral vessels allows even the strongly left-handed operators to get accustomed to using their nondominant hand with practice. This may be preferable to switching to the left side,” he said.

There are also some advantages to being left-handed, Dr. Prashant Patel said.

This is true “especially in the cath lab, for example, establishing antegrade right femoral access for peripheral interventions,” he noted. “Having a left-handed operator can also come in handy when two operators need to simultaneously and quickly work on both groins, as is often the case in complex coronary or structural interventions. Left-handed operators are also at ease obtaining left radial access, which has been shown to have certain advantages over right radial access.”

“We hope to raise awareness among the academic cardiology community about left-handedness,” Dr. Prashant Patel added. “We hope that acknowledgment, support, and minor modifications in work flow will allow a lot of young trainees in the early part of their career to stay on course and realize their full potential in this procedural specialty.”
 

An insightful paper

“This paper by Dr. Prashant Patel and Dr. Mandira Patel is most insightful about the unique challenges and occasional opportunities for the left-handed cardiologist,” wrote Simon Kendall, MBBS, president of the Society for Cardiothoracic Surgery Great Britain and Ireland, London, in an accompanying response.

“As a left-handed cardiac surgeon, I am embarrassed not to have considered such significant issues for my cardiology colleagues: the edict of examining a patient from the right side, performing echocardiography with the right hand, and the complex arena of catheter laboratory that is designed around the right-handed majority. Before reading this paper, I had not appreciated that for my whole career I have had to use my less-favored right hand when inserting a balloon pump,” Dr. Kendall wrote.

“Dr. Patel and Dr. Patel have written very sensible conclusions, such as that left-handedness should be acknowledged and adapted for and the training environment has to help access the specific tips and tricks from others, as shared in cardiac surgery, for instance. They rightly describe this as not a binary phenomenon and that there is a spectrum of laterality, so that some left-handers will adapt with ease and others will need more time and patience to learn the necessary skills,” he wrote. “We are fortunate to live in an era of increasing awareness and tolerance. Left-handedness is one small example of such progress.”

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

Last fall, health experts said it was possible the United States could experience an easy 2020-21 flu season because health measures to fight COVID-19 would also thwart the spread of influenza.

It looks like that happened – and then some. Numbers are strikingly low for cases of the flu and other common respiratory and gastrointestinal viruses, health experts told the Washington Post.

“It’s crazy,” Lynnette Brammer, MPH, who leads the domestic influenza surveillance team at the Centers for Disease Control and Prevention, told the Washington Post. “This is my 30th flu season. I never would have expected to see flu activity this low.”

Influenza A, influenza B, parainfluenza, norovirus, respiratory syncytial virus, human metapneumovirus, and the bacteria that cause whooping cough and pneumonia are circulating at near-record-low levels.

As an example, the Washington Post said in the third week of December 2019, the CDC’s network of clinical labs reported 16.2% of almost 30,000 samples tested positive for influenza A. During the same period in 2020, only 0.3% tested positive.

But there’s a possible downside to this suppression of viruses, because flu and other viruses may rebound once the coronavirus is brought under control.

“The best analogy is to a forest fire,” Bryan Grenfell, PhD, an epidemiologist and population biologist at Princeton (N.J.) University, told the Washington Post. “For the fire to spread, it needs to have unburned wood. For epidemics to spread, they require people who haven’t previously been infected. So if people don’t get infected this year by these viruses, they likely will at some point later on.”

American health experts like Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Disease, said last fall that they noticed Australia and other nations in the southern hemisphere had easy flu seasons, apparently because of COVID protection measures. The flu season there runs March through August.

COVID-19 now has a very low presence in Australia, but in recent months the flu has been making a comeback. Flu cases among children aged 5 and younger rose sixfold by December, when such cases are usually at their lowest, the Washington Post said.

“That’s an important cautionary tale for us,” said Kevin Messacar, MD, an infectious disease doctor at Children’s Hospital Colorado, Aurora. “Just because we get through the winter and don’t see much RSV or influenza doesn’t mean we’ll be out of the woods.”

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

Last fall, health experts said it was possible the United States could experience an easy 2020-21 flu season because health measures to fight COVID-19 would also thwart the spread of influenza.

It looks like that happened – and then some. Numbers are strikingly low for cases of the flu and other common respiratory and gastrointestinal viruses, health experts told the Washington Post.

“It’s crazy,” Lynnette Brammer, MPH, who leads the domestic influenza surveillance team at the Centers for Disease Control and Prevention, told the Washington Post. “This is my 30th flu season. I never would have expected to see flu activity this low.”

Influenza A, influenza B, parainfluenza, norovirus, respiratory syncytial virus, human metapneumovirus, and the bacteria that cause whooping cough and pneumonia are circulating at near-record-low levels.

As an example, the Washington Post said in the third week of December 2019, the CDC’s network of clinical labs reported 16.2% of almost 30,000 samples tested positive for influenza A. During the same period in 2020, only 0.3% tested positive.

But there’s a possible downside to this suppression of viruses, because flu and other viruses may rebound once the coronavirus is brought under control.

“The best analogy is to a forest fire,” Bryan Grenfell, PhD, an epidemiologist and population biologist at Princeton (N.J.) University, told the Washington Post. “For the fire to spread, it needs to have unburned wood. For epidemics to spread, they require people who haven’t previously been infected. So if people don’t get infected this year by these viruses, they likely will at some point later on.”

American health experts like Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Disease, said last fall that they noticed Australia and other nations in the southern hemisphere had easy flu seasons, apparently because of COVID protection measures. The flu season there runs March through August.

COVID-19 now has a very low presence in Australia, but in recent months the flu has been making a comeback. Flu cases among children aged 5 and younger rose sixfold by December, when such cases are usually at their lowest, the Washington Post said.

“That’s an important cautionary tale for us,” said Kevin Messacar, MD, an infectious disease doctor at Children’s Hospital Colorado, Aurora. “Just because we get through the winter and don’t see much RSV or influenza doesn’t mean we’ll be out of the woods.”

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

Last fall, health experts said it was possible the United States could experience an easy 2020-21 flu season because health measures to fight COVID-19 would also thwart the spread of influenza.

It looks like that happened – and then some. Numbers are strikingly low for cases of the flu and other common respiratory and gastrointestinal viruses, health experts told the Washington Post.

“It’s crazy,” Lynnette Brammer, MPH, who leads the domestic influenza surveillance team at the Centers for Disease Control and Prevention, told the Washington Post. “This is my 30th flu season. I never would have expected to see flu activity this low.”

Influenza A, influenza B, parainfluenza, norovirus, respiratory syncytial virus, human metapneumovirus, and the bacteria that cause whooping cough and pneumonia are circulating at near-record-low levels.

As an example, the Washington Post said in the third week of December 2019, the CDC’s network of clinical labs reported 16.2% of almost 30,000 samples tested positive for influenza A. During the same period in 2020, only 0.3% tested positive.

But there’s a possible downside to this suppression of viruses, because flu and other viruses may rebound once the coronavirus is brought under control.

“The best analogy is to a forest fire,” Bryan Grenfell, PhD, an epidemiologist and population biologist at Princeton (N.J.) University, told the Washington Post. “For the fire to spread, it needs to have unburned wood. For epidemics to spread, they require people who haven’t previously been infected. So if people don’t get infected this year by these viruses, they likely will at some point later on.”

American health experts like Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Disease, said last fall that they noticed Australia and other nations in the southern hemisphere had easy flu seasons, apparently because of COVID protection measures. The flu season there runs March through August.

COVID-19 now has a very low presence in Australia, but in recent months the flu has been making a comeback. Flu cases among children aged 5 and younger rose sixfold by December, when such cases are usually at their lowest, the Washington Post said.

“That’s an important cautionary tale for us,” said Kevin Messacar, MD, an infectious disease doctor at Children’s Hospital Colorado, Aurora. “Just because we get through the winter and don’t see much RSV or influenza doesn’t mean we’ll be out of the woods.”

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

The Endocrine Society has issued a new position statement calling on all stakeholders, including clinicians, to play a role in reducing the cost of insulin for patients with diabetes in the United States.

“Addressing Insulin Access and Affordability: An Endocrine Society Position Statement,” was published online Jan. 12 in the Journal of Clinical Endocrinology and Metabolism.

“The society believes all stakeholders across the supply chain have a role to play in addressing the high price of insulin,” said the 11 authors, who are all members of the society’s advocacy and public outreach core committee.  

This is the first such statement from a major professional organization in 2021, which is the 100th anniversary of the discovery of insulin.

And the call for action was issued just a week prior to the inauguration of incoming U.S. President Joe Biden, who has pledged to “build on the Affordable Care Act by giving Americans more choice, reducing health care costs, and making our health care system less complex to navigate.”

The cost of insulin has nearly tripled in the past 15 years in the United States, and a lack of transparency in the drug supply chain has made it challenging to identify and address the causes of soaring costs.

The high cost of insulin has made access particularly difficult for people with diabetes with a low income, who have high-deductible health plans, are Medicare beneficiaries using Part B to cover insulin delivered via pump, or are in the Medicare Part D “donut hole,” as well as young adults once they reach their 26th birthday and can no longer be covered under their parents’ insurance.

“Inventors Frederick Banting and Charles Best sold the insulin patent for a mere $1 in the 1920s because they wanted their discovery to save lives and for insulin to be affordable and accessible to everyone who needed it,” said Endocrine Society President-elect Carol Wysham, MD, of the Rockwood/MultiCare Health Systems, Spokane, Wash.

“People with diabetes without full insurance are often paying increasing out-of-pocket costs for insulin resulting in many rationing their medication or skipping lifesaving doses altogether,” she said.

The society’s statement called for allowing government negotiation of drug prices and greater transparency across the supply chain to elucidate the reasons for rising insulin costs.  

For physicians in particular, they advised training in use of lower-cost human NPH and regular insulin for appropriate patients with type 2 diabetes, and considering patients’ individual financial and coverage status when prescribing insulin.

Pharmacists are advised to learn about and share information with patients about lower-cost options offered by manufacturers.

Other policy recommendations for relevant stakeholders include:

• Limit future insulin list price increases to the rate of inflation.
• Limit out-of-pocket costs without increasing premiums or deductibles by limiting cost sharing to copays of no more than $35, providing first-dollar coverage, or capping costs at no more than $100 per month.
• Eliminate rebates or pass savings from rebates along to consumers without increasing premiums or deductibles.
• Expedite approval of insulin biosimilars to create market competition.
• Include real-time benefit information in electronic medical records.
• Develop a payment model for Medicare Part B beneficiaries, as well as Part D, to lower out-of-pocket copays.

For manufacturers, the society also recommended improving patient assistance programs to be less restrictive and more accountable. And employers, they said, should limit copays without increasing premiums or deductibles, and seek plan options that benefit people with diabetes and provide education about these options during open enrollment.   

Of the 11 writing panel members, 4 have pharmaceutical industry disclosures.

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

The Endocrine Society has issued a new position statement calling on all stakeholders, including clinicians, to play a role in reducing the cost of insulin for patients with diabetes in the United States.

“Addressing Insulin Access and Affordability: An Endocrine Society Position Statement,” was published online Jan. 12 in the Journal of Clinical Endocrinology and Metabolism.

“The society believes all stakeholders across the supply chain have a role to play in addressing the high price of insulin,” said the 11 authors, who are all members of the society’s advocacy and public outreach core committee.  

This is the first such statement from a major professional organization in 2021, which is the 100th anniversary of the discovery of insulin.

And the call for action was issued just a week prior to the inauguration of incoming U.S. President Joe Biden, who has pledged to “build on the Affordable Care Act by giving Americans more choice, reducing health care costs, and making our health care system less complex to navigate.”

The cost of insulin has nearly tripled in the past 15 years in the United States, and a lack of transparency in the drug supply chain has made it challenging to identify and address the causes of soaring costs.

The high cost of insulin has made access particularly difficult for people with diabetes with a low income, who have high-deductible health plans, are Medicare beneficiaries using Part B to cover insulin delivered via pump, or are in the Medicare Part D “donut hole,” as well as young adults once they reach their 26th birthday and can no longer be covered under their parents’ insurance.

“Inventors Frederick Banting and Charles Best sold the insulin patent for a mere $1 in the 1920s because they wanted their discovery to save lives and for insulin to be affordable and accessible to everyone who needed it,” said Endocrine Society President-elect Carol Wysham, MD, of the Rockwood/MultiCare Health Systems, Spokane, Wash.

“People with diabetes without full insurance are often paying increasing out-of-pocket costs for insulin resulting in many rationing their medication or skipping lifesaving doses altogether,” she said.

The society’s statement called for allowing government negotiation of drug prices and greater transparency across the supply chain to elucidate the reasons for rising insulin costs.  

For physicians in particular, they advised training in use of lower-cost human NPH and regular insulin for appropriate patients with type 2 diabetes, and considering patients’ individual financial and coverage status when prescribing insulin.

Pharmacists are advised to learn about and share information with patients about lower-cost options offered by manufacturers.

Other policy recommendations for relevant stakeholders include:

• Limit future insulin list price increases to the rate of inflation.
• Limit out-of-pocket costs without increasing premiums or deductibles by limiting cost sharing to copays of no more than $35, providing first-dollar coverage, or capping costs at no more than $100 per month.
• Eliminate rebates or pass savings from rebates along to consumers without increasing premiums or deductibles.
• Expedite approval of insulin biosimilars to create market competition.
• Include real-time benefit information in electronic medical records.
• Develop a payment model for Medicare Part B beneficiaries, as well as Part D, to lower out-of-pocket copays.

For manufacturers, the society also recommended improving patient assistance programs to be less restrictive and more accountable. And employers, they said, should limit copays without increasing premiums or deductibles, and seek plan options that benefit people with diabetes and provide education about these options during open enrollment.   

Of the 11 writing panel members, 4 have pharmaceutical industry disclosures.

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

The Endocrine Society has issued a new position statement calling on all stakeholders, including clinicians, to play a role in reducing the cost of insulin for patients with diabetes in the United States.

“Addressing Insulin Access and Affordability: An Endocrine Society Position Statement,” was published online Jan. 12 in the Journal of Clinical Endocrinology and Metabolism.

“The society believes all stakeholders across the supply chain have a role to play in addressing the high price of insulin,” said the 11 authors, who are all members of the society’s advocacy and public outreach core committee.  

This is the first such statement from a major professional organization in 2021, which is the 100th anniversary of the discovery of insulin.

And the call for action was issued just a week prior to the inauguration of incoming U.S. President Joe Biden, who has pledged to “build on the Affordable Care Act by giving Americans more choice, reducing health care costs, and making our health care system less complex to navigate.”

The cost of insulin has nearly tripled in the past 15 years in the United States, and a lack of transparency in the drug supply chain has made it challenging to identify and address the causes of soaring costs.

The high cost of insulin has made access particularly difficult for people with diabetes with a low income, who have high-deductible health plans, are Medicare beneficiaries using Part B to cover insulin delivered via pump, or are in the Medicare Part D “donut hole,” as well as young adults once they reach their 26th birthday and can no longer be covered under their parents’ insurance.

“Inventors Frederick Banting and Charles Best sold the insulin patent for a mere $1 in the 1920s because they wanted their discovery to save lives and for insulin to be affordable and accessible to everyone who needed it,” said Endocrine Society President-elect Carol Wysham, MD, of the Rockwood/MultiCare Health Systems, Spokane, Wash.

“People with diabetes without full insurance are often paying increasing out-of-pocket costs for insulin resulting in many rationing their medication or skipping lifesaving doses altogether,” she said.

The society’s statement called for allowing government negotiation of drug prices and greater transparency across the supply chain to elucidate the reasons for rising insulin costs.  

For physicians in particular, they advised training in use of lower-cost human NPH and regular insulin for appropriate patients with type 2 diabetes, and considering patients’ individual financial and coverage status when prescribing insulin.

Pharmacists are advised to learn about and share information with patients about lower-cost options offered by manufacturers.

Other policy recommendations for relevant stakeholders include:

• Limit future insulin list price increases to the rate of inflation.
• Limit out-of-pocket costs without increasing premiums or deductibles by limiting cost sharing to copays of no more than $35, providing first-dollar coverage, or capping costs at no more than $100 per month.
• Eliminate rebates or pass savings from rebates along to consumers without increasing premiums or deductibles.
• Expedite approval of insulin biosimilars to create market competition.
• Include real-time benefit information in electronic medical records.
• Develop a payment model for Medicare Part B beneficiaries, as well as Part D, to lower out-of-pocket copays.

For manufacturers, the society also recommended improving patient assistance programs to be less restrictive and more accountable. And employers, they said, should limit copays without increasing premiums or deductibles, and seek plan options that benefit people with diabetes and provide education about these options during open enrollment.   

Of the 11 writing panel members, 4 have pharmaceutical industry disclosures.

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

Nostrum Laboratories has voluntarily recalled another lot of metformin HCl extended-release tablets 750-mg dosage, expanding their initial announcement in November 2020. According to the new notice, issued by the Food and Drug Administration earlier this week, the recalled tablets are off-white and oblong with a debossed ID “NM7.”

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The lot number, NDC, and expiration dates can be found on the FDA website.

Nostrum noted that the tablets were distributed across the United States to wholesalers; these distributors are being notified of the recall and the company is arranging for the drug to be returned.

Metformin is the most prescribed medication worldwide for the treatment of type 2 diabetes.

Nostrum said that anyone in possession of any of the affected lots should consult their physician or pharmacist to obtain a replacement treatment option because it can be dangerous for patients with type 2 diabetes to stop taking metformin.

This new announcement expands further the number of metformin HCl extended-release tablets recalled in the United States because they contain potentially high levels of nitrosamines, also known as N-nitrosodimethylamine (NDMA), which are possible carcinogens.

The risks of nitrosamines are not clear. The FDA said they may increase the risk of cancer in people who are exposed to high levels over a long period of time, “but we do not anticipate that shorter-term exposure at levels above the acceptable intake limit would lead to an increase in the risk of cancer.”

As well as the November recall of 2 lots of metformin by Nostrum, 76 more lots of metformin extended-release tablets were flagged in October 2020 from various manufacturers for possible contamination with NDMA, on top of an earlier recall for the same problem in May 2020.

More than 175 different drug combinations, all extended release with either 500 mg or 750 mg of metformin, have now been recalled since late May 2020, and a list of those recalled to November 2020 is available here.

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

Nostrum Laboratories has voluntarily recalled another lot of metformin HCl extended-release tablets 750-mg dosage, expanding their initial announcement in November 2020. According to the new notice, issued by the Food and Drug Administration earlier this week, the recalled tablets are off-white and oblong with a debossed ID “NM7.”

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The lot number, NDC, and expiration dates can be found on the FDA website.

Nostrum noted that the tablets were distributed across the United States to wholesalers; these distributors are being notified of the recall and the company is arranging for the drug to be returned.

Metformin is the most prescribed medication worldwide for the treatment of type 2 diabetes.

Nostrum said that anyone in possession of any of the affected lots should consult their physician or pharmacist to obtain a replacement treatment option because it can be dangerous for patients with type 2 diabetes to stop taking metformin.

This new announcement expands further the number of metformin HCl extended-release tablets recalled in the United States because they contain potentially high levels of nitrosamines, also known as N-nitrosodimethylamine (NDMA), which are possible carcinogens.

The risks of nitrosamines are not clear. The FDA said they may increase the risk of cancer in people who are exposed to high levels over a long period of time, “but we do not anticipate that shorter-term exposure at levels above the acceptable intake limit would lead to an increase in the risk of cancer.”

As well as the November recall of 2 lots of metformin by Nostrum, 76 more lots of metformin extended-release tablets were flagged in October 2020 from various manufacturers for possible contamination with NDMA, on top of an earlier recall for the same problem in May 2020.

More than 175 different drug combinations, all extended release with either 500 mg or 750 mg of metformin, have now been recalled since late May 2020, and a list of those recalled to November 2020 is available here.

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

Nostrum Laboratories has voluntarily recalled another lot of metformin HCl extended-release tablets 750-mg dosage, expanding their initial announcement in November 2020. According to the new notice, issued by the Food and Drug Administration earlier this week, the recalled tablets are off-white and oblong with a debossed ID “NM7.”

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The lot number, NDC, and expiration dates can be found on the FDA website.

Nostrum noted that the tablets were distributed across the United States to wholesalers; these distributors are being notified of the recall and the company is arranging for the drug to be returned.

Metformin is the most prescribed medication worldwide for the treatment of type 2 diabetes.

Nostrum said that anyone in possession of any of the affected lots should consult their physician or pharmacist to obtain a replacement treatment option because it can be dangerous for patients with type 2 diabetes to stop taking metformin.

This new announcement expands further the number of metformin HCl extended-release tablets recalled in the United States because they contain potentially high levels of nitrosamines, also known as N-nitrosodimethylamine (NDMA), which are possible carcinogens.

The risks of nitrosamines are not clear. The FDA said they may increase the risk of cancer in people who are exposed to high levels over a long period of time, “but we do not anticipate that shorter-term exposure at levels above the acceptable intake limit would lead to an increase in the risk of cancer.”

As well as the November recall of 2 lots of metformin by Nostrum, 76 more lots of metformin extended-release tablets were flagged in October 2020 from various manufacturers for possible contamination with NDMA, on top of an earlier recall for the same problem in May 2020.

More than 175 different drug combinations, all extended release with either 500 mg or 750 mg of metformin, have now been recalled since late May 2020, and a list of those recalled to November 2020 is available here.

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

Inhaled treprostinil improved the exercise capacity of patients with pulmonary hypertension attributable to interstitial lung disease and was associated with some additional clinical benefits, according to a new study published in the New England Journal of Medicine.

To investigate treprostinil therapy for pulmonary hypertension in this subset of patients with lung disease, Aaron Waxman, MD, PhD, of Brigham and Women’s Hospital in Boston, and his fellow researchers launched the multicenter, randomized, double-blind, placebo-controlled INCREASE trial. They assigned 163 patients to the inhaled treprostinil group – administered via an ultrasonic, pulsed-delivery nebulizer over 16 weeks – and 163 patients to the placebo group. Their average age was 66.5 years, 73% were white, and 47% were female

At baseline, the mean 6-minute walk distance (6MWD) for all patients was 259.6 m. After 16 weeks, the treprostinil group gained a mean of 21.08 m in 6MWD, and the placebo group lost 10.04 m. The least-squares mean difference between the groups from baseline in the 6MWD was 31.12 m (95% confidence interval, 16.85-45.39; P < .001). After sensitivity analysis with multiple imputation, the difference remained significant at 30.97 m (95% CI, 16.53-45.41; P < .001).

In a comparison of N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels from baseline to 16 weeks, the treprostinil group saw a decrease of 15% while the placebo group’s levels increased by 46% (treatment ratio 0.58; 95% CI, 0.47-0.72; P < .001). Clinical worsening occurred in 37 patients (23%) in the treprostinil group and 54 patients (33%) in the placebo group (hazard ratio, 0.61; 95% CI, 0.40-0.92; P = .04), while serious adverse events occurred in 23.3% of the patients on treprostinil and 25.8% of the patients on placebo. There was no significant difference between groups in patient-reported quality of life, as assessed via the St. George’s Respiratory Questionnaire.

“There was no guarantee that this was going to work in this condition,” said Adriano Tonelli, MD, of the department of pulmonary medicine at the Cleveland Clinic, in an interview. “Several small studies have tried different medications, for pulmonary hypertension or otherwise, in patients with interstitial lung disease with minimal effect, if any. Given that all the prior studies were not categorically positive, the expectation, at least on my end, was that we needed to wait and see.” Dr. Tonelli and coauthors published a post hoc analysis of inhaled treprostinil studied in the TRIUMPH and BEAT trials.

Next steps: Assess clinical outcomes after inhaled treprostinil

Although the results of this study by Waxman et al, are encouraging, and the need for a treatment in this type of pulmonary hypertension is very real, more narrowing down will be needed to confirm the benefits of inhaled treprostinil, wrote Darren B. Taichman, MD, PhD, of the University of Pennsylvania in an accompanying editorial. He wrote, “After all, patients and physicians may reason, ‘It can’t hurt.’ Unfortunately, however, it could. Therapies approved for pulmonary arterial hypertension have been studied in patients with [ILD]-associated pulmonary hypertension and have shown inconsistent results, with some studies showing no benefit or suggesting harm.”

While the 6MWD has been used as an end point in previous drug trials for pulmonary arterial hypertension, Dr. Taichman wrote that improvements in such a variable were “probably too modest to be unequivocally consequential for many patients.” To confirm the benefits – and detriments – of treatments like inhaled treprostinil, it’s time for studies to focus on clinical end points, he stated, including hospitalizations, disease progression, and death.

He also highlighted the disparity between a treatment that led to increased walk distance and decreased clinical worsening yet did not register an improvement in health-related quality of life. He noted that the oft-cited minimal clinically important difference for 6MWD is approximately 30 m – similar to the difference recorded here. That said, he wrote, “prevention of deterioration is not to be ignored, even if it does not make a patient feel better.”

Regarding quality of life, Dr. Tonelli observed that this questionnaire, standard fare in respiratory research, may not have been perfectly suited for this particular study.

“You have to put it in the context of, ‘How good is the questionnaire to capture a difference in this particular disease over a 16-week period?’ ” he said. “It might not be sensitive enough to capture a significant change. The questionnaire was not developed for pulmonary hypertension in interstitial lung disease, of course. It was developed more generically. It may not capture all that you need to show significance.”

The investigators acknowledged the study’s other potential limitations, including a short duration, a notable percentage of patients who discontinued the trial early, and the fact that clinical worsening and exacerbation of disease were investigator reported and not confirmed by an independent committee.

As for next steps in assessing pulmonary hypertension treatments, Dr. Tonelli pointed to the direction of future research. “The other big study that needs to come out in our field, and I believe it’s being worked on, is inhaled treprostinil in pulmonary hypertension due to chronic obstructive pulmonary disease [COPD],” he said. “That’s a major unmet need; the COPD population is larger than the population for interstitial lung disease, and one would wonder whether inhaled treprostinil would benefit those patients as well. At the moment, we have no treatments for that condition. In the future, a COPD study will be needed.”

The study was supported by United Therapeutics. Author disclosures are listed on the New England Journal of Medicine website.

Inhaled treprostinil improved the exercise capacity of patients with pulmonary hypertension attributable to interstitial lung disease and was associated with some additional clinical benefits, according to a new study published in the New England Journal of Medicine.

To investigate treprostinil therapy for pulmonary hypertension in this subset of patients with lung disease, Aaron Waxman, MD, PhD, of Brigham and Women’s Hospital in Boston, and his fellow researchers launched the multicenter, randomized, double-blind, placebo-controlled INCREASE trial. They assigned 163 patients to the inhaled treprostinil group – administered via an ultrasonic, pulsed-delivery nebulizer over 16 weeks – and 163 patients to the placebo group. Their average age was 66.5 years, 73% were white, and 47% were female

At baseline, the mean 6-minute walk distance (6MWD) for all patients was 259.6 m. After 16 weeks, the treprostinil group gained a mean of 21.08 m in 6MWD, and the placebo group lost 10.04 m. The least-squares mean difference between the groups from baseline in the 6MWD was 31.12 m (95% confidence interval, 16.85-45.39; P < .001). After sensitivity analysis with multiple imputation, the difference remained significant at 30.97 m (95% CI, 16.53-45.41; P < .001).

In a comparison of N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels from baseline to 16 weeks, the treprostinil group saw a decrease of 15% while the placebo group’s levels increased by 46% (treatment ratio 0.58; 95% CI, 0.47-0.72; P < .001). Clinical worsening occurred in 37 patients (23%) in the treprostinil group and 54 patients (33%) in the placebo group (hazard ratio, 0.61; 95% CI, 0.40-0.92; P = .04), while serious adverse events occurred in 23.3% of the patients on treprostinil and 25.8% of the patients on placebo. There was no significant difference between groups in patient-reported quality of life, as assessed via the St. George’s Respiratory Questionnaire.

“There was no guarantee that this was going to work in this condition,” said Adriano Tonelli, MD, of the department of pulmonary medicine at the Cleveland Clinic, in an interview. “Several small studies have tried different medications, for pulmonary hypertension or otherwise, in patients with interstitial lung disease with minimal effect, if any. Given that all the prior studies were not categorically positive, the expectation, at least on my end, was that we needed to wait and see.” Dr. Tonelli and coauthors published a post hoc analysis of inhaled treprostinil studied in the TRIUMPH and BEAT trials.

Next steps: Assess clinical outcomes after inhaled treprostinil

Although the results of this study by Waxman et al, are encouraging, and the need for a treatment in this type of pulmonary hypertension is very real, more narrowing down will be needed to confirm the benefits of inhaled treprostinil, wrote Darren B. Taichman, MD, PhD, of the University of Pennsylvania in an accompanying editorial. He wrote, “After all, patients and physicians may reason, ‘It can’t hurt.’ Unfortunately, however, it could. Therapies approved for pulmonary arterial hypertension have been studied in patients with [ILD]-associated pulmonary hypertension and have shown inconsistent results, with some studies showing no benefit or suggesting harm.”

While the 6MWD has been used as an end point in previous drug trials for pulmonary arterial hypertension, Dr. Taichman wrote that improvements in such a variable were “probably too modest to be unequivocally consequential for many patients.” To confirm the benefits – and detriments – of treatments like inhaled treprostinil, it’s time for studies to focus on clinical end points, he stated, including hospitalizations, disease progression, and death.

He also highlighted the disparity between a treatment that led to increased walk distance and decreased clinical worsening yet did not register an improvement in health-related quality of life. He noted that the oft-cited minimal clinically important difference for 6MWD is approximately 30 m – similar to the difference recorded here. That said, he wrote, “prevention of deterioration is not to be ignored, even if it does not make a patient feel better.”

Regarding quality of life, Dr. Tonelli observed that this questionnaire, standard fare in respiratory research, may not have been perfectly suited for this particular study.

“You have to put it in the context of, ‘How good is the questionnaire to capture a difference in this particular disease over a 16-week period?’ ” he said. “It might not be sensitive enough to capture a significant change. The questionnaire was not developed for pulmonary hypertension in interstitial lung disease, of course. It was developed more generically. It may not capture all that you need to show significance.”

The investigators acknowledged the study’s other potential limitations, including a short duration, a notable percentage of patients who discontinued the trial early, and the fact that clinical worsening and exacerbation of disease were investigator reported and not confirmed by an independent committee.

As for next steps in assessing pulmonary hypertension treatments, Dr. Tonelli pointed to the direction of future research. “The other big study that needs to come out in our field, and I believe it’s being worked on, is inhaled treprostinil in pulmonary hypertension due to chronic obstructive pulmonary disease [COPD],” he said. “That’s a major unmet need; the COPD population is larger than the population for interstitial lung disease, and one would wonder whether inhaled treprostinil would benefit those patients as well. At the moment, we have no treatments for that condition. In the future, a COPD study will be needed.”

The study was supported by United Therapeutics. Author disclosures are listed on the New England Journal of Medicine website.

Inhaled treprostinil improved the exercise capacity of patients with pulmonary hypertension attributable to interstitial lung disease and was associated with some additional clinical benefits, according to a new study published in the New England Journal of Medicine.

To investigate treprostinil therapy for pulmonary hypertension in this subset of patients with lung disease, Aaron Waxman, MD, PhD, of Brigham and Women’s Hospital in Boston, and his fellow researchers launched the multicenter, randomized, double-blind, placebo-controlled INCREASE trial. They assigned 163 patients to the inhaled treprostinil group – administered via an ultrasonic, pulsed-delivery nebulizer over 16 weeks – and 163 patients to the placebo group. Their average age was 66.5 years, 73% were white, and 47% were female

At baseline, the mean 6-minute walk distance (6MWD) for all patients was 259.6 m. After 16 weeks, the treprostinil group gained a mean of 21.08 m in 6MWD, and the placebo group lost 10.04 m. The least-squares mean difference between the groups from baseline in the 6MWD was 31.12 m (95% confidence interval, 16.85-45.39; P < .001). After sensitivity analysis with multiple imputation, the difference remained significant at 30.97 m (95% CI, 16.53-45.41; P < .001).

In a comparison of N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels from baseline to 16 weeks, the treprostinil group saw a decrease of 15% while the placebo group’s levels increased by 46% (treatment ratio 0.58; 95% CI, 0.47-0.72; P < .001). Clinical worsening occurred in 37 patients (23%) in the treprostinil group and 54 patients (33%) in the placebo group (hazard ratio, 0.61; 95% CI, 0.40-0.92; P = .04), while serious adverse events occurred in 23.3% of the patients on treprostinil and 25.8% of the patients on placebo. There was no significant difference between groups in patient-reported quality of life, as assessed via the St. George’s Respiratory Questionnaire.

“There was no guarantee that this was going to work in this condition,” said Adriano Tonelli, MD, of the department of pulmonary medicine at the Cleveland Clinic, in an interview. “Several small studies have tried different medications, for pulmonary hypertension or otherwise, in patients with interstitial lung disease with minimal effect, if any. Given that all the prior studies were not categorically positive, the expectation, at least on my end, was that we needed to wait and see.” Dr. Tonelli and coauthors published a post hoc analysis of inhaled treprostinil studied in the TRIUMPH and BEAT trials.

Next steps: Assess clinical outcomes after inhaled treprostinil

Although the results of this study by Waxman et al, are encouraging, and the need for a treatment in this type of pulmonary hypertension is very real, more narrowing down will be needed to confirm the benefits of inhaled treprostinil, wrote Darren B. Taichman, MD, PhD, of the University of Pennsylvania in an accompanying editorial. He wrote, “After all, patients and physicians may reason, ‘It can’t hurt.’ Unfortunately, however, it could. Therapies approved for pulmonary arterial hypertension have been studied in patients with [ILD]-associated pulmonary hypertension and have shown inconsistent results, with some studies showing no benefit or suggesting harm.”

While the 6MWD has been used as an end point in previous drug trials for pulmonary arterial hypertension, Dr. Taichman wrote that improvements in such a variable were “probably too modest to be unequivocally consequential for many patients.” To confirm the benefits – and detriments – of treatments like inhaled treprostinil, it’s time for studies to focus on clinical end points, he stated, including hospitalizations, disease progression, and death.

He also highlighted the disparity between a treatment that led to increased walk distance and decreased clinical worsening yet did not register an improvement in health-related quality of life. He noted that the oft-cited minimal clinically important difference for 6MWD is approximately 30 m – similar to the difference recorded here. That said, he wrote, “prevention of deterioration is not to be ignored, even if it does not make a patient feel better.”

Regarding quality of life, Dr. Tonelli observed that this questionnaire, standard fare in respiratory research, may not have been perfectly suited for this particular study.

“You have to put it in the context of, ‘How good is the questionnaire to capture a difference in this particular disease over a 16-week period?’ ” he said. “It might not be sensitive enough to capture a significant change. The questionnaire was not developed for pulmonary hypertension in interstitial lung disease, of course. It was developed more generically. It may not capture all that you need to show significance.”

The investigators acknowledged the study’s other potential limitations, including a short duration, a notable percentage of patients who discontinued the trial early, and the fact that clinical worsening and exacerbation of disease were investigator reported and not confirmed by an independent committee.

As for next steps in assessing pulmonary hypertension treatments, Dr. Tonelli pointed to the direction of future research. “The other big study that needs to come out in our field, and I believe it’s being worked on, is inhaled treprostinil in pulmonary hypertension due to chronic obstructive pulmonary disease [COPD],” he said. “That’s a major unmet need; the COPD population is larger than the population for interstitial lung disease, and one would wonder whether inhaled treprostinil would benefit those patients as well. At the moment, we have no treatments for that condition. In the future, a COPD study will be needed.”

The study was supported by United Therapeutics. Author disclosures are listed on the New England Journal of Medicine website.

Intraoperative injection of calcium chloride into the four major atrial ganglionated plexi (GPs) reduced the incidence of early postoperative atrial fibrillation (POAF) in patients undergoing off-pump coronary artery bypass grafting (CABG) surgery, in a proof-of-concept study.

“[We] hypothesized that injecting [calcium chloride] into the major atrial GPs during isolated CABG can reduce the incidence of POAF by calcium-induced autonomic neurotoxicity,” wrote Huishan Wang, MD, of the General Hospital of Northern Theater Command in Shenyang, China, and colleagues. Their report was published in the Journal of the American College of Cardiology.

The single-center, sham-controlled, proof-of-concept study included 200 patients without a history of AF undergoing isolated, off-pump CABG surgery. Participants were randomized (1:1) to receive an injection of either 5% calcium chloride or 0.9% sodium chloride into the four major GPs during CABG.

Post surgery, patients were monitored for the occurrence of POAF using routine 12-lead ECG and 7-day continuous telemetry and Holter monitoring. The primary endpoint was the incidence of POAF lasting 30 seconds or longer through 7 days. Various secondary outcomes, including POAF burden and length of hospitalization, were also measured.

After analysis, the researchers found that 15 patients in the calcium chloride arm and 36 patients in the sodium chloride arm developed POAF during the first 7 days post CABG, corresponding to a POAF hazard reduction of 63% (hazard ratio, 0.37; 95% confidence interval, 0.21-0.64; P = .001) with no significant adverse effects observed among study patients.

The calcium chloride injection also resulted in reduced AF burden and lower rates of amiodarone and esmolol use to treat POAF; however, there was no difference in the length of hospitalization between the two groups. The incidences of nonsustained atrial tachyarrhythmia (less than 30 seconds) and atrial couplets were also significantly reduced in the calcium chloride group.

“We selected the 4 major atrial GPs as our targets because [of] their role in the initiation and maintenance of AF is more established than other cardiac neural plexi,” the researchers explained. “Interruption of the atrial neural network by Ca-mediated GP neurotoxicity may underlie the therapeutic effects.”
 

Is ‘nuisance’ arrhythmia worth targeting?

In an editorial accompanying the report, John H. Alexander, MD, MHS, wrote that intraoperative calcium chloride atrial ganglionic ablation can now be considered as an effective intervention to prevent POAF in patients undergoing cardiac surgery. “These investigators should be congratulated for studying post-operative atrial fibrillation in cardiac surgery,” he stated.

MDedge News

“However, this trial has two significant limitations. Firstly, it was conducted in a single center in a very homogeneous population; secondly, POAF, in and of itself, is largely a nuisance arrhythmia and hardly worth preventing, but is associated with a higher risk of other adverse outcomes,” Dr. Alexander, professor of medicine at Duke University, Durham, N.C., said in an interview.

“The unanswered question is whether preventing perioperative AF will prevent stroke, heart failure, and death,” he further explained. “Answering these questions would require a larger trial (or trials) with longer term (months to years) follow-up.”

Dr. Wang and colleagues acknowledged that the current study was underpowered for some secondary outcomes, such as length of hospitalization. They explained that a large sample size is needed to detect a difference in length of hospitalization, as well as other outcomes.

“Further studies are needed to confirm the safety and efficacy of calcium-induced atrial autonomic denervation in patients undergoing on-pump CABG and surgery for valvular heart disease,” they concluded.

The study was funded by the Provincial Key R & D Program in China. One author reported holding a U.S. patent related to the study. The remaining authors had no relevant relationships to disclose.

Intraoperative injection of calcium chloride into the four major atrial ganglionated plexi (GPs) reduced the incidence of early postoperative atrial fibrillation (POAF) in patients undergoing off-pump coronary artery bypass grafting (CABG) surgery, in a proof-of-concept study.

“[We] hypothesized that injecting [calcium chloride] into the major atrial GPs during isolated CABG can reduce the incidence of POAF by calcium-induced autonomic neurotoxicity,” wrote Huishan Wang, MD, of the General Hospital of Northern Theater Command in Shenyang, China, and colleagues. Their report was published in the Journal of the American College of Cardiology.

The single-center, sham-controlled, proof-of-concept study included 200 patients without a history of AF undergoing isolated, off-pump CABG surgery. Participants were randomized (1:1) to receive an injection of either 5% calcium chloride or 0.9% sodium chloride into the four major GPs during CABG.

Post surgery, patients were monitored for the occurrence of POAF using routine 12-lead ECG and 7-day continuous telemetry and Holter monitoring. The primary endpoint was the incidence of POAF lasting 30 seconds or longer through 7 days. Various secondary outcomes, including POAF burden and length of hospitalization, were also measured.

After analysis, the researchers found that 15 patients in the calcium chloride arm and 36 patients in the sodium chloride arm developed POAF during the first 7 days post CABG, corresponding to a POAF hazard reduction of 63% (hazard ratio, 0.37; 95% confidence interval, 0.21-0.64; P = .001) with no significant adverse effects observed among study patients.

The calcium chloride injection also resulted in reduced AF burden and lower rates of amiodarone and esmolol use to treat POAF; however, there was no difference in the length of hospitalization between the two groups. The incidences of nonsustained atrial tachyarrhythmia (less than 30 seconds) and atrial couplets were also significantly reduced in the calcium chloride group.

“We selected the 4 major atrial GPs as our targets because [of] their role in the initiation and maintenance of AF is more established than other cardiac neural plexi,” the researchers explained. “Interruption of the atrial neural network by Ca-mediated GP neurotoxicity may underlie the therapeutic effects.”
 

Is ‘nuisance’ arrhythmia worth targeting?

In an editorial accompanying the report, John H. Alexander, MD, MHS, wrote that intraoperative calcium chloride atrial ganglionic ablation can now be considered as an effective intervention to prevent POAF in patients undergoing cardiac surgery. “These investigators should be congratulated for studying post-operative atrial fibrillation in cardiac surgery,” he stated.

MDedge News

“However, this trial has two significant limitations. Firstly, it was conducted in a single center in a very homogeneous population; secondly, POAF, in and of itself, is largely a nuisance arrhythmia and hardly worth preventing, but is associated with a higher risk of other adverse outcomes,” Dr. Alexander, professor of medicine at Duke University, Durham, N.C., said in an interview.

“The unanswered question is whether preventing perioperative AF will prevent stroke, heart failure, and death,” he further explained. “Answering these questions would require a larger trial (or trials) with longer term (months to years) follow-up.”

Dr. Wang and colleagues acknowledged that the current study was underpowered for some secondary outcomes, such as length of hospitalization. They explained that a large sample size is needed to detect a difference in length of hospitalization, as well as other outcomes.

“Further studies are needed to confirm the safety and efficacy of calcium-induced atrial autonomic denervation in patients undergoing on-pump CABG and surgery for valvular heart disease,” they concluded.

The study was funded by the Provincial Key R & D Program in China. One author reported holding a U.S. patent related to the study. The remaining authors had no relevant relationships to disclose.

Intraoperative injection of calcium chloride into the four major atrial ganglionated plexi (GPs) reduced the incidence of early postoperative atrial fibrillation (POAF) in patients undergoing off-pump coronary artery bypass grafting (CABG) surgery, in a proof-of-concept study.

“[We] hypothesized that injecting [calcium chloride] into the major atrial GPs during isolated CABG can reduce the incidence of POAF by calcium-induced autonomic neurotoxicity,” wrote Huishan Wang, MD, of the General Hospital of Northern Theater Command in Shenyang, China, and colleagues. Their report was published in the Journal of the American College of Cardiology.

The single-center, sham-controlled, proof-of-concept study included 200 patients without a history of AF undergoing isolated, off-pump CABG surgery. Participants were randomized (1:1) to receive an injection of either 5% calcium chloride or 0.9% sodium chloride into the four major GPs during CABG.

Post surgery, patients were monitored for the occurrence of POAF using routine 12-lead ECG and 7-day continuous telemetry and Holter monitoring. The primary endpoint was the incidence of POAF lasting 30 seconds or longer through 7 days. Various secondary outcomes, including POAF burden and length of hospitalization, were also measured.

After analysis, the researchers found that 15 patients in the calcium chloride arm and 36 patients in the sodium chloride arm developed POAF during the first 7 days post CABG, corresponding to a POAF hazard reduction of 63% (hazard ratio, 0.37; 95% confidence interval, 0.21-0.64; P = .001) with no significant adverse effects observed among study patients.

The calcium chloride injection also resulted in reduced AF burden and lower rates of amiodarone and esmolol use to treat POAF; however, there was no difference in the length of hospitalization between the two groups. The incidences of nonsustained atrial tachyarrhythmia (less than 30 seconds) and atrial couplets were also significantly reduced in the calcium chloride group.

“We selected the 4 major atrial GPs as our targets because [of] their role in the initiation and maintenance of AF is more established than other cardiac neural plexi,” the researchers explained. “Interruption of the atrial neural network by Ca-mediated GP neurotoxicity may underlie the therapeutic effects.”
 

Is ‘nuisance’ arrhythmia worth targeting?

In an editorial accompanying the report, John H. Alexander, MD, MHS, wrote that intraoperative calcium chloride atrial ganglionic ablation can now be considered as an effective intervention to prevent POAF in patients undergoing cardiac surgery. “These investigators should be congratulated for studying post-operative atrial fibrillation in cardiac surgery,” he stated.

MDedge News

“However, this trial has two significant limitations. Firstly, it was conducted in a single center in a very homogeneous population; secondly, POAF, in and of itself, is largely a nuisance arrhythmia and hardly worth preventing, but is associated with a higher risk of other adverse outcomes,” Dr. Alexander, professor of medicine at Duke University, Durham, N.C., said in an interview.

“The unanswered question is whether preventing perioperative AF will prevent stroke, heart failure, and death,” he further explained. “Answering these questions would require a larger trial (or trials) with longer term (months to years) follow-up.”

Dr. Wang and colleagues acknowledged that the current study was underpowered for some secondary outcomes, such as length of hospitalization. They explained that a large sample size is needed to detect a difference in length of hospitalization, as well as other outcomes.

“Further studies are needed to confirm the safety and efficacy of calcium-induced atrial autonomic denervation in patients undergoing on-pump CABG and surgery for valvular heart disease,” they concluded.

The study was funded by the Provincial Key R & D Program in China. One author reported holding a U.S. patent related to the study. The remaining authors had no relevant relationships to disclose.

Physicians unaffiliated with health care systems continue to have difficulties obtaining COVID-19 vaccinations for themselves and their staffs, but that challenge appears to be fading in some states. Yet, in many places, primary care physicians (PCPs) still aren’t being enlisted in the national vaccination effort, despite their numbers and their relationships with patients.

In the first few weeks after the Pfizer and Moderna vaccines received emergency-use authorizations from the Food and Drug Administration, they were distributed mostly to hospitals, pharmacies, and long-term care facilities. Naturally, the hospitals and health care systems vaccinated their own staffs and employed physicians first.

So, even though the guidelines from the Centers for Disease Control and Prevention specify that all frontline health care workers should be included in the first vaccination group, many non–hospital-affiliated private practices have been left out in the cold. Non–patient-facing hospital staff members in some facilities, as well as first responders such as police officers and firefighters, have taken precedence over independent primary care physicians.

In Florida, residents older than 65 years were invited to get vaccinated before some physicians had received shots, Anders Gilberg, senior vice president of government affairs for the Medical Group Management Association, said in an interview.

While the Department of Health & Human Services is now telling states to give vaccinations to everyone over 65, that wasn’t the case back then.

Community doctors in some areas are still finding it hard to get vaccinated or even find out how to get shots. Yul Ejnes, MD, an internist and partner in Coastal Medical, an independent medical group based in Cranston, R.I., said in an interview that he and his practice staff haven’t been vaccinated, while the staffs of local hospitals have received their shots.

In response to repeated inquiries from his group, he said, the state health department recently said independent practice staffs will start getting vaccinated the week of Jan. 25.

Dr. Ejnes said he understood why hospital personnel went first: Hospitals have the necessary infrastructure, “and the staff in the emergency department and the ICU are caring for the sickest of the sick.”

For primary care doctors like himself who don’t work for the hospital, he said, “I don’t think an infrastructure to get us the vaccine in a timely manner was developed – or if it was developed, it hasn’t been communicated to us.”

Nevertheless, Dr. Ejnes stressed that primary care physicians in the community are just as vulnerable to the coronavirus as hospital clinicians. “We’re seeing patients who have COVID but don’t know they have it. I’m seeing 15 patients a day, and we screen them – as everyone else does – for symptoms and contact and travel, and check their temp,” he said. “But not a day goes by that one of the clinicians in this office doesn’t get a phone call from a patient who was seen a day or 2 earlier to tell them it turns out they were COVID positive. I’m spending 15 minutes in a 100–sq ft room with a patient for a routine visit. And as much as we’re masking and gloving and wearing eye protection, I wouldn’t consider us to be at low risk, especially with the high prevalence of disease.”

In some other states, the situation seems to be improving. Ada Stewart, MD, president of the American Academy of Family Physicians, said that she and her colleagues in a community health center in Columbia, S.C., are in the process of being vaccinated. She got her own shot Jan. 6 at a local hospital.

Her clinic’s staff hadn’t been vaccinated earlier, she said, because nobody in the practice knew the contact person at the hospital who could help access the vaccine doses. Other independent practices in her state are now getting vaccinated, she said, after Gov. Henry McMaster of South Carolina ordered that all health care providers in the top priority category be inoculated by Jan. 15. “At this point, the issues have been diminished.”

However, Dr. Stewart added, independent doctors in some states are still unable to get their shots. AAFP state chapters, as well as the national organization, are trying to persuade governors to ensure all of these physicians are vaccinated. “We’re trying to make sure that the voices of physicians not affiliated with health systems are being heard,” she said.
 

Lucky shot for doctor

David Boles, DO, a family doctor in Clarksville, Tenn., was able to get his first dose of vaccine just before Christmas, he said in an interview, because he was medical director of a hospice that had received vaccine doses for first responders. When some firefighters and police officers failed to show up for their appointments, the hospice called him and said he had 45 minutes to get to the site if he wanted to be vaccinated.

In early January, his colleagues and staff were also vaccinated, he said, after they were notified of their eligibility as frontline health care workers.

Dr. Boles agreed with Dr. Ejnes that community physicians and nurses are as much at risk as hospital clinicians, except for those intubating patients in the ICU. They may be even more vulnerable, he added, because they have less personal protective equipment than hospital doctors and nurses.

Jennifer Brull, MD, a family physician in Plainville, Kan., said there have been plenty of COVID-19 cases in her small rural community, and the local critical access hospital nearly ran out of beds at one point. Through a collaborative relationship among her clinic (the lone one in the area), the hospital, and the county health department, nearly every frontline health care worker has been vaccinated, and most clinicians in her group have gotten their second doses.

Both the hospital and the health department received vaccine supplies, she said, and everyone in the high-priority category was offered shots. So far, about 170 health care workers have been vaccinated, and only a few declined. More than 300 other people – most of them essential non–health care workers and people older than 65 – have signed up for the next round of shots.
 

Expanding vaccination effort

Dr. Brull’s practice is the exception among private medical groups around the country. Mr. Gilberg said the MGMA is “concerned that independent practices are playing second fiddle because they’ve been left behind.” Physicians and patient-facing staff in private groups should be getting vaccinated before hospital information technology workers and other non–patient-facing staffers.

Medical practices also can and should play a much bigger role in the overall vaccination effort. Mr. Gilberg has spoken to leaders of several large primary care groups “that have the freezers [for vaccines] and the capacity but haven’t been folded into the distribution plan, especially if they’re not part of the hospital system.”

While hospitals have the storage, he said, they’re not set up to distribute vaccines throughout their communities. “Most health care in this country is delivered outside of the hospital setting. That’s how you’re going to get people vaccinated.”

Ironically, he added, “the same PCPs that are having trouble getting themselves and their staffs vaccinated would be the physicians who could help with vaccine distribution.”

Dr. Brull’s clinic stands ready to help the hospital and health department vaccinate the local population. When sufficient vaccine supplies arrive, she said, she envisioned the doctors and staff administering 200-400 shots per day on Saturdays or weekends.

Dr. Brull was the exception – the other physicians interviewed hadn’t been invited to participate in vaccination efforts.

Dr. Ejnes said his group is capable of vaccinating its patients if it uses the Moderna vaccine, which doesn’t require a super-cold freezer. There are logistical challenges, including social distancing and finding space to observe vaccinated patients for 15 minutes after their shots, he noted. “We’re ready and willing, but realistic about how much we’ll be able to do in this effort.”

The fact that doctors haven’t been enlisted yet in this campaign speaks volumes about “the neglect of the public health infrastructure,” Dr. Ejnes said. “We’re not mobilizing as quickly as we should.”
 

Alternative routes

Dr. Boles’ group has a refrigerator for pediatric vaccines, which could be used to store the Moderna vaccine, he noted. Shots could be administered to patients in their cars in the parking lot, and they could wait for a while afterward until a nurse came out to verify they were okay.

Mass vaccination sites might also be deployed, as Los Angeles is doing with Dodger Stadium, and physicians could take shifts there in their spare time, Dr. Boles said. But for right now, he views pharmacies as the primary venues for community vaccination.

Of course, the number of pharmacists and pharmacy-employed advanced practice nurses is tiny, compared with the number of primary care doctors, mid-level practitioners, and nurses in ambulatory care practices. Moreover, Mr. Gilberg said, practices know from their electronic health records which patients are most at risk and should be vaccinated first. “Walgreens and CVS don’t know that.”

Physicians should also take the lead in vaccinations because of their patient relationships, he noted. “They can help educate [vaccine-hesitant] patients on why it’s important and dispel some of the rumors and the misinformation that has been politicized. That’s why we should engage physicians in an outpatient setting. And we have to vaccinate them and their staffs. Otherwise, we’re never going to get this rollout underway.”

Dr. Stewart agreed. “We are really the foundation of how we’re going to accomplish this. Most folks are seen by a primary care physician. We touch millions of lives,” she said. “We’re part of the community. Our patients trust us. We’re out there doing it already. We’re doing prevention, giving flu shots, and we’re trying to encourage people to get the COVID vaccine.”

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

Physicians unaffiliated with health care systems continue to have difficulties obtaining COVID-19 vaccinations for themselves and their staffs, but that challenge appears to be fading in some states. Yet, in many places, primary care physicians (PCPs) still aren’t being enlisted in the national vaccination effort, despite their numbers and their relationships with patients.

In the first few weeks after the Pfizer and Moderna vaccines received emergency-use authorizations from the Food and Drug Administration, they were distributed mostly to hospitals, pharmacies, and long-term care facilities. Naturally, the hospitals and health care systems vaccinated their own staffs and employed physicians first.

So, even though the guidelines from the Centers for Disease Control and Prevention specify that all frontline health care workers should be included in the first vaccination group, many non–hospital-affiliated private practices have been left out in the cold. Non–patient-facing hospital staff members in some facilities, as well as first responders such as police officers and firefighters, have taken precedence over independent primary care physicians.

In Florida, residents older than 65 years were invited to get vaccinated before some physicians had received shots, Anders Gilberg, senior vice president of government affairs for the Medical Group Management Association, said in an interview.

While the Department of Health & Human Services is now telling states to give vaccinations to everyone over 65, that wasn’t the case back then.

Community doctors in some areas are still finding it hard to get vaccinated or even find out how to get shots. Yul Ejnes, MD, an internist and partner in Coastal Medical, an independent medical group based in Cranston, R.I., said in an interview that he and his practice staff haven’t been vaccinated, while the staffs of local hospitals have received their shots.

In response to repeated inquiries from his group, he said, the state health department recently said independent practice staffs will start getting vaccinated the week of Jan. 25.

Dr. Ejnes said he understood why hospital personnel went first: Hospitals have the necessary infrastructure, “and the staff in the emergency department and the ICU are caring for the sickest of the sick.”

For primary care doctors like himself who don’t work for the hospital, he said, “I don’t think an infrastructure to get us the vaccine in a timely manner was developed – or if it was developed, it hasn’t been communicated to us.”

Nevertheless, Dr. Ejnes stressed that primary care physicians in the community are just as vulnerable to the coronavirus as hospital clinicians. “We’re seeing patients who have COVID but don’t know they have it. I’m seeing 15 patients a day, and we screen them – as everyone else does – for symptoms and contact and travel, and check their temp,” he said. “But not a day goes by that one of the clinicians in this office doesn’t get a phone call from a patient who was seen a day or 2 earlier to tell them it turns out they were COVID positive. I’m spending 15 minutes in a 100–sq ft room with a patient for a routine visit. And as much as we’re masking and gloving and wearing eye protection, I wouldn’t consider us to be at low risk, especially with the high prevalence of disease.”

In some other states, the situation seems to be improving. Ada Stewart, MD, president of the American Academy of Family Physicians, said that she and her colleagues in a community health center in Columbia, S.C., are in the process of being vaccinated. She got her own shot Jan. 6 at a local hospital.

Her clinic’s staff hadn’t been vaccinated earlier, she said, because nobody in the practice knew the contact person at the hospital who could help access the vaccine doses. Other independent practices in her state are now getting vaccinated, she said, after Gov. Henry McMaster of South Carolina ordered that all health care providers in the top priority category be inoculated by Jan. 15. “At this point, the issues have been diminished.”

However, Dr. Stewart added, independent doctors in some states are still unable to get their shots. AAFP state chapters, as well as the national organization, are trying to persuade governors to ensure all of these physicians are vaccinated. “We’re trying to make sure that the voices of physicians not affiliated with health systems are being heard,” she said.
 

Lucky shot for doctor

David Boles, DO, a family doctor in Clarksville, Tenn., was able to get his first dose of vaccine just before Christmas, he said in an interview, because he was medical director of a hospice that had received vaccine doses for first responders. When some firefighters and police officers failed to show up for their appointments, the hospice called him and said he had 45 minutes to get to the site if he wanted to be vaccinated.

In early January, his colleagues and staff were also vaccinated, he said, after they were notified of their eligibility as frontline health care workers.

Dr. Boles agreed with Dr. Ejnes that community physicians and nurses are as much at risk as hospital clinicians, except for those intubating patients in the ICU. They may be even more vulnerable, he added, because they have less personal protective equipment than hospital doctors and nurses.

Jennifer Brull, MD, a family physician in Plainville, Kan., said there have been plenty of COVID-19 cases in her small rural community, and the local critical access hospital nearly ran out of beds at one point. Through a collaborative relationship among her clinic (the lone one in the area), the hospital, and the county health department, nearly every frontline health care worker has been vaccinated, and most clinicians in her group have gotten their second doses.

Both the hospital and the health department received vaccine supplies, she said, and everyone in the high-priority category was offered shots. So far, about 170 health care workers have been vaccinated, and only a few declined. More than 300 other people – most of them essential non–health care workers and people older than 65 – have signed up for the next round of shots.
 

Expanding vaccination effort

Dr. Brull’s practice is the exception among private medical groups around the country. Mr. Gilberg said the MGMA is “concerned that independent practices are playing second fiddle because they’ve been left behind.” Physicians and patient-facing staff in private groups should be getting vaccinated before hospital information technology workers and other non–patient-facing staffers.

Medical practices also can and should play a much bigger role in the overall vaccination effort. Mr. Gilberg has spoken to leaders of several large primary care groups “that have the freezers [for vaccines] and the capacity but haven’t been folded into the distribution plan, especially if they’re not part of the hospital system.”

While hospitals have the storage, he said, they’re not set up to distribute vaccines throughout their communities. “Most health care in this country is delivered outside of the hospital setting. That’s how you’re going to get people vaccinated.”

Ironically, he added, “the same PCPs that are having trouble getting themselves and their staffs vaccinated would be the physicians who could help with vaccine distribution.”

Dr. Brull’s clinic stands ready to help the hospital and health department vaccinate the local population. When sufficient vaccine supplies arrive, she said, she envisioned the doctors and staff administering 200-400 shots per day on Saturdays or weekends.

Dr. Brull was the exception – the other physicians interviewed hadn’t been invited to participate in vaccination efforts.

Dr. Ejnes said his group is capable of vaccinating its patients if it uses the Moderna vaccine, which doesn’t require a super-cold freezer. There are logistical challenges, including social distancing and finding space to observe vaccinated patients for 15 minutes after their shots, he noted. “We’re ready and willing, but realistic about how much we’ll be able to do in this effort.”

The fact that doctors haven’t been enlisted yet in this campaign speaks volumes about “the neglect of the public health infrastructure,” Dr. Ejnes said. “We’re not mobilizing as quickly as we should.”
 

Alternative routes

Dr. Boles’ group has a refrigerator for pediatric vaccines, which could be used to store the Moderna vaccine, he noted. Shots could be administered to patients in their cars in the parking lot, and they could wait for a while afterward until a nurse came out to verify they were okay.

Mass vaccination sites might also be deployed, as Los Angeles is doing with Dodger Stadium, and physicians could take shifts there in their spare time, Dr. Boles said. But for right now, he views pharmacies as the primary venues for community vaccination.

Of course, the number of pharmacists and pharmacy-employed advanced practice nurses is tiny, compared with the number of primary care doctors, mid-level practitioners, and nurses in ambulatory care practices. Moreover, Mr. Gilberg said, practices know from their electronic health records which patients are most at risk and should be vaccinated first. “Walgreens and CVS don’t know that.”

Physicians should also take the lead in vaccinations because of their patient relationships, he noted. “They can help educate [vaccine-hesitant] patients on why it’s important and dispel some of the rumors and the misinformation that has been politicized. That’s why we should engage physicians in an outpatient setting. And we have to vaccinate them and their staffs. Otherwise, we’re never going to get this rollout underway.”

Dr. Stewart agreed. “We are really the foundation of how we’re going to accomplish this. Most folks are seen by a primary care physician. We touch millions of lives,” she said. “We’re part of the community. Our patients trust us. We’re out there doing it already. We’re doing prevention, giving flu shots, and we’re trying to encourage people to get the COVID vaccine.”

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

Physicians unaffiliated with health care systems continue to have difficulties obtaining COVID-19 vaccinations for themselves and their staffs, but that challenge appears to be fading in some states. Yet, in many places, primary care physicians (PCPs) still aren’t being enlisted in the national vaccination effort, despite their numbers and their relationships with patients.

In the first few weeks after the Pfizer and Moderna vaccines received emergency-use authorizations from the Food and Drug Administration, they were distributed mostly to hospitals, pharmacies, and long-term care facilities. Naturally, the hospitals and health care systems vaccinated their own staffs and employed physicians first.

So, even though the guidelines from the Centers for Disease Control and Prevention specify that all frontline health care workers should be included in the first vaccination group, many non–hospital-affiliated private practices have been left out in the cold. Non–patient-facing hospital staff members in some facilities, as well as first responders such as police officers and firefighters, have taken precedence over independent primary care physicians.

In Florida, residents older than 65 years were invited to get vaccinated before some physicians had received shots, Anders Gilberg, senior vice president of government affairs for the Medical Group Management Association, said in an interview.

While the Department of Health & Human Services is now telling states to give vaccinations to everyone over 65, that wasn’t the case back then.

Community doctors in some areas are still finding it hard to get vaccinated or even find out how to get shots. Yul Ejnes, MD, an internist and partner in Coastal Medical, an independent medical group based in Cranston, R.I., said in an interview that he and his practice staff haven’t been vaccinated, while the staffs of local hospitals have received their shots.

In response to repeated inquiries from his group, he said, the state health department recently said independent practice staffs will start getting vaccinated the week of Jan. 25.

Dr. Ejnes said he understood why hospital personnel went first: Hospitals have the necessary infrastructure, “and the staff in the emergency department and the ICU are caring for the sickest of the sick.”

For primary care doctors like himself who don’t work for the hospital, he said, “I don’t think an infrastructure to get us the vaccine in a timely manner was developed – or if it was developed, it hasn’t been communicated to us.”

Nevertheless, Dr. Ejnes stressed that primary care physicians in the community are just as vulnerable to the coronavirus as hospital clinicians. “We’re seeing patients who have COVID but don’t know they have it. I’m seeing 15 patients a day, and we screen them – as everyone else does – for symptoms and contact and travel, and check their temp,” he said. “But not a day goes by that one of the clinicians in this office doesn’t get a phone call from a patient who was seen a day or 2 earlier to tell them it turns out they were COVID positive. I’m spending 15 minutes in a 100–sq ft room with a patient for a routine visit. And as much as we’re masking and gloving and wearing eye protection, I wouldn’t consider us to be at low risk, especially with the high prevalence of disease.”

In some other states, the situation seems to be improving. Ada Stewart, MD, president of the American Academy of Family Physicians, said that she and her colleagues in a community health center in Columbia, S.C., are in the process of being vaccinated. She got her own shot Jan. 6 at a local hospital.

Her clinic’s staff hadn’t been vaccinated earlier, she said, because nobody in the practice knew the contact person at the hospital who could help access the vaccine doses. Other independent practices in her state are now getting vaccinated, she said, after Gov. Henry McMaster of South Carolina ordered that all health care providers in the top priority category be inoculated by Jan. 15. “At this point, the issues have been diminished.”

However, Dr. Stewart added, independent doctors in some states are still unable to get their shots. AAFP state chapters, as well as the national organization, are trying to persuade governors to ensure all of these physicians are vaccinated. “We’re trying to make sure that the voices of physicians not affiliated with health systems are being heard,” she said.
 

Lucky shot for doctor

David Boles, DO, a family doctor in Clarksville, Tenn., was able to get his first dose of vaccine just before Christmas, he said in an interview, because he was medical director of a hospice that had received vaccine doses for first responders. When some firefighters and police officers failed to show up for their appointments, the hospice called him and said he had 45 minutes to get to the site if he wanted to be vaccinated.

In early January, his colleagues and staff were also vaccinated, he said, after they were notified of their eligibility as frontline health care workers.

Dr. Boles agreed with Dr. Ejnes that community physicians and nurses are as much at risk as hospital clinicians, except for those intubating patients in the ICU. They may be even more vulnerable, he added, because they have less personal protective equipment than hospital doctors and nurses.

Jennifer Brull, MD, a family physician in Plainville, Kan., said there have been plenty of COVID-19 cases in her small rural community, and the local critical access hospital nearly ran out of beds at one point. Through a collaborative relationship among her clinic (the lone one in the area), the hospital, and the county health department, nearly every frontline health care worker has been vaccinated, and most clinicians in her group have gotten their second doses.

Both the hospital and the health department received vaccine supplies, she said, and everyone in the high-priority category was offered shots. So far, about 170 health care workers have been vaccinated, and only a few declined. More than 300 other people – most of them essential non–health care workers and people older than 65 – have signed up for the next round of shots.
 

Expanding vaccination effort

Dr. Brull’s practice is the exception among private medical groups around the country. Mr. Gilberg said the MGMA is “concerned that independent practices are playing second fiddle because they’ve been left behind.” Physicians and patient-facing staff in private groups should be getting vaccinated before hospital information technology workers and other non–patient-facing staffers.

Medical practices also can and should play a much bigger role in the overall vaccination effort. Mr. Gilberg has spoken to leaders of several large primary care groups “that have the freezers [for vaccines] and the capacity but haven’t been folded into the distribution plan, especially if they’re not part of the hospital system.”

While hospitals have the storage, he said, they’re not set up to distribute vaccines throughout their communities. “Most health care in this country is delivered outside of the hospital setting. That’s how you’re going to get people vaccinated.”

Ironically, he added, “the same PCPs that are having trouble getting themselves and their staffs vaccinated would be the physicians who could help with vaccine distribution.”

Dr. Brull’s clinic stands ready to help the hospital and health department vaccinate the local population. When sufficient vaccine supplies arrive, she said, she envisioned the doctors and staff administering 200-400 shots per day on Saturdays or weekends.

Dr. Brull was the exception – the other physicians interviewed hadn’t been invited to participate in vaccination efforts.

Dr. Ejnes said his group is capable of vaccinating its patients if it uses the Moderna vaccine, which doesn’t require a super-cold freezer. There are logistical challenges, including social distancing and finding space to observe vaccinated patients for 15 minutes after their shots, he noted. “We’re ready and willing, but realistic about how much we’ll be able to do in this effort.”

The fact that doctors haven’t been enlisted yet in this campaign speaks volumes about “the neglect of the public health infrastructure,” Dr. Ejnes said. “We’re not mobilizing as quickly as we should.”
 

Alternative routes

Dr. Boles’ group has a refrigerator for pediatric vaccines, which could be used to store the Moderna vaccine, he noted. Shots could be administered to patients in their cars in the parking lot, and they could wait for a while afterward until a nurse came out to verify they were okay.

Mass vaccination sites might also be deployed, as Los Angeles is doing with Dodger Stadium, and physicians could take shifts there in their spare time, Dr. Boles said. But for right now, he views pharmacies as the primary venues for community vaccination.

Of course, the number of pharmacists and pharmacy-employed advanced practice nurses is tiny, compared with the number of primary care doctors, mid-level practitioners, and nurses in ambulatory care practices. Moreover, Mr. Gilberg said, practices know from their electronic health records which patients are most at risk and should be vaccinated first. “Walgreens and CVS don’t know that.”

Physicians should also take the lead in vaccinations because of their patient relationships, he noted. “They can help educate [vaccine-hesitant] patients on why it’s important and dispel some of the rumors and the misinformation that has been politicized. That’s why we should engage physicians in an outpatient setting. And we have to vaccinate them and their staffs. Otherwise, we’re never going to get this rollout underway.”

Dr. Stewart agreed. “We are really the foundation of how we’re going to accomplish this. Most folks are seen by a primary care physician. We touch millions of lives,” she said. “We’re part of the community. Our patients trust us. We’re out there doing it already. We’re doing prevention, giving flu shots, and we’re trying to encourage people to get the COVID vaccine.”

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

Federal health officials are urging states to vaccinate all Americans over age 65 and those aged 16-64 who have a documented underlying health condition that makes them more vulnerable to COVID-19.

U.S. Department of Health and Human Services (HHS) Secretary Alex Azar and Centers for Disease Control and Prevention Director Robert Redfield, MD, made the recommendation in a briefing with reporters on Jan. 12, saying that the current vaccine supply was sufficient to meet demand for the next phase of immunization as recommended by the CDC’s Advisory Committee on Immunization Practices.

“We are ready for a transition that we outlined last September in the playbook we sent to states,” Mr. Azar said. Both he and U.S. Army General Gustave F. Perna, chief operations officer for Operation Warp Speed, said that confidence in the distribution system had led to the decision to urge wider access.

The federal government will also increase the number of sites eligible to receive vaccine – including some 13,000 federally qualified community health centers – and will not keep doses in reserve as insurance against issues that might prevent people from receiving a second dose on a timely basis. 

“We don’t need to hold back reserve doses,” Mr. Azar said, noting that if there were any “glitches in production” the federal government would move to fulfill obligations for second doses first and delay initial doses.
 

Azar: Use it or lose it

In a move that is sure to generate pushback, Mr. Azar said that states that don’t quickly administer vaccines will receive fewer doses in the future. That policy will not go into effect until later in February, which leaves open the possibility that it could be reversed by the incoming Biden administration.

“We have too much vaccine sitting in freezers at hospitals with hospitals not using it,” said Mr. Azar, who also blamed the slow administration process on a reporting lag and states being what he called “overly prescriptive” in who has been eligible to receive a shot.

“I would rather have people working to get appointments to get vaccinated than having vaccine going to waste sitting in freezers,” he told reporters.

Mr. Azar had already been pushing for broader vaccination, telling states to do so in an Operation Warp Speed briefing on Jan. 6. At that briefing, he also said that the federal government would be stepping up vaccination through an “early launch” of a federal partnership with 19 pharmacy chains, which will let states allocate vaccines directly to some 40,000 pharmacy sites.

Gen. Perna said during the Jan. 12 briefing that the aim is to further expand that to some 70,000 locations total.

The CDC reported that as of Jan. 11 some 25.4 million doses have been distributed, with 8.9 million administered. An additional 4.2 million doses were distributed to long-term care facilities, and 937,000 residents and staff have received a dose.
 

“Pace of administration”

Alaska, Connecticut, North Dakota, South Dakota, the District of Columbia, West Virginia, and the Northern Mariana Islands have administered the most vaccines per capita, according to the CDC. But even these locations have immunized only 4%-5% of their populations, the New York Times reports. At the bottom: Alabama, Arizona, Arkansas, Georgia, Mississippi, and South Carolina.

The federal government can encourage but not require states to move on to new phases of vaccination.

“States ultimately determine how they will proceed with vaccination,” said Marcus Plescia, MD, MPH, chief medical officer for the Association of State and Territorial Health Officials. “Most will be cautious about assuring there are doses for those needing a second dose,” he said in an interview.

Dr. Plescia said that ensuring a second dose is available is especially important for health care workers “who need to be confident that they are protected and not inadvertently transmitting the disease themselves.”

He added that “once we reach a steady state of supply and administration, the rate-limiting factor will be supply of vaccine.”

That supply could now be threatened if states don’t comply with a just-announced federal action that will change how doses are allocated.

Beginning in late February, vaccine allocations to states will be based on “the pace of administration reported by states,” and the size of the 65-and-older population, said Mr. Azar, who has previously criticized New York Governor Andrew Cuomo for fining hospitals that didn’t use up vaccine supply within a week.

“This new system gives states a strong incentive to ensure that all vaccinations are being promptly reported, which they currently are not,” he said.

Currently, allocations are based on a state’s or territory’s population.

Prepandemic, states were required to report vaccinations within 30 days. Since COVID-19 vaccines became available, the CDC has required reporting of shots within 72 hours.

Dr. Redfield said the requirement has caused some difficulty, and that the CDC is investigating why some states have reported using only 15% of doses while others have used 80%.

States have been scrambling to ramp up vaccinations.

Just ahead of the federal briefing, Gov. Cuomo tweeted that New York would be opening up vaccinations to anyone older than 65.

The Associated Press is reporting that some states have started mass vaccination sites.

Arizona has begun operating a 24/7 appointment-only vaccination program at State Farm Stadium outside of Phoenix, with the aim of immunizing 6,000 people each day, according to local radio station KJZZ.

California and Florida have also taken steps to use stadiums, while Michigan, New Jersey, New York, and Texas will use convention centers and fairgrounds, Axios has reported.

In Florida, Palm Beach County Health Director Alina Alonso, MD, told county commissioners on Jan. 12 that there isn’t enough vaccine to meet demand, WPTV reported. “We need to realize that there’s a shortage of vaccine. So it’s not the plan, it’s not our ability to do it. It’s simply supply and demand at this point,” Dr. Alonso said, according to the TV station report.

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

Federal health officials are urging states to vaccinate all Americans over age 65 and those aged 16-64 who have a documented underlying health condition that makes them more vulnerable to COVID-19.

U.S. Department of Health and Human Services (HHS) Secretary Alex Azar and Centers for Disease Control and Prevention Director Robert Redfield, MD, made the recommendation in a briefing with reporters on Jan. 12, saying that the current vaccine supply was sufficient to meet demand for the next phase of immunization as recommended by the CDC’s Advisory Committee on Immunization Practices.

“We are ready for a transition that we outlined last September in the playbook we sent to states,” Mr. Azar said. Both he and U.S. Army General Gustave F. Perna, chief operations officer for Operation Warp Speed, said that confidence in the distribution system had led to the decision to urge wider access.

The federal government will also increase the number of sites eligible to receive vaccine – including some 13,000 federally qualified community health centers – and will not keep doses in reserve as insurance against issues that might prevent people from receiving a second dose on a timely basis. 

“We don’t need to hold back reserve doses,” Mr. Azar said, noting that if there were any “glitches in production” the federal government would move to fulfill obligations for second doses first and delay initial doses.
 

Azar: Use it or lose it

In a move that is sure to generate pushback, Mr. Azar said that states that don’t quickly administer vaccines will receive fewer doses in the future. That policy will not go into effect until later in February, which leaves open the possibility that it could be reversed by the incoming Biden administration.

“We have too much vaccine sitting in freezers at hospitals with hospitals not using it,” said Mr. Azar, who also blamed the slow administration process on a reporting lag and states being what he called “overly prescriptive” in who has been eligible to receive a shot.

“I would rather have people working to get appointments to get vaccinated than having vaccine going to waste sitting in freezers,” he told reporters.

Mr. Azar had already been pushing for broader vaccination, telling states to do so in an Operation Warp Speed briefing on Jan. 6. At that briefing, he also said that the federal government would be stepping up vaccination through an “early launch” of a federal partnership with 19 pharmacy chains, which will let states allocate vaccines directly to some 40,000 pharmacy sites.

Gen. Perna said during the Jan. 12 briefing that the aim is to further expand that to some 70,000 locations total.

The CDC reported that as of Jan. 11 some 25.4 million doses have been distributed, with 8.9 million administered. An additional 4.2 million doses were distributed to long-term care facilities, and 937,000 residents and staff have received a dose.
 

“Pace of administration”

Alaska, Connecticut, North Dakota, South Dakota, the District of Columbia, West Virginia, and the Northern Mariana Islands have administered the most vaccines per capita, according to the CDC. But even these locations have immunized only 4%-5% of their populations, the New York Times reports. At the bottom: Alabama, Arizona, Arkansas, Georgia, Mississippi, and South Carolina.

The federal government can encourage but not require states to move on to new phases of vaccination.

“States ultimately determine how they will proceed with vaccination,” said Marcus Plescia, MD, MPH, chief medical officer for the Association of State and Territorial Health Officials. “Most will be cautious about assuring there are doses for those needing a second dose,” he said in an interview.

Dr. Plescia said that ensuring a second dose is available is especially important for health care workers “who need to be confident that they are protected and not inadvertently transmitting the disease themselves.”

He added that “once we reach a steady state of supply and administration, the rate-limiting factor will be supply of vaccine.”

That supply could now be threatened if states don’t comply with a just-announced federal action that will change how doses are allocated.

Beginning in late February, vaccine allocations to states will be based on “the pace of administration reported by states,” and the size of the 65-and-older population, said Mr. Azar, who has previously criticized New York Governor Andrew Cuomo for fining hospitals that didn’t use up vaccine supply within a week.

“This new system gives states a strong incentive to ensure that all vaccinations are being promptly reported, which they currently are not,” he said.

Currently, allocations are based on a state’s or territory’s population.

Prepandemic, states were required to report vaccinations within 30 days. Since COVID-19 vaccines became available, the CDC has required reporting of shots within 72 hours.

Dr. Redfield said the requirement has caused some difficulty, and that the CDC is investigating why some states have reported using only 15% of doses while others have used 80%.

States have been scrambling to ramp up vaccinations.

Just ahead of the federal briefing, Gov. Cuomo tweeted that New York would be opening up vaccinations to anyone older than 65.

The Associated Press is reporting that some states have started mass vaccination sites.

Arizona has begun operating a 24/7 appointment-only vaccination program at State Farm Stadium outside of Phoenix, with the aim of immunizing 6,000 people each day, according to local radio station KJZZ.

California and Florida have also taken steps to use stadiums, while Michigan, New Jersey, New York, and Texas will use convention centers and fairgrounds, Axios has reported.

In Florida, Palm Beach County Health Director Alina Alonso, MD, told county commissioners on Jan. 12 that there isn’t enough vaccine to meet demand, WPTV reported. “We need to realize that there’s a shortage of vaccine. So it’s not the plan, it’s not our ability to do it. It’s simply supply and demand at this point,” Dr. Alonso said, according to the TV station report.

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

Federal health officials are urging states to vaccinate all Americans over age 65 and those aged 16-64 who have a documented underlying health condition that makes them more vulnerable to COVID-19.

U.S. Department of Health and Human Services (HHS) Secretary Alex Azar and Centers for Disease Control and Prevention Director Robert Redfield, MD, made the recommendation in a briefing with reporters on Jan. 12, saying that the current vaccine supply was sufficient to meet demand for the next phase of immunization as recommended by the CDC’s Advisory Committee on Immunization Practices.

“We are ready for a transition that we outlined last September in the playbook we sent to states,” Mr. Azar said. Both he and U.S. Army General Gustave F. Perna, chief operations officer for Operation Warp Speed, said that confidence in the distribution system had led to the decision to urge wider access.

The federal government will also increase the number of sites eligible to receive vaccine – including some 13,000 federally qualified community health centers – and will not keep doses in reserve as insurance against issues that might prevent people from receiving a second dose on a timely basis. 

“We don’t need to hold back reserve doses,” Mr. Azar said, noting that if there were any “glitches in production” the federal government would move to fulfill obligations for second doses first and delay initial doses.
 

Azar: Use it or lose it

In a move that is sure to generate pushback, Mr. Azar said that states that don’t quickly administer vaccines will receive fewer doses in the future. That policy will not go into effect until later in February, which leaves open the possibility that it could be reversed by the incoming Biden administration.

“We have too much vaccine sitting in freezers at hospitals with hospitals not using it,” said Mr. Azar, who also blamed the slow administration process on a reporting lag and states being what he called “overly prescriptive” in who has been eligible to receive a shot.

“I would rather have people working to get appointments to get vaccinated than having vaccine going to waste sitting in freezers,” he told reporters.

Mr. Azar had already been pushing for broader vaccination, telling states to do so in an Operation Warp Speed briefing on Jan. 6. At that briefing, he also said that the federal government would be stepping up vaccination through an “early launch” of a federal partnership with 19 pharmacy chains, which will let states allocate vaccines directly to some 40,000 pharmacy sites.

Gen. Perna said during the Jan. 12 briefing that the aim is to further expand that to some 70,000 locations total.

The CDC reported that as of Jan. 11 some 25.4 million doses have been distributed, with 8.9 million administered. An additional 4.2 million doses were distributed to long-term care facilities, and 937,000 residents and staff have received a dose.
 

“Pace of administration”

Alaska, Connecticut, North Dakota, South Dakota, the District of Columbia, West Virginia, and the Northern Mariana Islands have administered the most vaccines per capita, according to the CDC. But even these locations have immunized only 4%-5% of their populations, the New York Times reports. At the bottom: Alabama, Arizona, Arkansas, Georgia, Mississippi, and South Carolina.

The federal government can encourage but not require states to move on to new phases of vaccination.

“States ultimately determine how they will proceed with vaccination,” said Marcus Plescia, MD, MPH, chief medical officer for the Association of State and Territorial Health Officials. “Most will be cautious about assuring there are doses for those needing a second dose,” he said in an interview.

Dr. Plescia said that ensuring a second dose is available is especially important for health care workers “who need to be confident that they are protected and not inadvertently transmitting the disease themselves.”

He added that “once we reach a steady state of supply and administration, the rate-limiting factor will be supply of vaccine.”

That supply could now be threatened if states don’t comply with a just-announced federal action that will change how doses are allocated.

Beginning in late February, vaccine allocations to states will be based on “the pace of administration reported by states,” and the size of the 65-and-older population, said Mr. Azar, who has previously criticized New York Governor Andrew Cuomo for fining hospitals that didn’t use up vaccine supply within a week.

“This new system gives states a strong incentive to ensure that all vaccinations are being promptly reported, which they currently are not,” he said.

Currently, allocations are based on a state’s or territory’s population.

Prepandemic, states were required to report vaccinations within 30 days. Since COVID-19 vaccines became available, the CDC has required reporting of shots within 72 hours.

Dr. Redfield said the requirement has caused some difficulty, and that the CDC is investigating why some states have reported using only 15% of doses while others have used 80%.

States have been scrambling to ramp up vaccinations.

Just ahead of the federal briefing, Gov. Cuomo tweeted that New York would be opening up vaccinations to anyone older than 65.

The Associated Press is reporting that some states have started mass vaccination sites.

Arizona has begun operating a 24/7 appointment-only vaccination program at State Farm Stadium outside of Phoenix, with the aim of immunizing 6,000 people each day, according to local radio station KJZZ.

California and Florida have also taken steps to use stadiums, while Michigan, New Jersey, New York, and Texas will use convention centers and fairgrounds, Axios has reported.

In Florida, Palm Beach County Health Director Alina Alonso, MD, told county commissioners on Jan. 12 that there isn’t enough vaccine to meet demand, WPTV reported. “We need to realize that there’s a shortage of vaccine. So it’s not the plan, it’s not our ability to do it. It’s simply supply and demand at this point,” Dr. Alonso said, according to the TV station report.

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

The United States has allocated more than 641,000 monoclonal antibody treatments for outpatients to ease pressure on strained hospitals, but officials from Operation Warp Speed report that more than half of that reserve sits unused as clinicians grapple with best practices.

There are space and personnel limitations in hospitals right now, Janet Woodcock, MD, therapeutics lead on Operation Warp Speed, acknowledges in an interview with this news organization. “Special areas and procedures must be set up.” And the operation is in the process of broadening availability beyond hospitals, she points out.

But for frontline clinicians, questions about treatment efficacy and the logistics of administering intravenous drugs to infectious outpatients loom large.

More than 50 monoclonal antibody products that target SARS-CoV-2 are now in development. The U.S. Food and Drug Administration has already issued Emergency Use Authorization (EUA) for two such drugs on the basis of phase 2 trial data – bamlanivimab, made by Eli Lilly, and a cocktail of casirivimab plus imdevimab, made by Regeneron – and another two-antibody cocktail from AstraZeneca, AZD7442, has started phase 3 clinical trials. The Regeneron combination was used to treat President Donald Trump when he contracted COVID-19 in October.

Monoclonal antibody drugs are based on the natural antibodies that the body uses to fight infections. They work by binding to a specific target and then blocking its action or flagging it for destruction by other parts of the immune system. Both bamlanivimab and the casirivimab plus imdevimab combination target the spike protein of the virus and stop it from attaching to and entering human cells.
 

Targeting the spike protein out of the hospital

The antibody drugs covered by EUAs do not cure COVID-19, but they have been shown to reduce hospitalizations and visits to the emergency department for patients at high risk for disease progression. They are approved to treat patients older than 12 years with mild to moderate COVID-19 who are at high risk of progressing to severe disease or hospitalization. They are not authorized for use in patients who have been hospitalized or who are on ventilators. The hope is that antibody drugs will reduce the number of severe cases of COVID-19 and ease pressure on overstretched hospitals.

Most COVID-19 patients are outpatients, so we need something to keep them from getting worse.

This is important because it targets the greatest need in COVID-19 therapeutics, says Rajesh Gandhi, MD, an infectious disease physician at Harvard Medical School in Boston, who is a member of two panels evaluating COVID-19 treatments: one for the Infectious Disease Society of America and the other for the National Institutes of Health. “Up to now, most of the focus has been on hospitalized patients,” he says, but “most COVID-19 patients are outpatients, so we need something to keep them from getting worse.”

Both panels have said that, despite the EUAs, more evidence is needed to be sure of the efficacy of the drugs and to determine which patients will benefit the most from them.

These aren’t the mature data from drug development that guideline groups are accustomed to working with, Dr. Woodcock points out. “But this is an emergency and the data taken as a whole are pretty convincing,” she says. “As I look at the totality of the evidence, monoclonal antibodies will have a big effect in keeping people out of the hospital and helping them recover faster.”

High-risk patients are eligible for treatment, especially those older than 65 years and those with comorbidities who are younger. Access to the drugs is increasing for clinicians who are able to infuse safely or work with a site that will.

In the Boston area, several hospitals, including Massachusetts General where Dr. Gandhi works, have set up infusion centers where newly diagnosed patients can get the antibody treatment if their doctor thinks it will benefit them. And Coram, a provider of at-home infusion therapy owned by the CVS pharmacy chain, is running a pilot program offering the Eli Lilly drug to people in seven cities – including Boston, Chicago, Los Angeles, and Tampa – and their surrounding communities with a physician referral.

Getting that referral could be tricky, however, for patients without a primary care physician or for those whose doctor isn’t already connected to one of the institutions providing the infusions. The hospitals are sending out communications on how patients and physicians can get the therapy, but Dr. Gandhi says that making information about access available should be a priority. The window for the effective treatment is small – the drugs appear to work best before patients begin to make their own antibodies, says Dr. Gandhi – so it’s vital that doctors act quickly if they have a patient who is eligible.

And rolling out the new therapies to patients around the world will be a major logistical undertaking.

The first hurdle will be making enough of them to go around. Case numbers are skyrocketing around the globe, and producing the drugs is a complex time- and labor-intensive process that requires specialized facilities. Antibodies are produced by cell lines in bioreactors, so a plant that churns out generic aspirin tablets can’t simply be converted into an antibody factory.

“These types of drugs are manufactured in a sterile injectables plant, which is different from a plant where oral solids are made,” says Kim Crabtree, senior director of pharma portfolio management for Henry Schein Medical, a medical supplies distributor. “Those are not as plentiful as a standard pill factory.”

The doses required are also relatively high – 1.2 g of each antibody in Regeneron’s cocktail – which will further strain production capacity. Leah Lipsich, PhD, vice president of strategic program direction at Regeneron, says the company is prepared for high demand and has been able to respond, thanks to its rapid development and manufacturing technology, known as VelociSuite, which allows it to rapidly scale-up from discovery to productions in weeks instead of months.

“We knew supply would be a huge problem for COVID-19, but because we had such confidence in our technology, we went immediately from research-scale to our largest-scale manufacturing,” she says. “We’ve been manufacturing our cocktail for months now.”

The company has also partnered with Roche, the biggest manufacturer and vendor of monoclonal antibodies in the world, to manufacture and supply the drugs. Once full manufacturing capacity is reached in 2021, the companies expect to produce at least 2 million doses a year.

Then there is the issue of getting the drugs from the factories to the places they will be used.

Antibodies are temperature sensitive and need to be refrigerated during transport and storage, so a cold-chain-compliant supply chain is required. Fortunately, they can be kept at standard refrigerator temperatures, ranging from 2° C to 8° C, rather than the ultra-low temperatures required by some COVID-19 vaccines.
 

Two million doses a year

Medical logistics companies have a lot of experience dealing with products like these and are well prepared to handle the new antibody drugs. “There are quite a few products like these on the market, and the supply chain is used to shipping them,” Ms. Crabtree says.

They will be shipped to distribution centers in refrigerated trucks, repacked into smaller lots that can sustain the correct temperature for 24 hours, and then sent to their final destination, often in something as simple as a Styrofoam cooler filled with dry ice.

The expected rise in demand shouldn’t be too much of an issue for distributors either, says Ms. Crabtree; they have built systems that can deal with short-term surges in volume. The annual flu vaccine, for example, involves shipping a lot of product in a very short time, usually from August to November. “The distribution system is used to seasonal variations and peaks in demand,” she says.

The next question is how the treatments will be administered. Although most patients who will receive monoclonal antibodies will be ambulatory and not hospitalized, the administration requires intravenous infusion. Hospitals, of course, have a lot of experience with intravenous drugs, but typically give them only to inpatients. Most other monoclonal antibody drugs – such as those for cancer and autoimmune disorders – are given in specialized suites in doctor’s offices or in stand-alone infusion clinics.

That means that the places best suited to treat COVID-19 patients with antibodies are those that regularly deal with people who are immunocompromised, and such patients should not be interacting with people who have an infectious disease. “How do we protect the staff and other patients?” Dr. Gandhi asks.
 

Protecting staff and other patients

This is not an insurmountable obstacle, he points out, but it is one that requires careful thought and planning to accommodate COVID-19 patients without unduly disrupting life-saving treatments for other patients. It might involve, for example, treating COVID-19 patients in sequestered parts of the clinic or at different times of day, with even greater attention paid to cleaning, he explains. “We now have many months of experience with infection control, so we know how to do this; it’s just a question of logistics.”

But even once all the details around manufacturing, transporting, and administering the drugs are sorted out, there is still the issue of how they will be distributed fairly and equitably.

Despite multiple companies working to produce an array of different antibody drugs, demand is still expected to exceed supply for many months. “With more than 200,000 new cases a day in the United States, there won’t be enough antibodies to treat all of the high-risk patients,” says Dr. Gandhi. “Most of us are worried that demand will far outstrip supply. People are talking about lotteries to determine who gets them.”

The Department of Health and Human Services will continue to distribute the drugs to states on the basis of their COVID-19 burdens, and the states will then decide how much to provide to each health care facility.

Although the HHS goal is to ensure that the drugs reach as many patients as possible, no matter where they live and regardless of their income, there are still concerns that larger facilities serving more affluent areas will end up being favored, if only because they are the ones best equipped to deal with the drugs right now.

“We are all aware that this has affected certain communities more, so we need to make sure that the drugs are used equitably and made available to the communities that were hardest hit,” says Dr. Gandhi. The ability to monitor drug distribution should be built into the rollout, so that institutions and governments will have some sense of whether they are being doled out evenly, he adds.

Equity in distribution will be an issue for the rest of the world as well. Currently, 80% of monoclonal antibodies are sold in Canada, Europe, and the United States; few, if any, are available in low- and middle-income countries. The treatments are expensive: the cost of producing one g of marketed monoclonal antibodies is between $95 and $200, which does not include the cost of R&D, packaging, shipping, or administration. The median price for antibody treatment not related to COVID-19 runs from $15,000 to $200,000 per year in the United States.

Regeneron’s Dr. Lipsich says that the company has not yet set a price for its antibody cocktail. The government paid $450 million for its 300,000 doses, but that price includes the costs of research, manufacturing, and distribution, so is not a useful indicator of the eventual per-dose price. “We’re not in a position to talk about how it will be priced yet, but we will do our best to make it affordable and accessible to all,” she says.

There are some projects underway to ensure that the drugs are made available in poorer countries. In April, the COVID-19 Therapeutics Accelerator – an initiative launched by the Bill & Melinda Gates Foundation, Wellcome, and Mastercard to speed-up the response to the global pandemic – reserved manufacturing capacity with Fujifilm Diosynth Biotechnologies in Denmark for future monoclonal antibody therapies that will supply low- and middle-income countries. In October, the initiative announced that Eli Lilly would use that reserved capacity to produce its antibody drug starting in April 2021.

In the meantime, Lilly will make some of its product manufactured in other facilities available to lower-income countries. To help keep costs down, the company’s collaborators have agreed to waive their royalties on antibodies distributed in low- and middle-income countries.

“Everyone is looking carefully at how the drugs are distributed to ensure all will get access,” said Dr. Lipsich.

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

The United States has allocated more than 641,000 monoclonal antibody treatments for outpatients to ease pressure on strained hospitals, but officials from Operation Warp Speed report that more than half of that reserve sits unused as clinicians grapple with best practices.

There are space and personnel limitations in hospitals right now, Janet Woodcock, MD, therapeutics lead on Operation Warp Speed, acknowledges in an interview with this news organization. “Special areas and procedures must be set up.” And the operation is in the process of broadening availability beyond hospitals, she points out.

But for frontline clinicians, questions about treatment efficacy and the logistics of administering intravenous drugs to infectious outpatients loom large.

More than 50 monoclonal antibody products that target SARS-CoV-2 are now in development. The U.S. Food and Drug Administration has already issued Emergency Use Authorization (EUA) for two such drugs on the basis of phase 2 trial data – bamlanivimab, made by Eli Lilly, and a cocktail of casirivimab plus imdevimab, made by Regeneron – and another two-antibody cocktail from AstraZeneca, AZD7442, has started phase 3 clinical trials. The Regeneron combination was used to treat President Donald Trump when he contracted COVID-19 in October.

Monoclonal antibody drugs are based on the natural antibodies that the body uses to fight infections. They work by binding to a specific target and then blocking its action or flagging it for destruction by other parts of the immune system. Both bamlanivimab and the casirivimab plus imdevimab combination target the spike protein of the virus and stop it from attaching to and entering human cells.
 

Targeting the spike protein out of the hospital

The antibody drugs covered by EUAs do not cure COVID-19, but they have been shown to reduce hospitalizations and visits to the emergency department for patients at high risk for disease progression. They are approved to treat patients older than 12 years with mild to moderate COVID-19 who are at high risk of progressing to severe disease or hospitalization. They are not authorized for use in patients who have been hospitalized or who are on ventilators. The hope is that antibody drugs will reduce the number of severe cases of COVID-19 and ease pressure on overstretched hospitals.

Most COVID-19 patients are outpatients, so we need something to keep them from getting worse.

This is important because it targets the greatest need in COVID-19 therapeutics, says Rajesh Gandhi, MD, an infectious disease physician at Harvard Medical School in Boston, who is a member of two panels evaluating COVID-19 treatments: one for the Infectious Disease Society of America and the other for the National Institutes of Health. “Up to now, most of the focus has been on hospitalized patients,” he says, but “most COVID-19 patients are outpatients, so we need something to keep them from getting worse.”

Both panels have said that, despite the EUAs, more evidence is needed to be sure of the efficacy of the drugs and to determine which patients will benefit the most from them.

These aren’t the mature data from drug development that guideline groups are accustomed to working with, Dr. Woodcock points out. “But this is an emergency and the data taken as a whole are pretty convincing,” she says. “As I look at the totality of the evidence, monoclonal antibodies will have a big effect in keeping people out of the hospital and helping them recover faster.”

High-risk patients are eligible for treatment, especially those older than 65 years and those with comorbidities who are younger. Access to the drugs is increasing for clinicians who are able to infuse safely or work with a site that will.

In the Boston area, several hospitals, including Massachusetts General where Dr. Gandhi works, have set up infusion centers where newly diagnosed patients can get the antibody treatment if their doctor thinks it will benefit them. And Coram, a provider of at-home infusion therapy owned by the CVS pharmacy chain, is running a pilot program offering the Eli Lilly drug to people in seven cities – including Boston, Chicago, Los Angeles, and Tampa – and their surrounding communities with a physician referral.

Getting that referral could be tricky, however, for patients without a primary care physician or for those whose doctor isn’t already connected to one of the institutions providing the infusions. The hospitals are sending out communications on how patients and physicians can get the therapy, but Dr. Gandhi says that making information about access available should be a priority. The window for the effective treatment is small – the drugs appear to work best before patients begin to make their own antibodies, says Dr. Gandhi – so it’s vital that doctors act quickly if they have a patient who is eligible.

And rolling out the new therapies to patients around the world will be a major logistical undertaking.

The first hurdle will be making enough of them to go around. Case numbers are skyrocketing around the globe, and producing the drugs is a complex time- and labor-intensive process that requires specialized facilities. Antibodies are produced by cell lines in bioreactors, so a plant that churns out generic aspirin tablets can’t simply be converted into an antibody factory.

“These types of drugs are manufactured in a sterile injectables plant, which is different from a plant where oral solids are made,” says Kim Crabtree, senior director of pharma portfolio management for Henry Schein Medical, a medical supplies distributor. “Those are not as plentiful as a standard pill factory.”

The doses required are also relatively high – 1.2 g of each antibody in Regeneron’s cocktail – which will further strain production capacity. Leah Lipsich, PhD, vice president of strategic program direction at Regeneron, says the company is prepared for high demand and has been able to respond, thanks to its rapid development and manufacturing technology, known as VelociSuite, which allows it to rapidly scale-up from discovery to productions in weeks instead of months.

“We knew supply would be a huge problem for COVID-19, but because we had such confidence in our technology, we went immediately from research-scale to our largest-scale manufacturing,” she says. “We’ve been manufacturing our cocktail for months now.”

The company has also partnered with Roche, the biggest manufacturer and vendor of monoclonal antibodies in the world, to manufacture and supply the drugs. Once full manufacturing capacity is reached in 2021, the companies expect to produce at least 2 million doses a year.

Then there is the issue of getting the drugs from the factories to the places they will be used.

Antibodies are temperature sensitive and need to be refrigerated during transport and storage, so a cold-chain-compliant supply chain is required. Fortunately, they can be kept at standard refrigerator temperatures, ranging from 2° C to 8° C, rather than the ultra-low temperatures required by some COVID-19 vaccines.
 

Two million doses a year

Medical logistics companies have a lot of experience dealing with products like these and are well prepared to handle the new antibody drugs. “There are quite a few products like these on the market, and the supply chain is used to shipping them,” Ms. Crabtree says.

They will be shipped to distribution centers in refrigerated trucks, repacked into smaller lots that can sustain the correct temperature for 24 hours, and then sent to their final destination, often in something as simple as a Styrofoam cooler filled with dry ice.

The expected rise in demand shouldn’t be too much of an issue for distributors either, says Ms. Crabtree; they have built systems that can deal with short-term surges in volume. The annual flu vaccine, for example, involves shipping a lot of product in a very short time, usually from August to November. “The distribution system is used to seasonal variations and peaks in demand,” she says.

The next question is how the treatments will be administered. Although most patients who will receive monoclonal antibodies will be ambulatory and not hospitalized, the administration requires intravenous infusion. Hospitals, of course, have a lot of experience with intravenous drugs, but typically give them only to inpatients. Most other monoclonal antibody drugs – such as those for cancer and autoimmune disorders – are given in specialized suites in doctor’s offices or in stand-alone infusion clinics.

That means that the places best suited to treat COVID-19 patients with antibodies are those that regularly deal with people who are immunocompromised, and such patients should not be interacting with people who have an infectious disease. “How do we protect the staff and other patients?” Dr. Gandhi asks.
 

Protecting staff and other patients

This is not an insurmountable obstacle, he points out, but it is one that requires careful thought and planning to accommodate COVID-19 patients without unduly disrupting life-saving treatments for other patients. It might involve, for example, treating COVID-19 patients in sequestered parts of the clinic or at different times of day, with even greater attention paid to cleaning, he explains. “We now have many months of experience with infection control, so we know how to do this; it’s just a question of logistics.”

But even once all the details around manufacturing, transporting, and administering the drugs are sorted out, there is still the issue of how they will be distributed fairly and equitably.

Despite multiple companies working to produce an array of different antibody drugs, demand is still expected to exceed supply for many months. “With more than 200,000 new cases a day in the United States, there won’t be enough antibodies to treat all of the high-risk patients,” says Dr. Gandhi. “Most of us are worried that demand will far outstrip supply. People are talking about lotteries to determine who gets them.”

The Department of Health and Human Services will continue to distribute the drugs to states on the basis of their COVID-19 burdens, and the states will then decide how much to provide to each health care facility.

Although the HHS goal is to ensure that the drugs reach as many patients as possible, no matter where they live and regardless of their income, there are still concerns that larger facilities serving more affluent areas will end up being favored, if only because they are the ones best equipped to deal with the drugs right now.

“We are all aware that this has affected certain communities more, so we need to make sure that the drugs are used equitably and made available to the communities that were hardest hit,” says Dr. Gandhi. The ability to monitor drug distribution should be built into the rollout, so that institutions and governments will have some sense of whether they are being doled out evenly, he adds.

Equity in distribution will be an issue for the rest of the world as well. Currently, 80% of monoclonal antibodies are sold in Canada, Europe, and the United States; few, if any, are available in low- and middle-income countries. The treatments are expensive: the cost of producing one g of marketed monoclonal antibodies is between $95 and $200, which does not include the cost of R&D, packaging, shipping, or administration. The median price for antibody treatment not related to COVID-19 runs from $15,000 to $200,000 per year in the United States.

Regeneron’s Dr. Lipsich says that the company has not yet set a price for its antibody cocktail. The government paid $450 million for its 300,000 doses, but that price includes the costs of research, manufacturing, and distribution, so is not a useful indicator of the eventual per-dose price. “We’re not in a position to talk about how it will be priced yet, but we will do our best to make it affordable and accessible to all,” she says.

There are some projects underway to ensure that the drugs are made available in poorer countries. In April, the COVID-19 Therapeutics Accelerator – an initiative launched by the Bill & Melinda Gates Foundation, Wellcome, and Mastercard to speed-up the response to the global pandemic – reserved manufacturing capacity with Fujifilm Diosynth Biotechnologies in Denmark for future monoclonal antibody therapies that will supply low- and middle-income countries. In October, the initiative announced that Eli Lilly would use that reserved capacity to produce its antibody drug starting in April 2021.

In the meantime, Lilly will make some of its product manufactured in other facilities available to lower-income countries. To help keep costs down, the company’s collaborators have agreed to waive their royalties on antibodies distributed in low- and middle-income countries.

“Everyone is looking carefully at how the drugs are distributed to ensure all will get access,” said Dr. Lipsich.

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

The United States has allocated more than 641,000 monoclonal antibody treatments for outpatients to ease pressure on strained hospitals, but officials from Operation Warp Speed report that more than half of that reserve sits unused as clinicians grapple with best practices.

There are space and personnel limitations in hospitals right now, Janet Woodcock, MD, therapeutics lead on Operation Warp Speed, acknowledges in an interview with this news organization. “Special areas and procedures must be set up.” And the operation is in the process of broadening availability beyond hospitals, she points out.

But for frontline clinicians, questions about treatment efficacy and the logistics of administering intravenous drugs to infectious outpatients loom large.

More than 50 monoclonal antibody products that target SARS-CoV-2 are now in development. The U.S. Food and Drug Administration has already issued Emergency Use Authorization (EUA) for two such drugs on the basis of phase 2 trial data – bamlanivimab, made by Eli Lilly, and a cocktail of casirivimab plus imdevimab, made by Regeneron – and another two-antibody cocktail from AstraZeneca, AZD7442, has started phase 3 clinical trials. The Regeneron combination was used to treat President Donald Trump when he contracted COVID-19 in October.

Monoclonal antibody drugs are based on the natural antibodies that the body uses to fight infections. They work by binding to a specific target and then blocking its action or flagging it for destruction by other parts of the immune system. Both bamlanivimab and the casirivimab plus imdevimab combination target the spike protein of the virus and stop it from attaching to and entering human cells.
 

Targeting the spike protein out of the hospital

The antibody drugs covered by EUAs do not cure COVID-19, but they have been shown to reduce hospitalizations and visits to the emergency department for patients at high risk for disease progression. They are approved to treat patients older than 12 years with mild to moderate COVID-19 who are at high risk of progressing to severe disease or hospitalization. They are not authorized for use in patients who have been hospitalized or who are on ventilators. The hope is that antibody drugs will reduce the number of severe cases of COVID-19 and ease pressure on overstretched hospitals.

Most COVID-19 patients are outpatients, so we need something to keep them from getting worse.

This is important because it targets the greatest need in COVID-19 therapeutics, says Rajesh Gandhi, MD, an infectious disease physician at Harvard Medical School in Boston, who is a member of two panels evaluating COVID-19 treatments: one for the Infectious Disease Society of America and the other for the National Institutes of Health. “Up to now, most of the focus has been on hospitalized patients,” he says, but “most COVID-19 patients are outpatients, so we need something to keep them from getting worse.”

Both panels have said that, despite the EUAs, more evidence is needed to be sure of the efficacy of the drugs and to determine which patients will benefit the most from them.

These aren’t the mature data from drug development that guideline groups are accustomed to working with, Dr. Woodcock points out. “But this is an emergency and the data taken as a whole are pretty convincing,” she says. “As I look at the totality of the evidence, monoclonal antibodies will have a big effect in keeping people out of the hospital and helping them recover faster.”

High-risk patients are eligible for treatment, especially those older than 65 years and those with comorbidities who are younger. Access to the drugs is increasing for clinicians who are able to infuse safely or work with a site that will.

In the Boston area, several hospitals, including Massachusetts General where Dr. Gandhi works, have set up infusion centers where newly diagnosed patients can get the antibody treatment if their doctor thinks it will benefit them. And Coram, a provider of at-home infusion therapy owned by the CVS pharmacy chain, is running a pilot program offering the Eli Lilly drug to people in seven cities – including Boston, Chicago, Los Angeles, and Tampa – and their surrounding communities with a physician referral.

Getting that referral could be tricky, however, for patients without a primary care physician or for those whose doctor isn’t already connected to one of the institutions providing the infusions. The hospitals are sending out communications on how patients and physicians can get the therapy, but Dr. Gandhi says that making information about access available should be a priority. The window for the effective treatment is small – the drugs appear to work best before patients begin to make their own antibodies, says Dr. Gandhi – so it’s vital that doctors act quickly if they have a patient who is eligible.

And rolling out the new therapies to patients around the world will be a major logistical undertaking.

The first hurdle will be making enough of them to go around. Case numbers are skyrocketing around the globe, and producing the drugs is a complex time- and labor-intensive process that requires specialized facilities. Antibodies are produced by cell lines in bioreactors, so a plant that churns out generic aspirin tablets can’t simply be converted into an antibody factory.

“These types of drugs are manufactured in a sterile injectables plant, which is different from a plant where oral solids are made,” says Kim Crabtree, senior director of pharma portfolio management for Henry Schein Medical, a medical supplies distributor. “Those are not as plentiful as a standard pill factory.”

The doses required are also relatively high – 1.2 g of each antibody in Regeneron’s cocktail – which will further strain production capacity. Leah Lipsich, PhD, vice president of strategic program direction at Regeneron, says the company is prepared for high demand and has been able to respond, thanks to its rapid development and manufacturing technology, known as VelociSuite, which allows it to rapidly scale-up from discovery to productions in weeks instead of months.

“We knew supply would be a huge problem for COVID-19, but because we had such confidence in our technology, we went immediately from research-scale to our largest-scale manufacturing,” she says. “We’ve been manufacturing our cocktail for months now.”

The company has also partnered with Roche, the biggest manufacturer and vendor of monoclonal antibodies in the world, to manufacture and supply the drugs. Once full manufacturing capacity is reached in 2021, the companies expect to produce at least 2 million doses a year.

Then there is the issue of getting the drugs from the factories to the places they will be used.

Antibodies are temperature sensitive and need to be refrigerated during transport and storage, so a cold-chain-compliant supply chain is required. Fortunately, they can be kept at standard refrigerator temperatures, ranging from 2° C to 8° C, rather than the ultra-low temperatures required by some COVID-19 vaccines.
 

Two million doses a year

Medical logistics companies have a lot of experience dealing with products like these and are well prepared to handle the new antibody drugs. “There are quite a few products like these on the market, and the supply chain is used to shipping them,” Ms. Crabtree says.

They will be shipped to distribution centers in refrigerated trucks, repacked into smaller lots that can sustain the correct temperature for 24 hours, and then sent to their final destination, often in something as simple as a Styrofoam cooler filled with dry ice.

The expected rise in demand shouldn’t be too much of an issue for distributors either, says Ms. Crabtree; they have built systems that can deal with short-term surges in volume. The annual flu vaccine, for example, involves shipping a lot of product in a very short time, usually from August to November. “The distribution system is used to seasonal variations and peaks in demand,” she says.

The next question is how the treatments will be administered. Although most patients who will receive monoclonal antibodies will be ambulatory and not hospitalized, the administration requires intravenous infusion. Hospitals, of course, have a lot of experience with intravenous drugs, but typically give them only to inpatients. Most other monoclonal antibody drugs – such as those for cancer and autoimmune disorders – are given in specialized suites in doctor’s offices or in stand-alone infusion clinics.

That means that the places best suited to treat COVID-19 patients with antibodies are those that regularly deal with people who are immunocompromised, and such patients should not be interacting with people who have an infectious disease. “How do we protect the staff and other patients?” Dr. Gandhi asks.
 

Protecting staff and other patients

This is not an insurmountable obstacle, he points out, but it is one that requires careful thought and planning to accommodate COVID-19 patients without unduly disrupting life-saving treatments for other patients. It might involve, for example, treating COVID-19 patients in sequestered parts of the clinic or at different times of day, with even greater attention paid to cleaning, he explains. “We now have many months of experience with infection control, so we know how to do this; it’s just a question of logistics.”

But even once all the details around manufacturing, transporting, and administering the drugs are sorted out, there is still the issue of how they will be distributed fairly and equitably.

Despite multiple companies working to produce an array of different antibody drugs, demand is still expected to exceed supply for many months. “With more than 200,000 new cases a day in the United States, there won’t be enough antibodies to treat all of the high-risk patients,” says Dr. Gandhi. “Most of us are worried that demand will far outstrip supply. People are talking about lotteries to determine who gets them.”

The Department of Health and Human Services will continue to distribute the drugs to states on the basis of their COVID-19 burdens, and the states will then decide how much to provide to each health care facility.

Although the HHS goal is to ensure that the drugs reach as many patients as possible, no matter where they live and regardless of their income, there are still concerns that larger facilities serving more affluent areas will end up being favored, if only because they are the ones best equipped to deal with the drugs right now.

“We are all aware that this has affected certain communities more, so we need to make sure that the drugs are used equitably and made available to the communities that were hardest hit,” says Dr. Gandhi. The ability to monitor drug distribution should be built into the rollout, so that institutions and governments will have some sense of whether they are being doled out evenly, he adds.

Equity in distribution will be an issue for the rest of the world as well. Currently, 80% of monoclonal antibodies are sold in Canada, Europe, and the United States; few, if any, are available in low- and middle-income countries. The treatments are expensive: the cost of producing one g of marketed monoclonal antibodies is between $95 and $200, which does not include the cost of R&D, packaging, shipping, or administration. The median price for antibody treatment not related to COVID-19 runs from $15,000 to $200,000 per year in the United States.

Regeneron’s Dr. Lipsich says that the company has not yet set a price for its antibody cocktail. The government paid $450 million for its 300,000 doses, but that price includes the costs of research, manufacturing, and distribution, so is not a useful indicator of the eventual per-dose price. “We’re not in a position to talk about how it will be priced yet, but we will do our best to make it affordable and accessible to all,” she says.

There are some projects underway to ensure that the drugs are made available in poorer countries. In April, the COVID-19 Therapeutics Accelerator – an initiative launched by the Bill & Melinda Gates Foundation, Wellcome, and Mastercard to speed-up the response to the global pandemic – reserved manufacturing capacity with Fujifilm Diosynth Biotechnologies in Denmark for future monoclonal antibody therapies that will supply low- and middle-income countries. In October, the initiative announced that Eli Lilly would use that reserved capacity to produce its antibody drug starting in April 2021.

In the meantime, Lilly will make some of its product manufactured in other facilities available to lower-income countries. To help keep costs down, the company’s collaborators have agreed to waive their royalties on antibodies distributed in low- and middle-income countries.

“Everyone is looking carefully at how the drugs are distributed to ensure all will get access,” said Dr. Lipsich.

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