Cardiology News

Critical care staff are less likely to acquire COVID-19 infection from ICU patients than they are from areas away from the bedside, a new study has found.

Courtesy NIAID

“Other staff, other areas of the hospital, and the wider community are more likely sources of infection,” said lead author Kate El Bouzidi, MRCP, South London Specialist Virology Centre, King’s College Hospital NHS Foundation Trust, London.

She noted that 60% of critical care staff were symptomatic during the first wave of the coronavirus pandemic and 20% were antibody positive, with 10% asymptomatic. “Staff acquisition peaked 3 weeks before the peak of COVID-19 ICU admission, and personal protective equipment (PPE) was effective at preventing transmission from patients.” Working in other areas of the hospital was associated with higher seroprevalence, Dr. El Bouzidi noted.

The findings were presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

The novel coronavirus was spreading around the world, and when it reached northern Italy, medical authorities began to think in terms of how it might overwhelm the health care system in the United Kingdom, explained Dr. El Bouzidi.

“There was a lot of interest at this time about health care workers who were particularly vulnerable and also about the allocation of resources and rationing of care, particularly in intensive care,” she said. “And this only intensified when our prime minister was admitted to intensive care. About this time, antibody testing also became available.”

The goal of their study was to determine the SARS-CoV-2 seroprevalence in critical care staff, as well as look at the correlation between antibody status, prior swab testing, and COVID-19 symptoms.

The survey was conducted at Kings College Hospital in London, which is a tertiary-care teaching center. The critical care department is one of the largest in the United Kingdom. The authors estimate that more than 800 people worked in the critical care units, and between March and April 2020, more than 2,000 patients with COVID-19 were admitted, of whom 180 required care in the ICU.

“There was good PPE available in the ICU units right from the start,” she said, “and staff testing was available.”

All staff working in the critical care department participated in the study, which required serum samples and completion of a questionnaire. The samples were tested via six different assays to measure receptor-binding domain, nucleoprotein, and tri-spike, with one antibody result determined for each sample.

Of the 625 staff members, 384 (61.4%) had previously reported experiencing symptoms and 124 (19.8%) had sent a swab for testing. COVID-19 infection had been confirmed in 37 of those health care workers (29.8%).

Overall, 21% were positive for SARS-CoV-2 antibodies, of whom 9.9% had been asymptomatic.

“We were surprised to find that 61% of staff reported symptoms they felt could be consistent with COVID-19,” she said, noting that fatigue, headache, and cough were the most common symptoms reported. “Seroprevalence was reported in 31% of symptomatic staff and in 5% of those without symptoms.”

Seroprevalence differed by role in a critical care unit, although it did not significantly differ by factors such as age, sex, ethnicity, or underlying conditions. Consultants, who are senior physicians, were twice as likely to test positive, compared with junior doctors. The reason for this finding is not clear, but it may lie in the nature of their work responsibilities, such as performing more aerosol-generating procedures in the ICU or in other departments.

The investigators looked at the timing of infections and found that they preceded peak of patient admissions by 3 weeks, with peak onset of staff symptoms in early March. At this time, Dr. El Bouzidi noted, there were very few patients with COVID-19 in the hospital, and good PPE was available throughout this time period.

“Staff were unlikely to be infected by ICU patients, and therefore PPE was largely effective,” she said. “Other sources of infection were more likely to be the cause, such as interactions with other staff, meetings, or contact in break rooms. Routine mask-wearing throughout the hospital was only encouraged as of June 15.”

There were several limitations to the study, such as the cross-sectional design, reliance on response/recall, the fact that antibody tests are unlikely to detect all previous infections, and no genomic data were available to confirm infections. Even though the study had limitations, Dr. El Bouzidi concluded that ICU staff are unlikely to contract COVID-19 from patients but that other staff, other areas of the hospital, and the wider community are more likely sources of infection.

These findings, she added, demonstrate that PPE was effective at preventing transmission from patients and that protective measures need to be maintained when staff is away from the bedside.

In commenting on the study, Greg S. Martin, MD, professor of medicine in the division of pulmonary, allergy, critical care and sleep medicine, Emory University, Atlanta, noted that, even though the study was conducted almost a year ago, the results are still relevant with regard to the effectiveness of PPE.

“There was a huge amount of uncertainty about PPE – what was most effective, could we reuse it, how to sterilize it, what about surfaces, and so on,” he said. “Even for people who work in ICU and who are familiar with the environment and familiar with the patients, there was 1,000 times more uncertainty about everything they were doing.”

Dr. Martin believes that the situation has improved. “It’s not that we take COVID more lightly, but I think the staff is more comfortable dealing with it,” he said. “They now know what they need to do on an hourly and daily basis to stay safe. The PPE had become second nature to them now, with all the other precautions.”

Critical care staff are less likely to acquire COVID-19 infection from ICU patients than they are from areas away from the bedside, a new study has found.

Courtesy NIAID

“Other staff, other areas of the hospital, and the wider community are more likely sources of infection,” said lead author Kate El Bouzidi, MRCP, South London Specialist Virology Centre, King’s College Hospital NHS Foundation Trust, London.

She noted that 60% of critical care staff were symptomatic during the first wave of the coronavirus pandemic and 20% were antibody positive, with 10% asymptomatic. “Staff acquisition peaked 3 weeks before the peak of COVID-19 ICU admission, and personal protective equipment (PPE) was effective at preventing transmission from patients.” Working in other areas of the hospital was associated with higher seroprevalence, Dr. El Bouzidi noted.

The findings were presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

The novel coronavirus was spreading around the world, and when it reached northern Italy, medical authorities began to think in terms of how it might overwhelm the health care system in the United Kingdom, explained Dr. El Bouzidi.

“There was a lot of interest at this time about health care workers who were particularly vulnerable and also about the allocation of resources and rationing of care, particularly in intensive care,” she said. “And this only intensified when our prime minister was admitted to intensive care. About this time, antibody testing also became available.”

The goal of their study was to determine the SARS-CoV-2 seroprevalence in critical care staff, as well as look at the correlation between antibody status, prior swab testing, and COVID-19 symptoms.

The survey was conducted at Kings College Hospital in London, which is a tertiary-care teaching center. The critical care department is one of the largest in the United Kingdom. The authors estimate that more than 800 people worked in the critical care units, and between March and April 2020, more than 2,000 patients with COVID-19 were admitted, of whom 180 required care in the ICU.

“There was good PPE available in the ICU units right from the start,” she said, “and staff testing was available.”

All staff working in the critical care department participated in the study, which required serum samples and completion of a questionnaire. The samples were tested via six different assays to measure receptor-binding domain, nucleoprotein, and tri-spike, with one antibody result determined for each sample.

Of the 625 staff members, 384 (61.4%) had previously reported experiencing symptoms and 124 (19.8%) had sent a swab for testing. COVID-19 infection had been confirmed in 37 of those health care workers (29.8%).

Overall, 21% were positive for SARS-CoV-2 antibodies, of whom 9.9% had been asymptomatic.

“We were surprised to find that 61% of staff reported symptoms they felt could be consistent with COVID-19,” she said, noting that fatigue, headache, and cough were the most common symptoms reported. “Seroprevalence was reported in 31% of symptomatic staff and in 5% of those without symptoms.”

Seroprevalence differed by role in a critical care unit, although it did not significantly differ by factors such as age, sex, ethnicity, or underlying conditions. Consultants, who are senior physicians, were twice as likely to test positive, compared with junior doctors. The reason for this finding is not clear, but it may lie in the nature of their work responsibilities, such as performing more aerosol-generating procedures in the ICU or in other departments.

The investigators looked at the timing of infections and found that they preceded peak of patient admissions by 3 weeks, with peak onset of staff symptoms in early March. At this time, Dr. El Bouzidi noted, there were very few patients with COVID-19 in the hospital, and good PPE was available throughout this time period.

“Staff were unlikely to be infected by ICU patients, and therefore PPE was largely effective,” she said. “Other sources of infection were more likely to be the cause, such as interactions with other staff, meetings, or contact in break rooms. Routine mask-wearing throughout the hospital was only encouraged as of June 15.”

There were several limitations to the study, such as the cross-sectional design, reliance on response/recall, the fact that antibody tests are unlikely to detect all previous infections, and no genomic data were available to confirm infections. Even though the study had limitations, Dr. El Bouzidi concluded that ICU staff are unlikely to contract COVID-19 from patients but that other staff, other areas of the hospital, and the wider community are more likely sources of infection.

These findings, she added, demonstrate that PPE was effective at preventing transmission from patients and that protective measures need to be maintained when staff is away from the bedside.

In commenting on the study, Greg S. Martin, MD, professor of medicine in the division of pulmonary, allergy, critical care and sleep medicine, Emory University, Atlanta, noted that, even though the study was conducted almost a year ago, the results are still relevant with regard to the effectiveness of PPE.

“There was a huge amount of uncertainty about PPE – what was most effective, could we reuse it, how to sterilize it, what about surfaces, and so on,” he said. “Even for people who work in ICU and who are familiar with the environment and familiar with the patients, there was 1,000 times more uncertainty about everything they were doing.”

Dr. Martin believes that the situation has improved. “It’s not that we take COVID more lightly, but I think the staff is more comfortable dealing with it,” he said. “They now know what they need to do on an hourly and daily basis to stay safe. The PPE had become second nature to them now, with all the other precautions.”

Critical care staff are less likely to acquire COVID-19 infection from ICU patients than they are from areas away from the bedside, a new study has found.

Courtesy NIAID

“Other staff, other areas of the hospital, and the wider community are more likely sources of infection,” said lead author Kate El Bouzidi, MRCP, South London Specialist Virology Centre, King’s College Hospital NHS Foundation Trust, London.

She noted that 60% of critical care staff were symptomatic during the first wave of the coronavirus pandemic and 20% were antibody positive, with 10% asymptomatic. “Staff acquisition peaked 3 weeks before the peak of COVID-19 ICU admission, and personal protective equipment (PPE) was effective at preventing transmission from patients.” Working in other areas of the hospital was associated with higher seroprevalence, Dr. El Bouzidi noted.

The findings were presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

The novel coronavirus was spreading around the world, and when it reached northern Italy, medical authorities began to think in terms of how it might overwhelm the health care system in the United Kingdom, explained Dr. El Bouzidi.

“There was a lot of interest at this time about health care workers who were particularly vulnerable and also about the allocation of resources and rationing of care, particularly in intensive care,” she said. “And this only intensified when our prime minister was admitted to intensive care. About this time, antibody testing also became available.”

The goal of their study was to determine the SARS-CoV-2 seroprevalence in critical care staff, as well as look at the correlation between antibody status, prior swab testing, and COVID-19 symptoms.

The survey was conducted at Kings College Hospital in London, which is a tertiary-care teaching center. The critical care department is one of the largest in the United Kingdom. The authors estimate that more than 800 people worked in the critical care units, and between March and April 2020, more than 2,000 patients with COVID-19 were admitted, of whom 180 required care in the ICU.

“There was good PPE available in the ICU units right from the start,” she said, “and staff testing was available.”

All staff working in the critical care department participated in the study, which required serum samples and completion of a questionnaire. The samples were tested via six different assays to measure receptor-binding domain, nucleoprotein, and tri-spike, with one antibody result determined for each sample.

Of the 625 staff members, 384 (61.4%) had previously reported experiencing symptoms and 124 (19.8%) had sent a swab for testing. COVID-19 infection had been confirmed in 37 of those health care workers (29.8%).

Overall, 21% were positive for SARS-CoV-2 antibodies, of whom 9.9% had been asymptomatic.

“We were surprised to find that 61% of staff reported symptoms they felt could be consistent with COVID-19,” she said, noting that fatigue, headache, and cough were the most common symptoms reported. “Seroprevalence was reported in 31% of symptomatic staff and in 5% of those without symptoms.”

Seroprevalence differed by role in a critical care unit, although it did not significantly differ by factors such as age, sex, ethnicity, or underlying conditions. Consultants, who are senior physicians, were twice as likely to test positive, compared with junior doctors. The reason for this finding is not clear, but it may lie in the nature of their work responsibilities, such as performing more aerosol-generating procedures in the ICU or in other departments.

The investigators looked at the timing of infections and found that they preceded peak of patient admissions by 3 weeks, with peak onset of staff symptoms in early March. At this time, Dr. El Bouzidi noted, there were very few patients with COVID-19 in the hospital, and good PPE was available throughout this time period.

“Staff were unlikely to be infected by ICU patients, and therefore PPE was largely effective,” she said. “Other sources of infection were more likely to be the cause, such as interactions with other staff, meetings, or contact in break rooms. Routine mask-wearing throughout the hospital was only encouraged as of June 15.”

There were several limitations to the study, such as the cross-sectional design, reliance on response/recall, the fact that antibody tests are unlikely to detect all previous infections, and no genomic data were available to confirm infections. Even though the study had limitations, Dr. El Bouzidi concluded that ICU staff are unlikely to contract COVID-19 from patients but that other staff, other areas of the hospital, and the wider community are more likely sources of infection.

These findings, she added, demonstrate that PPE was effective at preventing transmission from patients and that protective measures need to be maintained when staff is away from the bedside.

In commenting on the study, Greg S. Martin, MD, professor of medicine in the division of pulmonary, allergy, critical care and sleep medicine, Emory University, Atlanta, noted that, even though the study was conducted almost a year ago, the results are still relevant with regard to the effectiveness of PPE.

“There was a huge amount of uncertainty about PPE – what was most effective, could we reuse it, how to sterilize it, what about surfaces, and so on,” he said. “Even for people who work in ICU and who are familiar with the environment and familiar with the patients, there was 1,000 times more uncertainty about everything they were doing.”

Dr. Martin believes that the situation has improved. “It’s not that we take COVID more lightly, but I think the staff is more comfortable dealing with it,” he said. “They now know what they need to do on an hourly and daily basis to stay safe. The PPE had become second nature to them now, with all the other precautions.”

There are some differences in how women relative to men report symptoms of an acute coronary syndrome (ACS), but they should not be permitted to get in the way of prompt diagnosis and treatment, according to an expert review at the virtual Going Back to the Heart of Cardiology meeting.

“We need to get away from the idea that symptoms of a myocardial infarction in women are atypical, because women are also having typical symptoms,” said Martha Gulati, MD, chief of cardiology at the University of Arizona, Phoenix.
 

Sexes share key symptoms, but not treatment

Although “women are more likely to report additional symptoms,” chest pain “is pretty much equal between men and women” presenting with an ACS, according to Dr. Gulati.

There are several studies that have shown this, including the Variation in Recovery: Role of Gender on Outcomes of Young AMI patients (VIRGO). In VIRGO, which looked at ACS symptom presentation in younger patients (ages 18-55 years), 87.0% of women versus 89.5% of men presented with chest pain defined as pain, pressure, tightness, or discomfort.

Even among those who recognize that more women die of cardiovascular disease (CVD) disease than any other cause, nothing seems to erase the bias that women in an ED are less likely than men to be having a heart attack. About 60 million women in the United States have CVD, so no threat imposes a higher toll in morbidity and mortality.

In comparison, there are only about 3.5 million women with breast cancer. Even though this is a major cause of morbidity and mortality in women, it is dwarfed by CVD, according to statistics cited by Dr. Gulati. Yet, the data show women get inferior care by guideline-based standards.

“After a myocardial infarction, women relative to men are less likely to get aspirin or beta-blockers within 24 hours, they are less likely to undergo any type of invasive procedure, and they are less likely to meet the door-to-balloon time or receive any reperfusion therapy,” Dr. Gulati said. After a CVD event, “the only thing women do better is to die.”
 

Additional symptoms may muddy the diagnostic waters

In the setting of ACS, the problem is not that women fail to report symptoms that should lead clinicians to consider CVD, but that they report additional symptoms. For the clinician less inclined to consider CVD in women, particularly younger women, there is a greater risk of going down the wrong diagnostic pathway.

In other words, women report symptoms consistent with CVD, “but it is a question of whether we are hearing it,” Dr. Gulati said.

In the VIRGO study, 61.9% of women versus 54.8% of men (P < .001) presented three or more symptoms in addition to chest pain, such as epigastric symptoms, discomfort in the arms or neck, or palpitations. Women were more likely than men to attribute the symptoms to stress or anxiety (20.9% vs. 11.8%; P < .001), while less likely to consider them a result of muscle pain (15.4% vs. 21.2%; P = .029).

There are other gender differences for ACS. For example, women are more likely than men to presented ischemia without obstruction, but Dr. Gulati emphasized that lack of obstruction is not a reason to dismiss the potential for an underlying CV cause.
 

‘Yentl syndrome’ persists

“Women should not need to present exactly like men to be taken seriously,” she said, describing the “Yentl syndrome,” which now has its own Wikipedia page. A cardiovascular version of this syndrome was first described 30 years ago. Based on a movie of a woman who cross dresses in order to be allowed to undertake Jewish studies, the term captures the societal failure to adapt care for women who do not present disease the same way that men do.

Overall, inadequate urgency to pursue potential symptoms of ACS in women is just another manifestation of the “bikini approach to women’s health,” according to Dr. Gulati. This describes the focus on the breast and reproductive system to the exclusion or other organs and anatomy. Dr. Gulati speculated that this might be the reason that clinicians have failed to apply ACS guidelines to women with the same rigor that they apply to men.

This is hardly a new issue. Calls for improving cardiovascular care in women have been increasing in volume for more than past 20 years, but the issue has proven persistent, according to Dr. Gulati. As an example, she noted that the same types of gaps in care and in outcome reported in a 2008 registry study had not much changed in an article published 8 years later.

The solution is not complex, according to Dr. Gulati. In the ED, guideline-directed diagnostic tests should be offered to any man or woman, including younger women, who present with chest pain, ignoring gender bias that threatens misinterpretation of patient history and symptoms. Once CVD is diagnosed as promptly in women as it is in men, guideline-directed intervention would be expected to reduce the gender gap in outcomes.

“By applying standardized protocols, it will help us to the same for women as we do for men,” Dr. Gulati said.

The meeting was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

There are some differences in how women relative to men report symptoms of an acute coronary syndrome (ACS), but they should not be permitted to get in the way of prompt diagnosis and treatment, according to an expert review at the virtual Going Back to the Heart of Cardiology meeting.

“We need to get away from the idea that symptoms of a myocardial infarction in women are atypical, because women are also having typical symptoms,” said Martha Gulati, MD, chief of cardiology at the University of Arizona, Phoenix.
 

Sexes share key symptoms, but not treatment

Although “women are more likely to report additional symptoms,” chest pain “is pretty much equal between men and women” presenting with an ACS, according to Dr. Gulati.

There are several studies that have shown this, including the Variation in Recovery: Role of Gender on Outcomes of Young AMI patients (VIRGO). In VIRGO, which looked at ACS symptom presentation in younger patients (ages 18-55 years), 87.0% of women versus 89.5% of men presented with chest pain defined as pain, pressure, tightness, or discomfort.

Even among those who recognize that more women die of cardiovascular disease (CVD) disease than any other cause, nothing seems to erase the bias that women in an ED are less likely than men to be having a heart attack. About 60 million women in the United States have CVD, so no threat imposes a higher toll in morbidity and mortality.

In comparison, there are only about 3.5 million women with breast cancer. Even though this is a major cause of morbidity and mortality in women, it is dwarfed by CVD, according to statistics cited by Dr. Gulati. Yet, the data show women get inferior care by guideline-based standards.

“After a myocardial infarction, women relative to men are less likely to get aspirin or beta-blockers within 24 hours, they are less likely to undergo any type of invasive procedure, and they are less likely to meet the door-to-balloon time or receive any reperfusion therapy,” Dr. Gulati said. After a CVD event, “the only thing women do better is to die.”
 

Additional symptoms may muddy the diagnostic waters

In the setting of ACS, the problem is not that women fail to report symptoms that should lead clinicians to consider CVD, but that they report additional symptoms. For the clinician less inclined to consider CVD in women, particularly younger women, there is a greater risk of going down the wrong diagnostic pathway.

In other words, women report symptoms consistent with CVD, “but it is a question of whether we are hearing it,” Dr. Gulati said.

In the VIRGO study, 61.9% of women versus 54.8% of men (P < .001) presented three or more symptoms in addition to chest pain, such as epigastric symptoms, discomfort in the arms or neck, or palpitations. Women were more likely than men to attribute the symptoms to stress or anxiety (20.9% vs. 11.8%; P < .001), while less likely to consider them a result of muscle pain (15.4% vs. 21.2%; P = .029).

There are other gender differences for ACS. For example, women are more likely than men to presented ischemia without obstruction, but Dr. Gulati emphasized that lack of obstruction is not a reason to dismiss the potential for an underlying CV cause.
 

‘Yentl syndrome’ persists

“Women should not need to present exactly like men to be taken seriously,” she said, describing the “Yentl syndrome,” which now has its own Wikipedia page. A cardiovascular version of this syndrome was first described 30 years ago. Based on a movie of a woman who cross dresses in order to be allowed to undertake Jewish studies, the term captures the societal failure to adapt care for women who do not present disease the same way that men do.

Overall, inadequate urgency to pursue potential symptoms of ACS in women is just another manifestation of the “bikini approach to women’s health,” according to Dr. Gulati. This describes the focus on the breast and reproductive system to the exclusion or other organs and anatomy. Dr. Gulati speculated that this might be the reason that clinicians have failed to apply ACS guidelines to women with the same rigor that they apply to men.

This is hardly a new issue. Calls for improving cardiovascular care in women have been increasing in volume for more than past 20 years, but the issue has proven persistent, according to Dr. Gulati. As an example, she noted that the same types of gaps in care and in outcome reported in a 2008 registry study had not much changed in an article published 8 years later.

The solution is not complex, according to Dr. Gulati. In the ED, guideline-directed diagnostic tests should be offered to any man or woman, including younger women, who present with chest pain, ignoring gender bias that threatens misinterpretation of patient history and symptoms. Once CVD is diagnosed as promptly in women as it is in men, guideline-directed intervention would be expected to reduce the gender gap in outcomes.

“By applying standardized protocols, it will help us to the same for women as we do for men,” Dr. Gulati said.

The meeting was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

There are some differences in how women relative to men report symptoms of an acute coronary syndrome (ACS), but they should not be permitted to get in the way of prompt diagnosis and treatment, according to an expert review at the virtual Going Back to the Heart of Cardiology meeting.

“We need to get away from the idea that symptoms of a myocardial infarction in women are atypical, because women are also having typical symptoms,” said Martha Gulati, MD, chief of cardiology at the University of Arizona, Phoenix.
 

Sexes share key symptoms, but not treatment

Although “women are more likely to report additional symptoms,” chest pain “is pretty much equal between men and women” presenting with an ACS, according to Dr. Gulati.

There are several studies that have shown this, including the Variation in Recovery: Role of Gender on Outcomes of Young AMI patients (VIRGO). In VIRGO, which looked at ACS symptom presentation in younger patients (ages 18-55 years), 87.0% of women versus 89.5% of men presented with chest pain defined as pain, pressure, tightness, or discomfort.

Even among those who recognize that more women die of cardiovascular disease (CVD) disease than any other cause, nothing seems to erase the bias that women in an ED are less likely than men to be having a heart attack. About 60 million women in the United States have CVD, so no threat imposes a higher toll in morbidity and mortality.

In comparison, there are only about 3.5 million women with breast cancer. Even though this is a major cause of morbidity and mortality in women, it is dwarfed by CVD, according to statistics cited by Dr. Gulati. Yet, the data show women get inferior care by guideline-based standards.

“After a myocardial infarction, women relative to men are less likely to get aspirin or beta-blockers within 24 hours, they are less likely to undergo any type of invasive procedure, and they are less likely to meet the door-to-balloon time or receive any reperfusion therapy,” Dr. Gulati said. After a CVD event, “the only thing women do better is to die.”
 

Additional symptoms may muddy the diagnostic waters

In the setting of ACS, the problem is not that women fail to report symptoms that should lead clinicians to consider CVD, but that they report additional symptoms. For the clinician less inclined to consider CVD in women, particularly younger women, there is a greater risk of going down the wrong diagnostic pathway.

In other words, women report symptoms consistent with CVD, “but it is a question of whether we are hearing it,” Dr. Gulati said.

In the VIRGO study, 61.9% of women versus 54.8% of men (P < .001) presented three or more symptoms in addition to chest pain, such as epigastric symptoms, discomfort in the arms or neck, or palpitations. Women were more likely than men to attribute the symptoms to stress or anxiety (20.9% vs. 11.8%; P < .001), while less likely to consider them a result of muscle pain (15.4% vs. 21.2%; P = .029).

There are other gender differences for ACS. For example, women are more likely than men to presented ischemia without obstruction, but Dr. Gulati emphasized that lack of obstruction is not a reason to dismiss the potential for an underlying CV cause.
 

‘Yentl syndrome’ persists

“Women should not need to present exactly like men to be taken seriously,” she said, describing the “Yentl syndrome,” which now has its own Wikipedia page. A cardiovascular version of this syndrome was first described 30 years ago. Based on a movie of a woman who cross dresses in order to be allowed to undertake Jewish studies, the term captures the societal failure to adapt care for women who do not present disease the same way that men do.

Overall, inadequate urgency to pursue potential symptoms of ACS in women is just another manifestation of the “bikini approach to women’s health,” according to Dr. Gulati. This describes the focus on the breast and reproductive system to the exclusion or other organs and anatomy. Dr. Gulati speculated that this might be the reason that clinicians have failed to apply ACS guidelines to women with the same rigor that they apply to men.

This is hardly a new issue. Calls for improving cardiovascular care in women have been increasing in volume for more than past 20 years, but the issue has proven persistent, according to Dr. Gulati. As an example, she noted that the same types of gaps in care and in outcome reported in a 2008 registry study had not much changed in an article published 8 years later.

The solution is not complex, according to Dr. Gulati. In the ED, guideline-directed diagnostic tests should be offered to any man or woman, including younger women, who present with chest pain, ignoring gender bias that threatens misinterpretation of patient history and symptoms. Once CVD is diagnosed as promptly in women as it is in men, guideline-directed intervention would be expected to reduce the gender gap in outcomes.

“By applying standardized protocols, it will help us to the same for women as we do for men,” Dr. Gulati said.

The meeting was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

Patients who received intensive lifestyle training by coaches in the primary care setting experienced improvement in several indicators of cardiometabolic health in a 2-year trial.

The 803 trial participants comprised a racially diverse, low-income population with obesity. In this study, primary care clinics were randomly assigned to provide weight-loss coaching or usual care. Patients at the intensive training clinics lost significantly more weight than the other patients, as reported in a paper published in September in the New England Journal of Medicine on the PROmoting Successful Weight Loss in Primary CarE in Louisiana (PROPEL) trial. The patients who received weight loss coaching also had significantly more improvement in HDL cholesterol levels, total to HDL cholesterol ratios, and metabolic syndrome severity score, said researchers in the new paper on the PROPEL trial, which was published in Circulation on February 8 .

“We believe that one reason for success of the program was the use of a health coach [who] was embedded in the primary care office,” said lead author Peter Katzmarzyk, PhD, associate executive director for population and public health sciences at the Pennington Biomedical Research Center, Baton Rouge, La. “This way, the patients could get their counseling in a familiar environment and did not have to go to a different setting. The coaches developed close relationships with the patients over the 2 years, and this helped develop a sense of responsibility in the patients as the coaches were helping the patients to set goals and kept them accountable.”

In the PROPEL study, 67% of patients were Black and had low health literacy scores that corresponded with less than a ninth-grade education level. The intensive lifestyle intervention program included weekly sessions with the trained health coaches over the first 6 months — 16 face-to-face and 6 over the phone — and then at least monthly for the last 18 months. The coaches had higher education degrees in nutrition, physical activity, or behavioral medicine. Before the program started, the coaches also received training in the management of obesity and related health issues, health literacy, and patient communication and education. The goal of the program was 10% weight loss, using personalized action plans on eating, dieting, and physical activity.

Those in the usual-care clinics continued receiving normal care and received newsletters on health topics, such as the importance of sleep and tips for limiting time spent sitting. The primary care physicians at those clinics also were given a presentation with Centers for Medicare & Medicaid Services (CMS) information on intensive lifestyle interventions for obesity.
 

Cholesterol changes in intervention vs. control group

HDL cholesterol improved significantly among the coached patients, compared with the other patients, with a mean difference of 4.1 mg/dL at 1 year and 4.6 mg/dL at 2 years (P less than .01 for both). The total cholesterol to HDL cholesterol ratio showed a similarly significant difference in decline, with a between-group difference of –0.29 at 1 year and –0.31 at 2 years (P less than .01 for both). Also, the difference in the change in metabolic severity scores were –0.40 at 1 year and –0.21 at 2 years (P less than .01 for both).

Fasting blood glucose had declined after the 1st year by a significantly greater degree in the clinics with coaching, compared with the others, but not after the second year, researchers found.

There were no significant differences seen in total cholesterol, LDL cholesterol, non-HDL cholesterol, or blood pressure. Dr. Katzmarzyk said the likely reason for no change in blood pressure was that it was already relatively well-controlled at baseline for all the patients.
 

Funding barriers to obesity treatment

The CMS currently cover intensive training for obesity if delivered directly by a primary care physician, according to the authors of the new paper. Dr. Katzmarzyk said he hopes that will change.

“We are hoping that the evidence provided in this study may change the way that CMS funds obesity treatment in the future by allowing an expansion of the care team,” he said.

John Flack, MD, chair of internal medicine at Southern Illinois University, Springfield, said that the main achievement of the study was that it showed that intensive weight-loss training in the primary-care setting could be accomplished in a racially diverse population with low health literacy.

“You can’t just automatically assume just because you’ve seen it in some other populations that you can replicate this in every population, so they’ve done a really good job,” he said.

That programs are eligible for reimbursement only if they’re run by primary-care physicians is an ongoing problem, he said.

“You don’t necessarily need to be a physician to do this,” Dr. Flack said.

For best results, payment for coaching should not be tied to office visits, Dr. Flack noted.

“If they’re de-tethered from the office visits and you’re paid for quality ... you’re going to build out your infrastructure differently to care for people,” he said.

Andrew Freeman, MD, associate professor of medicine at the University of Colorado, Denver, and cochair of the American College of Cardiology’s nutrition and lifestyle work group, said the findings dovetail with his experience.

“I’m a huge believer that when people need to make lifestyle changes, having someone hold their hand and guide them through the effort is incredibly rewarding and incredibly powerful,” said Dr. Freeman, who also oversees the intensive cardiac rehab program at National Jewish Health in Denver.

A program like this needs proper funding in order to work, Dr, Freeman noted. He added that, even with coaches being paid well, “if you are able to prevent just one readmission for, say, heart failure a month . . . you could be saving millions of dollars over just a couple of years.”

Dr. Katzmarzyk, Dr. Flack, and Dr. Freeman reported no relevant disclosures. Louisiana State University, Pennington Biomedical Research Center, and Montclair State University have interest in the intellectual property surrounding a weight graph used in the study. The other researchers reported grants and/or fees from Bayer, Boehringer Ingelheim, Gilead, Takeda, Novo Nordisk, and other companies.
 

Patients who received intensive lifestyle training by coaches in the primary care setting experienced improvement in several indicators of cardiometabolic health in a 2-year trial.

The 803 trial participants comprised a racially diverse, low-income population with obesity. In this study, primary care clinics were randomly assigned to provide weight-loss coaching or usual care. Patients at the intensive training clinics lost significantly more weight than the other patients, as reported in a paper published in September in the New England Journal of Medicine on the PROmoting Successful Weight Loss in Primary CarE in Louisiana (PROPEL) trial. The patients who received weight loss coaching also had significantly more improvement in HDL cholesterol levels, total to HDL cholesterol ratios, and metabolic syndrome severity score, said researchers in the new paper on the PROPEL trial, which was published in Circulation on February 8 .

“We believe that one reason for success of the program was the use of a health coach [who] was embedded in the primary care office,” said lead author Peter Katzmarzyk, PhD, associate executive director for population and public health sciences at the Pennington Biomedical Research Center, Baton Rouge, La. “This way, the patients could get their counseling in a familiar environment and did not have to go to a different setting. The coaches developed close relationships with the patients over the 2 years, and this helped develop a sense of responsibility in the patients as the coaches were helping the patients to set goals and kept them accountable.”

In the PROPEL study, 67% of patients were Black and had low health literacy scores that corresponded with less than a ninth-grade education level. The intensive lifestyle intervention program included weekly sessions with the trained health coaches over the first 6 months — 16 face-to-face and 6 over the phone — and then at least monthly for the last 18 months. The coaches had higher education degrees in nutrition, physical activity, or behavioral medicine. Before the program started, the coaches also received training in the management of obesity and related health issues, health literacy, and patient communication and education. The goal of the program was 10% weight loss, using personalized action plans on eating, dieting, and physical activity.

Those in the usual-care clinics continued receiving normal care and received newsletters on health topics, such as the importance of sleep and tips for limiting time spent sitting. The primary care physicians at those clinics also were given a presentation with Centers for Medicare & Medicaid Services (CMS) information on intensive lifestyle interventions for obesity.
 

Cholesterol changes in intervention vs. control group

HDL cholesterol improved significantly among the coached patients, compared with the other patients, with a mean difference of 4.1 mg/dL at 1 year and 4.6 mg/dL at 2 years (P less than .01 for both). The total cholesterol to HDL cholesterol ratio showed a similarly significant difference in decline, with a between-group difference of –0.29 at 1 year and –0.31 at 2 years (P less than .01 for both). Also, the difference in the change in metabolic severity scores were –0.40 at 1 year and –0.21 at 2 years (P less than .01 for both).

Fasting blood glucose had declined after the 1st year by a significantly greater degree in the clinics with coaching, compared with the others, but not after the second year, researchers found.

There were no significant differences seen in total cholesterol, LDL cholesterol, non-HDL cholesterol, or blood pressure. Dr. Katzmarzyk said the likely reason for no change in blood pressure was that it was already relatively well-controlled at baseline for all the patients.
 

Funding barriers to obesity treatment

The CMS currently cover intensive training for obesity if delivered directly by a primary care physician, according to the authors of the new paper. Dr. Katzmarzyk said he hopes that will change.

“We are hoping that the evidence provided in this study may change the way that CMS funds obesity treatment in the future by allowing an expansion of the care team,” he said.

John Flack, MD, chair of internal medicine at Southern Illinois University, Springfield, said that the main achievement of the study was that it showed that intensive weight-loss training in the primary-care setting could be accomplished in a racially diverse population with low health literacy.

“You can’t just automatically assume just because you’ve seen it in some other populations that you can replicate this in every population, so they’ve done a really good job,” he said.

That programs are eligible for reimbursement only if they’re run by primary-care physicians is an ongoing problem, he said.

“You don’t necessarily need to be a physician to do this,” Dr. Flack said.

For best results, payment for coaching should not be tied to office visits, Dr. Flack noted.

“If they’re de-tethered from the office visits and you’re paid for quality ... you’re going to build out your infrastructure differently to care for people,” he said.

Andrew Freeman, MD, associate professor of medicine at the University of Colorado, Denver, and cochair of the American College of Cardiology’s nutrition and lifestyle work group, said the findings dovetail with his experience.

“I’m a huge believer that when people need to make lifestyle changes, having someone hold their hand and guide them through the effort is incredibly rewarding and incredibly powerful,” said Dr. Freeman, who also oversees the intensive cardiac rehab program at National Jewish Health in Denver.

A program like this needs proper funding in order to work, Dr, Freeman noted. He added that, even with coaches being paid well, “if you are able to prevent just one readmission for, say, heart failure a month . . . you could be saving millions of dollars over just a couple of years.”

Dr. Katzmarzyk, Dr. Flack, and Dr. Freeman reported no relevant disclosures. Louisiana State University, Pennington Biomedical Research Center, and Montclair State University have interest in the intellectual property surrounding a weight graph used in the study. The other researchers reported grants and/or fees from Bayer, Boehringer Ingelheim, Gilead, Takeda, Novo Nordisk, and other companies.
 

Patients who received intensive lifestyle training by coaches in the primary care setting experienced improvement in several indicators of cardiometabolic health in a 2-year trial.

The 803 trial participants comprised a racially diverse, low-income population with obesity. In this study, primary care clinics were randomly assigned to provide weight-loss coaching or usual care. Patients at the intensive training clinics lost significantly more weight than the other patients, as reported in a paper published in September in the New England Journal of Medicine on the PROmoting Successful Weight Loss in Primary CarE in Louisiana (PROPEL) trial. The patients who received weight loss coaching also had significantly more improvement in HDL cholesterol levels, total to HDL cholesterol ratios, and metabolic syndrome severity score, said researchers in the new paper on the PROPEL trial, which was published in Circulation on February 8 .

“We believe that one reason for success of the program was the use of a health coach [who] was embedded in the primary care office,” said lead author Peter Katzmarzyk, PhD, associate executive director for population and public health sciences at the Pennington Biomedical Research Center, Baton Rouge, La. “This way, the patients could get their counseling in a familiar environment and did not have to go to a different setting. The coaches developed close relationships with the patients over the 2 years, and this helped develop a sense of responsibility in the patients as the coaches were helping the patients to set goals and kept them accountable.”

In the PROPEL study, 67% of patients were Black and had low health literacy scores that corresponded with less than a ninth-grade education level. The intensive lifestyle intervention program included weekly sessions with the trained health coaches over the first 6 months — 16 face-to-face and 6 over the phone — and then at least monthly for the last 18 months. The coaches had higher education degrees in nutrition, physical activity, or behavioral medicine. Before the program started, the coaches also received training in the management of obesity and related health issues, health literacy, and patient communication and education. The goal of the program was 10% weight loss, using personalized action plans on eating, dieting, and physical activity.

Those in the usual-care clinics continued receiving normal care and received newsletters on health topics, such as the importance of sleep and tips for limiting time spent sitting. The primary care physicians at those clinics also were given a presentation with Centers for Medicare & Medicaid Services (CMS) information on intensive lifestyle interventions for obesity.
 

Cholesterol changes in intervention vs. control group

HDL cholesterol improved significantly among the coached patients, compared with the other patients, with a mean difference of 4.1 mg/dL at 1 year and 4.6 mg/dL at 2 years (P less than .01 for both). The total cholesterol to HDL cholesterol ratio showed a similarly significant difference in decline, with a between-group difference of –0.29 at 1 year and –0.31 at 2 years (P less than .01 for both). Also, the difference in the change in metabolic severity scores were –0.40 at 1 year and –0.21 at 2 years (P less than .01 for both).

Fasting blood glucose had declined after the 1st year by a significantly greater degree in the clinics with coaching, compared with the others, but not after the second year, researchers found.

There were no significant differences seen in total cholesterol, LDL cholesterol, non-HDL cholesterol, or blood pressure. Dr. Katzmarzyk said the likely reason for no change in blood pressure was that it was already relatively well-controlled at baseline for all the patients.
 

Funding barriers to obesity treatment

The CMS currently cover intensive training for obesity if delivered directly by a primary care physician, according to the authors of the new paper. Dr. Katzmarzyk said he hopes that will change.

“We are hoping that the evidence provided in this study may change the way that CMS funds obesity treatment in the future by allowing an expansion of the care team,” he said.

John Flack, MD, chair of internal medicine at Southern Illinois University, Springfield, said that the main achievement of the study was that it showed that intensive weight-loss training in the primary-care setting could be accomplished in a racially diverse population with low health literacy.

“You can’t just automatically assume just because you’ve seen it in some other populations that you can replicate this in every population, so they’ve done a really good job,” he said.

That programs are eligible for reimbursement only if they’re run by primary-care physicians is an ongoing problem, he said.

“You don’t necessarily need to be a physician to do this,” Dr. Flack said.

For best results, payment for coaching should not be tied to office visits, Dr. Flack noted.

“If they’re de-tethered from the office visits and you’re paid for quality ... you’re going to build out your infrastructure differently to care for people,” he said.

Andrew Freeman, MD, associate professor of medicine at the University of Colorado, Denver, and cochair of the American College of Cardiology’s nutrition and lifestyle work group, said the findings dovetail with his experience.

“I’m a huge believer that when people need to make lifestyle changes, having someone hold their hand and guide them through the effort is incredibly rewarding and incredibly powerful,” said Dr. Freeman, who also oversees the intensive cardiac rehab program at National Jewish Health in Denver.

A program like this needs proper funding in order to work, Dr, Freeman noted. He added that, even with coaches being paid well, “if you are able to prevent just one readmission for, say, heart failure a month . . . you could be saving millions of dollars over just a couple of years.”

Dr. Katzmarzyk, Dr. Flack, and Dr. Freeman reported no relevant disclosures. Louisiana State University, Pennington Biomedical Research Center, and Montclair State University have interest in the intellectual property surrounding a weight graph used in the study. The other researchers reported grants and/or fees from Bayer, Boehringer Ingelheim, Gilead, Takeda, Novo Nordisk, and other companies.
 

Science by press release and preprint has cooled clinician enthusiasm for the use of colchicine in nonhospitalized patients with COVID-19, despite a pressing need for early treatments.

Photo by Jimmy Hamelin

As previously reported by this news organization, a Jan. 22 press release announced that the massive ColCORONA study missed its primary endpoint of hospitalization or death among 4,488 newly diagnosed patients at increased risk for hospitalization.

But it also touted that use of the anti-inflammatory drug significantly reduced the primary endpoint in 4,159 of those patients with polymerase chain reaction–confirmed COVID and led to reductions of 25%, 50%, and 44%, respectively, for hospitalizations, ventilations, and death.

Lead investigator Jean-Claude Tardif, MD, director of the Montreal Heart Institute Research Centre, deemed the findings a “medical breakthrough.”

When the preprint released a few days later, however, newly revealed confidence intervals showed colchicine did not meaningfully reduce the need for mechanical ventilation (odds ratio, 0.50; 95% confidence interval, 0.23-1.07) or death alone (OR, 0.56; 95% CI, 0.19-1.66).

Further, the significant benefit on the primary outcome came at the cost of a fivefold increase in pulmonary embolism (11 vs. 2; P = .01), which was not mentioned in the press release.

“Whether this represents a real phenomenon or simply the play of chance is not known,” Dr. Tardif and colleagues noted later in the preprint.

“I read the preprint on colchicine and I have so many questions,” Aaron E. Glatt, MD, spokesperson for the Infectious Diseases Society of America and chief of infectious diseases, Mount Sinai South Nassau, Hewlett, N.Y., said in an interview. “I’ve been burned too many times with COVID and prefer to see better data.

“People sometimes say if you wait for perfect data, people are going to die,” he said. “Yeah, but we have no idea if people are going to die from getting this drug more than not getting it. That’s what concerns me. How many pulmonary emboli are going to be fatal versus the slight benefit that the study showed?”

The pushback to the non–peer-reviewed data on social media and via emails was so strong that Dr. Tardif posted a nearly 2,000-word letter responding to the many questions at play.

Chief among them was why the trial, originally planned for 6,000 patients, was stopped early by the investigators without consultation with the data safety monitoring board (DSMB).

The explanation in the letter that logistical issues like running the study call center, budget constraints, and a perceived need to quickly communicate the results left some calling foul that the study wasn’t allowed to finish and come to a more definitive conclusion.

“I can be a little bit sympathetic to their cause but at the same time the DSMB should have said no,” said David Boulware, MD, MPH, who led a recent hydroxychloroquine trial in COVID-19. “The problem is we’re sort of left in limbo, where some people kind of believe it and some say it’s not really a thing. So it’s not really moving the needle, as far as guidelines go.”

Indeed, a Twitter poll by cardiologist James Januzzi Jr., MD, captured the uncertainty, with 28% of respondents saying the trial was “neutral,” 58% saying “maybe but meh,” and 14% saying “colchicine for all.”

Another poll cheekily asked whether ColCORONA was the Gamestop/Reddit equivalent of COVID.

“The press release really didn’t help things because it very much oversold the effect. That, I think, poisoned the well,” said Dr. Boulware, professor of medicine in infectious diseases at the University of Minnesota, Minneapolis.

“The question I’m left with is not whether colchicine works, but who does it work in,” he said. “That’s really the fundamental question because it does seem that there are probably high-risk groups in their trial and others where they benefit, whereas other groups don’t benefit. In the subgroup analysis, there was absolutely no beneficial effect in women.”

According to the authors, the number needed to treat to prevent one death or hospitalization was 71 overall, but 29 for patients with diabetes, 31 for those aged 70 years and older, 53 for patients with respiratory disease, and 25 for those with coronary disease or heart failure.

Men are at higher risk overall for poor outcomes. But “the authors didn’t present a multivariable analysis, so it is unclear if another factor, such as a differential prevalence of smoking or cardiovascular risk factors, contributed to the differential benefit,” Rachel Bender Ignacio, MD, MPH, infectious disease specialist, University of Washington, Seattle, said in an interview.

Importantly, in this pragmatic study, duration and severity of symptoms were not reported, observed Dr. Bender Ignacio, who is also a STOP-COVID-2 investigator. “We don’t yet have data as to whether colchicine shortens duration or severity of symptoms or prevents long COVID, so we need more data on that.”

The overall risk for serious adverse events was lower in the colchicine group, but the difference in pulmonary embolism (PE) was striking, she said. This could be caused by a real biologic effect, or it’s possible that persons with shortness of breath and hypoxia, without evident viral pneumonia on chest x-ray after a positive COVID-19 test, were more likely to receive a CT-PE study.

The press release also failed to include information, later noted in the preprint, that the MHI has submitted two patents related to colchicine: “Methods of treating a coronavirus infection using colchicine” and “Early administration of low-dose colchicine after myocardial infarction.”

Reached for clarification, MHI communications adviser Camille Turbide said in an interview that the first patent “simply refers to the novel concept of preventing complications of COVID-19, such as admission to the hospital, with colchicine as tested in the ColCORONA study.”

The second patent, she said, refers to the “novel concept that administering colchicine early after a major adverse cardiovascular event is better than waiting several days,” as supported by the COLCOT study, which Dr. Tardif also led.

The patents are being reviewed by authorities and “Dr. Tardif has waived his rights in these patents and does not stand to benefit financially at all if colchicine becomes used as a treatment for COVID-19,” Ms. Turbide said.

Dr. Tardif did not respond to interview requests for this story. Dr. Glatt said conflicts of interest must be assessed and are “something that is of great concern in any scientific study.”

Cardiologist Steve Nissen, MD, of the Cleveland Clinic said in an interview that, “despite the negative results, the study does suggest that colchicine might have a benefit and should be studied in future trials. These findings are not sufficient evidence to suggest use of the drug in patients infected with COVID-19.”

He noted that adverse effects like diarrhea were expected but that the excess PE was unexpected and needs greater clarification.

“Stopping the trial for administrative reasons is puzzling and undermined the ability of the trial to give a reliable answer,” Dr. Nissen said. “This is a reasonable pilot study that should be viewed as hypothesis generating but inconclusive.”

Several sources said a new trial is unlikely, particularly given the cost and 28 trials already evaluating colchicine. Among these are RECOVERY and COLCOVID, testing whether colchicine can reduce the duration of hospitalization or death in hospitalized patients with COVID-19.

Because there are so many trials ongoing right now, including for antivirals and other immunomodulators, it’s important that, if colchicine comes to routine clinical use, it provides access to treatment for those not able or willing to access clinical trials, rather than impeding clinical trial enrollment, Dr. Bender Ignacio suggested.

“We have already learned the lesson in the pandemic that early adoption of potentially promising therapies can negatively impact our ability to study and develop other promising treatments,” she said.

The trial was coordinated by the Montreal Heart Institute and funded by the government of Quebec; the National Heart, Lung, and Blood Institute of the National Institutes of Health; Montreal philanthropist Sophie Desmarais, and the COVID-19 Therapeutics Accelerator launched by the Bill & Melinda Gates Foundation, Wellcome, and Mastercard. CGI, Dacima, and Pharmascience of Montreal were also collaborators. Dr. Glatt reported no conflicts of interest. Dr. Boulware reported receiving $18 in food and beverages from Gilead Sciences in 2018.
 

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

Science by press release and preprint has cooled clinician enthusiasm for the use of colchicine in nonhospitalized patients with COVID-19, despite a pressing need for early treatments.

Photo by Jimmy Hamelin

As previously reported by this news organization, a Jan. 22 press release announced that the massive ColCORONA study missed its primary endpoint of hospitalization or death among 4,488 newly diagnosed patients at increased risk for hospitalization.

But it also touted that use of the anti-inflammatory drug significantly reduced the primary endpoint in 4,159 of those patients with polymerase chain reaction–confirmed COVID and led to reductions of 25%, 50%, and 44%, respectively, for hospitalizations, ventilations, and death.

Lead investigator Jean-Claude Tardif, MD, director of the Montreal Heart Institute Research Centre, deemed the findings a “medical breakthrough.”

When the preprint released a few days later, however, newly revealed confidence intervals showed colchicine did not meaningfully reduce the need for mechanical ventilation (odds ratio, 0.50; 95% confidence interval, 0.23-1.07) or death alone (OR, 0.56; 95% CI, 0.19-1.66).

Further, the significant benefit on the primary outcome came at the cost of a fivefold increase in pulmonary embolism (11 vs. 2; P = .01), which was not mentioned in the press release.

“Whether this represents a real phenomenon or simply the play of chance is not known,” Dr. Tardif and colleagues noted later in the preprint.

“I read the preprint on colchicine and I have so many questions,” Aaron E. Glatt, MD, spokesperson for the Infectious Diseases Society of America and chief of infectious diseases, Mount Sinai South Nassau, Hewlett, N.Y., said in an interview. “I’ve been burned too many times with COVID and prefer to see better data.

“People sometimes say if you wait for perfect data, people are going to die,” he said. “Yeah, but we have no idea if people are going to die from getting this drug more than not getting it. That’s what concerns me. How many pulmonary emboli are going to be fatal versus the slight benefit that the study showed?”

The pushback to the non–peer-reviewed data on social media and via emails was so strong that Dr. Tardif posted a nearly 2,000-word letter responding to the many questions at play.

Chief among them was why the trial, originally planned for 6,000 patients, was stopped early by the investigators without consultation with the data safety monitoring board (DSMB).

The explanation in the letter that logistical issues like running the study call center, budget constraints, and a perceived need to quickly communicate the results left some calling foul that the study wasn’t allowed to finish and come to a more definitive conclusion.

“I can be a little bit sympathetic to their cause but at the same time the DSMB should have said no,” said David Boulware, MD, MPH, who led a recent hydroxychloroquine trial in COVID-19. “The problem is we’re sort of left in limbo, where some people kind of believe it and some say it’s not really a thing. So it’s not really moving the needle, as far as guidelines go.”

Indeed, a Twitter poll by cardiologist James Januzzi Jr., MD, captured the uncertainty, with 28% of respondents saying the trial was “neutral,” 58% saying “maybe but meh,” and 14% saying “colchicine for all.”

Another poll cheekily asked whether ColCORONA was the Gamestop/Reddit equivalent of COVID.

“The press release really didn’t help things because it very much oversold the effect. That, I think, poisoned the well,” said Dr. Boulware, professor of medicine in infectious diseases at the University of Minnesota, Minneapolis.

“The question I’m left with is not whether colchicine works, but who does it work in,” he said. “That’s really the fundamental question because it does seem that there are probably high-risk groups in their trial and others where they benefit, whereas other groups don’t benefit. In the subgroup analysis, there was absolutely no beneficial effect in women.”

According to the authors, the number needed to treat to prevent one death or hospitalization was 71 overall, but 29 for patients with diabetes, 31 for those aged 70 years and older, 53 for patients with respiratory disease, and 25 for those with coronary disease or heart failure.

Men are at higher risk overall for poor outcomes. But “the authors didn’t present a multivariable analysis, so it is unclear if another factor, such as a differential prevalence of smoking or cardiovascular risk factors, contributed to the differential benefit,” Rachel Bender Ignacio, MD, MPH, infectious disease specialist, University of Washington, Seattle, said in an interview.

Importantly, in this pragmatic study, duration and severity of symptoms were not reported, observed Dr. Bender Ignacio, who is also a STOP-COVID-2 investigator. “We don’t yet have data as to whether colchicine shortens duration or severity of symptoms or prevents long COVID, so we need more data on that.”

The overall risk for serious adverse events was lower in the colchicine group, but the difference in pulmonary embolism (PE) was striking, she said. This could be caused by a real biologic effect, or it’s possible that persons with shortness of breath and hypoxia, without evident viral pneumonia on chest x-ray after a positive COVID-19 test, were more likely to receive a CT-PE study.

The press release also failed to include information, later noted in the preprint, that the MHI has submitted two patents related to colchicine: “Methods of treating a coronavirus infection using colchicine” and “Early administration of low-dose colchicine after myocardial infarction.”

Reached for clarification, MHI communications adviser Camille Turbide said in an interview that the first patent “simply refers to the novel concept of preventing complications of COVID-19, such as admission to the hospital, with colchicine as tested in the ColCORONA study.”

The second patent, she said, refers to the “novel concept that administering colchicine early after a major adverse cardiovascular event is better than waiting several days,” as supported by the COLCOT study, which Dr. Tardif also led.

The patents are being reviewed by authorities and “Dr. Tardif has waived his rights in these patents and does not stand to benefit financially at all if colchicine becomes used as a treatment for COVID-19,” Ms. Turbide said.

Dr. Tardif did not respond to interview requests for this story. Dr. Glatt said conflicts of interest must be assessed and are “something that is of great concern in any scientific study.”

Cardiologist Steve Nissen, MD, of the Cleveland Clinic said in an interview that, “despite the negative results, the study does suggest that colchicine might have a benefit and should be studied in future trials. These findings are not sufficient evidence to suggest use of the drug in patients infected with COVID-19.”

He noted that adverse effects like diarrhea were expected but that the excess PE was unexpected and needs greater clarification.

“Stopping the trial for administrative reasons is puzzling and undermined the ability of the trial to give a reliable answer,” Dr. Nissen said. “This is a reasonable pilot study that should be viewed as hypothesis generating but inconclusive.”

Several sources said a new trial is unlikely, particularly given the cost and 28 trials already evaluating colchicine. Among these are RECOVERY and COLCOVID, testing whether colchicine can reduce the duration of hospitalization or death in hospitalized patients with COVID-19.

Because there are so many trials ongoing right now, including for antivirals and other immunomodulators, it’s important that, if colchicine comes to routine clinical use, it provides access to treatment for those not able or willing to access clinical trials, rather than impeding clinical trial enrollment, Dr. Bender Ignacio suggested.

“We have already learned the lesson in the pandemic that early adoption of potentially promising therapies can negatively impact our ability to study and develop other promising treatments,” she said.

The trial was coordinated by the Montreal Heart Institute and funded by the government of Quebec; the National Heart, Lung, and Blood Institute of the National Institutes of Health; Montreal philanthropist Sophie Desmarais, and the COVID-19 Therapeutics Accelerator launched by the Bill & Melinda Gates Foundation, Wellcome, and Mastercard. CGI, Dacima, and Pharmascience of Montreal were also collaborators. Dr. Glatt reported no conflicts of interest. Dr. Boulware reported receiving $18 in food and beverages from Gilead Sciences in 2018.
 

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

Science by press release and preprint has cooled clinician enthusiasm for the use of colchicine in nonhospitalized patients with COVID-19, despite a pressing need for early treatments.

Photo by Jimmy Hamelin

As previously reported by this news organization, a Jan. 22 press release announced that the massive ColCORONA study missed its primary endpoint of hospitalization or death among 4,488 newly diagnosed patients at increased risk for hospitalization.

But it also touted that use of the anti-inflammatory drug significantly reduced the primary endpoint in 4,159 of those patients with polymerase chain reaction–confirmed COVID and led to reductions of 25%, 50%, and 44%, respectively, for hospitalizations, ventilations, and death.

Lead investigator Jean-Claude Tardif, MD, director of the Montreal Heart Institute Research Centre, deemed the findings a “medical breakthrough.”

When the preprint released a few days later, however, newly revealed confidence intervals showed colchicine did not meaningfully reduce the need for mechanical ventilation (odds ratio, 0.50; 95% confidence interval, 0.23-1.07) or death alone (OR, 0.56; 95% CI, 0.19-1.66).

Further, the significant benefit on the primary outcome came at the cost of a fivefold increase in pulmonary embolism (11 vs. 2; P = .01), which was not mentioned in the press release.

“Whether this represents a real phenomenon or simply the play of chance is not known,” Dr. Tardif and colleagues noted later in the preprint.

“I read the preprint on colchicine and I have so many questions,” Aaron E. Glatt, MD, spokesperson for the Infectious Diseases Society of America and chief of infectious diseases, Mount Sinai South Nassau, Hewlett, N.Y., said in an interview. “I’ve been burned too many times with COVID and prefer to see better data.

“People sometimes say if you wait for perfect data, people are going to die,” he said. “Yeah, but we have no idea if people are going to die from getting this drug more than not getting it. That’s what concerns me. How many pulmonary emboli are going to be fatal versus the slight benefit that the study showed?”

The pushback to the non–peer-reviewed data on social media and via emails was so strong that Dr. Tardif posted a nearly 2,000-word letter responding to the many questions at play.

Chief among them was why the trial, originally planned for 6,000 patients, was stopped early by the investigators without consultation with the data safety monitoring board (DSMB).

The explanation in the letter that logistical issues like running the study call center, budget constraints, and a perceived need to quickly communicate the results left some calling foul that the study wasn’t allowed to finish and come to a more definitive conclusion.

“I can be a little bit sympathetic to their cause but at the same time the DSMB should have said no,” said David Boulware, MD, MPH, who led a recent hydroxychloroquine trial in COVID-19. “The problem is we’re sort of left in limbo, where some people kind of believe it and some say it’s not really a thing. So it’s not really moving the needle, as far as guidelines go.”

Indeed, a Twitter poll by cardiologist James Januzzi Jr., MD, captured the uncertainty, with 28% of respondents saying the trial was “neutral,” 58% saying “maybe but meh,” and 14% saying “colchicine for all.”

Another poll cheekily asked whether ColCORONA was the Gamestop/Reddit equivalent of COVID.

“The press release really didn’t help things because it very much oversold the effect. That, I think, poisoned the well,” said Dr. Boulware, professor of medicine in infectious diseases at the University of Minnesota, Minneapolis.

“The question I’m left with is not whether colchicine works, but who does it work in,” he said. “That’s really the fundamental question because it does seem that there are probably high-risk groups in their trial and others where they benefit, whereas other groups don’t benefit. In the subgroup analysis, there was absolutely no beneficial effect in women.”

According to the authors, the number needed to treat to prevent one death or hospitalization was 71 overall, but 29 for patients with diabetes, 31 for those aged 70 years and older, 53 for patients with respiratory disease, and 25 for those with coronary disease or heart failure.

Men are at higher risk overall for poor outcomes. But “the authors didn’t present a multivariable analysis, so it is unclear if another factor, such as a differential prevalence of smoking or cardiovascular risk factors, contributed to the differential benefit,” Rachel Bender Ignacio, MD, MPH, infectious disease specialist, University of Washington, Seattle, said in an interview.

Importantly, in this pragmatic study, duration and severity of symptoms were not reported, observed Dr. Bender Ignacio, who is also a STOP-COVID-2 investigator. “We don’t yet have data as to whether colchicine shortens duration or severity of symptoms or prevents long COVID, so we need more data on that.”

The overall risk for serious adverse events was lower in the colchicine group, but the difference in pulmonary embolism (PE) was striking, she said. This could be caused by a real biologic effect, or it’s possible that persons with shortness of breath and hypoxia, without evident viral pneumonia on chest x-ray after a positive COVID-19 test, were more likely to receive a CT-PE study.

The press release also failed to include information, later noted in the preprint, that the MHI has submitted two patents related to colchicine: “Methods of treating a coronavirus infection using colchicine” and “Early administration of low-dose colchicine after myocardial infarction.”

Reached for clarification, MHI communications adviser Camille Turbide said in an interview that the first patent “simply refers to the novel concept of preventing complications of COVID-19, such as admission to the hospital, with colchicine as tested in the ColCORONA study.”

The second patent, she said, refers to the “novel concept that administering colchicine early after a major adverse cardiovascular event is better than waiting several days,” as supported by the COLCOT study, which Dr. Tardif also led.

The patents are being reviewed by authorities and “Dr. Tardif has waived his rights in these patents and does not stand to benefit financially at all if colchicine becomes used as a treatment for COVID-19,” Ms. Turbide said.

Dr. Tardif did not respond to interview requests for this story. Dr. Glatt said conflicts of interest must be assessed and are “something that is of great concern in any scientific study.”

Cardiologist Steve Nissen, MD, of the Cleveland Clinic said in an interview that, “despite the negative results, the study does suggest that colchicine might have a benefit and should be studied in future trials. These findings are not sufficient evidence to suggest use of the drug in patients infected with COVID-19.”

He noted that adverse effects like diarrhea were expected but that the excess PE was unexpected and needs greater clarification.

“Stopping the trial for administrative reasons is puzzling and undermined the ability of the trial to give a reliable answer,” Dr. Nissen said. “This is a reasonable pilot study that should be viewed as hypothesis generating but inconclusive.”

Several sources said a new trial is unlikely, particularly given the cost and 28 trials already evaluating colchicine. Among these are RECOVERY and COLCOVID, testing whether colchicine can reduce the duration of hospitalization or death in hospitalized patients with COVID-19.

Because there are so many trials ongoing right now, including for antivirals and other immunomodulators, it’s important that, if colchicine comes to routine clinical use, it provides access to treatment for those not able or willing to access clinical trials, rather than impeding clinical trial enrollment, Dr. Bender Ignacio suggested.

“We have already learned the lesson in the pandemic that early adoption of potentially promising therapies can negatively impact our ability to study and develop other promising treatments,” she said.

The trial was coordinated by the Montreal Heart Institute and funded by the government of Quebec; the National Heart, Lung, and Blood Institute of the National Institutes of Health; Montreal philanthropist Sophie Desmarais, and the COVID-19 Therapeutics Accelerator launched by the Bill & Melinda Gates Foundation, Wellcome, and Mastercard. CGI, Dacima, and Pharmascience of Montreal were also collaborators. Dr. Glatt reported no conflicts of interest. Dr. Boulware reported receiving $18 in food and beverages from Gilead Sciences in 2018.
 

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

A meta-analysis of two randomized studies evaluating patent foramen ovale (PFO) closure as a treatment strategy for migraine has shown significant benefits in several key endpoints, prompting the authors to conclude the approach warrants reevaluation.
 

The pooled analysis of patient-level data from the PRIMA and PREMIUM studies, both of which evaluated the Amplatzer PFO Occluder device (Abbott Vascular), showed that PFO closure significantly reduced the mean number of monthly migraine days and monthly migraine attacks and resulted in a greater number of patients who experienced complete migraine cessation.

The study, led by Mohammad K. Mojadidi, MD, Virginia Commonwealth University, Richmond, was published online in the Journal of the American College of Cardiology on Feb. 8, 2021.

Commenting on the article, the coauthor of an accompanying editorial, Zubair Ahmed, MD, of the Cleveland Clinic said the meta-analysis gave some useful new information but is not enough to recommend PFO closure routinely for patients with migraine.

“This meta-analysis looked at different endpoints that are more relevant to current clinical practice than those in the two original studies, and the results show that we shouldn’t rule out PFO closure as a treatment strategy for some migraine patients,” Dr. Ahmed stated. “But we’re still not sure exactly which patients are most likely to benefit from this approach, and we need additional studies to gain more understanding on that.”

The study authors noted that there is an established link between the presence of PFO and migraine, especially migraine with aura. In observational studies of PFO closure for cryptogenic stroke, the vast majority of patients who also had migraine reported a more than 50% reduction in migraine days per month after PFO closure.

However, two recent randomized clinical trials evaluating the Amplatzer PFO Occluder device for reducing the frequency and duration of episodic migraine headaches did not meet their respective primary endpoints, although they did show significant benefit of PFO closure in most of their secondary endpoints.

The current meta-analysis pooled individual participant data from the two trials to increase the power to detect the effect of percutaneous PFO closure for treating patients with episodic migraine compared with medical therapy alone.

In the two studies including a total of 337 patients, 176 were randomized to PFO closure and 161 to medical treatment only. At 12 months, three of the four efficacy endpoints evaluated in the meta-analysis were significantly reduced in the PFO-closure group. These were mean reduction of monthly migraine days (–3.1 days vs. –1.9 days; P = .02), mean reduction of monthly migraine attacks (–2.0 vs. –1.4; P = .01), and number of patients who experienced complete cessation of migraine (9% vs. 0.7%; P < .001).

The responder rate, defined as more than a 50% reduction in migraine attacks, showed a trend towards an increase in the PFO-closure group but did not achieve statistical significance (38% vs. 29%; P = .13).  

For the safety analysis, nine procedure-related and four device-related adverse events occurred in 245 patients who eventually received devices. All events were transient and resolved.
 

Better effect in patients with aura

Patients with migraine with aura, in particular frequent aura, had a significantly greater reduction in migraine days and a higher incidence of complete migraine cessation following PFO closure versus no closure, the authors reported.

In those without aura, PFO closure did not significantly reduce migraine days or improve complete headache cessation. However, some patients without aura did respond to PFO closure, which was statistically significant for reduction of migraine attacks (–2.0 vs. –1.0; P = .03).

“The interaction between the brain that is susceptible to migraine and the plethora of potential triggers is complex. A PFO may be the potential pathway for a variety of chemical triggers, such as serotonin from platelets, and although less frequent, some people with migraine without aura may trigger their migraine through this mechanism,” the researchers suggested. This hypothesis will be tested in the RELIEF trial, which is now being planned.

In the accompanying editorial, Dr. Ahmed and coauthor Robert J. Sommer, MD, Columbia University Medical Center, New York, pointed out that the meta-analysis demonstrates benefit of PFO closure in the migraine population for the first time.

“Moreover, the investigators defined a population of patients who may benefit most from PFO closure, those with migraine with frequent aura, suggesting that these may be different physiologically than other migraine subtypes. The analysis also places the PRIMA and PREMIUM outcomes in the context of endpoints that are more practical and are more commonly assessed in current clinical trials,” the editorialists noted.
 

Many unanswered questions

But the editorialists highlighted several significant limitations of the analysis, including “pooling of patient cohorts, methods, and outcome measures that might not be entirely comparable,” which they say could have introduced bias.

They also pointed out that the underlying pathophysiological mechanism linking migraine symptoms to PFO remains unknown. They explain that the mechanism is thought to involve the right-to-left passage of systemic venous blood, with some component – which would normally be eliminated or reduced on passage through the pulmonary vasculature – reaching the cerebral circulation via the PFO in supranormal concentrations and acting as a trigger for migraine activity in patients with susceptible brains.

But not all patients with migraine who have PFO benefit from PFO closure, they noted, and therefore presumably have PFO-unrelated migraines. There is no verified way to distinguish between these two groups at present.

“Once we learn to identify the subset of migraine patients in whom PFOs are actually causal of headache symptoms, screening and treatment of PFO for migraine can become a reality,” they wrote.

Although the meta-analysis is a step in the right direction, “it is not a home run,” Dr. Ahmed elaborated. “This was a post hoc analysis of two studies, neither of which showed significant benefits on their primary endpoints. That weakens the findings somewhat.”

He added: “At present, PFO closure is not routinely recommended as a migraine treatment strategy as we haven’t been sure which patients are most likely to benefit. And while this meta-analysis suggests patients with aura may be more likely to benefit, one quarter of patients without aura in the PREMIUM trial responded to PFO closure, so it’s not just about aura.

“There are still many unanswered questions.

“I don’t think the new information from this meta-analysis is enough to persuade me to change my practice, but it is a small building block in the overall picture and suggests this may be a suitable strategy for some patients in future,” he concluded.

The study had no outside funding. Participant-level data were provided by Abbott. Several coauthors were on the steering committee for the PREMIUM or PRIMA trials. Dr. Ahmed reported receiving consulting fees from, Amgen, AbbVie, electroCore, and Eli Lilly; serving on advisory boards for Amgen and Supernus; serving as a speaker for AbbVie; and receiving funding for an investigator-initiated trial from Teva and Eli Lilly.

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

A meta-analysis of two randomized studies evaluating patent foramen ovale (PFO) closure as a treatment strategy for migraine has shown significant benefits in several key endpoints, prompting the authors to conclude the approach warrants reevaluation.
 

The pooled analysis of patient-level data from the PRIMA and PREMIUM studies, both of which evaluated the Amplatzer PFO Occluder device (Abbott Vascular), showed that PFO closure significantly reduced the mean number of monthly migraine days and monthly migraine attacks and resulted in a greater number of patients who experienced complete migraine cessation.

The study, led by Mohammad K. Mojadidi, MD, Virginia Commonwealth University, Richmond, was published online in the Journal of the American College of Cardiology on Feb. 8, 2021.

Commenting on the article, the coauthor of an accompanying editorial, Zubair Ahmed, MD, of the Cleveland Clinic said the meta-analysis gave some useful new information but is not enough to recommend PFO closure routinely for patients with migraine.

“This meta-analysis looked at different endpoints that are more relevant to current clinical practice than those in the two original studies, and the results show that we shouldn’t rule out PFO closure as a treatment strategy for some migraine patients,” Dr. Ahmed stated. “But we’re still not sure exactly which patients are most likely to benefit from this approach, and we need additional studies to gain more understanding on that.”

The study authors noted that there is an established link between the presence of PFO and migraine, especially migraine with aura. In observational studies of PFO closure for cryptogenic stroke, the vast majority of patients who also had migraine reported a more than 50% reduction in migraine days per month after PFO closure.

However, two recent randomized clinical trials evaluating the Amplatzer PFO Occluder device for reducing the frequency and duration of episodic migraine headaches did not meet their respective primary endpoints, although they did show significant benefit of PFO closure in most of their secondary endpoints.

The current meta-analysis pooled individual participant data from the two trials to increase the power to detect the effect of percutaneous PFO closure for treating patients with episodic migraine compared with medical therapy alone.

In the two studies including a total of 337 patients, 176 were randomized to PFO closure and 161 to medical treatment only. At 12 months, three of the four efficacy endpoints evaluated in the meta-analysis were significantly reduced in the PFO-closure group. These were mean reduction of monthly migraine days (–3.1 days vs. –1.9 days; P = .02), mean reduction of monthly migraine attacks (–2.0 vs. –1.4; P = .01), and number of patients who experienced complete cessation of migraine (9% vs. 0.7%; P < .001).

The responder rate, defined as more than a 50% reduction in migraine attacks, showed a trend towards an increase in the PFO-closure group but did not achieve statistical significance (38% vs. 29%; P = .13).  

For the safety analysis, nine procedure-related and four device-related adverse events occurred in 245 patients who eventually received devices. All events were transient and resolved.
 

Better effect in patients with aura

Patients with migraine with aura, in particular frequent aura, had a significantly greater reduction in migraine days and a higher incidence of complete migraine cessation following PFO closure versus no closure, the authors reported.

In those without aura, PFO closure did not significantly reduce migraine days or improve complete headache cessation. However, some patients without aura did respond to PFO closure, which was statistically significant for reduction of migraine attacks (–2.0 vs. –1.0; P = .03).

“The interaction between the brain that is susceptible to migraine and the plethora of potential triggers is complex. A PFO may be the potential pathway for a variety of chemical triggers, such as serotonin from platelets, and although less frequent, some people with migraine without aura may trigger their migraine through this mechanism,” the researchers suggested. This hypothesis will be tested in the RELIEF trial, which is now being planned.

In the accompanying editorial, Dr. Ahmed and coauthor Robert J. Sommer, MD, Columbia University Medical Center, New York, pointed out that the meta-analysis demonstrates benefit of PFO closure in the migraine population for the first time.

“Moreover, the investigators defined a population of patients who may benefit most from PFO closure, those with migraine with frequent aura, suggesting that these may be different physiologically than other migraine subtypes. The analysis also places the PRIMA and PREMIUM outcomes in the context of endpoints that are more practical and are more commonly assessed in current clinical trials,” the editorialists noted.
 

Many unanswered questions

But the editorialists highlighted several significant limitations of the analysis, including “pooling of patient cohorts, methods, and outcome measures that might not be entirely comparable,” which they say could have introduced bias.

They also pointed out that the underlying pathophysiological mechanism linking migraine symptoms to PFO remains unknown. They explain that the mechanism is thought to involve the right-to-left passage of systemic venous blood, with some component – which would normally be eliminated or reduced on passage through the pulmonary vasculature – reaching the cerebral circulation via the PFO in supranormal concentrations and acting as a trigger for migraine activity in patients with susceptible brains.

But not all patients with migraine who have PFO benefit from PFO closure, they noted, and therefore presumably have PFO-unrelated migraines. There is no verified way to distinguish between these two groups at present.

“Once we learn to identify the subset of migraine patients in whom PFOs are actually causal of headache symptoms, screening and treatment of PFO for migraine can become a reality,” they wrote.

Although the meta-analysis is a step in the right direction, “it is not a home run,” Dr. Ahmed elaborated. “This was a post hoc analysis of two studies, neither of which showed significant benefits on their primary endpoints. That weakens the findings somewhat.”

He added: “At present, PFO closure is not routinely recommended as a migraine treatment strategy as we haven’t been sure which patients are most likely to benefit. And while this meta-analysis suggests patients with aura may be more likely to benefit, one quarter of patients without aura in the PREMIUM trial responded to PFO closure, so it’s not just about aura.

“There are still many unanswered questions.

“I don’t think the new information from this meta-analysis is enough to persuade me to change my practice, but it is a small building block in the overall picture and suggests this may be a suitable strategy for some patients in future,” he concluded.

The study had no outside funding. Participant-level data were provided by Abbott. Several coauthors were on the steering committee for the PREMIUM or PRIMA trials. Dr. Ahmed reported receiving consulting fees from, Amgen, AbbVie, electroCore, and Eli Lilly; serving on advisory boards for Amgen and Supernus; serving as a speaker for AbbVie; and receiving funding for an investigator-initiated trial from Teva and Eli Lilly.

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

A meta-analysis of two randomized studies evaluating patent foramen ovale (PFO) closure as a treatment strategy for migraine has shown significant benefits in several key endpoints, prompting the authors to conclude the approach warrants reevaluation.
 

The pooled analysis of patient-level data from the PRIMA and PREMIUM studies, both of which evaluated the Amplatzer PFO Occluder device (Abbott Vascular), showed that PFO closure significantly reduced the mean number of monthly migraine days and monthly migraine attacks and resulted in a greater number of patients who experienced complete migraine cessation.

The study, led by Mohammad K. Mojadidi, MD, Virginia Commonwealth University, Richmond, was published online in the Journal of the American College of Cardiology on Feb. 8, 2021.

Commenting on the article, the coauthor of an accompanying editorial, Zubair Ahmed, MD, of the Cleveland Clinic said the meta-analysis gave some useful new information but is not enough to recommend PFO closure routinely for patients with migraine.

“This meta-analysis looked at different endpoints that are more relevant to current clinical practice than those in the two original studies, and the results show that we shouldn’t rule out PFO closure as a treatment strategy for some migraine patients,” Dr. Ahmed stated. “But we’re still not sure exactly which patients are most likely to benefit from this approach, and we need additional studies to gain more understanding on that.”

The study authors noted that there is an established link between the presence of PFO and migraine, especially migraine with aura. In observational studies of PFO closure for cryptogenic stroke, the vast majority of patients who also had migraine reported a more than 50% reduction in migraine days per month after PFO closure.

However, two recent randomized clinical trials evaluating the Amplatzer PFO Occluder device for reducing the frequency and duration of episodic migraine headaches did not meet their respective primary endpoints, although they did show significant benefit of PFO closure in most of their secondary endpoints.

The current meta-analysis pooled individual participant data from the two trials to increase the power to detect the effect of percutaneous PFO closure for treating patients with episodic migraine compared with medical therapy alone.

In the two studies including a total of 337 patients, 176 were randomized to PFO closure and 161 to medical treatment only. At 12 months, three of the four efficacy endpoints evaluated in the meta-analysis were significantly reduced in the PFO-closure group. These were mean reduction of monthly migraine days (–3.1 days vs. –1.9 days; P = .02), mean reduction of monthly migraine attacks (–2.0 vs. –1.4; P = .01), and number of patients who experienced complete cessation of migraine (9% vs. 0.7%; P < .001).

The responder rate, defined as more than a 50% reduction in migraine attacks, showed a trend towards an increase in the PFO-closure group but did not achieve statistical significance (38% vs. 29%; P = .13).  

For the safety analysis, nine procedure-related and four device-related adverse events occurred in 245 patients who eventually received devices. All events were transient and resolved.
 

Better effect in patients with aura

Patients with migraine with aura, in particular frequent aura, had a significantly greater reduction in migraine days and a higher incidence of complete migraine cessation following PFO closure versus no closure, the authors reported.

In those without aura, PFO closure did not significantly reduce migraine days or improve complete headache cessation. However, some patients without aura did respond to PFO closure, which was statistically significant for reduction of migraine attacks (–2.0 vs. –1.0; P = .03).

“The interaction between the brain that is susceptible to migraine and the plethora of potential triggers is complex. A PFO may be the potential pathway for a variety of chemical triggers, such as serotonin from platelets, and although less frequent, some people with migraine without aura may trigger their migraine through this mechanism,” the researchers suggested. This hypothesis will be tested in the RELIEF trial, which is now being planned.

In the accompanying editorial, Dr. Ahmed and coauthor Robert J. Sommer, MD, Columbia University Medical Center, New York, pointed out that the meta-analysis demonstrates benefit of PFO closure in the migraine population for the first time.

“Moreover, the investigators defined a population of patients who may benefit most from PFO closure, those with migraine with frequent aura, suggesting that these may be different physiologically than other migraine subtypes. The analysis also places the PRIMA and PREMIUM outcomes in the context of endpoints that are more practical and are more commonly assessed in current clinical trials,” the editorialists noted.
 

Many unanswered questions

But the editorialists highlighted several significant limitations of the analysis, including “pooling of patient cohorts, methods, and outcome measures that might not be entirely comparable,” which they say could have introduced bias.

They also pointed out that the underlying pathophysiological mechanism linking migraine symptoms to PFO remains unknown. They explain that the mechanism is thought to involve the right-to-left passage of systemic venous blood, with some component – which would normally be eliminated or reduced on passage through the pulmonary vasculature – reaching the cerebral circulation via the PFO in supranormal concentrations and acting as a trigger for migraine activity in patients with susceptible brains.

But not all patients with migraine who have PFO benefit from PFO closure, they noted, and therefore presumably have PFO-unrelated migraines. There is no verified way to distinguish between these two groups at present.

“Once we learn to identify the subset of migraine patients in whom PFOs are actually causal of headache symptoms, screening and treatment of PFO for migraine can become a reality,” they wrote.

Although the meta-analysis is a step in the right direction, “it is not a home run,” Dr. Ahmed elaborated. “This was a post hoc analysis of two studies, neither of which showed significant benefits on their primary endpoints. That weakens the findings somewhat.”

He added: “At present, PFO closure is not routinely recommended as a migraine treatment strategy as we haven’t been sure which patients are most likely to benefit. And while this meta-analysis suggests patients with aura may be more likely to benefit, one quarter of patients without aura in the PREMIUM trial responded to PFO closure, so it’s not just about aura.

“There are still many unanswered questions.

“I don’t think the new information from this meta-analysis is enough to persuade me to change my practice, but it is a small building block in the overall picture and suggests this may be a suitable strategy for some patients in future,” he concluded.

The study had no outside funding. Participant-level data were provided by Abbott. Several coauthors were on the steering committee for the PREMIUM or PRIMA trials. Dr. Ahmed reported receiving consulting fees from, Amgen, AbbVie, electroCore, and Eli Lilly; serving on advisory boards for Amgen and Supernus; serving as a speaker for AbbVie; and receiving funding for an investigator-initiated trial from Teva and Eli Lilly.

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

Large numbers of COVID-19 cases have been undetected and unreported, which has resulted in severe undercounting of the total number of people who have been infected during the pandemic, according to a new study published Monday in the journal PLOS ONE.

In the United States, the number of COVID-19 cases is likely three times that of reported cases. According to the study, more than 71 million Americans have contracted the virus during the pandemic, and 7 million were infected or potentially contagious last week.

Public health officials rely on case counts to guide decisions, so the undercounting should be considered while trying to end the pandemic.

“The estimates of actual infections reveal for the first time the true severity of COVID-19 across the U.S. and in countries worldwide,” Jungsik Noh, PhD, a bioinformatics professor at the University of Texas Southwestern Medical Center, said in a statement.

Dr. Noh and colleague Gaudenz Danuser created a computational model that uses machine-learning strategies to estimate the actual number of daily cases in the United States and the 50 most-infected countries.

The model pulls data from the Johns Hopkins University database and the COVID Tracking Project, as well as large-scale surveys conducted by the CDC and several states. The algorithm uses the number of reported deaths, which is thought to be more accurate than the number of lab-confirmed cases, as the basis for calculations.

In 25 of the 50 countries, the “actual” cumulative cases were estimated to be 5-20 times greater than the confirmed cases. In the United States, Belgium, and Brazil, about 10% of the population has contracted the coronavirus, according to the model. At the beginning of February, about 11% of the population in Pennsylvania had current infections, which was the highest rate of any state. About 0.15% of residents in Minnesota had infections, and about 2.5% of residents in New York and Texas had infections.

“Knowing the true severity in different regions will help us effectively fight against the virus spreading,” Dr. Noh said. “The currently infected population is the cause of future infections and deaths. Its actual size in a region is a crucial variable required when determining the severity of COVID-19 and building strategies against regional outbreaks.”

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

Large numbers of COVID-19 cases have been undetected and unreported, which has resulted in severe undercounting of the total number of people who have been infected during the pandemic, according to a new study published Monday in the journal PLOS ONE.

In the United States, the number of COVID-19 cases is likely three times that of reported cases. According to the study, more than 71 million Americans have contracted the virus during the pandemic, and 7 million were infected or potentially contagious last week.

Public health officials rely on case counts to guide decisions, so the undercounting should be considered while trying to end the pandemic.

“The estimates of actual infections reveal for the first time the true severity of COVID-19 across the U.S. and in countries worldwide,” Jungsik Noh, PhD, a bioinformatics professor at the University of Texas Southwestern Medical Center, said in a statement.

Dr. Noh and colleague Gaudenz Danuser created a computational model that uses machine-learning strategies to estimate the actual number of daily cases in the United States and the 50 most-infected countries.

The model pulls data from the Johns Hopkins University database and the COVID Tracking Project, as well as large-scale surveys conducted by the CDC and several states. The algorithm uses the number of reported deaths, which is thought to be more accurate than the number of lab-confirmed cases, as the basis for calculations.

In 25 of the 50 countries, the “actual” cumulative cases were estimated to be 5-20 times greater than the confirmed cases. In the United States, Belgium, and Brazil, about 10% of the population has contracted the coronavirus, according to the model. At the beginning of February, about 11% of the population in Pennsylvania had current infections, which was the highest rate of any state. About 0.15% of residents in Minnesota had infections, and about 2.5% of residents in New York and Texas had infections.

“Knowing the true severity in different regions will help us effectively fight against the virus spreading,” Dr. Noh said. “The currently infected population is the cause of future infections and deaths. Its actual size in a region is a crucial variable required when determining the severity of COVID-19 and building strategies against regional outbreaks.”

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

Large numbers of COVID-19 cases have been undetected and unreported, which has resulted in severe undercounting of the total number of people who have been infected during the pandemic, according to a new study published Monday in the journal PLOS ONE.

In the United States, the number of COVID-19 cases is likely three times that of reported cases. According to the study, more than 71 million Americans have contracted the virus during the pandemic, and 7 million were infected or potentially contagious last week.

Public health officials rely on case counts to guide decisions, so the undercounting should be considered while trying to end the pandemic.

“The estimates of actual infections reveal for the first time the true severity of COVID-19 across the U.S. and in countries worldwide,” Jungsik Noh, PhD, a bioinformatics professor at the University of Texas Southwestern Medical Center, said in a statement.

Dr. Noh and colleague Gaudenz Danuser created a computational model that uses machine-learning strategies to estimate the actual number of daily cases in the United States and the 50 most-infected countries.

The model pulls data from the Johns Hopkins University database and the COVID Tracking Project, as well as large-scale surveys conducted by the CDC and several states. The algorithm uses the number of reported deaths, which is thought to be more accurate than the number of lab-confirmed cases, as the basis for calculations.

In 25 of the 50 countries, the “actual” cumulative cases were estimated to be 5-20 times greater than the confirmed cases. In the United States, Belgium, and Brazil, about 10% of the population has contracted the coronavirus, according to the model. At the beginning of February, about 11% of the population in Pennsylvania had current infections, which was the highest rate of any state. About 0.15% of residents in Minnesota had infections, and about 2.5% of residents in New York and Texas had infections.

“Knowing the true severity in different regions will help us effectively fight against the virus spreading,” Dr. Noh said. “The currently infected population is the cause of future infections and deaths. Its actual size in a region is a crucial variable required when determining the severity of COVID-19 and building strategies against regional outbreaks.”

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

In outpatients with COVID-19, peginterferon lambda has the potential to prevent clinical deterioration and shorten the duration of viral shedding, according to results of a double-blind, placebo-controlled trial (NCT04354259).

Reductions in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA were greater with peginterferon lambda than with placebo from day 3 onward in the phase 2 study led by Jordan J. Feld, MD, of the Toronto Centre for Liver Disease. The findings were reported in The Lancet Respiratory Medicine.
 

Fewer side effects

To date in randomized clinical trials, efficacy in treatment of COVID-19 has been shown only for remdesivir and dexamethasone in hospitalized patients, and in an interim analysis of accelerated viral clearance for a monoclonal antibody infusion in outpatients.

Activity against respiratory pathogens has been demonstrated for interferon lambda-1, a type III interferon shown to be involved in innate antiviral responses. Interferons, Dr. Feld and coauthors stated, drive induction of genes with antiviral, antiproliferative and immunoregulatory properties, and early treatment with interferons might halt clinical progression and shorten the duration of viral shedding with reduced onward transmission. In addition, interferon lambdas (type III) use a distinct receptor complex with high expression levels limited to epithelial cells in the lung, liver, and intestine, leading to fewer side effects than other interferons, including avoiding risk of promoting cytokine storm syndrome.

The researchers investigated peginterferon lambda safety and efficacy in treatment of patients with laboratory-confirmed, mild to moderate COVID-19. Sixty patients (median age 46 years, about 60% female, about 50% White) were recruited from outpatient testing centers at six institutions in Toronto, and referred to a single ambulatory site. Patients were randomly assigned 1:1 to a single subcutaneous injection of peginterferon lambda 180 mcg or placebo within 7 days of symptom onset or, if asymptomatic, of their first positive swab. Mean time from symptom onset to injection was about 4.5 days, and about 18.5% were asymptomatic. The primary outcome was the proportion of patients negative for SARS-CoV-2 RNA on day 7 after the injection.
 

Greater benefit with higher baseline load

A higher baseline SARS-CoV-2 RNA concentration found in the peginterferon lambda group was found to be significantly associated with day 7 clearance (odds ratio [OR] 0.69 [95% confidence interval 0.51-0.87]; P = ·001). In the peginterferon lambda group, also, the mean decline in SARS-CoV-2 RNA was significantly larger than in the placebo group across all time points (days 3, 5, 7, and14). While viral load decline was 0.81 log greater in the treatment group (P = .14) by day 3, viral load decline increased to 1.67 log copies per mL by day 5 (P = .013) and 2.42 log copies per mL by day 7 (P = .0041). At day 14, the viral decline was 1.77 log copies per mL larger in the peginterferon lambda group (P = .048). The investigators pointed out that the difference in viral load decline between groups was greater in patients with high baseline viral load (at or above 106 copies per mL). In the peginterferon lambda high baseline viral load group, the reduction was 7.17 log copies per mL, versus 4.92 log copies per mL in the placebo group (P = .004).
 

More patients SARS-CoV-2 RNA negative

By day 7, 80% of patients in the peginterferon lambda group were negative for SARS-CoV-2 RNA, compared with 63% in the placebo group (P = .15). After baseline load adjustment, however, the peginterferon lambda treatment was significantly associated with day 7 clearance (OR 4·12 [95% CI 1·15-16·73]; P = .029).
 

Respiratory symptoms improved faster

Most symptoms in both groups were mild to moderate, without difference in frequency or severity. While symptom improvement was generally similar over time for both groups, respiratory symptoms improved faster with peginterferon lambda, with the effect more pronounced in the high baseline viral load group (OR 5·88 (0·81-42·46; P =. 079).

Laboratory adverse events, similar for both groups, were mild.

“Peginterferon lambda has potential to prevent clinical deterioration and shorten duration of viral shedding,” the investigators concluded.

“This clinical trial is important” because it suggests that a single intravenous dose of peginterferon lambda administered to outpatients with a positive SARS-CoV-2 nasopharyngeal swab speeds reduction of SARS-CoV-2 viral load, David L. Bowton, MD, FCCP, professor emeritus, Wake Forest Baptist Health, Winston-Salem, N.C., said in an interview. He observed that the smaller viral load difference observed at day 14 likely reflects host immune responses.

Dr. Bowton also noted that two placebo group baseline characteristics (five placebo group patients with anti-SARS-CoV-2 S protein IgG antibodies; two times more undetectable SARS-CoV-2 RNA at baseline assessment) would tend to reduce differences between the peginterferon lambda and placebo groups. He added that the study findings were concordant with another phase 2 trial of hospitalized COVID-19 patients receiving inhaled interferon beta-1a.

“Thus, interferons may find a place in the treatment of COVID-19 and perhaps other severe viral illnesses,” Dr. Bowton said.

The study was funded by the Toronto COVID-19 Action Initiative, University of Toronto, and the Ontario First COVID-19 Rapid Research Fund, Toronto General & Western Hospital Foundation.

Dr. Bowton had no disclosures. Disclosures for Dr. Feld and coauthors are listed on the Lancet Respiratory Medicine website.

In outpatients with COVID-19, peginterferon lambda has the potential to prevent clinical deterioration and shorten the duration of viral shedding, according to results of a double-blind, placebo-controlled trial (NCT04354259).

Reductions in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA were greater with peginterferon lambda than with placebo from day 3 onward in the phase 2 study led by Jordan J. Feld, MD, of the Toronto Centre for Liver Disease. The findings were reported in The Lancet Respiratory Medicine.
 

Fewer side effects

To date in randomized clinical trials, efficacy in treatment of COVID-19 has been shown only for remdesivir and dexamethasone in hospitalized patients, and in an interim analysis of accelerated viral clearance for a monoclonal antibody infusion in outpatients.

Activity against respiratory pathogens has been demonstrated for interferon lambda-1, a type III interferon shown to be involved in innate antiviral responses. Interferons, Dr. Feld and coauthors stated, drive induction of genes with antiviral, antiproliferative and immunoregulatory properties, and early treatment with interferons might halt clinical progression and shorten the duration of viral shedding with reduced onward transmission. In addition, interferon lambdas (type III) use a distinct receptor complex with high expression levels limited to epithelial cells in the lung, liver, and intestine, leading to fewer side effects than other interferons, including avoiding risk of promoting cytokine storm syndrome.

The researchers investigated peginterferon lambda safety and efficacy in treatment of patients with laboratory-confirmed, mild to moderate COVID-19. Sixty patients (median age 46 years, about 60% female, about 50% White) were recruited from outpatient testing centers at six institutions in Toronto, and referred to a single ambulatory site. Patients were randomly assigned 1:1 to a single subcutaneous injection of peginterferon lambda 180 mcg or placebo within 7 days of symptom onset or, if asymptomatic, of their first positive swab. Mean time from symptom onset to injection was about 4.5 days, and about 18.5% were asymptomatic. The primary outcome was the proportion of patients negative for SARS-CoV-2 RNA on day 7 after the injection.
 

Greater benefit with higher baseline load

A higher baseline SARS-CoV-2 RNA concentration found in the peginterferon lambda group was found to be significantly associated with day 7 clearance (odds ratio [OR] 0.69 [95% confidence interval 0.51-0.87]; P = ·001). In the peginterferon lambda group, also, the mean decline in SARS-CoV-2 RNA was significantly larger than in the placebo group across all time points (days 3, 5, 7, and14). While viral load decline was 0.81 log greater in the treatment group (P = .14) by day 3, viral load decline increased to 1.67 log copies per mL by day 5 (P = .013) and 2.42 log copies per mL by day 7 (P = .0041). At day 14, the viral decline was 1.77 log copies per mL larger in the peginterferon lambda group (P = .048). The investigators pointed out that the difference in viral load decline between groups was greater in patients with high baseline viral load (at or above 106 copies per mL). In the peginterferon lambda high baseline viral load group, the reduction was 7.17 log copies per mL, versus 4.92 log copies per mL in the placebo group (P = .004).
 

More patients SARS-CoV-2 RNA negative

By day 7, 80% of patients in the peginterferon lambda group were negative for SARS-CoV-2 RNA, compared with 63% in the placebo group (P = .15). After baseline load adjustment, however, the peginterferon lambda treatment was significantly associated with day 7 clearance (OR 4·12 [95% CI 1·15-16·73]; P = .029).
 

Respiratory symptoms improved faster

Most symptoms in both groups were mild to moderate, without difference in frequency or severity. While symptom improvement was generally similar over time for both groups, respiratory symptoms improved faster with peginterferon lambda, with the effect more pronounced in the high baseline viral load group (OR 5·88 (0·81-42·46; P =. 079).

Laboratory adverse events, similar for both groups, were mild.

“Peginterferon lambda has potential to prevent clinical deterioration and shorten duration of viral shedding,” the investigators concluded.

“This clinical trial is important” because it suggests that a single intravenous dose of peginterferon lambda administered to outpatients with a positive SARS-CoV-2 nasopharyngeal swab speeds reduction of SARS-CoV-2 viral load, David L. Bowton, MD, FCCP, professor emeritus, Wake Forest Baptist Health, Winston-Salem, N.C., said in an interview. He observed that the smaller viral load difference observed at day 14 likely reflects host immune responses.

Dr. Bowton also noted that two placebo group baseline characteristics (five placebo group patients with anti-SARS-CoV-2 S protein IgG antibodies; two times more undetectable SARS-CoV-2 RNA at baseline assessment) would tend to reduce differences between the peginterferon lambda and placebo groups. He added that the study findings were concordant with another phase 2 trial of hospitalized COVID-19 patients receiving inhaled interferon beta-1a.

“Thus, interferons may find a place in the treatment of COVID-19 and perhaps other severe viral illnesses,” Dr. Bowton said.

The study was funded by the Toronto COVID-19 Action Initiative, University of Toronto, and the Ontario First COVID-19 Rapid Research Fund, Toronto General & Western Hospital Foundation.

Dr. Bowton had no disclosures. Disclosures for Dr. Feld and coauthors are listed on the Lancet Respiratory Medicine website.

In outpatients with COVID-19, peginterferon lambda has the potential to prevent clinical deterioration and shorten the duration of viral shedding, according to results of a double-blind, placebo-controlled trial (NCT04354259).

Reductions in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA were greater with peginterferon lambda than with placebo from day 3 onward in the phase 2 study led by Jordan J. Feld, MD, of the Toronto Centre for Liver Disease. The findings were reported in The Lancet Respiratory Medicine.
 

Fewer side effects

To date in randomized clinical trials, efficacy in treatment of COVID-19 has been shown only for remdesivir and dexamethasone in hospitalized patients, and in an interim analysis of accelerated viral clearance for a monoclonal antibody infusion in outpatients.

Activity against respiratory pathogens has been demonstrated for interferon lambda-1, a type III interferon shown to be involved in innate antiviral responses. Interferons, Dr. Feld and coauthors stated, drive induction of genes with antiviral, antiproliferative and immunoregulatory properties, and early treatment with interferons might halt clinical progression and shorten the duration of viral shedding with reduced onward transmission. In addition, interferon lambdas (type III) use a distinct receptor complex with high expression levels limited to epithelial cells in the lung, liver, and intestine, leading to fewer side effects than other interferons, including avoiding risk of promoting cytokine storm syndrome.

The researchers investigated peginterferon lambda safety and efficacy in treatment of patients with laboratory-confirmed, mild to moderate COVID-19. Sixty patients (median age 46 years, about 60% female, about 50% White) were recruited from outpatient testing centers at six institutions in Toronto, and referred to a single ambulatory site. Patients were randomly assigned 1:1 to a single subcutaneous injection of peginterferon lambda 180 mcg or placebo within 7 days of symptom onset or, if asymptomatic, of their first positive swab. Mean time from symptom onset to injection was about 4.5 days, and about 18.5% were asymptomatic. The primary outcome was the proportion of patients negative for SARS-CoV-2 RNA on day 7 after the injection.
 

Greater benefit with higher baseline load

A higher baseline SARS-CoV-2 RNA concentration found in the peginterferon lambda group was found to be significantly associated with day 7 clearance (odds ratio [OR] 0.69 [95% confidence interval 0.51-0.87]; P = ·001). In the peginterferon lambda group, also, the mean decline in SARS-CoV-2 RNA was significantly larger than in the placebo group across all time points (days 3, 5, 7, and14). While viral load decline was 0.81 log greater in the treatment group (P = .14) by day 3, viral load decline increased to 1.67 log copies per mL by day 5 (P = .013) and 2.42 log copies per mL by day 7 (P = .0041). At day 14, the viral decline was 1.77 log copies per mL larger in the peginterferon lambda group (P = .048). The investigators pointed out that the difference in viral load decline between groups was greater in patients with high baseline viral load (at or above 106 copies per mL). In the peginterferon lambda high baseline viral load group, the reduction was 7.17 log copies per mL, versus 4.92 log copies per mL in the placebo group (P = .004).
 

More patients SARS-CoV-2 RNA negative

By day 7, 80% of patients in the peginterferon lambda group were negative for SARS-CoV-2 RNA, compared with 63% in the placebo group (P = .15). After baseline load adjustment, however, the peginterferon lambda treatment was significantly associated with day 7 clearance (OR 4·12 [95% CI 1·15-16·73]; P = .029).
 

Respiratory symptoms improved faster

Most symptoms in both groups were mild to moderate, without difference in frequency or severity. While symptom improvement was generally similar over time for both groups, respiratory symptoms improved faster with peginterferon lambda, with the effect more pronounced in the high baseline viral load group (OR 5·88 (0·81-42·46; P =. 079).

Laboratory adverse events, similar for both groups, were mild.

“Peginterferon lambda has potential to prevent clinical deterioration and shorten duration of viral shedding,” the investigators concluded.

“This clinical trial is important” because it suggests that a single intravenous dose of peginterferon lambda administered to outpatients with a positive SARS-CoV-2 nasopharyngeal swab speeds reduction of SARS-CoV-2 viral load, David L. Bowton, MD, FCCP, professor emeritus, Wake Forest Baptist Health, Winston-Salem, N.C., said in an interview. He observed that the smaller viral load difference observed at day 14 likely reflects host immune responses.

Dr. Bowton also noted that two placebo group baseline characteristics (five placebo group patients with anti-SARS-CoV-2 S protein IgG antibodies; two times more undetectable SARS-CoV-2 RNA at baseline assessment) would tend to reduce differences between the peginterferon lambda and placebo groups. He added that the study findings were concordant with another phase 2 trial of hospitalized COVID-19 patients receiving inhaled interferon beta-1a.

“Thus, interferons may find a place in the treatment of COVID-19 and perhaps other severe viral illnesses,” Dr. Bowton said.

The study was funded by the Toronto COVID-19 Action Initiative, University of Toronto, and the Ontario First COVID-19 Rapid Research Fund, Toronto General & Western Hospital Foundation.

Dr. Bowton had no disclosures. Disclosures for Dr. Feld and coauthors are listed on the Lancet Respiratory Medicine website.

While 34 million adults in the United States have received a COVID-19 vaccine, children and teenagers are waiting at the back of the line, mostly ineligible for the authorized vaccines. That secondary status is rapidly changing though, as experts expect vaccinations of adolescents to begin by this summer.

The vaccinations can’t come soon enough for parents like Stacy Hillenburg, a developmental therapist in Aurora, Ill., whose 9-year-old son takes immunosuppressants because he had a heart transplant when he was 7 weeks old. Although school-age children aren’t yet included in clinical trials, if her 12- and 13-year-old daughters could get vaccinated, along with both parents, then the family could relax some of the protocols they currently follow to prevent infection.

Whenever they are around other people, even masked and socially distanced, they come home and immediately shower and change their clothes. So far, no one in the family has been infected with COVID, but the anxiety is ever-present. “I can’t wait for it to come out,” Ms. Hillenburg said of a pediatric COVID vaccine. “It will ease my mind so much.”

She isn’t alone in that anticipation. In the fall, the American Academy of Pediatrics and other pediatric vaccine experts urged faster action on pediatric vaccine trials and worried that children would be left behind as adults gained protection from COVID. But recent developments have eased those concerns.

“Over the next couple of months, we will be doing trials in an age-deescalation manner,” with studies moving gradually to younger children, Anthony S. Fauci, MD, chief medical adviser on COVID-19 to the president, said in a coronavirus response team briefing on Jan. 29. “So that hopefully, as we get to the late spring and summer, we will have children being able to be vaccinated.”

Pfizer completed enrollment of 2,259 teens aged 12-15 years in late January and expects to move forward with a separate pediatric trial of children aged 5-11 years by this spring, Keanna Ghazvini, senior associate for global media relations at Pfizer, said in an interview.

Enrollment in Moderna’s TeenCove study of adolescents ages 12-17 years began slowly in late December, but the pace has since picked up, said company spokesperson Colleen Hussey. “We continue to bring clinical trial sites online, and we are on track to provide updated data around mid-year 2021.” A trial extension in children 11 years and younger is expected to begin later in 2021.

Johnson & Johnson and AstraZeneca said they expect to begin adolescent trials in early 2021, according to data shared by the Advisory Committee on Immunization Practices. An interim analysis of J&J’s Janssen COVID-19 vaccine trial data, released on Jan. 29, showed it was 72% effective in US participants aged 18 years or older. AstraZeneca’s U.S. trial in adults is ongoing.
 

Easing the burden

Vaccination could lessen children’s risk of severe disease as well as the social and emotional burdens of the pandemic, says James Campbell, MD, a pediatric infectious disease specialist at the University of Maryland’s Center for Vaccine Development in Baltimore, which was involved in the Moderna and early-phase Pfizer trials. He coauthored a September 2020 article in Clinical Infectious Diseases titled: “Warp Speed for COVID-19 vaccines: Why are children stuck in neutral?”

The adolescent trials are a vital step to ensure timely vaccine access for teens and younger children. “It is reasonable, when you have limited vaccine, that your rollout goes to the highest priority and then moves to lower and lower priorities. In adults, we’re just saying: ‘Wait your turn,’ ” he said of the current vaccination effort. “If we didn’t have the [vaccine trial] data in children, we’d be saying: ‘You don’t have a turn.’ ”

As the pandemic has worn on, the burden on children has grown. As of Tuesday, 269 children had died of COVID-19. That is well above the highest annual death toll recorded during a regular flu season – 188 flu deaths among children and adolescents under 18 in the 2019-2020 and 2017-2018 flu seasons.

Children are less likely to transmit COVID-19 in their household than adults, according to a meta-analysis of 54 studies published in JAMA Network Open. But that does not necessarily mean children are less infectious, the authors said, noting that unmeasured factors could have affected the spread of infection among adults.

Moreover, children and adolescents need protection from COVID infection – and from the potential for severe disease or lingering effects – and, given that there are 74 million children and teens in the United States, their vaccination is an important part of stopping the pandemic, said Grace Lee, MD, professor of pediatrics at Stanford (Calif.) University, and cochair of ACIP’s COVID-19 Vaccine Safety Technical Subgroup.

“In order to interrupt transmission, I don’t see how we’re going to do that without vaccinating children and adolescents,” she said.

Dr. Lee said her 16-year-old daughter misses the normal teenage social life and is excited about getting the vaccine when she is eligible. (Adolescents without high-risk conditions are in the lowest vaccination tier, according to ACIP recommendations.) “There is truly individual protection to be gained,” Dr. Lee said.

She noted that researchers continue to assess the immune responses to the adult vaccines – even looking at immune characteristics of the small percentage of people who aren’t protected from infection – and that information helps in the evaluation of the pediatric immune responses. As the trials expand to younger children and infants, dosing will be a major focus. “How many doses do they need they need to receive the same immunity? Safety considerations will be critically important,” she said.
 

Teen trials underway

Pfizer/BioNTech extended its adult trial to 16- and 17-year-olds in October, which enabled older teens to be included in its emergency-use authorization. They and younger teens, ages 12-15, receive the same dose as adults.

The ongoing trials with Pfizer and Moderna vaccines are immunobridging trials, designed to study safety and immunogenicity. Investigators will compare the teens’ immune response with the findings from the larger adult trials. When the trials expand to school-age children (6-12 years), protocols call for testing the safety and immunogenicity of a half-dose vaccine as well as the full dose.

Children ages 2-5 years and infants and toddlers will be enrolled in future trials, studying safety and immunogenicity of full, half, or even quarter dosages. The Pediatric Research Equity Act of 2003 requires licensed vaccines to be tested for safety and efficacy in children, unless they are not appropriate for a pediatric population.

Demand for the teen trials has been strong. At Cincinnati Children’s Hospital Medical Center, 259 teenagers joined the Pfizer/BioNTech trial, but some teenagers were turned away when the trial’s national enrollment closed in late January.

“Many of the children are having no side effects, and if they are, they’re having the same [effects] as the young adults – local redness or pain, fatigue, and headaches,” said Robert Frenck, MD, director of the Cincinnati Children’s Gamble Program for Clinical Studies.

Parents may share some of the vaccine hesitancy that has affected adult vaccination. But that is balanced by the hope that vaccines will end the pandemic and usher in a new normal. “If it looks like [vaccines] will increase the likelihood of children returning to school safely, that may be a motivating factor,” Dr. Frenck said.

Cody Meissner, MD, chief of the pediatric infectious disease service at Tufts Medical Center, Boston, was initially cautious about the extension of vaccination to adolescents. A member of the Vaccine and Related Biological Products Advisory Committee, which evaluates data and makes recommendations to the Food and Drug Administration, Dr. Meissner initially abstained in the vote on the Pfizer/BioNTech emergency-use authorization for people 16 and older.

He noted that, at the time the committee reviewed the Pfizer vaccine, the company had data available for just 134 teenagers, half of whom received a placebo. But the vaccination of 34 million adults has provided robust data about the vaccine’s safety, and the trial expansion into adolescents is important.

“I’m comfortable with the way these trials are going now,” he said. “This is the way I was hoping they would go.”

Ms. Hillenburg is on the parent advisory board of Voices for Vaccines, an organization of parents supporting vaccination that is affiliated with the Task Force for Global Health, an Atlanta-based independent public health organization. Dr. Campbell’s institution has received funds to conduct clinical trials from the National Institutes of Health and several companies, including Merck, GlaxoSmithKline, Sanofi, Pfizer, and Moderna. He has served pro bono on many safety and data monitoring committees. Dr. Frenck’s institution is receiving funds to conduct the Pfizer trial. In the past 5 years, he has also participated in clinical trials for GlaxoSmithKline, Merck, and Meissa vaccines. Dr. Lee and Dr. Meissner disclosed no relevant financial relationships.

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

While 34 million adults in the United States have received a COVID-19 vaccine, children and teenagers are waiting at the back of the line, mostly ineligible for the authorized vaccines. That secondary status is rapidly changing though, as experts expect vaccinations of adolescents to begin by this summer.

The vaccinations can’t come soon enough for parents like Stacy Hillenburg, a developmental therapist in Aurora, Ill., whose 9-year-old son takes immunosuppressants because he had a heart transplant when he was 7 weeks old. Although school-age children aren’t yet included in clinical trials, if her 12- and 13-year-old daughters could get vaccinated, along with both parents, then the family could relax some of the protocols they currently follow to prevent infection.

Whenever they are around other people, even masked and socially distanced, they come home and immediately shower and change their clothes. So far, no one in the family has been infected with COVID, but the anxiety is ever-present. “I can’t wait for it to come out,” Ms. Hillenburg said of a pediatric COVID vaccine. “It will ease my mind so much.”

She isn’t alone in that anticipation. In the fall, the American Academy of Pediatrics and other pediatric vaccine experts urged faster action on pediatric vaccine trials and worried that children would be left behind as adults gained protection from COVID. But recent developments have eased those concerns.

“Over the next couple of months, we will be doing trials in an age-deescalation manner,” with studies moving gradually to younger children, Anthony S. Fauci, MD, chief medical adviser on COVID-19 to the president, said in a coronavirus response team briefing on Jan. 29. “So that hopefully, as we get to the late spring and summer, we will have children being able to be vaccinated.”

Pfizer completed enrollment of 2,259 teens aged 12-15 years in late January and expects to move forward with a separate pediatric trial of children aged 5-11 years by this spring, Keanna Ghazvini, senior associate for global media relations at Pfizer, said in an interview.

Enrollment in Moderna’s TeenCove study of adolescents ages 12-17 years began slowly in late December, but the pace has since picked up, said company spokesperson Colleen Hussey. “We continue to bring clinical trial sites online, and we are on track to provide updated data around mid-year 2021.” A trial extension in children 11 years and younger is expected to begin later in 2021.

Johnson & Johnson and AstraZeneca said they expect to begin adolescent trials in early 2021, according to data shared by the Advisory Committee on Immunization Practices. An interim analysis of J&J’s Janssen COVID-19 vaccine trial data, released on Jan. 29, showed it was 72% effective in US participants aged 18 years or older. AstraZeneca’s U.S. trial in adults is ongoing.
 

Easing the burden

Vaccination could lessen children’s risk of severe disease as well as the social and emotional burdens of the pandemic, says James Campbell, MD, a pediatric infectious disease specialist at the University of Maryland’s Center for Vaccine Development in Baltimore, which was involved in the Moderna and early-phase Pfizer trials. He coauthored a September 2020 article in Clinical Infectious Diseases titled: “Warp Speed for COVID-19 vaccines: Why are children stuck in neutral?”

The adolescent trials are a vital step to ensure timely vaccine access for teens and younger children. “It is reasonable, when you have limited vaccine, that your rollout goes to the highest priority and then moves to lower and lower priorities. In adults, we’re just saying: ‘Wait your turn,’ ” he said of the current vaccination effort. “If we didn’t have the [vaccine trial] data in children, we’d be saying: ‘You don’t have a turn.’ ”

As the pandemic has worn on, the burden on children has grown. As of Tuesday, 269 children had died of COVID-19. That is well above the highest annual death toll recorded during a regular flu season – 188 flu deaths among children and adolescents under 18 in the 2019-2020 and 2017-2018 flu seasons.

Children are less likely to transmit COVID-19 in their household than adults, according to a meta-analysis of 54 studies published in JAMA Network Open. But that does not necessarily mean children are less infectious, the authors said, noting that unmeasured factors could have affected the spread of infection among adults.

Moreover, children and adolescents need protection from COVID infection – and from the potential for severe disease or lingering effects – and, given that there are 74 million children and teens in the United States, their vaccination is an important part of stopping the pandemic, said Grace Lee, MD, professor of pediatrics at Stanford (Calif.) University, and cochair of ACIP’s COVID-19 Vaccine Safety Technical Subgroup.

“In order to interrupt transmission, I don’t see how we’re going to do that without vaccinating children and adolescents,” she said.

Dr. Lee said her 16-year-old daughter misses the normal teenage social life and is excited about getting the vaccine when she is eligible. (Adolescents without high-risk conditions are in the lowest vaccination tier, according to ACIP recommendations.) “There is truly individual protection to be gained,” Dr. Lee said.

She noted that researchers continue to assess the immune responses to the adult vaccines – even looking at immune characteristics of the small percentage of people who aren’t protected from infection – and that information helps in the evaluation of the pediatric immune responses. As the trials expand to younger children and infants, dosing will be a major focus. “How many doses do they need they need to receive the same immunity? Safety considerations will be critically important,” she said.
 

Teen trials underway

Pfizer/BioNTech extended its adult trial to 16- and 17-year-olds in October, which enabled older teens to be included in its emergency-use authorization. They and younger teens, ages 12-15, receive the same dose as adults.

The ongoing trials with Pfizer and Moderna vaccines are immunobridging trials, designed to study safety and immunogenicity. Investigators will compare the teens’ immune response with the findings from the larger adult trials. When the trials expand to school-age children (6-12 years), protocols call for testing the safety and immunogenicity of a half-dose vaccine as well as the full dose.

Children ages 2-5 years and infants and toddlers will be enrolled in future trials, studying safety and immunogenicity of full, half, or even quarter dosages. The Pediatric Research Equity Act of 2003 requires licensed vaccines to be tested for safety and efficacy in children, unless they are not appropriate for a pediatric population.

Demand for the teen trials has been strong. At Cincinnati Children’s Hospital Medical Center, 259 teenagers joined the Pfizer/BioNTech trial, but some teenagers were turned away when the trial’s national enrollment closed in late January.

“Many of the children are having no side effects, and if they are, they’re having the same [effects] as the young adults – local redness or pain, fatigue, and headaches,” said Robert Frenck, MD, director of the Cincinnati Children’s Gamble Program for Clinical Studies.

Parents may share some of the vaccine hesitancy that has affected adult vaccination. But that is balanced by the hope that vaccines will end the pandemic and usher in a new normal. “If it looks like [vaccines] will increase the likelihood of children returning to school safely, that may be a motivating factor,” Dr. Frenck said.

Cody Meissner, MD, chief of the pediatric infectious disease service at Tufts Medical Center, Boston, was initially cautious about the extension of vaccination to adolescents. A member of the Vaccine and Related Biological Products Advisory Committee, which evaluates data and makes recommendations to the Food and Drug Administration, Dr. Meissner initially abstained in the vote on the Pfizer/BioNTech emergency-use authorization for people 16 and older.

He noted that, at the time the committee reviewed the Pfizer vaccine, the company had data available for just 134 teenagers, half of whom received a placebo. But the vaccination of 34 million adults has provided robust data about the vaccine’s safety, and the trial expansion into adolescents is important.

“I’m comfortable with the way these trials are going now,” he said. “This is the way I was hoping they would go.”

Ms. Hillenburg is on the parent advisory board of Voices for Vaccines, an organization of parents supporting vaccination that is affiliated with the Task Force for Global Health, an Atlanta-based independent public health organization. Dr. Campbell’s institution has received funds to conduct clinical trials from the National Institutes of Health and several companies, including Merck, GlaxoSmithKline, Sanofi, Pfizer, and Moderna. He has served pro bono on many safety and data monitoring committees. Dr. Frenck’s institution is receiving funds to conduct the Pfizer trial. In the past 5 years, he has also participated in clinical trials for GlaxoSmithKline, Merck, and Meissa vaccines. Dr. Lee and Dr. Meissner disclosed no relevant financial relationships.

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

While 34 million adults in the United States have received a COVID-19 vaccine, children and teenagers are waiting at the back of the line, mostly ineligible for the authorized vaccines. That secondary status is rapidly changing though, as experts expect vaccinations of adolescents to begin by this summer.

The vaccinations can’t come soon enough for parents like Stacy Hillenburg, a developmental therapist in Aurora, Ill., whose 9-year-old son takes immunosuppressants because he had a heart transplant when he was 7 weeks old. Although school-age children aren’t yet included in clinical trials, if her 12- and 13-year-old daughters could get vaccinated, along with both parents, then the family could relax some of the protocols they currently follow to prevent infection.

Whenever they are around other people, even masked and socially distanced, they come home and immediately shower and change their clothes. So far, no one in the family has been infected with COVID, but the anxiety is ever-present. “I can’t wait for it to come out,” Ms. Hillenburg said of a pediatric COVID vaccine. “It will ease my mind so much.”

She isn’t alone in that anticipation. In the fall, the American Academy of Pediatrics and other pediatric vaccine experts urged faster action on pediatric vaccine trials and worried that children would be left behind as adults gained protection from COVID. But recent developments have eased those concerns.

“Over the next couple of months, we will be doing trials in an age-deescalation manner,” with studies moving gradually to younger children, Anthony S. Fauci, MD, chief medical adviser on COVID-19 to the president, said in a coronavirus response team briefing on Jan. 29. “So that hopefully, as we get to the late spring and summer, we will have children being able to be vaccinated.”

Pfizer completed enrollment of 2,259 teens aged 12-15 years in late January and expects to move forward with a separate pediatric trial of children aged 5-11 years by this spring, Keanna Ghazvini, senior associate for global media relations at Pfizer, said in an interview.

Enrollment in Moderna’s TeenCove study of adolescents ages 12-17 years began slowly in late December, but the pace has since picked up, said company spokesperson Colleen Hussey. “We continue to bring clinical trial sites online, and we are on track to provide updated data around mid-year 2021.” A trial extension in children 11 years and younger is expected to begin later in 2021.

Johnson & Johnson and AstraZeneca said they expect to begin adolescent trials in early 2021, according to data shared by the Advisory Committee on Immunization Practices. An interim analysis of J&J’s Janssen COVID-19 vaccine trial data, released on Jan. 29, showed it was 72% effective in US participants aged 18 years or older. AstraZeneca’s U.S. trial in adults is ongoing.
 

Easing the burden

Vaccination could lessen children’s risk of severe disease as well as the social and emotional burdens of the pandemic, says James Campbell, MD, a pediatric infectious disease specialist at the University of Maryland’s Center for Vaccine Development in Baltimore, which was involved in the Moderna and early-phase Pfizer trials. He coauthored a September 2020 article in Clinical Infectious Diseases titled: “Warp Speed for COVID-19 vaccines: Why are children stuck in neutral?”

The adolescent trials are a vital step to ensure timely vaccine access for teens and younger children. “It is reasonable, when you have limited vaccine, that your rollout goes to the highest priority and then moves to lower and lower priorities. In adults, we’re just saying: ‘Wait your turn,’ ” he said of the current vaccination effort. “If we didn’t have the [vaccine trial] data in children, we’d be saying: ‘You don’t have a turn.’ ”

As the pandemic has worn on, the burden on children has grown. As of Tuesday, 269 children had died of COVID-19. That is well above the highest annual death toll recorded during a regular flu season – 188 flu deaths among children and adolescents under 18 in the 2019-2020 and 2017-2018 flu seasons.

Children are less likely to transmit COVID-19 in their household than adults, according to a meta-analysis of 54 studies published in JAMA Network Open. But that does not necessarily mean children are less infectious, the authors said, noting that unmeasured factors could have affected the spread of infection among adults.

Moreover, children and adolescents need protection from COVID infection – and from the potential for severe disease or lingering effects – and, given that there are 74 million children and teens in the United States, their vaccination is an important part of stopping the pandemic, said Grace Lee, MD, professor of pediatrics at Stanford (Calif.) University, and cochair of ACIP’s COVID-19 Vaccine Safety Technical Subgroup.

“In order to interrupt transmission, I don’t see how we’re going to do that without vaccinating children and adolescents,” she said.

Dr. Lee said her 16-year-old daughter misses the normal teenage social life and is excited about getting the vaccine when she is eligible. (Adolescents without high-risk conditions are in the lowest vaccination tier, according to ACIP recommendations.) “There is truly individual protection to be gained,” Dr. Lee said.

She noted that researchers continue to assess the immune responses to the adult vaccines – even looking at immune characteristics of the small percentage of people who aren’t protected from infection – and that information helps in the evaluation of the pediatric immune responses. As the trials expand to younger children and infants, dosing will be a major focus. “How many doses do they need they need to receive the same immunity? Safety considerations will be critically important,” she said.
 

Teen trials underway

Pfizer/BioNTech extended its adult trial to 16- and 17-year-olds in October, which enabled older teens to be included in its emergency-use authorization. They and younger teens, ages 12-15, receive the same dose as adults.

The ongoing trials with Pfizer and Moderna vaccines are immunobridging trials, designed to study safety and immunogenicity. Investigators will compare the teens’ immune response with the findings from the larger adult trials. When the trials expand to school-age children (6-12 years), protocols call for testing the safety and immunogenicity of a half-dose vaccine as well as the full dose.

Children ages 2-5 years and infants and toddlers will be enrolled in future trials, studying safety and immunogenicity of full, half, or even quarter dosages. The Pediatric Research Equity Act of 2003 requires licensed vaccines to be tested for safety and efficacy in children, unless they are not appropriate for a pediatric population.

Demand for the teen trials has been strong. At Cincinnati Children’s Hospital Medical Center, 259 teenagers joined the Pfizer/BioNTech trial, but some teenagers were turned away when the trial’s national enrollment closed in late January.

“Many of the children are having no side effects, and if they are, they’re having the same [effects] as the young adults – local redness or pain, fatigue, and headaches,” said Robert Frenck, MD, director of the Cincinnati Children’s Gamble Program for Clinical Studies.

Parents may share some of the vaccine hesitancy that has affected adult vaccination. But that is balanced by the hope that vaccines will end the pandemic and usher in a new normal. “If it looks like [vaccines] will increase the likelihood of children returning to school safely, that may be a motivating factor,” Dr. Frenck said.

Cody Meissner, MD, chief of the pediatric infectious disease service at Tufts Medical Center, Boston, was initially cautious about the extension of vaccination to adolescents. A member of the Vaccine and Related Biological Products Advisory Committee, which evaluates data and makes recommendations to the Food and Drug Administration, Dr. Meissner initially abstained in the vote on the Pfizer/BioNTech emergency-use authorization for people 16 and older.

He noted that, at the time the committee reviewed the Pfizer vaccine, the company had data available for just 134 teenagers, half of whom received a placebo. But the vaccination of 34 million adults has provided robust data about the vaccine’s safety, and the trial expansion into adolescents is important.

“I’m comfortable with the way these trials are going now,” he said. “This is the way I was hoping they would go.”

Ms. Hillenburg is on the parent advisory board of Voices for Vaccines, an organization of parents supporting vaccination that is affiliated with the Task Force for Global Health, an Atlanta-based independent public health organization. Dr. Campbell’s institution has received funds to conduct clinical trials from the National Institutes of Health and several companies, including Merck, GlaxoSmithKline, Sanofi, Pfizer, and Moderna. He has served pro bono on many safety and data monitoring committees. Dr. Frenck’s institution is receiving funds to conduct the Pfizer trial. In the past 5 years, he has also participated in clinical trials for GlaxoSmithKline, Merck, and Meissa vaccines. Dr. Lee and Dr. Meissner disclosed no relevant financial relationships.

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

Higher coffee consumption is associated with a lower risk of heart failure, according to a machine learning–based algorithm that analyzed data from three large observational trials.

“Coffee consumption actually was predictive on top of known risk factors originally identified from those three trials.” The study is significant because it underscores the potential of big data for individualizing patient management, lead investigator David Kao, MD, said in an interview. “We in fact adjusted for the scores that are commonly used to predict heart disease, and coffee consumption remained a predictor even on top of that.”

The study used supervised machine learning to analyze data on diet and other variables from three well-known observational studies: Framingham Heart Study (FHS), Cardiovascular Heart Study (CHS), and ARIC (Atherosclerosis Risk in Communities). The goal of the study, published online on Feb. 9, 2021*, was to identify potential novel risk factors for incident coronary heart disease, stroke, and heart failure.

“The main difference of the relationship between coffee and heart disease, compared with prior analyses, is that we’re able to find it in these well-known and well-accepted studies that have helped us find risk factors before,” Dr. Kao said

The study included 2,732 FHS participants aged 30-62 years, 3,704 CHS patients aged 65 and older, and 14,925 ARIC subjects aged 45-64, all of whom had no history of cardiovascular disease events when they enrolled. Primary outcomes for the machine-learning study were times to incident coronary heart disease, heart failure, and stroke.
 

Mathematics, not hypotheses

To compensate for variations in methodologies between the three observational trials, the study used 204 data measurements collected at the first FHS exam, including 16 dietary variables and for which similar data were collected for the other two studies.

The machine-learning model used what’s known as a random forest analysis to identify the leading potential risk factors from among the 204 variables. To confirm findings between studies, the authors used a technique called “data harmonization” to smooth variations in the methodologies of the trials, not only with participant age and duration and date of the trials, but also in how data on coffee consumption were gathered. For example, FHS collected that data as cups per day, whereas CHS and ARIC collected that as monthly, weekly, and daily consumption. The study converted the coffee consumption data from CHS and ARIC to cups per day to conform to FHS data.

Random forest analysis is a type of machine learning that randomly creates a cluster of decision trees – the “forest” – to determine which variables, such as dietary factors, are important in predicting a result. The analysis uses mathematics, not hypotheses, to identify important variables.
 

Heart failure and risk reduced

In this study, the analysis determined that each cup of caffeinated coffee daily was linked with a 5% reduction in the risk of heart failure (hazard ratio, 0.95; P = .02) and 6% reduction in stroke risk (HR, 0.94; P = .02), but had no significant impact on risk for coronary heart disease or cardiovascular disease.

When the data were adjusted for the FHS CVD risk score, increasing coffee consumption remained significantly associated with an identical lower risk of heart failure (P = .03) but not stroke (P = .33).

While the study supports an association between coffee consumption and heart failure risk, it doesn’t establish causation, noted Alice H. Lichtenstein, DSc, director and senior scientist at the Cardiovascular Nutrition Laboratory at Tufts University, Boston. “The authors could not rule out the possibility that caffeinated coffee intake was a proxy for other heart-healthy lifestyle behaviors,” Dr. Lichtenstein said. “Perhaps the best message from the study is that there appears to be no adverse effects of drinking moderate amounts of caffeinated coffee, and there may be benefits.”

She added a note of caution. “This result does not suggest coffee intake should be increased, nor does it give license to increasing coffee drinks with a lot of added cream and sugar.”
 

Machine learning mines observational trials

Dr. Kao explained the rationale for applying a machine-learning algorithm to the three observational trials. “When these trials were designed in general, they had an idea of what they were looking for in terms of what might be a risk factor,” said Dr. Kao, of the University of Colorado at Denver, Aurora. “What we were interested in doing was to look for risk factors that nobody really thought about ahead of time and let the data show us what might be a predictor without any bias of what we imagined to be true.”

He described the role of machine learning in extracting and “filtering” data from the trials. “Machine learning allows us to look at a very large number of factors or variables and identify the most important ones in predicting a specific outcome,” he said. This study evaluated the 204 variables and focused on dietary factors because they’re modifiable.

“We looked at them in these different studies where we could, and coffee was the one that was reproducible in all of them,” he said. “Machine learning helped filter down these very large numbers of variables in ways you can’t do with traditional statistics. It’s useful in studies like this because they gather thousands and thousands of variables that generally nobody uses, but these methods allow you to actually do something with them – to determine which ones are most important.”

He added: “These methods I think will take us toward personalized medicine where you’re really individualizing a plan for keeping a patient healthy. We still have a lot of work to do, but there’s a lot of promise for really helping each of us to figure out the ways we can become the healthiest that we can be.”

The study was supported with funding from the National Heart, Lung, and Blood Institute and the American Heart Association. Dr. Kao and coauthors, as well as Dr. Lichtenstein, had no relevant financial relationships to disclose.

*Correction, 2/10/21: An earlier version of this article misstated the study's publication date.

Higher coffee consumption is associated with a lower risk of heart failure, according to a machine learning–based algorithm that analyzed data from three large observational trials.

“Coffee consumption actually was predictive on top of known risk factors originally identified from those three trials.” The study is significant because it underscores the potential of big data for individualizing patient management, lead investigator David Kao, MD, said in an interview. “We in fact adjusted for the scores that are commonly used to predict heart disease, and coffee consumption remained a predictor even on top of that.”

The study used supervised machine learning to analyze data on diet and other variables from three well-known observational studies: Framingham Heart Study (FHS), Cardiovascular Heart Study (CHS), and ARIC (Atherosclerosis Risk in Communities). The goal of the study, published online on Feb. 9, 2021*, was to identify potential novel risk factors for incident coronary heart disease, stroke, and heart failure.

“The main difference of the relationship between coffee and heart disease, compared with prior analyses, is that we’re able to find it in these well-known and well-accepted studies that have helped us find risk factors before,” Dr. Kao said

The study included 2,732 FHS participants aged 30-62 years, 3,704 CHS patients aged 65 and older, and 14,925 ARIC subjects aged 45-64, all of whom had no history of cardiovascular disease events when they enrolled. Primary outcomes for the machine-learning study were times to incident coronary heart disease, heart failure, and stroke.
 

Mathematics, not hypotheses

To compensate for variations in methodologies between the three observational trials, the study used 204 data measurements collected at the first FHS exam, including 16 dietary variables and for which similar data were collected for the other two studies.

The machine-learning model used what’s known as a random forest analysis to identify the leading potential risk factors from among the 204 variables. To confirm findings between studies, the authors used a technique called “data harmonization” to smooth variations in the methodologies of the trials, not only with participant age and duration and date of the trials, but also in how data on coffee consumption were gathered. For example, FHS collected that data as cups per day, whereas CHS and ARIC collected that as monthly, weekly, and daily consumption. The study converted the coffee consumption data from CHS and ARIC to cups per day to conform to FHS data.

Random forest analysis is a type of machine learning that randomly creates a cluster of decision trees – the “forest” – to determine which variables, such as dietary factors, are important in predicting a result. The analysis uses mathematics, not hypotheses, to identify important variables.
 

Heart failure and risk reduced

In this study, the analysis determined that each cup of caffeinated coffee daily was linked with a 5% reduction in the risk of heart failure (hazard ratio, 0.95; P = .02) and 6% reduction in stroke risk (HR, 0.94; P = .02), but had no significant impact on risk for coronary heart disease or cardiovascular disease.

When the data were adjusted for the FHS CVD risk score, increasing coffee consumption remained significantly associated with an identical lower risk of heart failure (P = .03) but not stroke (P = .33).

While the study supports an association between coffee consumption and heart failure risk, it doesn’t establish causation, noted Alice H. Lichtenstein, DSc, director and senior scientist at the Cardiovascular Nutrition Laboratory at Tufts University, Boston. “The authors could not rule out the possibility that caffeinated coffee intake was a proxy for other heart-healthy lifestyle behaviors,” Dr. Lichtenstein said. “Perhaps the best message from the study is that there appears to be no adverse effects of drinking moderate amounts of caffeinated coffee, and there may be benefits.”

She added a note of caution. “This result does not suggest coffee intake should be increased, nor does it give license to increasing coffee drinks with a lot of added cream and sugar.”
 

Machine learning mines observational trials

Dr. Kao explained the rationale for applying a machine-learning algorithm to the three observational trials. “When these trials were designed in general, they had an idea of what they were looking for in terms of what might be a risk factor,” said Dr. Kao, of the University of Colorado at Denver, Aurora. “What we were interested in doing was to look for risk factors that nobody really thought about ahead of time and let the data show us what might be a predictor without any bias of what we imagined to be true.”

He described the role of machine learning in extracting and “filtering” data from the trials. “Machine learning allows us to look at a very large number of factors or variables and identify the most important ones in predicting a specific outcome,” he said. This study evaluated the 204 variables and focused on dietary factors because they’re modifiable.

“We looked at them in these different studies where we could, and coffee was the one that was reproducible in all of them,” he said. “Machine learning helped filter down these very large numbers of variables in ways you can’t do with traditional statistics. It’s useful in studies like this because they gather thousands and thousands of variables that generally nobody uses, but these methods allow you to actually do something with them – to determine which ones are most important.”

He added: “These methods I think will take us toward personalized medicine where you’re really individualizing a plan for keeping a patient healthy. We still have a lot of work to do, but there’s a lot of promise for really helping each of us to figure out the ways we can become the healthiest that we can be.”

The study was supported with funding from the National Heart, Lung, and Blood Institute and the American Heart Association. Dr. Kao and coauthors, as well as Dr. Lichtenstein, had no relevant financial relationships to disclose.

*Correction, 2/10/21: An earlier version of this article misstated the study's publication date.

Higher coffee consumption is associated with a lower risk of heart failure, according to a machine learning–based algorithm that analyzed data from three large observational trials.

“Coffee consumption actually was predictive on top of known risk factors originally identified from those three trials.” The study is significant because it underscores the potential of big data for individualizing patient management, lead investigator David Kao, MD, said in an interview. “We in fact adjusted for the scores that are commonly used to predict heart disease, and coffee consumption remained a predictor even on top of that.”

The study used supervised machine learning to analyze data on diet and other variables from three well-known observational studies: Framingham Heart Study (FHS), Cardiovascular Heart Study (CHS), and ARIC (Atherosclerosis Risk in Communities). The goal of the study, published online on Feb. 9, 2021*, was to identify potential novel risk factors for incident coronary heart disease, stroke, and heart failure.

“The main difference of the relationship between coffee and heart disease, compared with prior analyses, is that we’re able to find it in these well-known and well-accepted studies that have helped us find risk factors before,” Dr. Kao said

The study included 2,732 FHS participants aged 30-62 years, 3,704 CHS patients aged 65 and older, and 14,925 ARIC subjects aged 45-64, all of whom had no history of cardiovascular disease events when they enrolled. Primary outcomes for the machine-learning study were times to incident coronary heart disease, heart failure, and stroke.
 

Mathematics, not hypotheses

To compensate for variations in methodologies between the three observational trials, the study used 204 data measurements collected at the first FHS exam, including 16 dietary variables and for which similar data were collected for the other two studies.

The machine-learning model used what’s known as a random forest analysis to identify the leading potential risk factors from among the 204 variables. To confirm findings between studies, the authors used a technique called “data harmonization” to smooth variations in the methodologies of the trials, not only with participant age and duration and date of the trials, but also in how data on coffee consumption were gathered. For example, FHS collected that data as cups per day, whereas CHS and ARIC collected that as monthly, weekly, and daily consumption. The study converted the coffee consumption data from CHS and ARIC to cups per day to conform to FHS data.

Random forest analysis is a type of machine learning that randomly creates a cluster of decision trees – the “forest” – to determine which variables, such as dietary factors, are important in predicting a result. The analysis uses mathematics, not hypotheses, to identify important variables.
 

Heart failure and risk reduced

In this study, the analysis determined that each cup of caffeinated coffee daily was linked with a 5% reduction in the risk of heart failure (hazard ratio, 0.95; P = .02) and 6% reduction in stroke risk (HR, 0.94; P = .02), but had no significant impact on risk for coronary heart disease or cardiovascular disease.

When the data were adjusted for the FHS CVD risk score, increasing coffee consumption remained significantly associated with an identical lower risk of heart failure (P = .03) but not stroke (P = .33).

While the study supports an association between coffee consumption and heart failure risk, it doesn’t establish causation, noted Alice H. Lichtenstein, DSc, director and senior scientist at the Cardiovascular Nutrition Laboratory at Tufts University, Boston. “The authors could not rule out the possibility that caffeinated coffee intake was a proxy for other heart-healthy lifestyle behaviors,” Dr. Lichtenstein said. “Perhaps the best message from the study is that there appears to be no adverse effects of drinking moderate amounts of caffeinated coffee, and there may be benefits.”

She added a note of caution. “This result does not suggest coffee intake should be increased, nor does it give license to increasing coffee drinks with a lot of added cream and sugar.”
 

Machine learning mines observational trials

Dr. Kao explained the rationale for applying a machine-learning algorithm to the three observational trials. “When these trials were designed in general, they had an idea of what they were looking for in terms of what might be a risk factor,” said Dr. Kao, of the University of Colorado at Denver, Aurora. “What we were interested in doing was to look for risk factors that nobody really thought about ahead of time and let the data show us what might be a predictor without any bias of what we imagined to be true.”

He described the role of machine learning in extracting and “filtering” data from the trials. “Machine learning allows us to look at a very large number of factors or variables and identify the most important ones in predicting a specific outcome,” he said. This study evaluated the 204 variables and focused on dietary factors because they’re modifiable.

“We looked at them in these different studies where we could, and coffee was the one that was reproducible in all of them,” he said. “Machine learning helped filter down these very large numbers of variables in ways you can’t do with traditional statistics. It’s useful in studies like this because they gather thousands and thousands of variables that generally nobody uses, but these methods allow you to actually do something with them – to determine which ones are most important.”

He added: “These methods I think will take us toward personalized medicine where you’re really individualizing a plan for keeping a patient healthy. We still have a lot of work to do, but there’s a lot of promise for really helping each of us to figure out the ways we can become the healthiest that we can be.”

The study was supported with funding from the National Heart, Lung, and Blood Institute and the American Heart Association. Dr. Kao and coauthors, as well as Dr. Lichtenstein, had no relevant financial relationships to disclose.

*Correction, 2/10/21: An earlier version of this article misstated the study's publication date.

The SARS-CoV-2 variant first detected in the United Kingdom is rapidly becoming the dominant strain in several countries and is doubling every 10 days in the United States, according to new data.

The findings by Nicole L. Washington, PhD, associate director of research at the genomics company Helix, and colleagues were posted Feb. 7, 2021, on the preprint server medRxiv. The paper has not been peer-reviewed in a scientific journal.

The researchers also found that the transmission rate in the United States of the variant, labeled B.1.1.7, is 30%-40% higher than that of more common lineages.

While clinical outcomes initially were thought to be similar to those of other SARS-CoV-2 variants, early reports suggest that infection with the B.1.1.7 variant may increase death risk by about 30%. 

A coauthor of the current study, Kristian Andersen, PhD, told the New York Times , “Nothing in this paper is surprising, but people need to see it.”

Dr. Andersen, a virologist at the Scripps Research Institute in La Jolla, Calif., added that “we should probably prepare for this being the predominant lineage in most places in the United States by March.”

The study of the B.1.1.7 variant adds support for the Centers for Disease Control and Prevention prediction in January that it would dominate by March.

“Our study shows that the U.S. is on a similar trajectory as other countries where B.1.1.7 rapidly became the dominant SARS-CoV-2 variant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality,” the researchers wrote.

The authors pointed out that the B.1.1.7 variant became the dominant SARS-CoV-2 strain in the United Kingdom within a couple of months of its detection.

“Since then, the variant has been increasingly observed across many European countries, including Portugal and Ireland, which, like the U.K., observed devastating waves of COVID-19 after B.1.1.7 became dominant,” the authors wrote.
 

“Category 5” storm

The B.1.1.7 variant has likely been spreading between U.S. states since at least December, they wrote.

This news organization reported on Jan. 15 that, as of Jan. 13, the B.1.1.7 variant was seen in 76 cases across 12 U.S. states, according to an early release of the CDC’s Morbidity and Mortality Weekly Report. 

As of Feb. 7, there were 690 cases of the B.1.1.7 variant in the US in 33 states, according to the CDC.

Dr. Washington and colleagues examined more than 500,000 coronavirus test samples from cases across the United States that were tested at San Mateo, Calif.–based Helix facilities since July.

In the study, they found inconsistent prevalence of the variant across states. By the last week in January, the researchers estimated the proportion of B.1.1.7 in the U.S. population to be about 2.1% of all COVID-19 cases, though they found it made up about 2% of all COVID-19 cases in California and about 4.5% of cases in Florida. The authors acknowledged that their data is less robust outside of those two states.

Though that seems a relatively low frequency, “our estimates show that its growth rate is at least 35%-45% increased and doubling every week and a half,” the authors wrote.

“Because laboratories in the U.S. are only sequencing a small subset of SARS-CoV-2 samples, the true sequence diversity of SARS-CoV-2 in this country is still unknown,” they noted.

Michael Osterholm, PhD, MPH, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, Minneapolis, said last week that the United States is facing a “Category 5” storm with the spread of the B.1.1.7 variant as well as the variants first identified in South Africa and Brazil.

“We are going to see something like we have not seen yet in this country,” Dr. Osterholm said recently on NBC’s Meet the Press.

Lead author Nicole L. Washington and many of the coauthors are employees of Helix. Other coauthors are employees of Illumina. Three coauthors own stock in ILMN. The work was funded by Illumina, Helix, the Innovative Genomics Institute, and the New Frontiers in Research Fund provided by the Canadian Institutes of Health Research.

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

The SARS-CoV-2 variant first detected in the United Kingdom is rapidly becoming the dominant strain in several countries and is doubling every 10 days in the United States, according to new data.

The findings by Nicole L. Washington, PhD, associate director of research at the genomics company Helix, and colleagues were posted Feb. 7, 2021, on the preprint server medRxiv. The paper has not been peer-reviewed in a scientific journal.

The researchers also found that the transmission rate in the United States of the variant, labeled B.1.1.7, is 30%-40% higher than that of more common lineages.

While clinical outcomes initially were thought to be similar to those of other SARS-CoV-2 variants, early reports suggest that infection with the B.1.1.7 variant may increase death risk by about 30%. 

A coauthor of the current study, Kristian Andersen, PhD, told the New York Times , “Nothing in this paper is surprising, but people need to see it.”

Dr. Andersen, a virologist at the Scripps Research Institute in La Jolla, Calif., added that “we should probably prepare for this being the predominant lineage in most places in the United States by March.”

The study of the B.1.1.7 variant adds support for the Centers for Disease Control and Prevention prediction in January that it would dominate by March.

“Our study shows that the U.S. is on a similar trajectory as other countries where B.1.1.7 rapidly became the dominant SARS-CoV-2 variant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality,” the researchers wrote.

The authors pointed out that the B.1.1.7 variant became the dominant SARS-CoV-2 strain in the United Kingdom within a couple of months of its detection.

“Since then, the variant has been increasingly observed across many European countries, including Portugal and Ireland, which, like the U.K., observed devastating waves of COVID-19 after B.1.1.7 became dominant,” the authors wrote.
 

“Category 5” storm

The B.1.1.7 variant has likely been spreading between U.S. states since at least December, they wrote.

This news organization reported on Jan. 15 that, as of Jan. 13, the B.1.1.7 variant was seen in 76 cases across 12 U.S. states, according to an early release of the CDC’s Morbidity and Mortality Weekly Report. 

As of Feb. 7, there were 690 cases of the B.1.1.7 variant in the US in 33 states, according to the CDC.

Dr. Washington and colleagues examined more than 500,000 coronavirus test samples from cases across the United States that were tested at San Mateo, Calif.–based Helix facilities since July.

In the study, they found inconsistent prevalence of the variant across states. By the last week in January, the researchers estimated the proportion of B.1.1.7 in the U.S. population to be about 2.1% of all COVID-19 cases, though they found it made up about 2% of all COVID-19 cases in California and about 4.5% of cases in Florida. The authors acknowledged that their data is less robust outside of those two states.

Though that seems a relatively low frequency, “our estimates show that its growth rate is at least 35%-45% increased and doubling every week and a half,” the authors wrote.

“Because laboratories in the U.S. are only sequencing a small subset of SARS-CoV-2 samples, the true sequence diversity of SARS-CoV-2 in this country is still unknown,” they noted.

Michael Osterholm, PhD, MPH, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, Minneapolis, said last week that the United States is facing a “Category 5” storm with the spread of the B.1.1.7 variant as well as the variants first identified in South Africa and Brazil.

“We are going to see something like we have not seen yet in this country,” Dr. Osterholm said recently on NBC’s Meet the Press.

Lead author Nicole L. Washington and many of the coauthors are employees of Helix. Other coauthors are employees of Illumina. Three coauthors own stock in ILMN. The work was funded by Illumina, Helix, the Innovative Genomics Institute, and the New Frontiers in Research Fund provided by the Canadian Institutes of Health Research.

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

The SARS-CoV-2 variant first detected in the United Kingdom is rapidly becoming the dominant strain in several countries and is doubling every 10 days in the United States, according to new data.

The findings by Nicole L. Washington, PhD, associate director of research at the genomics company Helix, and colleagues were posted Feb. 7, 2021, on the preprint server medRxiv. The paper has not been peer-reviewed in a scientific journal.

The researchers also found that the transmission rate in the United States of the variant, labeled B.1.1.7, is 30%-40% higher than that of more common lineages.

While clinical outcomes initially were thought to be similar to those of other SARS-CoV-2 variants, early reports suggest that infection with the B.1.1.7 variant may increase death risk by about 30%. 

A coauthor of the current study, Kristian Andersen, PhD, told the New York Times , “Nothing in this paper is surprising, but people need to see it.”

Dr. Andersen, a virologist at the Scripps Research Institute in La Jolla, Calif., added that “we should probably prepare for this being the predominant lineage in most places in the United States by March.”

The study of the B.1.1.7 variant adds support for the Centers for Disease Control and Prevention prediction in January that it would dominate by March.

“Our study shows that the U.S. is on a similar trajectory as other countries where B.1.1.7 rapidly became the dominant SARS-CoV-2 variant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality,” the researchers wrote.

The authors pointed out that the B.1.1.7 variant became the dominant SARS-CoV-2 strain in the United Kingdom within a couple of months of its detection.

“Since then, the variant has been increasingly observed across many European countries, including Portugal and Ireland, which, like the U.K., observed devastating waves of COVID-19 after B.1.1.7 became dominant,” the authors wrote.
 

“Category 5” storm

The B.1.1.7 variant has likely been spreading between U.S. states since at least December, they wrote.

This news organization reported on Jan. 15 that, as of Jan. 13, the B.1.1.7 variant was seen in 76 cases across 12 U.S. states, according to an early release of the CDC’s Morbidity and Mortality Weekly Report. 

As of Feb. 7, there were 690 cases of the B.1.1.7 variant in the US in 33 states, according to the CDC.

Dr. Washington and colleagues examined more than 500,000 coronavirus test samples from cases across the United States that were tested at San Mateo, Calif.–based Helix facilities since July.

In the study, they found inconsistent prevalence of the variant across states. By the last week in January, the researchers estimated the proportion of B.1.1.7 in the U.S. population to be about 2.1% of all COVID-19 cases, though they found it made up about 2% of all COVID-19 cases in California and about 4.5% of cases in Florida. The authors acknowledged that their data is less robust outside of those two states.

Though that seems a relatively low frequency, “our estimates show that its growth rate is at least 35%-45% increased and doubling every week and a half,” the authors wrote.

“Because laboratories in the U.S. are only sequencing a small subset of SARS-CoV-2 samples, the true sequence diversity of SARS-CoV-2 in this country is still unknown,” they noted.

Michael Osterholm, PhD, MPH, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, Minneapolis, said last week that the United States is facing a “Category 5” storm with the spread of the B.1.1.7 variant as well as the variants first identified in South Africa and Brazil.

“We are going to see something like we have not seen yet in this country,” Dr. Osterholm said recently on NBC’s Meet the Press.

Lead author Nicole L. Washington and many of the coauthors are employees of Helix. Other coauthors are employees of Illumina. Three coauthors own stock in ILMN. The work was funded by Illumina, Helix, the Innovative Genomics Institute, and the New Frontiers in Research Fund provided by the Canadian Institutes of Health Research.

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