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FDA could authorize COVID-19 vaccine for ages 5-11 in October
The timeline is based on the expectation that Pfizer will have enough data from clinical trials to request Food and Drug Administration emergency use authorization for the age group near the end of September. Then the FDA would likely make a decision about the vaccine’s safety and effectiveness in children within about 3 weeks, two sources told Reuters.
Anthony Fauci, MD, chief medical adviser to President Joe Biden and director of the National Institute of Allergy and Infectious Diseases, spoke about the timeline during an online town hall meeting Friday, Reuters reported. The meeting was attended by thousands of staff members at the National Institutes of Health.
If Pfizer submits paperwork to the FDA by the end of September, the vaccine could be available for kids around mid-October, Dr. Fauci said, and approval for the Moderna vaccine could come in November. Moderna will take about 3 weeks longer to collect and analyze data for ages 5-11.
Pfizer has said it would have enough data for ages 5-11 in September and would submit its documentation for FDA authorization soon after. Moderna told investors on Sept. 9 that data for ages 6-11 would be available by the end of the year.
On Sept. 10, the FDA said it would work to approve COVID-19 vaccines for children quickly once companies submit their data, according to Reuters. The agency said it would consider applications for emergency use, which would allow for faster approval.
Pfizer’s vaccine is the only one to receive full FDA approval, but only for people ages 16 and older. Adolescents ages 12-15 can receive the Pfizer vaccine under the FDA’s emergency use authorization.
For emergency use authorization, companies must submit 2 months of safety data versus 6 months for full approval. The FDA said on Sept. 10 that children in clinical trials should be monitored for at least 2 months to observe side effects.
BioNTech, Pfizer’s vaccine manufacturing partner, told a news outlet in Germany that it plans to request authorization globally for ages 5-11 in coming weeks, according to Reuters.
“Already over the next few weeks, we will file the results of our trial in 5- to 11-year-olds with regulators across the world and will request approval of the vaccine in this age group, also here in Europe,” Oezlem Tuereci, MD, the chief medical officer for BioNTech, told Der Spiegel.
The company is completing the final production steps to make the vaccine at lower doses for the younger age group, she said. Pfizer and BioNTech will also seek vaccine approval for ages 6 months to 2 years later this year.
“Things are looking good, everything is going according to plan,” Ugur Sahin, MD, the CEO of BioNTech, told Der Spiegel.
A version of this article first appeared on WebMD.com.
The timeline is based on the expectation that Pfizer will have enough data from clinical trials to request Food and Drug Administration emergency use authorization for the age group near the end of September. Then the FDA would likely make a decision about the vaccine’s safety and effectiveness in children within about 3 weeks, two sources told Reuters.
Anthony Fauci, MD, chief medical adviser to President Joe Biden and director of the National Institute of Allergy and Infectious Diseases, spoke about the timeline during an online town hall meeting Friday, Reuters reported. The meeting was attended by thousands of staff members at the National Institutes of Health.
If Pfizer submits paperwork to the FDA by the end of September, the vaccine could be available for kids around mid-October, Dr. Fauci said, and approval for the Moderna vaccine could come in November. Moderna will take about 3 weeks longer to collect and analyze data for ages 5-11.
Pfizer has said it would have enough data for ages 5-11 in September and would submit its documentation for FDA authorization soon after. Moderna told investors on Sept. 9 that data for ages 6-11 would be available by the end of the year.
On Sept. 10, the FDA said it would work to approve COVID-19 vaccines for children quickly once companies submit their data, according to Reuters. The agency said it would consider applications for emergency use, which would allow for faster approval.
Pfizer’s vaccine is the only one to receive full FDA approval, but only for people ages 16 and older. Adolescents ages 12-15 can receive the Pfizer vaccine under the FDA’s emergency use authorization.
For emergency use authorization, companies must submit 2 months of safety data versus 6 months for full approval. The FDA said on Sept. 10 that children in clinical trials should be monitored for at least 2 months to observe side effects.
BioNTech, Pfizer’s vaccine manufacturing partner, told a news outlet in Germany that it plans to request authorization globally for ages 5-11 in coming weeks, according to Reuters.
“Already over the next few weeks, we will file the results of our trial in 5- to 11-year-olds with regulators across the world and will request approval of the vaccine in this age group, also here in Europe,” Oezlem Tuereci, MD, the chief medical officer for BioNTech, told Der Spiegel.
The company is completing the final production steps to make the vaccine at lower doses for the younger age group, she said. Pfizer and BioNTech will also seek vaccine approval for ages 6 months to 2 years later this year.
“Things are looking good, everything is going according to plan,” Ugur Sahin, MD, the CEO of BioNTech, told Der Spiegel.
A version of this article first appeared on WebMD.com.
The timeline is based on the expectation that Pfizer will have enough data from clinical trials to request Food and Drug Administration emergency use authorization for the age group near the end of September. Then the FDA would likely make a decision about the vaccine’s safety and effectiveness in children within about 3 weeks, two sources told Reuters.
Anthony Fauci, MD, chief medical adviser to President Joe Biden and director of the National Institute of Allergy and Infectious Diseases, spoke about the timeline during an online town hall meeting Friday, Reuters reported. The meeting was attended by thousands of staff members at the National Institutes of Health.
If Pfizer submits paperwork to the FDA by the end of September, the vaccine could be available for kids around mid-October, Dr. Fauci said, and approval for the Moderna vaccine could come in November. Moderna will take about 3 weeks longer to collect and analyze data for ages 5-11.
Pfizer has said it would have enough data for ages 5-11 in September and would submit its documentation for FDA authorization soon after. Moderna told investors on Sept. 9 that data for ages 6-11 would be available by the end of the year.
On Sept. 10, the FDA said it would work to approve COVID-19 vaccines for children quickly once companies submit their data, according to Reuters. The agency said it would consider applications for emergency use, which would allow for faster approval.
Pfizer’s vaccine is the only one to receive full FDA approval, but only for people ages 16 and older. Adolescents ages 12-15 can receive the Pfizer vaccine under the FDA’s emergency use authorization.
For emergency use authorization, companies must submit 2 months of safety data versus 6 months for full approval. The FDA said on Sept. 10 that children in clinical trials should be monitored for at least 2 months to observe side effects.
BioNTech, Pfizer’s vaccine manufacturing partner, told a news outlet in Germany that it plans to request authorization globally for ages 5-11 in coming weeks, according to Reuters.
“Already over the next few weeks, we will file the results of our trial in 5- to 11-year-olds with regulators across the world and will request approval of the vaccine in this age group, also here in Europe,” Oezlem Tuereci, MD, the chief medical officer for BioNTech, told Der Spiegel.
The company is completing the final production steps to make the vaccine at lower doses for the younger age group, she said. Pfizer and BioNTech will also seek vaccine approval for ages 6 months to 2 years later this year.
“Things are looking good, everything is going according to plan,” Ugur Sahin, MD, the CEO of BioNTech, told Der Spiegel.
A version of this article first appeared on WebMD.com.
Biden vaccine mandate rule could be ready within weeks
The emergency rule ordering large employers to require COVID-19 vaccines or weekly tests for their workers could be ready “within weeks,” officials said in a news briefing Sept. 10.
Labor Secretary Martin Walsh will oversee the Occupational Safety and Health Administration as the agency drafts what’s known as an emergency temporary standard, similar to the one that was issued a few months ago to protect health care workers during the pandemic.
The rule should be ready within weeks, said Jeff Zients, coordinator of the White House COVID-19 response team.
He said the ultimate goal of the president’s plan is to increase vaccinations as quickly as possible to keep schools open, the economy recovering, and to decrease hospitalizations and deaths from COVID.
Mr. Zients declined to set hard numbers around those goals, but other experts did.
“What we need to get to is 85% to 90% population immunity, and that’s going to be immunity both from vaccines and infections, before that really begins to have a substantial dampening effect on viral spread,” Ashish Jha, MD, dean of the Brown University School of Public Health, Providence, R.I., said on a call with reporters Sept. 9.
He said immunity needs to be that high because the Delta variant is so contagious.
Mandates are seen as the most effective way to increase immunity and do it quickly.
David Michaels, PhD, an epidemiologist and professor at George Washington University, Washington, says OSHA will have to work through a number of steps to develop the rule.
“OSHA will have to write a preamble explaining the standard, its justifications, its costs, and how it will be enforced,” says Dr. Michaels, who led OSHA for the Obama administration. After that, the rule will be reviewed by the White House. Then employers will have some time – typically 30 days – to comply.
In addition to drafting the standard, OSHA will oversee its enforcement.
Companies that refuse to follow the standard could be fined $13,600 per violation, Mr. Zients said.
Dr. Michaels said he doesn’t expect enforcement to be a big issue, and he said we’re likely to see the rule well before it is final.
“Most employers are law-abiding. When OSHA issues a standard, they try to meet whatever those requirements are, and generally that starts to happen when the rule is announced, even before it goes into effect,” he said.
The rule may face legal challenges as well. Several governors and state attorneys general, as well as the Republican National Committee, have promised lawsuits to stop the vaccine mandates.
Critics of the new mandates say they impinge on personal freedom and impose burdens on businesses.
But the president hit back at that notion Sept. 10.
“Look, I am so disappointed that, particularly some of the Republican governors, have been so cavalier with the health of these kids, so cavalier of the health of their communities,” President Biden told reporters.
“I don’t know of any scientist out there in this field who doesn’t think it makes considerable sense to do the six things I’ve suggested.”
Yet, others feel the new requirements didn’t go far enough.
“These are good steps in the right direction, but they’re not enough to get the job done,” said Leana Wen, MD, in an op-ed for The Washington Post.
Dr. Wen, an expert in public health, wondered why President Biden didn’t mandate vaccinations for plane and train travel. She was disappointed that children 12 and older weren’t required to be vaccinated, too.
“There are mandates for childhood immunizations in every state. The coronavirus vaccine should be no different,” she wrote.
Vaccines remain the cornerstone of U.S. plans to control the pandemic.
On Sept. 10, there was new research from the CDC and state health departments showing that the COVID-19 vaccines continue to be highly effective at preventing severe illness and death.
But the study also found that the vaccines became less effective in the United States after Delta became the dominant cause of infections here.
The study, which included more than 600,000 COVID-19 cases, analyzed breakthrough infections – cases where people got sick despite being fully vaccinated – in 13 jurisdictions in the United States between April 4 and July 17, 2021.
Epidemiologists compared breakthrough infections between two distinct points in time: Before and after the period when the Delta variant began causing most infections.
From April 4 to June 19, fully vaccinated people made up just 5% of cases, 7% of hospitalizations, and 8% of deaths. From June 20 to July 17, 18% of cases, 14% of hospitalizations, and 16% of deaths occurred in fully vaccinated people.
“After the week of June 20, 2021, when the SARS-CoV-2 Delta variant became predominant, the percentage of fully vaccinated persons among cases increased more than expected,” the study authors wrote.
Even after Delta swept the United States, fully vaccinated people were 5 times less likely to get a COVID-19 infection and more than 10 times less likely to be hospitalized or die from one.
“As we have shown in study after study, vaccination works,” CDC Director Rochelle Walensky, MD, said during the White House news briefing.
“We have the scientific tools we need to turn the corner on this pandemic. Vaccination works and will protect us from the severe complications of COVID-19,” she said.
A version of this article first appeared on WebMD.com.
The emergency rule ordering large employers to require COVID-19 vaccines or weekly tests for their workers could be ready “within weeks,” officials said in a news briefing Sept. 10.
Labor Secretary Martin Walsh will oversee the Occupational Safety and Health Administration as the agency drafts what’s known as an emergency temporary standard, similar to the one that was issued a few months ago to protect health care workers during the pandemic.
The rule should be ready within weeks, said Jeff Zients, coordinator of the White House COVID-19 response team.
He said the ultimate goal of the president’s plan is to increase vaccinations as quickly as possible to keep schools open, the economy recovering, and to decrease hospitalizations and deaths from COVID.
Mr. Zients declined to set hard numbers around those goals, but other experts did.
“What we need to get to is 85% to 90% population immunity, and that’s going to be immunity both from vaccines and infections, before that really begins to have a substantial dampening effect on viral spread,” Ashish Jha, MD, dean of the Brown University School of Public Health, Providence, R.I., said on a call with reporters Sept. 9.
He said immunity needs to be that high because the Delta variant is so contagious.
Mandates are seen as the most effective way to increase immunity and do it quickly.
David Michaels, PhD, an epidemiologist and professor at George Washington University, Washington, says OSHA will have to work through a number of steps to develop the rule.
“OSHA will have to write a preamble explaining the standard, its justifications, its costs, and how it will be enforced,” says Dr. Michaels, who led OSHA for the Obama administration. After that, the rule will be reviewed by the White House. Then employers will have some time – typically 30 days – to comply.
In addition to drafting the standard, OSHA will oversee its enforcement.
Companies that refuse to follow the standard could be fined $13,600 per violation, Mr. Zients said.
Dr. Michaels said he doesn’t expect enforcement to be a big issue, and he said we’re likely to see the rule well before it is final.
“Most employers are law-abiding. When OSHA issues a standard, they try to meet whatever those requirements are, and generally that starts to happen when the rule is announced, even before it goes into effect,” he said.
The rule may face legal challenges as well. Several governors and state attorneys general, as well as the Republican National Committee, have promised lawsuits to stop the vaccine mandates.
Critics of the new mandates say they impinge on personal freedom and impose burdens on businesses.
But the president hit back at that notion Sept. 10.
“Look, I am so disappointed that, particularly some of the Republican governors, have been so cavalier with the health of these kids, so cavalier of the health of their communities,” President Biden told reporters.
“I don’t know of any scientist out there in this field who doesn’t think it makes considerable sense to do the six things I’ve suggested.”
Yet, others feel the new requirements didn’t go far enough.
“These are good steps in the right direction, but they’re not enough to get the job done,” said Leana Wen, MD, in an op-ed for The Washington Post.
Dr. Wen, an expert in public health, wondered why President Biden didn’t mandate vaccinations for plane and train travel. She was disappointed that children 12 and older weren’t required to be vaccinated, too.
“There are mandates for childhood immunizations in every state. The coronavirus vaccine should be no different,” she wrote.
Vaccines remain the cornerstone of U.S. plans to control the pandemic.
On Sept. 10, there was new research from the CDC and state health departments showing that the COVID-19 vaccines continue to be highly effective at preventing severe illness and death.
But the study also found that the vaccines became less effective in the United States after Delta became the dominant cause of infections here.
The study, which included more than 600,000 COVID-19 cases, analyzed breakthrough infections – cases where people got sick despite being fully vaccinated – in 13 jurisdictions in the United States between April 4 and July 17, 2021.
Epidemiologists compared breakthrough infections between two distinct points in time: Before and after the period when the Delta variant began causing most infections.
From April 4 to June 19, fully vaccinated people made up just 5% of cases, 7% of hospitalizations, and 8% of deaths. From June 20 to July 17, 18% of cases, 14% of hospitalizations, and 16% of deaths occurred in fully vaccinated people.
“After the week of June 20, 2021, when the SARS-CoV-2 Delta variant became predominant, the percentage of fully vaccinated persons among cases increased more than expected,” the study authors wrote.
Even after Delta swept the United States, fully vaccinated people were 5 times less likely to get a COVID-19 infection and more than 10 times less likely to be hospitalized or die from one.
“As we have shown in study after study, vaccination works,” CDC Director Rochelle Walensky, MD, said during the White House news briefing.
“We have the scientific tools we need to turn the corner on this pandemic. Vaccination works and will protect us from the severe complications of COVID-19,” she said.
A version of this article first appeared on WebMD.com.
The emergency rule ordering large employers to require COVID-19 vaccines or weekly tests for their workers could be ready “within weeks,” officials said in a news briefing Sept. 10.
Labor Secretary Martin Walsh will oversee the Occupational Safety and Health Administration as the agency drafts what’s known as an emergency temporary standard, similar to the one that was issued a few months ago to protect health care workers during the pandemic.
The rule should be ready within weeks, said Jeff Zients, coordinator of the White House COVID-19 response team.
He said the ultimate goal of the president’s plan is to increase vaccinations as quickly as possible to keep schools open, the economy recovering, and to decrease hospitalizations and deaths from COVID.
Mr. Zients declined to set hard numbers around those goals, but other experts did.
“What we need to get to is 85% to 90% population immunity, and that’s going to be immunity both from vaccines and infections, before that really begins to have a substantial dampening effect on viral spread,” Ashish Jha, MD, dean of the Brown University School of Public Health, Providence, R.I., said on a call with reporters Sept. 9.
He said immunity needs to be that high because the Delta variant is so contagious.
Mandates are seen as the most effective way to increase immunity and do it quickly.
David Michaels, PhD, an epidemiologist and professor at George Washington University, Washington, says OSHA will have to work through a number of steps to develop the rule.
“OSHA will have to write a preamble explaining the standard, its justifications, its costs, and how it will be enforced,” says Dr. Michaels, who led OSHA for the Obama administration. After that, the rule will be reviewed by the White House. Then employers will have some time – typically 30 days – to comply.
In addition to drafting the standard, OSHA will oversee its enforcement.
Companies that refuse to follow the standard could be fined $13,600 per violation, Mr. Zients said.
Dr. Michaels said he doesn’t expect enforcement to be a big issue, and he said we’re likely to see the rule well before it is final.
“Most employers are law-abiding. When OSHA issues a standard, they try to meet whatever those requirements are, and generally that starts to happen when the rule is announced, even before it goes into effect,” he said.
The rule may face legal challenges as well. Several governors and state attorneys general, as well as the Republican National Committee, have promised lawsuits to stop the vaccine mandates.
Critics of the new mandates say they impinge on personal freedom and impose burdens on businesses.
But the president hit back at that notion Sept. 10.
“Look, I am so disappointed that, particularly some of the Republican governors, have been so cavalier with the health of these kids, so cavalier of the health of their communities,” President Biden told reporters.
“I don’t know of any scientist out there in this field who doesn’t think it makes considerable sense to do the six things I’ve suggested.”
Yet, others feel the new requirements didn’t go far enough.
“These are good steps in the right direction, but they’re not enough to get the job done,” said Leana Wen, MD, in an op-ed for The Washington Post.
Dr. Wen, an expert in public health, wondered why President Biden didn’t mandate vaccinations for plane and train travel. She was disappointed that children 12 and older weren’t required to be vaccinated, too.
“There are mandates for childhood immunizations in every state. The coronavirus vaccine should be no different,” she wrote.
Vaccines remain the cornerstone of U.S. plans to control the pandemic.
On Sept. 10, there was new research from the CDC and state health departments showing that the COVID-19 vaccines continue to be highly effective at preventing severe illness and death.
But the study also found that the vaccines became less effective in the United States after Delta became the dominant cause of infections here.
The study, which included more than 600,000 COVID-19 cases, analyzed breakthrough infections – cases where people got sick despite being fully vaccinated – in 13 jurisdictions in the United States between April 4 and July 17, 2021.
Epidemiologists compared breakthrough infections between two distinct points in time: Before and after the period when the Delta variant began causing most infections.
From April 4 to June 19, fully vaccinated people made up just 5% of cases, 7% of hospitalizations, and 8% of deaths. From June 20 to July 17, 18% of cases, 14% of hospitalizations, and 16% of deaths occurred in fully vaccinated people.
“After the week of June 20, 2021, when the SARS-CoV-2 Delta variant became predominant, the percentage of fully vaccinated persons among cases increased more than expected,” the study authors wrote.
Even after Delta swept the United States, fully vaccinated people were 5 times less likely to get a COVID-19 infection and more than 10 times less likely to be hospitalized or die from one.
“As we have shown in study after study, vaccination works,” CDC Director Rochelle Walensky, MD, said during the White House news briefing.
“We have the scientific tools we need to turn the corner on this pandemic. Vaccination works and will protect us from the severe complications of COVID-19,” she said.
A version of this article first appeared on WebMD.com.
Even those who just test positive at more risk for long COVID: CDC
Long-term symptoms, like those linked with COVID-19, were common in people who had even just a single positive test, new Centers for Disease Control and Prevention data show.
The data show that symptoms in this group – including fatigue, cough, and headache – tended to last for more than a month.
Frequency of symptoms in people with a positive test was 1.5 times higher, compared with people whose tests had always been negative, according to the research published in the CDC’s latest Morbidity and Mortality Weekly Report.
Lead author Valentine Wanga, PhD, with the CDC’s COVID-19 response team, and colleagues conducted a non–probability-based internet panel survey of about 6,000 U.S. adults to assess long-term symptoms often associated with COVID-19 among those who had ever tested positive or always tested negative for COVID-19 between January 2020 and April 2021.
William Schaffner, MD, an infectious disease expert at Vanderbilt University, Nashville, Tenn., said in an interview that this research “establishes more securely than before that you don’t have to be hospitalized with COVID in order to develop long COVID symptoms.”
That’s better known among infectious disease experts, he said, but added that “this survey really gives a firm database for that.”
Study results
The study’s results showed that, compared with respondents who had a negative test result, those who received a positive result reported a significantly higher prevalence of any long-term symptom (65.9% vs. 42.9%), fatigue (22.5% vs. 12.0%), change in sense of smell or taste (17.3% vs. 1.7%), shortness of breath (15.5% vs. 5.2%), cough (14.5% vs. 4.9%), and headache (13.8% vs. 9.9%).
More people who had a positive test result (76.2%) reported persistence for more than a month of at least one initially occurring symptom, compared with those whose test results were always negative (69.6%).
The numbers are further proof, Dr. Schaffner said, that COVID not only will be an acute stressor on the health care system but patients with long COVID will need help with managing care for the long term.
“We still don’t know what the COVID virus does that results in these long COVID symptoms,” he said. Vanderbilt and many other institutions have developed “long COVID” centers as a testament to how important the problem is.
Long COVID symptoms are not well understood and most studies have looked at the effects from patients who had been hospitalized with COVID-19.
In this survey, respondents self-reported whether they had ever had a positive SARS-CoV-2 test result (698), always received a negative test result (2,437), or never were tested for SARS-CoV-2 (2,750).
Compared with those who always tested negative, a larger proportion of those who tested positive (28.7% vs. 15.7%) reported believing that receiving a COVID-19 vaccine made their long-term symptoms better. No difference was found in reported beliefs that a vaccine made long-term symptoms worse.
Dr. Schaffner said he found that survey result interesting, but said that is not backed up by current data and would need further study.
“I would treat that with great caution,” he said. “I’m not dismissing it, but you can’t take that at face value. All of us who get sick and those of us who care for people who are sick – if there’s an intervention, we all hope for the best. We’re being optimistic. It’s when you do a randomized, double-blind, placebo-controlled study that you can find out whether your instincts or hopes were correct.”
The authors said that findings can inform public health preparedness, help guide care for people with post-COVID conditions, and help make the case for vaccines.
The study authors and Dr. Schaffner disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Long-term symptoms, like those linked with COVID-19, were common in people who had even just a single positive test, new Centers for Disease Control and Prevention data show.
The data show that symptoms in this group – including fatigue, cough, and headache – tended to last for more than a month.
Frequency of symptoms in people with a positive test was 1.5 times higher, compared with people whose tests had always been negative, according to the research published in the CDC’s latest Morbidity and Mortality Weekly Report.
Lead author Valentine Wanga, PhD, with the CDC’s COVID-19 response team, and colleagues conducted a non–probability-based internet panel survey of about 6,000 U.S. adults to assess long-term symptoms often associated with COVID-19 among those who had ever tested positive or always tested negative for COVID-19 between January 2020 and April 2021.
William Schaffner, MD, an infectious disease expert at Vanderbilt University, Nashville, Tenn., said in an interview that this research “establishes more securely than before that you don’t have to be hospitalized with COVID in order to develop long COVID symptoms.”
That’s better known among infectious disease experts, he said, but added that “this survey really gives a firm database for that.”
Study results
The study’s results showed that, compared with respondents who had a negative test result, those who received a positive result reported a significantly higher prevalence of any long-term symptom (65.9% vs. 42.9%), fatigue (22.5% vs. 12.0%), change in sense of smell or taste (17.3% vs. 1.7%), shortness of breath (15.5% vs. 5.2%), cough (14.5% vs. 4.9%), and headache (13.8% vs. 9.9%).
More people who had a positive test result (76.2%) reported persistence for more than a month of at least one initially occurring symptom, compared with those whose test results were always negative (69.6%).
The numbers are further proof, Dr. Schaffner said, that COVID not only will be an acute stressor on the health care system but patients with long COVID will need help with managing care for the long term.
“We still don’t know what the COVID virus does that results in these long COVID symptoms,” he said. Vanderbilt and many other institutions have developed “long COVID” centers as a testament to how important the problem is.
Long COVID symptoms are not well understood and most studies have looked at the effects from patients who had been hospitalized with COVID-19.
In this survey, respondents self-reported whether they had ever had a positive SARS-CoV-2 test result (698), always received a negative test result (2,437), or never were tested for SARS-CoV-2 (2,750).
Compared with those who always tested negative, a larger proportion of those who tested positive (28.7% vs. 15.7%) reported believing that receiving a COVID-19 vaccine made their long-term symptoms better. No difference was found in reported beliefs that a vaccine made long-term symptoms worse.
Dr. Schaffner said he found that survey result interesting, but said that is not backed up by current data and would need further study.
“I would treat that with great caution,” he said. “I’m not dismissing it, but you can’t take that at face value. All of us who get sick and those of us who care for people who are sick – if there’s an intervention, we all hope for the best. We’re being optimistic. It’s when you do a randomized, double-blind, placebo-controlled study that you can find out whether your instincts or hopes were correct.”
The authors said that findings can inform public health preparedness, help guide care for people with post-COVID conditions, and help make the case for vaccines.
The study authors and Dr. Schaffner disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Long-term symptoms, like those linked with COVID-19, were common in people who had even just a single positive test, new Centers for Disease Control and Prevention data show.
The data show that symptoms in this group – including fatigue, cough, and headache – tended to last for more than a month.
Frequency of symptoms in people with a positive test was 1.5 times higher, compared with people whose tests had always been negative, according to the research published in the CDC’s latest Morbidity and Mortality Weekly Report.
Lead author Valentine Wanga, PhD, with the CDC’s COVID-19 response team, and colleagues conducted a non–probability-based internet panel survey of about 6,000 U.S. adults to assess long-term symptoms often associated with COVID-19 among those who had ever tested positive or always tested negative for COVID-19 between January 2020 and April 2021.
William Schaffner, MD, an infectious disease expert at Vanderbilt University, Nashville, Tenn., said in an interview that this research “establishes more securely than before that you don’t have to be hospitalized with COVID in order to develop long COVID symptoms.”
That’s better known among infectious disease experts, he said, but added that “this survey really gives a firm database for that.”
Study results
The study’s results showed that, compared with respondents who had a negative test result, those who received a positive result reported a significantly higher prevalence of any long-term symptom (65.9% vs. 42.9%), fatigue (22.5% vs. 12.0%), change in sense of smell or taste (17.3% vs. 1.7%), shortness of breath (15.5% vs. 5.2%), cough (14.5% vs. 4.9%), and headache (13.8% vs. 9.9%).
More people who had a positive test result (76.2%) reported persistence for more than a month of at least one initially occurring symptom, compared with those whose test results were always negative (69.6%).
The numbers are further proof, Dr. Schaffner said, that COVID not only will be an acute stressor on the health care system but patients with long COVID will need help with managing care for the long term.
“We still don’t know what the COVID virus does that results in these long COVID symptoms,” he said. Vanderbilt and many other institutions have developed “long COVID” centers as a testament to how important the problem is.
Long COVID symptoms are not well understood and most studies have looked at the effects from patients who had been hospitalized with COVID-19.
In this survey, respondents self-reported whether they had ever had a positive SARS-CoV-2 test result (698), always received a negative test result (2,437), or never were tested for SARS-CoV-2 (2,750).
Compared with those who always tested negative, a larger proportion of those who tested positive (28.7% vs. 15.7%) reported believing that receiving a COVID-19 vaccine made their long-term symptoms better. No difference was found in reported beliefs that a vaccine made long-term symptoms worse.
Dr. Schaffner said he found that survey result interesting, but said that is not backed up by current data and would need further study.
“I would treat that with great caution,” he said. “I’m not dismissing it, but you can’t take that at face value. All of us who get sick and those of us who care for people who are sick – if there’s an intervention, we all hope for the best. We’re being optimistic. It’s when you do a randomized, double-blind, placebo-controlled study that you can find out whether your instincts or hopes were correct.”
The authors said that findings can inform public health preparedness, help guide care for people with post-COVID conditions, and help make the case for vaccines.
The study authors and Dr. Schaffner disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Sweeping new vaccine mandates will impact most U.S. workers
, including sweeping vaccine mandates that will affect 100 million American workers, nearly two-thirds of the country’s workforce.
“As your president, I’m announcing tonight a new plan to get more Americans vaccinated to combat those blocking public health,” he said Sept. 9.
As part of a six-part plan unveiled in a speech from the State Dining Room of the White House, President Biden said he would require vaccinations for nearly 4 million federal workers and the employees of companies that contract with the federal government.
He has also directed the Occupational Safety and Health Administration to develop a rule that will require large employers -- those with at least 100 employees -- to ensure their workers are vaccinated or tested weekly.
Nearly 17 million health care workers will face new vaccine mandates as part of the conditions of participation in the Medicare and Medicaid programs.
President Biden said the federal government will require staff at federally funded Head Start programs and schools to be vaccinated. He’s also calling on all states to mandate vaccines for teachers.
“A distinct minority of Americans, supported by a distinct minority of elected officials, are keeping us from turning the corner,” PresidentBiden said. “These pandemic politics, as I refer to them, are making people sick, causing unvaccinated people to die.”
One public health official said he was glad to see the president’s bold action.
“What I saw today was the federal government trying to use its powers to create greater safety in the American population,” said Ashish K. Jha, MD, dean of the school of public health at Brown University, Providence, R.I., in a call with reporters after the speech.
National Nurses United, the largest union of registered nurses in the United States, issued a statement in support of President Biden’s new vaccination requirements, but pushed back on his language.
“…as advocates for public health, registered nurses want to be extremely clear: There is no such thing as a pandemic of only the unvaccinated. The science of epidemiology tells us there is just one deadly, global pandemic that has not yet ended, and we are all in it together. To get out of it, we must act together. All of us,” the statement says.
A host of other professional groups, including the American Medical Association and the Association of State and Territorial Health Officials, also issued statements of support for President Biden’s plan.
But the plan was not well received by all.
“I will pursue every legal option available to the state of Georgia to stop this blatantly unlawful overreach by the Biden Administration,” said Georgia Governor Brian Kemp, a Republican, in a Tweet.
The National Council for Occupational Safety and Health called the plan “a missed opportunity” because it failed to include workplace protections for essential workers such as grocery, postal, and transit workers.
“Social distancing, improved ventilation, shift rotation, and protective equipment to reduce exposure are important components of an overall plan to reduce risk and stop the virus. These tools are missing from the new steps President Biden announced today,” said Jessica Martinez, co-executive director of the group.
In addition to the new vaccination requirements, President Biden said extra doses would be on the way for people who have already been fully vaccinated in order to protect against waning immunity, starting on Sept. 20. But he noted that those plans would be contingent on the Food and Drug Administration’s approval for third doses and the Centers for Disease Control and Prevention’s recommendation of the shots.
President Biden pledged to use the Defense Production Act to ramp up production of at-home tests, which have been selling out across the nation as the Delta variant spreads.
He also announced plans to expand access to COVID-19 testing, including offering testing for free at thousands of pharmacies nationwide and getting major retailers to sell at-home COVID-19 tests at cost.
The BinaxNow test kit, which currently retails for $23.99, will now cost about $15 for two tests at Kroger, Amazon, and Walmart, according to the White House. Food banks and community health centers will get free tests, too.
He called on states to set up COVID-19 testing programs at all schools.
Jha said that in his view, the big, game-changing news out of the president’s speech was the expansion of testing.
“Our country has failed to deploy tests in a way that can really bring this pandemic under control,” Jha said. “There are plenty of reasons, data, experience to indicate that if these were widely available, it would make a dramatic difference in reducing infection numbers across our country.”.
Dr. Jha said the private market had not worked effectively to make testing more widely available, so it was “absolutely a requirement of the federal government to step in and make testing more widely available,” he said.
President Biden also announced new economic stimulus programs, saying he’s expanding loan programs to small businesses and streamlining the loan forgiveness process.
President Biden said he’s boosting help for overburdened hospitals, doubling the number of federal surge response teams sent to hard-hit areas to reduce the strain on local health care workers. He said he would increase the pace of antibody treatments to states by 50%.
“We made so much progress during the past 7 months of this pandemic. Even so, we remain at a critical moment, a critical time,” he said. “We have the tools. Now, we just have to finish the job with truth, with science, with confidence and together as one nation.”
A version of this article first appeared on WebMD.com.
, including sweeping vaccine mandates that will affect 100 million American workers, nearly two-thirds of the country’s workforce.
“As your president, I’m announcing tonight a new plan to get more Americans vaccinated to combat those blocking public health,” he said Sept. 9.
As part of a six-part plan unveiled in a speech from the State Dining Room of the White House, President Biden said he would require vaccinations for nearly 4 million federal workers and the employees of companies that contract with the federal government.
He has also directed the Occupational Safety and Health Administration to develop a rule that will require large employers -- those with at least 100 employees -- to ensure their workers are vaccinated or tested weekly.
Nearly 17 million health care workers will face new vaccine mandates as part of the conditions of participation in the Medicare and Medicaid programs.
President Biden said the federal government will require staff at federally funded Head Start programs and schools to be vaccinated. He’s also calling on all states to mandate vaccines for teachers.
“A distinct minority of Americans, supported by a distinct minority of elected officials, are keeping us from turning the corner,” PresidentBiden said. “These pandemic politics, as I refer to them, are making people sick, causing unvaccinated people to die.”
One public health official said he was glad to see the president’s bold action.
“What I saw today was the federal government trying to use its powers to create greater safety in the American population,” said Ashish K. Jha, MD, dean of the school of public health at Brown University, Providence, R.I., in a call with reporters after the speech.
National Nurses United, the largest union of registered nurses in the United States, issued a statement in support of President Biden’s new vaccination requirements, but pushed back on his language.
“…as advocates for public health, registered nurses want to be extremely clear: There is no such thing as a pandemic of only the unvaccinated. The science of epidemiology tells us there is just one deadly, global pandemic that has not yet ended, and we are all in it together. To get out of it, we must act together. All of us,” the statement says.
A host of other professional groups, including the American Medical Association and the Association of State and Territorial Health Officials, also issued statements of support for President Biden’s plan.
But the plan was not well received by all.
“I will pursue every legal option available to the state of Georgia to stop this blatantly unlawful overreach by the Biden Administration,” said Georgia Governor Brian Kemp, a Republican, in a Tweet.
The National Council for Occupational Safety and Health called the plan “a missed opportunity” because it failed to include workplace protections for essential workers such as grocery, postal, and transit workers.
“Social distancing, improved ventilation, shift rotation, and protective equipment to reduce exposure are important components of an overall plan to reduce risk and stop the virus. These tools are missing from the new steps President Biden announced today,” said Jessica Martinez, co-executive director of the group.
In addition to the new vaccination requirements, President Biden said extra doses would be on the way for people who have already been fully vaccinated in order to protect against waning immunity, starting on Sept. 20. But he noted that those plans would be contingent on the Food and Drug Administration’s approval for third doses and the Centers for Disease Control and Prevention’s recommendation of the shots.
President Biden pledged to use the Defense Production Act to ramp up production of at-home tests, which have been selling out across the nation as the Delta variant spreads.
He also announced plans to expand access to COVID-19 testing, including offering testing for free at thousands of pharmacies nationwide and getting major retailers to sell at-home COVID-19 tests at cost.
The BinaxNow test kit, which currently retails for $23.99, will now cost about $15 for two tests at Kroger, Amazon, and Walmart, according to the White House. Food banks and community health centers will get free tests, too.
He called on states to set up COVID-19 testing programs at all schools.
Jha said that in his view, the big, game-changing news out of the president’s speech was the expansion of testing.
“Our country has failed to deploy tests in a way that can really bring this pandemic under control,” Jha said. “There are plenty of reasons, data, experience to indicate that if these were widely available, it would make a dramatic difference in reducing infection numbers across our country.”.
Dr. Jha said the private market had not worked effectively to make testing more widely available, so it was “absolutely a requirement of the federal government to step in and make testing more widely available,” he said.
President Biden also announced new economic stimulus programs, saying he’s expanding loan programs to small businesses and streamlining the loan forgiveness process.
President Biden said he’s boosting help for overburdened hospitals, doubling the number of federal surge response teams sent to hard-hit areas to reduce the strain on local health care workers. He said he would increase the pace of antibody treatments to states by 50%.
“We made so much progress during the past 7 months of this pandemic. Even so, we remain at a critical moment, a critical time,” he said. “We have the tools. Now, we just have to finish the job with truth, with science, with confidence and together as one nation.”
A version of this article first appeared on WebMD.com.
, including sweeping vaccine mandates that will affect 100 million American workers, nearly two-thirds of the country’s workforce.
“As your president, I’m announcing tonight a new plan to get more Americans vaccinated to combat those blocking public health,” he said Sept. 9.
As part of a six-part plan unveiled in a speech from the State Dining Room of the White House, President Biden said he would require vaccinations for nearly 4 million federal workers and the employees of companies that contract with the federal government.
He has also directed the Occupational Safety and Health Administration to develop a rule that will require large employers -- those with at least 100 employees -- to ensure their workers are vaccinated or tested weekly.
Nearly 17 million health care workers will face new vaccine mandates as part of the conditions of participation in the Medicare and Medicaid programs.
President Biden said the federal government will require staff at federally funded Head Start programs and schools to be vaccinated. He’s also calling on all states to mandate vaccines for teachers.
“A distinct minority of Americans, supported by a distinct minority of elected officials, are keeping us from turning the corner,” PresidentBiden said. “These pandemic politics, as I refer to them, are making people sick, causing unvaccinated people to die.”
One public health official said he was glad to see the president’s bold action.
“What I saw today was the federal government trying to use its powers to create greater safety in the American population,” said Ashish K. Jha, MD, dean of the school of public health at Brown University, Providence, R.I., in a call with reporters after the speech.
National Nurses United, the largest union of registered nurses in the United States, issued a statement in support of President Biden’s new vaccination requirements, but pushed back on his language.
“…as advocates for public health, registered nurses want to be extremely clear: There is no such thing as a pandemic of only the unvaccinated. The science of epidemiology tells us there is just one deadly, global pandemic that has not yet ended, and we are all in it together. To get out of it, we must act together. All of us,” the statement says.
A host of other professional groups, including the American Medical Association and the Association of State and Territorial Health Officials, also issued statements of support for President Biden’s plan.
But the plan was not well received by all.
“I will pursue every legal option available to the state of Georgia to stop this blatantly unlawful overreach by the Biden Administration,” said Georgia Governor Brian Kemp, a Republican, in a Tweet.
The National Council for Occupational Safety and Health called the plan “a missed opportunity” because it failed to include workplace protections for essential workers such as grocery, postal, and transit workers.
“Social distancing, improved ventilation, shift rotation, and protective equipment to reduce exposure are important components of an overall plan to reduce risk and stop the virus. These tools are missing from the new steps President Biden announced today,” said Jessica Martinez, co-executive director of the group.
In addition to the new vaccination requirements, President Biden said extra doses would be on the way for people who have already been fully vaccinated in order to protect against waning immunity, starting on Sept. 20. But he noted that those plans would be contingent on the Food and Drug Administration’s approval for third doses and the Centers for Disease Control and Prevention’s recommendation of the shots.
President Biden pledged to use the Defense Production Act to ramp up production of at-home tests, which have been selling out across the nation as the Delta variant spreads.
He also announced plans to expand access to COVID-19 testing, including offering testing for free at thousands of pharmacies nationwide and getting major retailers to sell at-home COVID-19 tests at cost.
The BinaxNow test kit, which currently retails for $23.99, will now cost about $15 for two tests at Kroger, Amazon, and Walmart, according to the White House. Food banks and community health centers will get free tests, too.
He called on states to set up COVID-19 testing programs at all schools.
Jha said that in his view, the big, game-changing news out of the president’s speech was the expansion of testing.
“Our country has failed to deploy tests in a way that can really bring this pandemic under control,” Jha said. “There are plenty of reasons, data, experience to indicate that if these were widely available, it would make a dramatic difference in reducing infection numbers across our country.”.
Dr. Jha said the private market had not worked effectively to make testing more widely available, so it was “absolutely a requirement of the federal government to step in and make testing more widely available,” he said.
President Biden also announced new economic stimulus programs, saying he’s expanding loan programs to small businesses and streamlining the loan forgiveness process.
President Biden said he’s boosting help for overburdened hospitals, doubling the number of federal surge response teams sent to hard-hit areas to reduce the strain on local health care workers. He said he would increase the pace of antibody treatments to states by 50%.
“We made so much progress during the past 7 months of this pandemic. Even so, we remain at a critical moment, a critical time,” he said. “We have the tools. Now, we just have to finish the job with truth, with science, with confidence and together as one nation.”
A version of this article first appeared on WebMD.com.
Long COVID could spell kidney troubles down the line
Physicians caring for COVID-19 survivors should routinely check kidney function, which is often damaged by the SARS-CoV-2 virus months after both severe and milder cases, new research indicates.
The largest study to date with the longest follow-up of COVID-19-related kidney outcomes also found that every type of kidney problem, including end-stage kidney disease (ESKD), was far more common in COVID-19 survivors who were admitted to the ICU or experienced acute kidney injury (AKI) while hospitalized.
Researchers analyzed U.S. Veterans Health Administration data from more than 1.7 million patients, including more than 89,000 who tested positive for COVID-19, for the study, which was published online Sept. 1, 2021, in the Journal of the American Society of Nephrology.
The risk of kidney problems “is more robust or pronounced in people who have had severe infection, but present in even asymptomatic and mild disease, which shouldn’t be discounted. Those people represent the majority of those with COVID-19,” said senior author Ziyad Al-Aly, MD, of the Veteran Affairs St. Louis Health Care System.
“That’s why the results are important, because even in people with mild disease to start with, the risk of kidney problems is not trivial,” he told this news organization. “It’s smaller than in people who were in the ICU, but it’s not ... zero.”
Experts aren’t yet certain how COVID-19 can damage the kidneys, hypothesizing that several factors may be at play. The virus may directly infect kidney cells rich in ACE2 receptors, which are key to infection, said nephrologist F. Perry Wilson, MD, of Yale University, New Haven, Conn., and a member of Medscape’s advisory board.
Kidneys might also be particularly vulnerable to the inflammatory cascade or blood clotting often seen in COVID-19, Dr. Al-Aly and Wilson both suggested.
COVID-19 survivors more likely to have kidney damage than controls
“A lot of health systems either have or are establishing post-COVID care clinics, which we think should definitely incorporate a kidney component,” Dr. Al-Aly advised. “They should check patients’ blood and urine for kidney problems.”
This is particularly important because “kidney problems, for the most part, are painless and silent,” he added.
“Realizing 2 years down the road that someone has ESKD, where they need dialysis or a kidney transplant, is what we don’t want. We don’t want this to be unrecognized, uncared for, unattended to,” he said.
Dr. Al-Aly and colleagues evaluated VA health system records, including data from 89,216 patients who tested positive for COVID-19 between March 2020 and March 2021, as well as 1.7 million controls who did not have COVID-19. Over a median follow-up of about 5.5 months, participants’ estimated glomerular filtration rate and serum creatinine levels were tracked to assess kidney health and outcomes according to infection severity.
Results were striking, with COVID-19 survivors about one-third more likely than controls to have kidney damage or significant declines in kidney function between 1 and 6 months after infection. More than 4,700 COVID-19 survivors had lost at least 30% of their kidney function within a year, and these patients were 25% more likely to reach that level of decline than controls.
Additionally, COVID-19 survivors were nearly twice as likely to experience AKI and almost three times as likely to be diagnosed with ESKD as controls.
If your patient had COVID-19, ‘it’s reasonable to check kidney function’
“This information tells us that if your patient was sick with COVID-19 and comes for follow-up visits, it’s reasonable to check their kidney function,” Dr. Wilson, who was not involved with the research, told this news organization.
“Even for patients who were not hospitalized, if they were laid low or dehydrated ... it should be part of the post-COVID care package,” he said.
If just a fraction of the millions of COVID-19 survivors in the United States develop long-term kidney problems, the ripple effect on American health care could be substantial, Dr. Wilson and Dr. Al-Aly agreed.
“We’re still living in a pandemic, so it’s hard to tell the total impact,” Dr. Al-Aly said. “But this ultimately will contribute to a rise in burden of kidney disease. This and other long COVID manifestations are going to alter the landscape of clinical care and health care in the United States for a decade or more.”
Because renal problems can limit a patient’s treatment options for other major diseases, including diabetes and cancer, COVID-related kidney damage can ultimately impact survivability.
“There are a lot of medications you can’t use in people with advanced kidney problems,” Dr. Al-Aly said.
The main study limitation was that patients were mostly older White men (median age, 68 years), although more than 9,000 women were included in the VA data, Dr. Al-Aly noted. Additionally, controls were more likely to be younger, Black, living in long-term care, and have higher rates of chronic health conditions and medication use.
The experts agreed that ongoing research tracking kidney outcomes is crucial for years to come.
“We also need to be following a cohort of these patients as part of a research protocol where they come in every 6 months for a standard set of lab tests to really understand what’s going on with their kidneys,” Dr. Wilson said.
“Lastly – and a much tougher sell – is we need biopsies. It’s very hard to infer what’s going on in complex disease with the kidneys without biopsy tissue,” he added.
The study was funded by the American Society of Nephrology and the Department of Veterans Affairs. Dr. Al-Aly and Dr. Wilson reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Physicians caring for COVID-19 survivors should routinely check kidney function, which is often damaged by the SARS-CoV-2 virus months after both severe and milder cases, new research indicates.
The largest study to date with the longest follow-up of COVID-19-related kidney outcomes also found that every type of kidney problem, including end-stage kidney disease (ESKD), was far more common in COVID-19 survivors who were admitted to the ICU or experienced acute kidney injury (AKI) while hospitalized.
Researchers analyzed U.S. Veterans Health Administration data from more than 1.7 million patients, including more than 89,000 who tested positive for COVID-19, for the study, which was published online Sept. 1, 2021, in the Journal of the American Society of Nephrology.
The risk of kidney problems “is more robust or pronounced in people who have had severe infection, but present in even asymptomatic and mild disease, which shouldn’t be discounted. Those people represent the majority of those with COVID-19,” said senior author Ziyad Al-Aly, MD, of the Veteran Affairs St. Louis Health Care System.
“That’s why the results are important, because even in people with mild disease to start with, the risk of kidney problems is not trivial,” he told this news organization. “It’s smaller than in people who were in the ICU, but it’s not ... zero.”
Experts aren’t yet certain how COVID-19 can damage the kidneys, hypothesizing that several factors may be at play. The virus may directly infect kidney cells rich in ACE2 receptors, which are key to infection, said nephrologist F. Perry Wilson, MD, of Yale University, New Haven, Conn., and a member of Medscape’s advisory board.
Kidneys might also be particularly vulnerable to the inflammatory cascade or blood clotting often seen in COVID-19, Dr. Al-Aly and Wilson both suggested.
COVID-19 survivors more likely to have kidney damage than controls
“A lot of health systems either have or are establishing post-COVID care clinics, which we think should definitely incorporate a kidney component,” Dr. Al-Aly advised. “They should check patients’ blood and urine for kidney problems.”
This is particularly important because “kidney problems, for the most part, are painless and silent,” he added.
“Realizing 2 years down the road that someone has ESKD, where they need dialysis or a kidney transplant, is what we don’t want. We don’t want this to be unrecognized, uncared for, unattended to,” he said.
Dr. Al-Aly and colleagues evaluated VA health system records, including data from 89,216 patients who tested positive for COVID-19 between March 2020 and March 2021, as well as 1.7 million controls who did not have COVID-19. Over a median follow-up of about 5.5 months, participants’ estimated glomerular filtration rate and serum creatinine levels were tracked to assess kidney health and outcomes according to infection severity.
Results were striking, with COVID-19 survivors about one-third more likely than controls to have kidney damage or significant declines in kidney function between 1 and 6 months after infection. More than 4,700 COVID-19 survivors had lost at least 30% of their kidney function within a year, and these patients were 25% more likely to reach that level of decline than controls.
Additionally, COVID-19 survivors were nearly twice as likely to experience AKI and almost three times as likely to be diagnosed with ESKD as controls.
If your patient had COVID-19, ‘it’s reasonable to check kidney function’
“This information tells us that if your patient was sick with COVID-19 and comes for follow-up visits, it’s reasonable to check their kidney function,” Dr. Wilson, who was not involved with the research, told this news organization.
“Even for patients who were not hospitalized, if they were laid low or dehydrated ... it should be part of the post-COVID care package,” he said.
If just a fraction of the millions of COVID-19 survivors in the United States develop long-term kidney problems, the ripple effect on American health care could be substantial, Dr. Wilson and Dr. Al-Aly agreed.
“We’re still living in a pandemic, so it’s hard to tell the total impact,” Dr. Al-Aly said. “But this ultimately will contribute to a rise in burden of kidney disease. This and other long COVID manifestations are going to alter the landscape of clinical care and health care in the United States for a decade or more.”
Because renal problems can limit a patient’s treatment options for other major diseases, including diabetes and cancer, COVID-related kidney damage can ultimately impact survivability.
“There are a lot of medications you can’t use in people with advanced kidney problems,” Dr. Al-Aly said.
The main study limitation was that patients were mostly older White men (median age, 68 years), although more than 9,000 women were included in the VA data, Dr. Al-Aly noted. Additionally, controls were more likely to be younger, Black, living in long-term care, and have higher rates of chronic health conditions and medication use.
The experts agreed that ongoing research tracking kidney outcomes is crucial for years to come.
“We also need to be following a cohort of these patients as part of a research protocol where they come in every 6 months for a standard set of lab tests to really understand what’s going on with their kidneys,” Dr. Wilson said.
“Lastly – and a much tougher sell – is we need biopsies. It’s very hard to infer what’s going on in complex disease with the kidneys without biopsy tissue,” he added.
The study was funded by the American Society of Nephrology and the Department of Veterans Affairs. Dr. Al-Aly and Dr. Wilson reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Physicians caring for COVID-19 survivors should routinely check kidney function, which is often damaged by the SARS-CoV-2 virus months after both severe and milder cases, new research indicates.
The largest study to date with the longest follow-up of COVID-19-related kidney outcomes also found that every type of kidney problem, including end-stage kidney disease (ESKD), was far more common in COVID-19 survivors who were admitted to the ICU or experienced acute kidney injury (AKI) while hospitalized.
Researchers analyzed U.S. Veterans Health Administration data from more than 1.7 million patients, including more than 89,000 who tested positive for COVID-19, for the study, which was published online Sept. 1, 2021, in the Journal of the American Society of Nephrology.
The risk of kidney problems “is more robust or pronounced in people who have had severe infection, but present in even asymptomatic and mild disease, which shouldn’t be discounted. Those people represent the majority of those with COVID-19,” said senior author Ziyad Al-Aly, MD, of the Veteran Affairs St. Louis Health Care System.
“That’s why the results are important, because even in people with mild disease to start with, the risk of kidney problems is not trivial,” he told this news organization. “It’s smaller than in people who were in the ICU, but it’s not ... zero.”
Experts aren’t yet certain how COVID-19 can damage the kidneys, hypothesizing that several factors may be at play. The virus may directly infect kidney cells rich in ACE2 receptors, which are key to infection, said nephrologist F. Perry Wilson, MD, of Yale University, New Haven, Conn., and a member of Medscape’s advisory board.
Kidneys might also be particularly vulnerable to the inflammatory cascade or blood clotting often seen in COVID-19, Dr. Al-Aly and Wilson both suggested.
COVID-19 survivors more likely to have kidney damage than controls
“A lot of health systems either have or are establishing post-COVID care clinics, which we think should definitely incorporate a kidney component,” Dr. Al-Aly advised. “They should check patients’ blood and urine for kidney problems.”
This is particularly important because “kidney problems, for the most part, are painless and silent,” he added.
“Realizing 2 years down the road that someone has ESKD, where they need dialysis or a kidney transplant, is what we don’t want. We don’t want this to be unrecognized, uncared for, unattended to,” he said.
Dr. Al-Aly and colleagues evaluated VA health system records, including data from 89,216 patients who tested positive for COVID-19 between March 2020 and March 2021, as well as 1.7 million controls who did not have COVID-19. Over a median follow-up of about 5.5 months, participants’ estimated glomerular filtration rate and serum creatinine levels were tracked to assess kidney health and outcomes according to infection severity.
Results were striking, with COVID-19 survivors about one-third more likely than controls to have kidney damage or significant declines in kidney function between 1 and 6 months after infection. More than 4,700 COVID-19 survivors had lost at least 30% of their kidney function within a year, and these patients were 25% more likely to reach that level of decline than controls.
Additionally, COVID-19 survivors were nearly twice as likely to experience AKI and almost three times as likely to be diagnosed with ESKD as controls.
If your patient had COVID-19, ‘it’s reasonable to check kidney function’
“This information tells us that if your patient was sick with COVID-19 and comes for follow-up visits, it’s reasonable to check their kidney function,” Dr. Wilson, who was not involved with the research, told this news organization.
“Even for patients who were not hospitalized, if they were laid low or dehydrated ... it should be part of the post-COVID care package,” he said.
If just a fraction of the millions of COVID-19 survivors in the United States develop long-term kidney problems, the ripple effect on American health care could be substantial, Dr. Wilson and Dr. Al-Aly agreed.
“We’re still living in a pandemic, so it’s hard to tell the total impact,” Dr. Al-Aly said. “But this ultimately will contribute to a rise in burden of kidney disease. This and other long COVID manifestations are going to alter the landscape of clinical care and health care in the United States for a decade or more.”
Because renal problems can limit a patient’s treatment options for other major diseases, including diabetes and cancer, COVID-related kidney damage can ultimately impact survivability.
“There are a lot of medications you can’t use in people with advanced kidney problems,” Dr. Al-Aly said.
The main study limitation was that patients were mostly older White men (median age, 68 years), although more than 9,000 women were included in the VA data, Dr. Al-Aly noted. Additionally, controls were more likely to be younger, Black, living in long-term care, and have higher rates of chronic health conditions and medication use.
The experts agreed that ongoing research tracking kidney outcomes is crucial for years to come.
“We also need to be following a cohort of these patients as part of a research protocol where they come in every 6 months for a standard set of lab tests to really understand what’s going on with their kidneys,” Dr. Wilson said.
“Lastly – and a much tougher sell – is we need biopsies. It’s very hard to infer what’s going on in complex disease with the kidneys without biopsy tissue,” he added.
The study was funded by the American Society of Nephrology and the Department of Veterans Affairs. Dr. Al-Aly and Dr. Wilson reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
STOP-DAPT 2 ACS: 1 month of DAPT proves inadequate for patients with recent ACS
One month of dual antiplatelet therapy followed by 11 months of clopidogrel monotherapy failed to prove noninferiority to 12 unbroken months of DAPT for net clinical benefit in a multicenter Japanese trial that randomized more than 4,000 patients who underwent percutaneous coronary intervention (PCI) after a recent acute coronary syndrome episode.
The outcomes showed that while truncating DAPT duration could, as expected, cut major bleeding episodes roughly in half, it also led to a significant near doubling of myocardial infarction and showed a strong trend toward also increasing a composite tally of several types of ischemic events. These data were reported this week by Hirotoshi Watanabe, MD, PhD, at the virtual annual congress of the European Society of Cardiology. All study patients had undergone PCI with cobalt-chromium everolimus-eluting (CCEE) coronary stents (Xience).
These findings from the STOPDAPT-2 ACS trial highlighted the limits of minimizing DAPT after PCI in patients at high ischemic risk, such as after an acute coronary syndrome (ACS) event.
It also was a counterpoint to a somewhat similar study also reported at the congress, MASTER DAPT, which showed that 1 month of DAPT was noninferior to 3 or more months of DAPT for net clinical benefit in a distinctly different population of patients undergoing PCI (and using a different type of coronary stent) – those at high bleeding risk and with only about half the patients having had a recent ACS.
The results of STOPDAPT-2 ACS “do not support use of 1 month of DAPT followed by P2Y12 inhibitor monotherapy with clopidogrel compared with standard DAPT,” commented Robert A. Byrne, MBBCh, PhD, designated discussant for the report and professor at the RCSI University of Medicine and Health Sciences in Dublin.
“Although major bleeding was significantly reduced with this approach, there appeared to be a significant increase in adverse ischemic events, and there was a clear signal in relation to overall mortality, the ultimate arbiter of net clinical benefit,” added Dr. Byrne, who is also director of cardiology at Mater Private Hospital in Dublin.
He suggested that a mechanistic explanation for the signal of harm seem in STOPDAPT-2 ACS was the relatively low potency of clopidogrel (Plavix) as an antiplatelet agent, compared with other P2Y12 inhibitors such as prasugrel (Effient) and ticagrelor (Brilinta), as well as the genetically driven variability in response to clopidogrel that’s also absent with alternative agents.
These between-agent differences are of “particular clinical relevance in the early aftermath of an ACS event,” Dr. Byrne said.
12-month DAPT remains standard for PCI patients with recent ACS
The totality of clinical evidence “continues to support a standard 12-month duration of DAPT – using aspirin and either prasugrel or ticagrelor – as the preferred default approach,” Dr. Byrne concluded.
He acknowledged that an abbreviated duration of DAPT followed by P2Y12 inhibitor monotherapy “might be considered as an alternative.” In patients following an ACS event who do not have high risk for bleeding, he said, the minimum duration of DAPT should be at least 3 months and with preferential use of a more potent P2Y12 inhibitor.
Twelve months of DAPT treatment with aspirin and a P2Y12 inhibitor for patients following PCI “remains the standard of care in guidelines,” noted Marco Roffi, MD, a second discussant at the congress. But several questions remain, he added, such as which P2Y12 inhibitors work best and whether DAPT can be less than 12 months.
“The investigators [for STOPDAPT-2 ACS] pushed these questions to the limit with 1 month of DAPT and clopidogrel monotherapy,” said Dr. Roffi, professor and director of interventional cardiology at University Hospital, Geneva.
“This was a risky bet, and the investigators lost by not proving noninferiority and with excess ischemic events,” he commented.
First came STOPDAPT-2
Dr. Watanabe and colleagues designed STOPDAPT-2 ACS as a follow-up to their prior STOPDAPT-2 trial, which randomly assigned slightly more than 3000 patients at 90 Japanese centers to the identical two treatment options: 1 month of DAPT followed by 11 months of clopidogrel monotherapy or 12 months of DAPT, except the trial enrolled all types of patients undergoing PCI. This meant that a minority, 38%, had a recent ACS event, while the remaining patients had chronic coronary artery disease. As in STOPDAPT-2 ACS, all patients in STOPDAPT-2 had received a CCEE stent.
STOPDAPT-2 also used the same primary endpoint to tally net clinical benefit as STOPDAPT-2 ACS: cardiovascular death, MI, stroke of any type, definite stent thrombosis, or TIMI major or minor bleeding classification.
In STOPDAPT-2, using the mixed population with both recent ACS and chronic coronary disease, the regimen of 1 month of DAPT followed by 11 months of clopidogrel monotherapy was both noninferior to and superior to 12 months of DAPT, reducing the net adverse-event tally by 36% relative to 12-month DAPT and by an absolute reduction of 1.34%, as reported in 2019.
Despite this superiority, the results from STOPDAPT-2 had little impact on global practice, commented Kurt Huber, MD, professor and director of the cardiology ICU at the Medical University of Vienna.
“STOP-DAPT-2 did not give us a clear message with respect to reducing antiplatelet treatment after 1 month. I thought that for ACS patients 1 month might be too short,” Dr. Huber said during a press briefing.
Focusing on post-ACS
To directly address this issue, the investigators launched STOPDAPT-2 ACS, which used the same design as the preceding study but only enrolled patients soon after an ACS event. The trial included for its main analysis 3,008 newly enrolled patients with recent ACS, and 1,161 patients who had a recent ACS event and had been randomly assigned in STOPDAPT-2, creating a total study cohort for the new analysis of 4136 patients treated and followed for the study’s full 12 months.
The patients averaged 67 years old, 79% were men, and 30% had diabetes. About 56% had a recent ST-elevation MI, about 20% a recent non–ST-elevation MI, and the remaining 24% had unstable angina. For their unspecified P2Y12 inhibition, roughly half the patients received clopidogrel and the rest received prasugrel. Adherence to the two assigned treatment regimens was very good, with a very small number of patients not adhering to their assigned protocol.
The composite adverse event incidence over 12 months was 3.2% among those who received 1-month DAPT and 2.83% in those on DAPT for 12 months, a difference that failed to achieve the prespecified definition of noninferiority for 1-month DAPT, reported Dr. Watanabe, an interventional cardiologist at Kyoto University.
The ischemic event composite was 50% lower among those on 12-month DAPT, compared with 1 month of DAPT, a difference that just missed significance. The rate of MI was 91% higher with 1-month DAPT, compared with 12 months, a significant difference.
One-month DAPT also significantly reduced the primary measure of bleeding events – the combination of TIMI major and minor bleeds – by a significant 54%, compared with 12-month DAPT. A second metric of clinically meaningful bleeds, those that meet either the type 3 or 5 definition of the Bleeding Academic Research Consortium, were reduced by a significant 59% by 1-month DAPT, compared with 12 months of DAPT.
The new findings from STOPDAPT-2 ACS contrasted with those from MASTER DAPT, but in an explicable way that related to different patient types, different P2Y12 inhibitors, different treatment durations, and different stents.
“We’ve seen in MASTER DAPT that if you use the right stent and use ticagrelor for monotherapy there may be some ability to shorten DAPT, but we still do not know what would happen in patients with very high ischemic risk,” concluded Dr. Huber.
“A reduction in DAPT duration might work in patients without high bleeding risk, but I would exclude patients with very high ischemic risk,” he added. “I also can’t tell you whether 1 month or 3 months is the right approach, and I think clopidogrel is not the right drug to use for monotherapy after ACS.”
STOPDAPT-2 and STOPDAPT-2 ACS were both sponsored by Abbott Vascular, which markets the CCEE (Xience) stents used in both studies. Dr. Watanabe has received lecture fees from Abbott and from Daiichi-Sankyo. Dr. Byrne has received research funding from Abbott Vascular as well as from Biosensors, Biotronik, and Boston Scientific. Roffi has received research funding from Biotronik, Boston Scientific, GE Healthcare, Medtronic, and Terumo. Dr. Huber has received lecture fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, Pfizer, Sanofi-Aventis, and The Medicines Company.
A version of this article first appeared on Medscape.com.
One month of dual antiplatelet therapy followed by 11 months of clopidogrel monotherapy failed to prove noninferiority to 12 unbroken months of DAPT for net clinical benefit in a multicenter Japanese trial that randomized more than 4,000 patients who underwent percutaneous coronary intervention (PCI) after a recent acute coronary syndrome episode.
The outcomes showed that while truncating DAPT duration could, as expected, cut major bleeding episodes roughly in half, it also led to a significant near doubling of myocardial infarction and showed a strong trend toward also increasing a composite tally of several types of ischemic events. These data were reported this week by Hirotoshi Watanabe, MD, PhD, at the virtual annual congress of the European Society of Cardiology. All study patients had undergone PCI with cobalt-chromium everolimus-eluting (CCEE) coronary stents (Xience).
These findings from the STOPDAPT-2 ACS trial highlighted the limits of minimizing DAPT after PCI in patients at high ischemic risk, such as after an acute coronary syndrome (ACS) event.
It also was a counterpoint to a somewhat similar study also reported at the congress, MASTER DAPT, which showed that 1 month of DAPT was noninferior to 3 or more months of DAPT for net clinical benefit in a distinctly different population of patients undergoing PCI (and using a different type of coronary stent) – those at high bleeding risk and with only about half the patients having had a recent ACS.
The results of STOPDAPT-2 ACS “do not support use of 1 month of DAPT followed by P2Y12 inhibitor monotherapy with clopidogrel compared with standard DAPT,” commented Robert A. Byrne, MBBCh, PhD, designated discussant for the report and professor at the RCSI University of Medicine and Health Sciences in Dublin.
“Although major bleeding was significantly reduced with this approach, there appeared to be a significant increase in adverse ischemic events, and there was a clear signal in relation to overall mortality, the ultimate arbiter of net clinical benefit,” added Dr. Byrne, who is also director of cardiology at Mater Private Hospital in Dublin.
He suggested that a mechanistic explanation for the signal of harm seem in STOPDAPT-2 ACS was the relatively low potency of clopidogrel (Plavix) as an antiplatelet agent, compared with other P2Y12 inhibitors such as prasugrel (Effient) and ticagrelor (Brilinta), as well as the genetically driven variability in response to clopidogrel that’s also absent with alternative agents.
These between-agent differences are of “particular clinical relevance in the early aftermath of an ACS event,” Dr. Byrne said.
12-month DAPT remains standard for PCI patients with recent ACS
The totality of clinical evidence “continues to support a standard 12-month duration of DAPT – using aspirin and either prasugrel or ticagrelor – as the preferred default approach,” Dr. Byrne concluded.
He acknowledged that an abbreviated duration of DAPT followed by P2Y12 inhibitor monotherapy “might be considered as an alternative.” In patients following an ACS event who do not have high risk for bleeding, he said, the minimum duration of DAPT should be at least 3 months and with preferential use of a more potent P2Y12 inhibitor.
Twelve months of DAPT treatment with aspirin and a P2Y12 inhibitor for patients following PCI “remains the standard of care in guidelines,” noted Marco Roffi, MD, a second discussant at the congress. But several questions remain, he added, such as which P2Y12 inhibitors work best and whether DAPT can be less than 12 months.
“The investigators [for STOPDAPT-2 ACS] pushed these questions to the limit with 1 month of DAPT and clopidogrel monotherapy,” said Dr. Roffi, professor and director of interventional cardiology at University Hospital, Geneva.
“This was a risky bet, and the investigators lost by not proving noninferiority and with excess ischemic events,” he commented.
First came STOPDAPT-2
Dr. Watanabe and colleagues designed STOPDAPT-2 ACS as a follow-up to their prior STOPDAPT-2 trial, which randomly assigned slightly more than 3000 patients at 90 Japanese centers to the identical two treatment options: 1 month of DAPT followed by 11 months of clopidogrel monotherapy or 12 months of DAPT, except the trial enrolled all types of patients undergoing PCI. This meant that a minority, 38%, had a recent ACS event, while the remaining patients had chronic coronary artery disease. As in STOPDAPT-2 ACS, all patients in STOPDAPT-2 had received a CCEE stent.
STOPDAPT-2 also used the same primary endpoint to tally net clinical benefit as STOPDAPT-2 ACS: cardiovascular death, MI, stroke of any type, definite stent thrombosis, or TIMI major or minor bleeding classification.
In STOPDAPT-2, using the mixed population with both recent ACS and chronic coronary disease, the regimen of 1 month of DAPT followed by 11 months of clopidogrel monotherapy was both noninferior to and superior to 12 months of DAPT, reducing the net adverse-event tally by 36% relative to 12-month DAPT and by an absolute reduction of 1.34%, as reported in 2019.
Despite this superiority, the results from STOPDAPT-2 had little impact on global practice, commented Kurt Huber, MD, professor and director of the cardiology ICU at the Medical University of Vienna.
“STOP-DAPT-2 did not give us a clear message with respect to reducing antiplatelet treatment after 1 month. I thought that for ACS patients 1 month might be too short,” Dr. Huber said during a press briefing.
Focusing on post-ACS
To directly address this issue, the investigators launched STOPDAPT-2 ACS, which used the same design as the preceding study but only enrolled patients soon after an ACS event. The trial included for its main analysis 3,008 newly enrolled patients with recent ACS, and 1,161 patients who had a recent ACS event and had been randomly assigned in STOPDAPT-2, creating a total study cohort for the new analysis of 4136 patients treated and followed for the study’s full 12 months.
The patients averaged 67 years old, 79% were men, and 30% had diabetes. About 56% had a recent ST-elevation MI, about 20% a recent non–ST-elevation MI, and the remaining 24% had unstable angina. For their unspecified P2Y12 inhibition, roughly half the patients received clopidogrel and the rest received prasugrel. Adherence to the two assigned treatment regimens was very good, with a very small number of patients not adhering to their assigned protocol.
The composite adverse event incidence over 12 months was 3.2% among those who received 1-month DAPT and 2.83% in those on DAPT for 12 months, a difference that failed to achieve the prespecified definition of noninferiority for 1-month DAPT, reported Dr. Watanabe, an interventional cardiologist at Kyoto University.
The ischemic event composite was 50% lower among those on 12-month DAPT, compared with 1 month of DAPT, a difference that just missed significance. The rate of MI was 91% higher with 1-month DAPT, compared with 12 months, a significant difference.
One-month DAPT also significantly reduced the primary measure of bleeding events – the combination of TIMI major and minor bleeds – by a significant 54%, compared with 12-month DAPT. A second metric of clinically meaningful bleeds, those that meet either the type 3 or 5 definition of the Bleeding Academic Research Consortium, were reduced by a significant 59% by 1-month DAPT, compared with 12 months of DAPT.
The new findings from STOPDAPT-2 ACS contrasted with those from MASTER DAPT, but in an explicable way that related to different patient types, different P2Y12 inhibitors, different treatment durations, and different stents.
“We’ve seen in MASTER DAPT that if you use the right stent and use ticagrelor for monotherapy there may be some ability to shorten DAPT, but we still do not know what would happen in patients with very high ischemic risk,” concluded Dr. Huber.
“A reduction in DAPT duration might work in patients without high bleeding risk, but I would exclude patients with very high ischemic risk,” he added. “I also can’t tell you whether 1 month or 3 months is the right approach, and I think clopidogrel is not the right drug to use for monotherapy after ACS.”
STOPDAPT-2 and STOPDAPT-2 ACS were both sponsored by Abbott Vascular, which markets the CCEE (Xience) stents used in both studies. Dr. Watanabe has received lecture fees from Abbott and from Daiichi-Sankyo. Dr. Byrne has received research funding from Abbott Vascular as well as from Biosensors, Biotronik, and Boston Scientific. Roffi has received research funding from Biotronik, Boston Scientific, GE Healthcare, Medtronic, and Terumo. Dr. Huber has received lecture fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, Pfizer, Sanofi-Aventis, and The Medicines Company.
A version of this article first appeared on Medscape.com.
One month of dual antiplatelet therapy followed by 11 months of clopidogrel monotherapy failed to prove noninferiority to 12 unbroken months of DAPT for net clinical benefit in a multicenter Japanese trial that randomized more than 4,000 patients who underwent percutaneous coronary intervention (PCI) after a recent acute coronary syndrome episode.
The outcomes showed that while truncating DAPT duration could, as expected, cut major bleeding episodes roughly in half, it also led to a significant near doubling of myocardial infarction and showed a strong trend toward also increasing a composite tally of several types of ischemic events. These data were reported this week by Hirotoshi Watanabe, MD, PhD, at the virtual annual congress of the European Society of Cardiology. All study patients had undergone PCI with cobalt-chromium everolimus-eluting (CCEE) coronary stents (Xience).
These findings from the STOPDAPT-2 ACS trial highlighted the limits of minimizing DAPT after PCI in patients at high ischemic risk, such as after an acute coronary syndrome (ACS) event.
It also was a counterpoint to a somewhat similar study also reported at the congress, MASTER DAPT, which showed that 1 month of DAPT was noninferior to 3 or more months of DAPT for net clinical benefit in a distinctly different population of patients undergoing PCI (and using a different type of coronary stent) – those at high bleeding risk and with only about half the patients having had a recent ACS.
The results of STOPDAPT-2 ACS “do not support use of 1 month of DAPT followed by P2Y12 inhibitor monotherapy with clopidogrel compared with standard DAPT,” commented Robert A. Byrne, MBBCh, PhD, designated discussant for the report and professor at the RCSI University of Medicine and Health Sciences in Dublin.
“Although major bleeding was significantly reduced with this approach, there appeared to be a significant increase in adverse ischemic events, and there was a clear signal in relation to overall mortality, the ultimate arbiter of net clinical benefit,” added Dr. Byrne, who is also director of cardiology at Mater Private Hospital in Dublin.
He suggested that a mechanistic explanation for the signal of harm seem in STOPDAPT-2 ACS was the relatively low potency of clopidogrel (Plavix) as an antiplatelet agent, compared with other P2Y12 inhibitors such as prasugrel (Effient) and ticagrelor (Brilinta), as well as the genetically driven variability in response to clopidogrel that’s also absent with alternative agents.
These between-agent differences are of “particular clinical relevance in the early aftermath of an ACS event,” Dr. Byrne said.
12-month DAPT remains standard for PCI patients with recent ACS
The totality of clinical evidence “continues to support a standard 12-month duration of DAPT – using aspirin and either prasugrel or ticagrelor – as the preferred default approach,” Dr. Byrne concluded.
He acknowledged that an abbreviated duration of DAPT followed by P2Y12 inhibitor monotherapy “might be considered as an alternative.” In patients following an ACS event who do not have high risk for bleeding, he said, the minimum duration of DAPT should be at least 3 months and with preferential use of a more potent P2Y12 inhibitor.
Twelve months of DAPT treatment with aspirin and a P2Y12 inhibitor for patients following PCI “remains the standard of care in guidelines,” noted Marco Roffi, MD, a second discussant at the congress. But several questions remain, he added, such as which P2Y12 inhibitors work best and whether DAPT can be less than 12 months.
“The investigators [for STOPDAPT-2 ACS] pushed these questions to the limit with 1 month of DAPT and clopidogrel monotherapy,” said Dr. Roffi, professor and director of interventional cardiology at University Hospital, Geneva.
“This was a risky bet, and the investigators lost by not proving noninferiority and with excess ischemic events,” he commented.
First came STOPDAPT-2
Dr. Watanabe and colleagues designed STOPDAPT-2 ACS as a follow-up to their prior STOPDAPT-2 trial, which randomly assigned slightly more than 3000 patients at 90 Japanese centers to the identical two treatment options: 1 month of DAPT followed by 11 months of clopidogrel monotherapy or 12 months of DAPT, except the trial enrolled all types of patients undergoing PCI. This meant that a minority, 38%, had a recent ACS event, while the remaining patients had chronic coronary artery disease. As in STOPDAPT-2 ACS, all patients in STOPDAPT-2 had received a CCEE stent.
STOPDAPT-2 also used the same primary endpoint to tally net clinical benefit as STOPDAPT-2 ACS: cardiovascular death, MI, stroke of any type, definite stent thrombosis, or TIMI major or minor bleeding classification.
In STOPDAPT-2, using the mixed population with both recent ACS and chronic coronary disease, the regimen of 1 month of DAPT followed by 11 months of clopidogrel monotherapy was both noninferior to and superior to 12 months of DAPT, reducing the net adverse-event tally by 36% relative to 12-month DAPT and by an absolute reduction of 1.34%, as reported in 2019.
Despite this superiority, the results from STOPDAPT-2 had little impact on global practice, commented Kurt Huber, MD, professor and director of the cardiology ICU at the Medical University of Vienna.
“STOP-DAPT-2 did not give us a clear message with respect to reducing antiplatelet treatment after 1 month. I thought that for ACS patients 1 month might be too short,” Dr. Huber said during a press briefing.
Focusing on post-ACS
To directly address this issue, the investigators launched STOPDAPT-2 ACS, which used the same design as the preceding study but only enrolled patients soon after an ACS event. The trial included for its main analysis 3,008 newly enrolled patients with recent ACS, and 1,161 patients who had a recent ACS event and had been randomly assigned in STOPDAPT-2, creating a total study cohort for the new analysis of 4136 patients treated and followed for the study’s full 12 months.
The patients averaged 67 years old, 79% were men, and 30% had diabetes. About 56% had a recent ST-elevation MI, about 20% a recent non–ST-elevation MI, and the remaining 24% had unstable angina. For their unspecified P2Y12 inhibition, roughly half the patients received clopidogrel and the rest received prasugrel. Adherence to the two assigned treatment regimens was very good, with a very small number of patients not adhering to their assigned protocol.
The composite adverse event incidence over 12 months was 3.2% among those who received 1-month DAPT and 2.83% in those on DAPT for 12 months, a difference that failed to achieve the prespecified definition of noninferiority for 1-month DAPT, reported Dr. Watanabe, an interventional cardiologist at Kyoto University.
The ischemic event composite was 50% lower among those on 12-month DAPT, compared with 1 month of DAPT, a difference that just missed significance. The rate of MI was 91% higher with 1-month DAPT, compared with 12 months, a significant difference.
One-month DAPT also significantly reduced the primary measure of bleeding events – the combination of TIMI major and minor bleeds – by a significant 54%, compared with 12-month DAPT. A second metric of clinically meaningful bleeds, those that meet either the type 3 or 5 definition of the Bleeding Academic Research Consortium, were reduced by a significant 59% by 1-month DAPT, compared with 12 months of DAPT.
The new findings from STOPDAPT-2 ACS contrasted with those from MASTER DAPT, but in an explicable way that related to different patient types, different P2Y12 inhibitors, different treatment durations, and different stents.
“We’ve seen in MASTER DAPT that if you use the right stent and use ticagrelor for monotherapy there may be some ability to shorten DAPT, but we still do not know what would happen in patients with very high ischemic risk,” concluded Dr. Huber.
“A reduction in DAPT duration might work in patients without high bleeding risk, but I would exclude patients with very high ischemic risk,” he added. “I also can’t tell you whether 1 month or 3 months is the right approach, and I think clopidogrel is not the right drug to use for monotherapy after ACS.”
STOPDAPT-2 and STOPDAPT-2 ACS were both sponsored by Abbott Vascular, which markets the CCEE (Xience) stents used in both studies. Dr. Watanabe has received lecture fees from Abbott and from Daiichi-Sankyo. Dr. Byrne has received research funding from Abbott Vascular as well as from Biosensors, Biotronik, and Boston Scientific. Roffi has received research funding from Biotronik, Boston Scientific, GE Healthcare, Medtronic, and Terumo. Dr. Huber has received lecture fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, Pfizer, Sanofi-Aventis, and The Medicines Company.
A version of this article first appeared on Medscape.com.
Elderly mice receive the gift of warmth
Steal from the warm, give to the cold
If there’s one constant in life other than taxes, it’s elderly people moving to Florida. The Sunshine State’s reputation as a giant retirement home needs no elaboration, but why do senior citizens gravitate there? Well, many reasons, but a big one is that, the older you get, the more susceptible and sensitive you are to the cold. And now, according to a new study, we may have identified a culprit.
Researchers from Yale University examined a group of mice and found that the older ones lacked ICL2 cells in their fatty tissue. These cells, at least in younger mice, help restore body heat when exposed to cold temperatures. Lacking these cells meant that older mice had a limited ability to burn their fat and raise their temperature in response to cold.
Well, job done, all we need to do now is stimulate production of ICL2 cells in elderly people, and they’ll be able to go outside in 80-degree weather without a sweater again. Except there’s a problem. In a cruel twist of fate, when the elderly mice were given a molecule to boost ICL2 cell production, they actually became less tolerant of the cold than at baseline. Oops.
The scientists didn’t give up though, and gave their elderly mice ICL2 cells from young mice. This finally did the trick, though we have to admit, if that treatment does eventually scale up to humans, the prospect of a bunch of senior citizens taking ICL2 cells from young people to stay warm does sound a bit like a bad vampire movie premise. “I vant to suck your immune cell group 2 innate lymphoid cells!” Not the most pithy catch phrase in the world.
Grocery store tapping your subconscious? It’s a good thing
We all know there’s marketing and functionality elements to grocery stores and how they’re set up for your shopping pleasure. But what if I told you that the good old supermarket subconscious trick works on how healthy food decisions are?
In a recent study, researchers at the University of Southampton in England found that if you placed a wider selection of fruits and vegetables near the entrances and more nonfood items near checkouts, sales decreased on the sweets and increased on the produce. “The findings of our study suggest that a healthier store layout could lead to nearly 10,000 extra portions of fruit and vegetables and approximately 1,500 fewer portions of confectionery being sold on a weekly basis in each store,” lead author Dr. Christina Vogel explained.
You’re probably thinking that food placement studies aren’t new. That’s true, but this one went above and beyond. Instead of just looking at the influence placement has on purchase, this one took it further by trying to reduce the consumers’ “calorie opportunities” and examining the effect on sales. Also, customer loyalty, patterns, and diets were taken into account across multiple household members.
The researchers think shifting the layouts in grocery stores could shift people’s food choices, producing a domino effect on the population’s overall diet. With obesity, diabetes, and cardiology concerns always looming, swaying consumers toward healthier food choices makes for better public health overall.
So if you feel like you’re being subconsciously assaulted by veggies every time you walk into Trader Joe’s, just know it’s for your own good.
TikTokers take on tics
We know TikTok is what makes a lot of teens and young adults tick, but what if TikTokers are actually catching tic disorders from other TikTokers?
TikTok blew up during the pandemic. Many people were stuck at home and had nothing better to do than make and watch TikTok videos. The pandemic brought isolation, uncertainty, and anxiety. The stress that followed may have caused many people, mostly women and young girls, to develop tic disorders.
There’s a TikTok for everything, whether it’s a new dance or a recipe. Many people even use TikTok to speak out about their illnesses. Several TikTokers have Tourette’s syndrome and show their tics on their videos. It appears that some audience members actually “catch” the tics from watching the videos and are then unable to stop certain jerking movements or saying specific words.
Neurologists at the University of Calgary (Alta.), who were hearing from colleagues and getting referrals of such patients, called it “an epidemic within the pandemic.” The behavior is not actually Tourette’s, they told Vice, but the patients “cannot stop, and we have absolutely witnessed that.”
There is, of course, controversy over the issue. One individual with the condition said, “I feel like there’s a lot of really weird, backwards stigma on TikTok about tic disorders. Like, you aren’t allowed to have one unless it’s this one.”
Who would have guessed that people would disagree over stuff on the Internet?
Look on the bright side: Obesity edition
The pandemic may have postponed “Top Gun: Maverick” and “The Marvelous Mrs. Maisel” until who-knows-when, but we here at LOTME are happy to announce the nearly-as-anticipated return of Bacteria vs. the World.
As you may recall from our last edition of BVTW, bacteria battled the ghost of Charles Darwin, who had taken the earthly form of antibiotics capable of stopping bacterial evolution. Tonight, our prokaryotic protagonists take on an equally relentless and ubiquitous challenger: obesity.
Specifically, we’re putting bacteria up against the obesity survival paradox, that phenomenon in which obesity and overweight seem to protect against – yes, you guessed it – bacterial infections.
A Swedish research team observed a group of 2,196 individual adults who received care for suspected severe bacterial infection at Skaraborg Hospital in Skövde. One year after hospitalization, 26% of normal-weight (body mass index, 18.5-24.99) patients were dead, compared with 17% of overweight (BMI, 25.0-29.99), 16% of obese (BMI, 30.0-34.99), and 9% of very obese (BMI >35) patients.
These results confirm the obesity survival paradox, but “what we don’t know is how being overweight can benefit the patient with a bacterial infection, or whether it’s connected with functions in the immune system and how they’re regulated,” lead author Dr. Åsa Alsiö said in a written statement.
A spokes-cell for the bacteria disputed the results and challenged the legitimacy of the investigators. When asked if there should be some sort of reexamination of the findings, he/she/it replied: “You bet your flagella.” We then pointed out that humans don’t have flagellum, and the representative raised his/her/its flagella in what could only be considered an obscene gesture.
Steal from the warm, give to the cold
If there’s one constant in life other than taxes, it’s elderly people moving to Florida. The Sunshine State’s reputation as a giant retirement home needs no elaboration, but why do senior citizens gravitate there? Well, many reasons, but a big one is that, the older you get, the more susceptible and sensitive you are to the cold. And now, according to a new study, we may have identified a culprit.
Researchers from Yale University examined a group of mice and found that the older ones lacked ICL2 cells in their fatty tissue. These cells, at least in younger mice, help restore body heat when exposed to cold temperatures. Lacking these cells meant that older mice had a limited ability to burn their fat and raise their temperature in response to cold.
Well, job done, all we need to do now is stimulate production of ICL2 cells in elderly people, and they’ll be able to go outside in 80-degree weather without a sweater again. Except there’s a problem. In a cruel twist of fate, when the elderly mice were given a molecule to boost ICL2 cell production, they actually became less tolerant of the cold than at baseline. Oops.
The scientists didn’t give up though, and gave their elderly mice ICL2 cells from young mice. This finally did the trick, though we have to admit, if that treatment does eventually scale up to humans, the prospect of a bunch of senior citizens taking ICL2 cells from young people to stay warm does sound a bit like a bad vampire movie premise. “I vant to suck your immune cell group 2 innate lymphoid cells!” Not the most pithy catch phrase in the world.
Grocery store tapping your subconscious? It’s a good thing
We all know there’s marketing and functionality elements to grocery stores and how they’re set up for your shopping pleasure. But what if I told you that the good old supermarket subconscious trick works on how healthy food decisions are?
In a recent study, researchers at the University of Southampton in England found that if you placed a wider selection of fruits and vegetables near the entrances and more nonfood items near checkouts, sales decreased on the sweets and increased on the produce. “The findings of our study suggest that a healthier store layout could lead to nearly 10,000 extra portions of fruit and vegetables and approximately 1,500 fewer portions of confectionery being sold on a weekly basis in each store,” lead author Dr. Christina Vogel explained.
You’re probably thinking that food placement studies aren’t new. That’s true, but this one went above and beyond. Instead of just looking at the influence placement has on purchase, this one took it further by trying to reduce the consumers’ “calorie opportunities” and examining the effect on sales. Also, customer loyalty, patterns, and diets were taken into account across multiple household members.
The researchers think shifting the layouts in grocery stores could shift people’s food choices, producing a domino effect on the population’s overall diet. With obesity, diabetes, and cardiology concerns always looming, swaying consumers toward healthier food choices makes for better public health overall.
So if you feel like you’re being subconsciously assaulted by veggies every time you walk into Trader Joe’s, just know it’s for your own good.
TikTokers take on tics
We know TikTok is what makes a lot of teens and young adults tick, but what if TikTokers are actually catching tic disorders from other TikTokers?
TikTok blew up during the pandemic. Many people were stuck at home and had nothing better to do than make and watch TikTok videos. The pandemic brought isolation, uncertainty, and anxiety. The stress that followed may have caused many people, mostly women and young girls, to develop tic disorders.
There’s a TikTok for everything, whether it’s a new dance or a recipe. Many people even use TikTok to speak out about their illnesses. Several TikTokers have Tourette’s syndrome and show their tics on their videos. It appears that some audience members actually “catch” the tics from watching the videos and are then unable to stop certain jerking movements or saying specific words.
Neurologists at the University of Calgary (Alta.), who were hearing from colleagues and getting referrals of such patients, called it “an epidemic within the pandemic.” The behavior is not actually Tourette’s, they told Vice, but the patients “cannot stop, and we have absolutely witnessed that.”
There is, of course, controversy over the issue. One individual with the condition said, “I feel like there’s a lot of really weird, backwards stigma on TikTok about tic disorders. Like, you aren’t allowed to have one unless it’s this one.”
Who would have guessed that people would disagree over stuff on the Internet?
Look on the bright side: Obesity edition
The pandemic may have postponed “Top Gun: Maverick” and “The Marvelous Mrs. Maisel” until who-knows-when, but we here at LOTME are happy to announce the nearly-as-anticipated return of Bacteria vs. the World.
As you may recall from our last edition of BVTW, bacteria battled the ghost of Charles Darwin, who had taken the earthly form of antibiotics capable of stopping bacterial evolution. Tonight, our prokaryotic protagonists take on an equally relentless and ubiquitous challenger: obesity.
Specifically, we’re putting bacteria up against the obesity survival paradox, that phenomenon in which obesity and overweight seem to protect against – yes, you guessed it – bacterial infections.
A Swedish research team observed a group of 2,196 individual adults who received care for suspected severe bacterial infection at Skaraborg Hospital in Skövde. One year after hospitalization, 26% of normal-weight (body mass index, 18.5-24.99) patients were dead, compared with 17% of overweight (BMI, 25.0-29.99), 16% of obese (BMI, 30.0-34.99), and 9% of very obese (BMI >35) patients.
These results confirm the obesity survival paradox, but “what we don’t know is how being overweight can benefit the patient with a bacterial infection, or whether it’s connected with functions in the immune system and how they’re regulated,” lead author Dr. Åsa Alsiö said in a written statement.
A spokes-cell for the bacteria disputed the results and challenged the legitimacy of the investigators. When asked if there should be some sort of reexamination of the findings, he/she/it replied: “You bet your flagella.” We then pointed out that humans don’t have flagellum, and the representative raised his/her/its flagella in what could only be considered an obscene gesture.
Steal from the warm, give to the cold
If there’s one constant in life other than taxes, it’s elderly people moving to Florida. The Sunshine State’s reputation as a giant retirement home needs no elaboration, but why do senior citizens gravitate there? Well, many reasons, but a big one is that, the older you get, the more susceptible and sensitive you are to the cold. And now, according to a new study, we may have identified a culprit.
Researchers from Yale University examined a group of mice and found that the older ones lacked ICL2 cells in their fatty tissue. These cells, at least in younger mice, help restore body heat when exposed to cold temperatures. Lacking these cells meant that older mice had a limited ability to burn their fat and raise their temperature in response to cold.
Well, job done, all we need to do now is stimulate production of ICL2 cells in elderly people, and they’ll be able to go outside in 80-degree weather without a sweater again. Except there’s a problem. In a cruel twist of fate, when the elderly mice were given a molecule to boost ICL2 cell production, they actually became less tolerant of the cold than at baseline. Oops.
The scientists didn’t give up though, and gave their elderly mice ICL2 cells from young mice. This finally did the trick, though we have to admit, if that treatment does eventually scale up to humans, the prospect of a bunch of senior citizens taking ICL2 cells from young people to stay warm does sound a bit like a bad vampire movie premise. “I vant to suck your immune cell group 2 innate lymphoid cells!” Not the most pithy catch phrase in the world.
Grocery store tapping your subconscious? It’s a good thing
We all know there’s marketing and functionality elements to grocery stores and how they’re set up for your shopping pleasure. But what if I told you that the good old supermarket subconscious trick works on how healthy food decisions are?
In a recent study, researchers at the University of Southampton in England found that if you placed a wider selection of fruits and vegetables near the entrances and more nonfood items near checkouts, sales decreased on the sweets and increased on the produce. “The findings of our study suggest that a healthier store layout could lead to nearly 10,000 extra portions of fruit and vegetables and approximately 1,500 fewer portions of confectionery being sold on a weekly basis in each store,” lead author Dr. Christina Vogel explained.
You’re probably thinking that food placement studies aren’t new. That’s true, but this one went above and beyond. Instead of just looking at the influence placement has on purchase, this one took it further by trying to reduce the consumers’ “calorie opportunities” and examining the effect on sales. Also, customer loyalty, patterns, and diets were taken into account across multiple household members.
The researchers think shifting the layouts in grocery stores could shift people’s food choices, producing a domino effect on the population’s overall diet. With obesity, diabetes, and cardiology concerns always looming, swaying consumers toward healthier food choices makes for better public health overall.
So if you feel like you’re being subconsciously assaulted by veggies every time you walk into Trader Joe’s, just know it’s for your own good.
TikTokers take on tics
We know TikTok is what makes a lot of teens and young adults tick, but what if TikTokers are actually catching tic disorders from other TikTokers?
TikTok blew up during the pandemic. Many people were stuck at home and had nothing better to do than make and watch TikTok videos. The pandemic brought isolation, uncertainty, and anxiety. The stress that followed may have caused many people, mostly women and young girls, to develop tic disorders.
There’s a TikTok for everything, whether it’s a new dance or a recipe. Many people even use TikTok to speak out about their illnesses. Several TikTokers have Tourette’s syndrome and show their tics on their videos. It appears that some audience members actually “catch” the tics from watching the videos and are then unable to stop certain jerking movements or saying specific words.
Neurologists at the University of Calgary (Alta.), who were hearing from colleagues and getting referrals of such patients, called it “an epidemic within the pandemic.” The behavior is not actually Tourette’s, they told Vice, but the patients “cannot stop, and we have absolutely witnessed that.”
There is, of course, controversy over the issue. One individual with the condition said, “I feel like there’s a lot of really weird, backwards stigma on TikTok about tic disorders. Like, you aren’t allowed to have one unless it’s this one.”
Who would have guessed that people would disagree over stuff on the Internet?
Look on the bright side: Obesity edition
The pandemic may have postponed “Top Gun: Maverick” and “The Marvelous Mrs. Maisel” until who-knows-when, but we here at LOTME are happy to announce the nearly-as-anticipated return of Bacteria vs. the World.
As you may recall from our last edition of BVTW, bacteria battled the ghost of Charles Darwin, who had taken the earthly form of antibiotics capable of stopping bacterial evolution. Tonight, our prokaryotic protagonists take on an equally relentless and ubiquitous challenger: obesity.
Specifically, we’re putting bacteria up against the obesity survival paradox, that phenomenon in which obesity and overweight seem to protect against – yes, you guessed it – bacterial infections.
A Swedish research team observed a group of 2,196 individual adults who received care for suspected severe bacterial infection at Skaraborg Hospital in Skövde. One year after hospitalization, 26% of normal-weight (body mass index, 18.5-24.99) patients were dead, compared with 17% of overweight (BMI, 25.0-29.99), 16% of obese (BMI, 30.0-34.99), and 9% of very obese (BMI >35) patients.
These results confirm the obesity survival paradox, but “what we don’t know is how being overweight can benefit the patient with a bacterial infection, or whether it’s connected with functions in the immune system and how they’re regulated,” lead author Dr. Åsa Alsiö said in a written statement.
A spokes-cell for the bacteria disputed the results and challenged the legitimacy of the investigators. When asked if there should be some sort of reexamination of the findings, he/she/it replied: “You bet your flagella.” We then pointed out that humans don’t have flagellum, and the representative raised his/her/its flagella in what could only be considered an obscene gesture.
Genetic shift increases susceptibility to childhood ALL
A genetically induced shift toward higher lymphocyte counts was found to increase susceptibility to childhood acute lymphoblastic leukemia, according to the results of a large genome-wide association study of 2,666 childhood patients with ALL as compared with 60,272 control individuals.
The development of ALL is thought to follow a two-hit model of leukemogenesis; in utero formation of a preleukemic clone and subsequent postnatal acquisition of secondary somatic mutations that leads to overt leukemia, according to Linda Kachuri, PhD, of the department of epidemiology and biostatistics, University of California, San Francisco, and colleagues.
The development of ALL is thought to follow a two-hit model of leukemogenesis; in utero formation of a preleukemic clone and subsequent postnatal acquisition of secondary somatic mutations that leads to overt leukemia, according to Linda Kachuri, PhD, of the Department of Epidemiology and Biostatistics, University of California San Francisco, and colleagues.
Previous research has shown that several childhood-ALL–risk regions have also been associated with variation in blood-cell traits and a recent phenome-wide association study of childhood ALL identified platelet count as the most enriched trait among known ALL-risk loci. To further explore this issue, the researchers conducted their comprehensive study of the role of blood-cell-trait variation in the etiology of childhood ALL.
The researchers identified 3,000 blood-cell-trait–associated variants, which accounted for 4.0% to 23.9% of trait variation and included 115 loci associated with blood-cell ratios: lymphocyte-to-monocyte ratio (LMR); neutrophil-to-lymphocyte ratio (NLR); and platelet-to-lymphocyte ratio (PLR), according to a report published online in The American Journal of Human Genetics.
Lymphocyte risk
The researchers found that ALL susceptibility was genetically correlated with lymphocyte counts (rg = 0.088, P = .0004) and PLR (rg = 0.072, P = .0017).
Using Mendelian randomization analyses, a genetically predicted increase in lymphocyte counts was found to be associated with increased ALL risk (odds ratio [OR] = 1.16, P = .031). This correlation was strengthened after the researchers accounted for other cell types (OR = 1.43, P = .0009).
The researchers observed positive associations with increasing LMR (OR = 1.22, P = .0017) as well as inverse effects for NLR (OR = 0.67, P = .0003) and PLR (OR = 0.80, P = .002).
“We identified the cell-type ratios LMR, NLR, and PLR as independent risk factors for ALL and found evidence that these ratios have distinct genetic mechanisms that are not captured by their component traits. In multivariable MR analyses that concurrently modeled the effects of lymphocyte, monocyte, neutrophil, and platelet counts on ALL, lymphocytes remained as the only independent risk factor and this association with ALL strengthened compared to univariate analyses,” the researchers stated.
They reported that they had no competing interests.
A genetically induced shift toward higher lymphocyte counts was found to increase susceptibility to childhood acute lymphoblastic leukemia, according to the results of a large genome-wide association study of 2,666 childhood patients with ALL as compared with 60,272 control individuals.
The development of ALL is thought to follow a two-hit model of leukemogenesis; in utero formation of a preleukemic clone and subsequent postnatal acquisition of secondary somatic mutations that leads to overt leukemia, according to Linda Kachuri, PhD, of the department of epidemiology and biostatistics, University of California, San Francisco, and colleagues.
The development of ALL is thought to follow a two-hit model of leukemogenesis; in utero formation of a preleukemic clone and subsequent postnatal acquisition of secondary somatic mutations that leads to overt leukemia, according to Linda Kachuri, PhD, of the Department of Epidemiology and Biostatistics, University of California San Francisco, and colleagues.
Previous research has shown that several childhood-ALL–risk regions have also been associated with variation in blood-cell traits and a recent phenome-wide association study of childhood ALL identified platelet count as the most enriched trait among known ALL-risk loci. To further explore this issue, the researchers conducted their comprehensive study of the role of blood-cell-trait variation in the etiology of childhood ALL.
The researchers identified 3,000 blood-cell-trait–associated variants, which accounted for 4.0% to 23.9% of trait variation and included 115 loci associated with blood-cell ratios: lymphocyte-to-monocyte ratio (LMR); neutrophil-to-lymphocyte ratio (NLR); and platelet-to-lymphocyte ratio (PLR), according to a report published online in The American Journal of Human Genetics.
Lymphocyte risk
The researchers found that ALL susceptibility was genetically correlated with lymphocyte counts (rg = 0.088, P = .0004) and PLR (rg = 0.072, P = .0017).
Using Mendelian randomization analyses, a genetically predicted increase in lymphocyte counts was found to be associated with increased ALL risk (odds ratio [OR] = 1.16, P = .031). This correlation was strengthened after the researchers accounted for other cell types (OR = 1.43, P = .0009).
The researchers observed positive associations with increasing LMR (OR = 1.22, P = .0017) as well as inverse effects for NLR (OR = 0.67, P = .0003) and PLR (OR = 0.80, P = .002).
“We identified the cell-type ratios LMR, NLR, and PLR as independent risk factors for ALL and found evidence that these ratios have distinct genetic mechanisms that are not captured by their component traits. In multivariable MR analyses that concurrently modeled the effects of lymphocyte, monocyte, neutrophil, and platelet counts on ALL, lymphocytes remained as the only independent risk factor and this association with ALL strengthened compared to univariate analyses,” the researchers stated.
They reported that they had no competing interests.
A genetically induced shift toward higher lymphocyte counts was found to increase susceptibility to childhood acute lymphoblastic leukemia, according to the results of a large genome-wide association study of 2,666 childhood patients with ALL as compared with 60,272 control individuals.
The development of ALL is thought to follow a two-hit model of leukemogenesis; in utero formation of a preleukemic clone and subsequent postnatal acquisition of secondary somatic mutations that leads to overt leukemia, according to Linda Kachuri, PhD, of the department of epidemiology and biostatistics, University of California, San Francisco, and colleagues.
The development of ALL is thought to follow a two-hit model of leukemogenesis; in utero formation of a preleukemic clone and subsequent postnatal acquisition of secondary somatic mutations that leads to overt leukemia, according to Linda Kachuri, PhD, of the Department of Epidemiology and Biostatistics, University of California San Francisco, and colleagues.
Previous research has shown that several childhood-ALL–risk regions have also been associated with variation in blood-cell traits and a recent phenome-wide association study of childhood ALL identified platelet count as the most enriched trait among known ALL-risk loci. To further explore this issue, the researchers conducted their comprehensive study of the role of blood-cell-trait variation in the etiology of childhood ALL.
The researchers identified 3,000 blood-cell-trait–associated variants, which accounted for 4.0% to 23.9% of trait variation and included 115 loci associated with blood-cell ratios: lymphocyte-to-monocyte ratio (LMR); neutrophil-to-lymphocyte ratio (NLR); and platelet-to-lymphocyte ratio (PLR), according to a report published online in The American Journal of Human Genetics.
Lymphocyte risk
The researchers found that ALL susceptibility was genetically correlated with lymphocyte counts (rg = 0.088, P = .0004) and PLR (rg = 0.072, P = .0017).
Using Mendelian randomization analyses, a genetically predicted increase in lymphocyte counts was found to be associated with increased ALL risk (odds ratio [OR] = 1.16, P = .031). This correlation was strengthened after the researchers accounted for other cell types (OR = 1.43, P = .0009).
The researchers observed positive associations with increasing LMR (OR = 1.22, P = .0017) as well as inverse effects for NLR (OR = 0.67, P = .0003) and PLR (OR = 0.80, P = .002).
“We identified the cell-type ratios LMR, NLR, and PLR as independent risk factors for ALL and found evidence that these ratios have distinct genetic mechanisms that are not captured by their component traits. In multivariable MR analyses that concurrently modeled the effects of lymphocyte, monocyte, neutrophil, and platelet counts on ALL, lymphocytes remained as the only independent risk factor and this association with ALL strengthened compared to univariate analyses,” the researchers stated.
They reported that they had no competing interests.
FROM THE AMERICAN JOURNAL OF HUMAN GENETICS
New gene variant found for hereditary bleeding disorder
Clinical symptoms in a 19-year-old Vietnamese woman who experienced several life-threatening bleeding events, including ovarian hemorrhage, led to the discovery of a novel gene variant causing her bleeding disorder.
Blood analysis of the patients showed decreased fibrinogen level with “markedly elevated fibrinogen/fibrin degradation products and D-dimer levels.” Attempts to treat the patient with hemostatic surgery, administration of several medications, including nafamostat mesylate, tranexamic acid, and unfractionated heparin, produced no correction of her coagulation abnormalities, and the patient experienced repeated hemorrhagic events, according to researchers from the Tokyo Saiseikai Central Hospital, Japan, and colleagues.
However, the researchers found that treatment with recombinant human thrombomodulin (rhTM) remarkably improved the patient’s pathophysiology, according to the results of a case study reported in Blood Advances.
Genetic analysis
Upon screening and sequencing of the patient’s thrombomodulin gene, a previously unreported homozygous variation, c.793T>A (p.Cys265Ser) was discovered. Under normal circumstances, the Cys265 residue forms one of three disulfide bonds in the epidermal growth factor (EGF)-like domain 1 of thrombomoduliin (TM), according to the researchers.
However, transient expression analysis of the patient’s mutation using COS-1 cells demonstrated markedly reduced expression of TM-Cys265Ser on the plasma membrane relative to wild-type TM. The TM-Cys265Ser mutant was intracellularly degraded, probably due to EGF-like domain 1 misfolding, according to the researchers and the reduced expression of TM on the endothelial cell membrane may be responsible for the disseminated intravascular coagulation-like symptoms observed in the patient, the speculated.
“The clinical symptoms of the patient in this study were characterized by recurrent hemorrhage, indicating that TM-C265S mainly causes hyperfibrinolysis rather than hypercoagulation. The C265S mutation may disrupt the timely and delicate balance between coagulation and fibrinolysis,” the researchers suggested.
The authors reported that they had no conflicts of interest.
Clinical symptoms in a 19-year-old Vietnamese woman who experienced several life-threatening bleeding events, including ovarian hemorrhage, led to the discovery of a novel gene variant causing her bleeding disorder.
Blood analysis of the patients showed decreased fibrinogen level with “markedly elevated fibrinogen/fibrin degradation products and D-dimer levels.” Attempts to treat the patient with hemostatic surgery, administration of several medications, including nafamostat mesylate, tranexamic acid, and unfractionated heparin, produced no correction of her coagulation abnormalities, and the patient experienced repeated hemorrhagic events, according to researchers from the Tokyo Saiseikai Central Hospital, Japan, and colleagues.
However, the researchers found that treatment with recombinant human thrombomodulin (rhTM) remarkably improved the patient’s pathophysiology, according to the results of a case study reported in Blood Advances.
Genetic analysis
Upon screening and sequencing of the patient’s thrombomodulin gene, a previously unreported homozygous variation, c.793T>A (p.Cys265Ser) was discovered. Under normal circumstances, the Cys265 residue forms one of three disulfide bonds in the epidermal growth factor (EGF)-like domain 1 of thrombomoduliin (TM), according to the researchers.
However, transient expression analysis of the patient’s mutation using COS-1 cells demonstrated markedly reduced expression of TM-Cys265Ser on the plasma membrane relative to wild-type TM. The TM-Cys265Ser mutant was intracellularly degraded, probably due to EGF-like domain 1 misfolding, according to the researchers and the reduced expression of TM on the endothelial cell membrane may be responsible for the disseminated intravascular coagulation-like symptoms observed in the patient, the speculated.
“The clinical symptoms of the patient in this study were characterized by recurrent hemorrhage, indicating that TM-C265S mainly causes hyperfibrinolysis rather than hypercoagulation. The C265S mutation may disrupt the timely and delicate balance between coagulation and fibrinolysis,” the researchers suggested.
The authors reported that they had no conflicts of interest.
Clinical symptoms in a 19-year-old Vietnamese woman who experienced several life-threatening bleeding events, including ovarian hemorrhage, led to the discovery of a novel gene variant causing her bleeding disorder.
Blood analysis of the patients showed decreased fibrinogen level with “markedly elevated fibrinogen/fibrin degradation products and D-dimer levels.” Attempts to treat the patient with hemostatic surgery, administration of several medications, including nafamostat mesylate, tranexamic acid, and unfractionated heparin, produced no correction of her coagulation abnormalities, and the patient experienced repeated hemorrhagic events, according to researchers from the Tokyo Saiseikai Central Hospital, Japan, and colleagues.
However, the researchers found that treatment with recombinant human thrombomodulin (rhTM) remarkably improved the patient’s pathophysiology, according to the results of a case study reported in Blood Advances.
Genetic analysis
Upon screening and sequencing of the patient’s thrombomodulin gene, a previously unreported homozygous variation, c.793T>A (p.Cys265Ser) was discovered. Under normal circumstances, the Cys265 residue forms one of three disulfide bonds in the epidermal growth factor (EGF)-like domain 1 of thrombomoduliin (TM), according to the researchers.
However, transient expression analysis of the patient’s mutation using COS-1 cells demonstrated markedly reduced expression of TM-Cys265Ser on the plasma membrane relative to wild-type TM. The TM-Cys265Ser mutant was intracellularly degraded, probably due to EGF-like domain 1 misfolding, according to the researchers and the reduced expression of TM on the endothelial cell membrane may be responsible for the disseminated intravascular coagulation-like symptoms observed in the patient, the speculated.
“The clinical symptoms of the patient in this study were characterized by recurrent hemorrhage, indicating that TM-C265S mainly causes hyperfibrinolysis rather than hypercoagulation. The C265S mutation may disrupt the timely and delicate balance between coagulation and fibrinolysis,” the researchers suggested.
The authors reported that they had no conflicts of interest.
FROM BLOOD ADVANCES
FDA approves zanubrutinib in Waldenström’s macroglobulinemia
The Food and Drug Administration has approved zanubrutinib (Brukinsa) capsules for use in the treatment of adult patients with Waldenström’s macroglobulinemia (WM), a rare non-Hodgkin lymphoma, according to an approval letter from the agency to BeiGene, the drug’s maker.
The FDA stipulated that the company conduct an additional clinical trial (rather than an observational study) to assess the “known serious risk of second primary malignancies” associated with use of zanubrutinib. The study should further characterize the clinical benefit and safety of zanubrutinib for the treatment of patients with newly diagnosed WM with MYD88 mutation, the agency said.
The drug, which is a small-molecule inhibitor of Bruton’s tyrosine kinase (BTK), previously received accelerated approval for use in patients with mantle cell lymphoma who have received one prior therapy. It is also being studied for the treatment of chronic lymphocytic leukemia.
The new approval is primarily based on results from ASPEN, a randomized, active control, open-label trial that compared zanubrutinib and ibrutinib.
The ASPEN trial provided “compelling evidence” that zanubrutinib is a highly active BTK inhibitor in WM and that it showed improved tolerability across a number of clinically important side effects in comparison with the first-generation BTK inhibitor ibrutinib, said study investigator Steven Treon, MD, PhD, director of the Bing Center for Waldenström’s Macroglobulinemia Research at the Dana-Farber Cancer Institute, Boston. “The approval of [zanubrutinib] provides an important new option for targeted therapy in Waldenström’s macroglobulinemia,” he added in a company press statement.
The recommended dosage is 160 mg orally twice daily or 320 mg orally once; the drug should be swallowed whole with water with or without food.
In ASPEN, all patients had MYD88 mutation WM. Patients in cohort 1 (n = 201) were randomly assigned in a 1:1 ratio to receive zanubrutinib 160 mg twice daily or ibrutinib 420 mg once daily until disease progression or unacceptable toxicity. A total of 82% of patients had relapsed/refractory disease.
The major efficacy outcome was the response rate, defined as partial response or better (i.e., partial response, very good partial response, and complete response), as determined on the basis of standard consensus response criteria from the International Workshop on Waldenström’s Macroglobulinemia (IWWM-6) criteria.
The drugs had nearly identical response rates (roughly 77%). There were no complete responses with either drug. However, zanubrutinib had twice the rate of very good partial responses compared with ibrutinib (15.7% vs. 7.1%). In addition, on the basis of modified IWWM-6 criteria, the very good partial response rate was 28% with zanubrutinib, compared to 19% with ibrutinib.
An additional efficacy outcome measure was duration of response, which was measured by the percentage of patients who were event free at 12 months. Zanubrutinib bested ibrutinib in this measure (94.4% vs. 87.9%).
The safety of zanubrutinib was also investigated in the ASPEN trial. Among patients who received zanubrutinib, 93% were exposed for 6 months or longer, and 89% were exposed for longer than 1 year. In cohort 1, serious adverse reactions occurred in 44% of patients who received zanubrutinib. Serious adverse reactions that occurred in > 2% of patients included influenza (3%), pneumonia (4%), neutropenia and decreased neutrophil count (3%), hemorrhage (4%), pyrexia (3%), and febrile neutropenia (3%).
In the FDA’s prescribing information for the drug, which includes approved indications and pooled safety data, the most common adverse reactions for zanubrutinib (≥ 20%) are listed as decreased neutrophil count, upper respiratory tract infection, decreased platelet count, rash, hemorrhage, musculoskeletal pain, decreased hemoglobin, bruising, diarrhea, pneumonia, and cough.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved zanubrutinib (Brukinsa) capsules for use in the treatment of adult patients with Waldenström’s macroglobulinemia (WM), a rare non-Hodgkin lymphoma, according to an approval letter from the agency to BeiGene, the drug’s maker.
The FDA stipulated that the company conduct an additional clinical trial (rather than an observational study) to assess the “known serious risk of second primary malignancies” associated with use of zanubrutinib. The study should further characterize the clinical benefit and safety of zanubrutinib for the treatment of patients with newly diagnosed WM with MYD88 mutation, the agency said.
The drug, which is a small-molecule inhibitor of Bruton’s tyrosine kinase (BTK), previously received accelerated approval for use in patients with mantle cell lymphoma who have received one prior therapy. It is also being studied for the treatment of chronic lymphocytic leukemia.
The new approval is primarily based on results from ASPEN, a randomized, active control, open-label trial that compared zanubrutinib and ibrutinib.
The ASPEN trial provided “compelling evidence” that zanubrutinib is a highly active BTK inhibitor in WM and that it showed improved tolerability across a number of clinically important side effects in comparison with the first-generation BTK inhibitor ibrutinib, said study investigator Steven Treon, MD, PhD, director of the Bing Center for Waldenström’s Macroglobulinemia Research at the Dana-Farber Cancer Institute, Boston. “The approval of [zanubrutinib] provides an important new option for targeted therapy in Waldenström’s macroglobulinemia,” he added in a company press statement.
The recommended dosage is 160 mg orally twice daily or 320 mg orally once; the drug should be swallowed whole with water with or without food.
In ASPEN, all patients had MYD88 mutation WM. Patients in cohort 1 (n = 201) were randomly assigned in a 1:1 ratio to receive zanubrutinib 160 mg twice daily or ibrutinib 420 mg once daily until disease progression or unacceptable toxicity. A total of 82% of patients had relapsed/refractory disease.
The major efficacy outcome was the response rate, defined as partial response or better (i.e., partial response, very good partial response, and complete response), as determined on the basis of standard consensus response criteria from the International Workshop on Waldenström’s Macroglobulinemia (IWWM-6) criteria.
The drugs had nearly identical response rates (roughly 77%). There were no complete responses with either drug. However, zanubrutinib had twice the rate of very good partial responses compared with ibrutinib (15.7% vs. 7.1%). In addition, on the basis of modified IWWM-6 criteria, the very good partial response rate was 28% with zanubrutinib, compared to 19% with ibrutinib.
An additional efficacy outcome measure was duration of response, which was measured by the percentage of patients who were event free at 12 months. Zanubrutinib bested ibrutinib in this measure (94.4% vs. 87.9%).
The safety of zanubrutinib was also investigated in the ASPEN trial. Among patients who received zanubrutinib, 93% were exposed for 6 months or longer, and 89% were exposed for longer than 1 year. In cohort 1, serious adverse reactions occurred in 44% of patients who received zanubrutinib. Serious adverse reactions that occurred in > 2% of patients included influenza (3%), pneumonia (4%), neutropenia and decreased neutrophil count (3%), hemorrhage (4%), pyrexia (3%), and febrile neutropenia (3%).
In the FDA’s prescribing information for the drug, which includes approved indications and pooled safety data, the most common adverse reactions for zanubrutinib (≥ 20%) are listed as decreased neutrophil count, upper respiratory tract infection, decreased platelet count, rash, hemorrhage, musculoskeletal pain, decreased hemoglobin, bruising, diarrhea, pneumonia, and cough.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved zanubrutinib (Brukinsa) capsules for use in the treatment of adult patients with Waldenström’s macroglobulinemia (WM), a rare non-Hodgkin lymphoma, according to an approval letter from the agency to BeiGene, the drug’s maker.
The FDA stipulated that the company conduct an additional clinical trial (rather than an observational study) to assess the “known serious risk of second primary malignancies” associated with use of zanubrutinib. The study should further characterize the clinical benefit and safety of zanubrutinib for the treatment of patients with newly diagnosed WM with MYD88 mutation, the agency said.
The drug, which is a small-molecule inhibitor of Bruton’s tyrosine kinase (BTK), previously received accelerated approval for use in patients with mantle cell lymphoma who have received one prior therapy. It is also being studied for the treatment of chronic lymphocytic leukemia.
The new approval is primarily based on results from ASPEN, a randomized, active control, open-label trial that compared zanubrutinib and ibrutinib.
The ASPEN trial provided “compelling evidence” that zanubrutinib is a highly active BTK inhibitor in WM and that it showed improved tolerability across a number of clinically important side effects in comparison with the first-generation BTK inhibitor ibrutinib, said study investigator Steven Treon, MD, PhD, director of the Bing Center for Waldenström’s Macroglobulinemia Research at the Dana-Farber Cancer Institute, Boston. “The approval of [zanubrutinib] provides an important new option for targeted therapy in Waldenström’s macroglobulinemia,” he added in a company press statement.
The recommended dosage is 160 mg orally twice daily or 320 mg orally once; the drug should be swallowed whole with water with or without food.
In ASPEN, all patients had MYD88 mutation WM. Patients in cohort 1 (n = 201) were randomly assigned in a 1:1 ratio to receive zanubrutinib 160 mg twice daily or ibrutinib 420 mg once daily until disease progression or unacceptable toxicity. A total of 82% of patients had relapsed/refractory disease.
The major efficacy outcome was the response rate, defined as partial response or better (i.e., partial response, very good partial response, and complete response), as determined on the basis of standard consensus response criteria from the International Workshop on Waldenström’s Macroglobulinemia (IWWM-6) criteria.
The drugs had nearly identical response rates (roughly 77%). There were no complete responses with either drug. However, zanubrutinib had twice the rate of very good partial responses compared with ibrutinib (15.7% vs. 7.1%). In addition, on the basis of modified IWWM-6 criteria, the very good partial response rate was 28% with zanubrutinib, compared to 19% with ibrutinib.
An additional efficacy outcome measure was duration of response, which was measured by the percentage of patients who were event free at 12 months. Zanubrutinib bested ibrutinib in this measure (94.4% vs. 87.9%).
The safety of zanubrutinib was also investigated in the ASPEN trial. Among patients who received zanubrutinib, 93% were exposed for 6 months or longer, and 89% were exposed for longer than 1 year. In cohort 1, serious adverse reactions occurred in 44% of patients who received zanubrutinib. Serious adverse reactions that occurred in > 2% of patients included influenza (3%), pneumonia (4%), neutropenia and decreased neutrophil count (3%), hemorrhage (4%), pyrexia (3%), and febrile neutropenia (3%).
In the FDA’s prescribing information for the drug, which includes approved indications and pooled safety data, the most common adverse reactions for zanubrutinib (≥ 20%) are listed as decreased neutrophil count, upper respiratory tract infection, decreased platelet count, rash, hemorrhage, musculoskeletal pain, decreased hemoglobin, bruising, diarrhea, pneumonia, and cough.
A version of this article first appeared on Medscape.com.