CHEST Physician

A number of fatal child poisonings have been linked to common cough and cold medications, according to a report.

The Pediatric Cough and Cold Safety Surveillance System, which tracks fatal child poisonings, has identified 40 such deaths in recent years and raised particular concern about medications containing diphenhydramine, a common antihistamine that can be sedating.

“There is little evidence that cough and cold medicines make children feel better or reduce their symptoms, but there is evidence they can suffer harm,” says Kevin Osterhoudt, MD, medical director of the Poison Control Center at the Children’s Hospital of Philadelphia.

In recent years, the FDA has advised labeling changes and recommended that cough and cold medications not be given to children younger than 2. Drugmakers also voluntarily relabeled these products to state “do not use in children under 4 years of age.”

Compared to older children or adults, young children have a different physiology when they breathe, so any product containing antihistamines can be a danger to little kids, Dr. Osterhoudt says.

But a recent survey shows about half of American parents gave their child cough and cold medication the last time they were ill, Dr. Osterhoudt says. And the findings suggest that cough and cold medications are in homes where children might find them.

Using the new evidence from the national surveillance system, investigators set up an expert panel to review the results. They found that most of the deaths were in children under the age of 2. The results were reported in the October issue of Pediatrics.

In seven instances, death followed the intentional use of medication to sedate the child, reports lead investigator Laurie Seidel Halmo, MD, from Children’s Hospital Colorado, Aurora.

“It’s not uncommon for parents to use sedatives like diphenhydramine to make their child sleepy for activities like air travel,” Dr. Osterhoudt says.

While antihistamines can be sedating, “an overdose of antihistamines like diphenhydramine can paradoxically become a stimulant,” having the opposite effect, he explains.

Adults and teens who take overdoses will sometimes become delirious, hallucinate, and have a racing heart.

But in young children, “if not careful with your dosing, you could actually give too much and create this stimulant activity,” Dr. Osterhoudt says.

In six other cases, the cough and cold medication was given to murder the child, the investigators reported.

The findings are “concerning,” especially with “more than one-half of nontherapeutic intent cases determined to be malicious in nature,” Michele Burns, MD, from Boston Children’s Hospital, and Madeline Renny, MD, from the Grossman School of Medicine in New York, wrote in a commentary with the report.

This important fatality review shows that despite safety efforts, young children remain at risk for death, they report.

The investigators point out that labeling changes do not seem to have protected vulnerable children, and they recommend that doctors educate parents and caregivers about the risk of cough and cold medications.

Dr. Halmo and her team also recommend that the medical community and child welfare advocates be on the lookout for medication use as a source of child abuse.

At home, preventing accidental ingestion could go along with other practices already ingrained in the minds of many, Dr. Osterhoudt says.

“We know to change the clocks in the spring and fall and make sure your smoke detector and carbon monoxide detector has fresh batteries, but maybe it’s also a good time to look at medicines in the house.”

In other words, after you change the clocks, it’s time to take inventory of medications around the house, and if they’re no longer in use, safely dispose of them.

The American Academy of Pediatrics offers guidelines on the safe home storage of medications to keep them out of reach of children and the use of protective caps on drugs.

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

A number of fatal child poisonings have been linked to common cough and cold medications, according to a report.

The Pediatric Cough and Cold Safety Surveillance System, which tracks fatal child poisonings, has identified 40 such deaths in recent years and raised particular concern about medications containing diphenhydramine, a common antihistamine that can be sedating.

“There is little evidence that cough and cold medicines make children feel better or reduce their symptoms, but there is evidence they can suffer harm,” says Kevin Osterhoudt, MD, medical director of the Poison Control Center at the Children’s Hospital of Philadelphia.

In recent years, the FDA has advised labeling changes and recommended that cough and cold medications not be given to children younger than 2. Drugmakers also voluntarily relabeled these products to state “do not use in children under 4 years of age.”

Compared to older children or adults, young children have a different physiology when they breathe, so any product containing antihistamines can be a danger to little kids, Dr. Osterhoudt says.

But a recent survey shows about half of American parents gave their child cough and cold medication the last time they were ill, Dr. Osterhoudt says. And the findings suggest that cough and cold medications are in homes where children might find them.

Using the new evidence from the national surveillance system, investigators set up an expert panel to review the results. They found that most of the deaths were in children under the age of 2. The results were reported in the October issue of Pediatrics.

In seven instances, death followed the intentional use of medication to sedate the child, reports lead investigator Laurie Seidel Halmo, MD, from Children’s Hospital Colorado, Aurora.

“It’s not uncommon for parents to use sedatives like diphenhydramine to make their child sleepy for activities like air travel,” Dr. Osterhoudt says.

While antihistamines can be sedating, “an overdose of antihistamines like diphenhydramine can paradoxically become a stimulant,” having the opposite effect, he explains.

Adults and teens who take overdoses will sometimes become delirious, hallucinate, and have a racing heart.

But in young children, “if not careful with your dosing, you could actually give too much and create this stimulant activity,” Dr. Osterhoudt says.

In six other cases, the cough and cold medication was given to murder the child, the investigators reported.

The findings are “concerning,” especially with “more than one-half of nontherapeutic intent cases determined to be malicious in nature,” Michele Burns, MD, from Boston Children’s Hospital, and Madeline Renny, MD, from the Grossman School of Medicine in New York, wrote in a commentary with the report.

This important fatality review shows that despite safety efforts, young children remain at risk for death, they report.

The investigators point out that labeling changes do not seem to have protected vulnerable children, and they recommend that doctors educate parents and caregivers about the risk of cough and cold medications.

Dr. Halmo and her team also recommend that the medical community and child welfare advocates be on the lookout for medication use as a source of child abuse.

At home, preventing accidental ingestion could go along with other practices already ingrained in the minds of many, Dr. Osterhoudt says.

“We know to change the clocks in the spring and fall and make sure your smoke detector and carbon monoxide detector has fresh batteries, but maybe it’s also a good time to look at medicines in the house.”

In other words, after you change the clocks, it’s time to take inventory of medications around the house, and if they’re no longer in use, safely dispose of them.

The American Academy of Pediatrics offers guidelines on the safe home storage of medications to keep them out of reach of children and the use of protective caps on drugs.

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

A number of fatal child poisonings have been linked to common cough and cold medications, according to a report.

The Pediatric Cough and Cold Safety Surveillance System, which tracks fatal child poisonings, has identified 40 such deaths in recent years and raised particular concern about medications containing diphenhydramine, a common antihistamine that can be sedating.

“There is little evidence that cough and cold medicines make children feel better or reduce their symptoms, but there is evidence they can suffer harm,” says Kevin Osterhoudt, MD, medical director of the Poison Control Center at the Children’s Hospital of Philadelphia.

In recent years, the FDA has advised labeling changes and recommended that cough and cold medications not be given to children younger than 2. Drugmakers also voluntarily relabeled these products to state “do not use in children under 4 years of age.”

Compared to older children or adults, young children have a different physiology when they breathe, so any product containing antihistamines can be a danger to little kids, Dr. Osterhoudt says.

But a recent survey shows about half of American parents gave their child cough and cold medication the last time they were ill, Dr. Osterhoudt says. And the findings suggest that cough and cold medications are in homes where children might find them.

Using the new evidence from the national surveillance system, investigators set up an expert panel to review the results. They found that most of the deaths were in children under the age of 2. The results were reported in the October issue of Pediatrics.

In seven instances, death followed the intentional use of medication to sedate the child, reports lead investigator Laurie Seidel Halmo, MD, from Children’s Hospital Colorado, Aurora.

“It’s not uncommon for parents to use sedatives like diphenhydramine to make their child sleepy for activities like air travel,” Dr. Osterhoudt says.

While antihistamines can be sedating, “an overdose of antihistamines like diphenhydramine can paradoxically become a stimulant,” having the opposite effect, he explains.

Adults and teens who take overdoses will sometimes become delirious, hallucinate, and have a racing heart.

But in young children, “if not careful with your dosing, you could actually give too much and create this stimulant activity,” Dr. Osterhoudt says.

In six other cases, the cough and cold medication was given to murder the child, the investigators reported.

The findings are “concerning,” especially with “more than one-half of nontherapeutic intent cases determined to be malicious in nature,” Michele Burns, MD, from Boston Children’s Hospital, and Madeline Renny, MD, from the Grossman School of Medicine in New York, wrote in a commentary with the report.

This important fatality review shows that despite safety efforts, young children remain at risk for death, they report.

The investigators point out that labeling changes do not seem to have protected vulnerable children, and they recommend that doctors educate parents and caregivers about the risk of cough and cold medications.

Dr. Halmo and her team also recommend that the medical community and child welfare advocates be on the lookout for medication use as a source of child abuse.

At home, preventing accidental ingestion could go along with other practices already ingrained in the minds of many, Dr. Osterhoudt says.

“We know to change the clocks in the spring and fall and make sure your smoke detector and carbon monoxide detector has fresh batteries, but maybe it’s also a good time to look at medicines in the house.”

In other words, after you change the clocks, it’s time to take inventory of medications around the house, and if they’re no longer in use, safely dispose of them.

The American Academy of Pediatrics offers guidelines on the safe home storage of medications to keep them out of reach of children and the use of protective caps on drugs.

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

Clinicians should use standardized risk assessments, clinical pathways, and tools to evaluate and communicate with patients who present with chest pain (angina), advises a joint clinical practice guideline released by American Heart Association and American College of Cardiology.

Rawpixel/iStock/Getty Images

While evaluation of chest pain has been covered in previous guidelines, this is the first comprehensive guideline from the AHA and ACC focused exclusively on the evaluation and diagnosis of chest pain.

“As our imaging technologies have evolved, we needed a contemporary approach to which patients need further testing, and which do not, in addition to what testing is effective,” Martha Gulati, MD, University of Arizona, Phoenix, and chair of the guideline writing group, said in an interview.

“Our hope is that we have provided an evidence-based approach to evaluating patients that will assist all of us who manage, diagnose, and treat patients who experience chest pain,” said Dr. Gulati, who is also president-elect of the American Society for Preventive Cardiology.

The guideline was simultaneously published online Oct. 28, 2021, in Circulation and the Journal of the American College of Cardiology.
 

‘Atypical’ is out, ‘noncardiac’ is in

Each year, chest pain sends more than 6.5 million adults to the ED and more than 4 million to outpatient clinics in the United States.

Yet, among all patients who come to the ED, only 5% will have acute coronary syndrome (ACS). More than half will ultimately have a noncardiac reason for their chest pain, including respiratory, musculoskeletal, gastrointestinal, psychological, or other causes.

The guideline says evaluating the severity and the cause of chest pain is essential and advises using standard risk assessments to determine if a patient is at low, intermediate, or high risk for having a cardiac event.

“I hope clinicians take from our guidelines the understanding that low-risk patients often do not need additional testing. And if we communicate this effectively with our patients – incorporating shared decision-making into our practice – we can reduce ‘overtesting’ in low-risk patients,” Dr. Gulati said in an interview.

The guideline notes that women are unique when presenting with ACS symptoms. While chest pain is the dominant and most common symptom for both men and women, women may be more likely to also have symptoms such as nausea and shortness of breath.

The guideline also encourages using the term “noncardiac” if heart disease is not suspected in a patient with angina and says the term “atypical” is a “misleading” descriptor of chest pain and should not be used.

“Words matter, and we need to move away from describing chest pain as ‘atypical’ because it has resulted in confusion when these words are used,” Dr. Gulati stressed.

“Rather than meaning a different way of presenting, it has taken on a meaning to imply it is not cardiac. It is more useful to talk about the probability of the pain being cardiac vs noncardiac,” Dr. Gulati explained.
 

No one best test for everyone

There is also a focus on evaluation of patients with chest pain who present to the ED. The initial goals of ED physicians should be to identify if there are life-threatening causes and to determine if there is a need for hospital admission or testing, the guideline states.

Thorough screening in the ED may help determine who is at high risk versus intermediate or low risk for a cardiac event. An individual deemed to be at low risk may be referred for additional evaluation in an outpatient setting rather than being admitted to the hospital, the authors wrote.

High-sensitivity cardiac troponins are the “preferred standard” for establishing a biomarker diagnosis of acute myocardial infarction, allowing for more accurate detection and exclusion of myocardial injury, they added.

“While there is no one ‘best test’ for every patient, the guideline emphasizes the tests that may be most appropriate, depending on the individual situation, and which ones won’t provide additional information; therefore, these tests should not be done just for the sake of doing them,” Dr. Gulati said in a news release.

“Appropriate testing is also dependent upon the technology and screening devices that are available at the hospital or healthcare center where the patient is receiving care. All imaging modalities highlighted in the guideline have an important role in the assessment of chest pain to help determine the underlying cause, with the goal of preventing a serious cardiac event,” Dr. Gulati added.

The guideline was prepared on behalf of and approved by the AHA and ACC Joint Committee on Clinical Practice Guidelines.

Five other partnering organizations participated in and approved the guideline: the American Society of Echocardiography, the American College of Chest Physicians, the Society for Academic Emergency Medicine, the Society of Cardiovascular Computed Tomography, and the Society for Cardiovascular Magnetic Resonance.

The writing group included representatives from each of the partnering organizations and experts in the field (cardiac intensivists, cardiac interventionalists, cardiac surgeons, cardiologists, emergency physicians, and epidemiologists), as well as a lay/patient representative.

The research had no commercial funding.

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

Clinicians should use standardized risk assessments, clinical pathways, and tools to evaluate and communicate with patients who present with chest pain (angina), advises a joint clinical practice guideline released by American Heart Association and American College of Cardiology.

Rawpixel/iStock/Getty Images

While evaluation of chest pain has been covered in previous guidelines, this is the first comprehensive guideline from the AHA and ACC focused exclusively on the evaluation and diagnosis of chest pain.

“As our imaging technologies have evolved, we needed a contemporary approach to which patients need further testing, and which do not, in addition to what testing is effective,” Martha Gulati, MD, University of Arizona, Phoenix, and chair of the guideline writing group, said in an interview.

“Our hope is that we have provided an evidence-based approach to evaluating patients that will assist all of us who manage, diagnose, and treat patients who experience chest pain,” said Dr. Gulati, who is also president-elect of the American Society for Preventive Cardiology.

The guideline was simultaneously published online Oct. 28, 2021, in Circulation and the Journal of the American College of Cardiology.
 

‘Atypical’ is out, ‘noncardiac’ is in

Each year, chest pain sends more than 6.5 million adults to the ED and more than 4 million to outpatient clinics in the United States.

Yet, among all patients who come to the ED, only 5% will have acute coronary syndrome (ACS). More than half will ultimately have a noncardiac reason for their chest pain, including respiratory, musculoskeletal, gastrointestinal, psychological, or other causes.

The guideline says evaluating the severity and the cause of chest pain is essential and advises using standard risk assessments to determine if a patient is at low, intermediate, or high risk for having a cardiac event.

“I hope clinicians take from our guidelines the understanding that low-risk patients often do not need additional testing. And if we communicate this effectively with our patients – incorporating shared decision-making into our practice – we can reduce ‘overtesting’ in low-risk patients,” Dr. Gulati said in an interview.

The guideline notes that women are unique when presenting with ACS symptoms. While chest pain is the dominant and most common symptom for both men and women, women may be more likely to also have symptoms such as nausea and shortness of breath.

The guideline also encourages using the term “noncardiac” if heart disease is not suspected in a patient with angina and says the term “atypical” is a “misleading” descriptor of chest pain and should not be used.

“Words matter, and we need to move away from describing chest pain as ‘atypical’ because it has resulted in confusion when these words are used,” Dr. Gulati stressed.

“Rather than meaning a different way of presenting, it has taken on a meaning to imply it is not cardiac. It is more useful to talk about the probability of the pain being cardiac vs noncardiac,” Dr. Gulati explained.
 

No one best test for everyone

There is also a focus on evaluation of patients with chest pain who present to the ED. The initial goals of ED physicians should be to identify if there are life-threatening causes and to determine if there is a need for hospital admission or testing, the guideline states.

Thorough screening in the ED may help determine who is at high risk versus intermediate or low risk for a cardiac event. An individual deemed to be at low risk may be referred for additional evaluation in an outpatient setting rather than being admitted to the hospital, the authors wrote.

High-sensitivity cardiac troponins are the “preferred standard” for establishing a biomarker diagnosis of acute myocardial infarction, allowing for more accurate detection and exclusion of myocardial injury, they added.

“While there is no one ‘best test’ for every patient, the guideline emphasizes the tests that may be most appropriate, depending on the individual situation, and which ones won’t provide additional information; therefore, these tests should not be done just for the sake of doing them,” Dr. Gulati said in a news release.

“Appropriate testing is also dependent upon the technology and screening devices that are available at the hospital or healthcare center where the patient is receiving care. All imaging modalities highlighted in the guideline have an important role in the assessment of chest pain to help determine the underlying cause, with the goal of preventing a serious cardiac event,” Dr. Gulati added.

The guideline was prepared on behalf of and approved by the AHA and ACC Joint Committee on Clinical Practice Guidelines.

Five other partnering organizations participated in and approved the guideline: the American Society of Echocardiography, the American College of Chest Physicians, the Society for Academic Emergency Medicine, the Society of Cardiovascular Computed Tomography, and the Society for Cardiovascular Magnetic Resonance.

The writing group included representatives from each of the partnering organizations and experts in the field (cardiac intensivists, cardiac interventionalists, cardiac surgeons, cardiologists, emergency physicians, and epidemiologists), as well as a lay/patient representative.

The research had no commercial funding.

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

Clinicians should use standardized risk assessments, clinical pathways, and tools to evaluate and communicate with patients who present with chest pain (angina), advises a joint clinical practice guideline released by American Heart Association and American College of Cardiology.

Rawpixel/iStock/Getty Images

While evaluation of chest pain has been covered in previous guidelines, this is the first comprehensive guideline from the AHA and ACC focused exclusively on the evaluation and diagnosis of chest pain.

“As our imaging technologies have evolved, we needed a contemporary approach to which patients need further testing, and which do not, in addition to what testing is effective,” Martha Gulati, MD, University of Arizona, Phoenix, and chair of the guideline writing group, said in an interview.

“Our hope is that we have provided an evidence-based approach to evaluating patients that will assist all of us who manage, diagnose, and treat patients who experience chest pain,” said Dr. Gulati, who is also president-elect of the American Society for Preventive Cardiology.

The guideline was simultaneously published online Oct. 28, 2021, in Circulation and the Journal of the American College of Cardiology.
 

‘Atypical’ is out, ‘noncardiac’ is in

Each year, chest pain sends more than 6.5 million adults to the ED and more than 4 million to outpatient clinics in the United States.

Yet, among all patients who come to the ED, only 5% will have acute coronary syndrome (ACS). More than half will ultimately have a noncardiac reason for their chest pain, including respiratory, musculoskeletal, gastrointestinal, psychological, or other causes.

The guideline says evaluating the severity and the cause of chest pain is essential and advises using standard risk assessments to determine if a patient is at low, intermediate, or high risk for having a cardiac event.

“I hope clinicians take from our guidelines the understanding that low-risk patients often do not need additional testing. And if we communicate this effectively with our patients – incorporating shared decision-making into our practice – we can reduce ‘overtesting’ in low-risk patients,” Dr. Gulati said in an interview.

The guideline notes that women are unique when presenting with ACS symptoms. While chest pain is the dominant and most common symptom for both men and women, women may be more likely to also have symptoms such as nausea and shortness of breath.

The guideline also encourages using the term “noncardiac” if heart disease is not suspected in a patient with angina and says the term “atypical” is a “misleading” descriptor of chest pain and should not be used.

“Words matter, and we need to move away from describing chest pain as ‘atypical’ because it has resulted in confusion when these words are used,” Dr. Gulati stressed.

“Rather than meaning a different way of presenting, it has taken on a meaning to imply it is not cardiac. It is more useful to talk about the probability of the pain being cardiac vs noncardiac,” Dr. Gulati explained.
 

No one best test for everyone

There is also a focus on evaluation of patients with chest pain who present to the ED. The initial goals of ED physicians should be to identify if there are life-threatening causes and to determine if there is a need for hospital admission or testing, the guideline states.

Thorough screening in the ED may help determine who is at high risk versus intermediate or low risk for a cardiac event. An individual deemed to be at low risk may be referred for additional evaluation in an outpatient setting rather than being admitted to the hospital, the authors wrote.

High-sensitivity cardiac troponins are the “preferred standard” for establishing a biomarker diagnosis of acute myocardial infarction, allowing for more accurate detection and exclusion of myocardial injury, they added.

“While there is no one ‘best test’ for every patient, the guideline emphasizes the tests that may be most appropriate, depending on the individual situation, and which ones won’t provide additional information; therefore, these tests should not be done just for the sake of doing them,” Dr. Gulati said in a news release.

“Appropriate testing is also dependent upon the technology and screening devices that are available at the hospital or healthcare center where the patient is receiving care. All imaging modalities highlighted in the guideline have an important role in the assessment of chest pain to help determine the underlying cause, with the goal of preventing a serious cardiac event,” Dr. Gulati added.

The guideline was prepared on behalf of and approved by the AHA and ACC Joint Committee on Clinical Practice Guidelines.

Five other partnering organizations participated in and approved the guideline: the American Society of Echocardiography, the American College of Chest Physicians, the Society for Academic Emergency Medicine, the Society of Cardiovascular Computed Tomography, and the Society for Cardiovascular Magnetic Resonance.

The writing group included representatives from each of the partnering organizations and experts in the field (cardiac intensivists, cardiac interventionalists, cardiac surgeons, cardiologists, emergency physicians, and epidemiologists), as well as a lay/patient representative.

The research had no commercial funding.

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

The CDC is urging parents and guardians to vaccinate children ages 5-11 against COVID-19 once the shot is fully approved, despite questions from FDA advisers about the urgency given falling national case rates.

On Oct. 26, the FDA’s Vaccines and Related Biological Products Advisory Committee voted to recommend a 10-microgram shot for children. Though 17 of the 18 panelists voted in favor of it, some members said it was a hard decision and questioned the need for it now that cases and hospitalizations are down.

“There’s urgency because we’re seeing disease in children, we’ve seen deaths in children, we’ve seen long COVID,” CDC Director Rochelle Walensky, MD, said at a White House briefing on Oct. 27. “Certainly we’ve seen cases come down before, and the way to prevent surges again is to get more and more people vaccinated.”

CDC data presented at an Oct. 26 advisory committee meeting show that among children 5-11, COVID-19 was one of top 10 causes of death over last year, Dr. Walensky said. There have been more than 8,300 hospitalizations and 745 deaths in children under 18.

As of yesterday, the 7-day average of daily COVID-19 cases was 65,900, a 16% decrease from the prior week. Hospitalizations are down 54% from the week of Aug. 28, Dr. Walensky said.

“If the trends continue the way they are going, the emergency for children is not what we might think it would be. That was my concern,” James Hildreth, MD, president and CEO at Meharry Medical College in Nashville, said at the advisory committee meeting on Oct. 26.

But according to one CDC study, hospitalization rates for adolescents were 10 times higher in those who were unvaccinated. Another study found that COVID-related emergency room visits and hospital admissions among children were more than 3 times as high in states with the lowest vaccination rates.

“We are down from our peak in early September, and we are now heading in the right direction, but with cases still high, we must remain vigilant heading into the colder, drier winter months,” Dr. Walensky said, noting that the 7-day average of daily deaths still exceeds 1,000.

Meanwhile, the booster program is off to a “very strong start,” said White House COVID-19 Response Coordinator Jeff Zients.

In the 5 days since authorizations, about 15 million people have received an additional dose of the Pfizer, Moderna, and Johnson & Johnson vaccines.

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

The CDC is urging parents and guardians to vaccinate children ages 5-11 against COVID-19 once the shot is fully approved, despite questions from FDA advisers about the urgency given falling national case rates.

On Oct. 26, the FDA’s Vaccines and Related Biological Products Advisory Committee voted to recommend a 10-microgram shot for children. Though 17 of the 18 panelists voted in favor of it, some members said it was a hard decision and questioned the need for it now that cases and hospitalizations are down.

“There’s urgency because we’re seeing disease in children, we’ve seen deaths in children, we’ve seen long COVID,” CDC Director Rochelle Walensky, MD, said at a White House briefing on Oct. 27. “Certainly we’ve seen cases come down before, and the way to prevent surges again is to get more and more people vaccinated.”

CDC data presented at an Oct. 26 advisory committee meeting show that among children 5-11, COVID-19 was one of top 10 causes of death over last year, Dr. Walensky said. There have been more than 8,300 hospitalizations and 745 deaths in children under 18.

As of yesterday, the 7-day average of daily COVID-19 cases was 65,900, a 16% decrease from the prior week. Hospitalizations are down 54% from the week of Aug. 28, Dr. Walensky said.

“If the trends continue the way they are going, the emergency for children is not what we might think it would be. That was my concern,” James Hildreth, MD, president and CEO at Meharry Medical College in Nashville, said at the advisory committee meeting on Oct. 26.

But according to one CDC study, hospitalization rates for adolescents were 10 times higher in those who were unvaccinated. Another study found that COVID-related emergency room visits and hospital admissions among children were more than 3 times as high in states with the lowest vaccination rates.

“We are down from our peak in early September, and we are now heading in the right direction, but with cases still high, we must remain vigilant heading into the colder, drier winter months,” Dr. Walensky said, noting that the 7-day average of daily deaths still exceeds 1,000.

Meanwhile, the booster program is off to a “very strong start,” said White House COVID-19 Response Coordinator Jeff Zients.

In the 5 days since authorizations, about 15 million people have received an additional dose of the Pfizer, Moderna, and Johnson & Johnson vaccines.

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

The CDC is urging parents and guardians to vaccinate children ages 5-11 against COVID-19 once the shot is fully approved, despite questions from FDA advisers about the urgency given falling national case rates.

On Oct. 26, the FDA’s Vaccines and Related Biological Products Advisory Committee voted to recommend a 10-microgram shot for children. Though 17 of the 18 panelists voted in favor of it, some members said it was a hard decision and questioned the need for it now that cases and hospitalizations are down.

“There’s urgency because we’re seeing disease in children, we’ve seen deaths in children, we’ve seen long COVID,” CDC Director Rochelle Walensky, MD, said at a White House briefing on Oct. 27. “Certainly we’ve seen cases come down before, and the way to prevent surges again is to get more and more people vaccinated.”

CDC data presented at an Oct. 26 advisory committee meeting show that among children 5-11, COVID-19 was one of top 10 causes of death over last year, Dr. Walensky said. There have been more than 8,300 hospitalizations and 745 deaths in children under 18.

As of yesterday, the 7-day average of daily COVID-19 cases was 65,900, a 16% decrease from the prior week. Hospitalizations are down 54% from the week of Aug. 28, Dr. Walensky said.

“If the trends continue the way they are going, the emergency for children is not what we might think it would be. That was my concern,” James Hildreth, MD, president and CEO at Meharry Medical College in Nashville, said at the advisory committee meeting on Oct. 26.

But according to one CDC study, hospitalization rates for adolescents were 10 times higher in those who were unvaccinated. Another study found that COVID-related emergency room visits and hospital admissions among children were more than 3 times as high in states with the lowest vaccination rates.

“We are down from our peak in early September, and we are now heading in the right direction, but with cases still high, we must remain vigilant heading into the colder, drier winter months,” Dr. Walensky said, noting that the 7-day average of daily deaths still exceeds 1,000.

Meanwhile, the booster program is off to a “very strong start,” said White House COVID-19 Response Coordinator Jeff Zients.

In the 5 days since authorizations, about 15 million people have received an additional dose of the Pfizer, Moderna, and Johnson & Johnson vaccines.

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

Takeda Pharmaceuticals is now the latest pharmaceutical company to offer a value-based agreement on one of its new targeted therapies.

The rebate offer is for brigatinib (Alunbrig) which is approved for the treatment of adults with anaplastic lymphoma kinase positive (ALK+) metastatic non–small cell lung cancer (NSCLC) as detected by an FDA-approved test.

The move follows a rebate offer from Pfizer for crizotinib (Xalkori), which is also approved for ALK+ (as well as ROS1+) NSCLC, and also for ALK+ anaplastic large cell lymphoma

For its offer, Takeda has teamed up with Point32Health, the second-largest health plan in New England with about 2.3 million members. The new agreement will make brigatinib widely available to patients who may benefit from its use, say the companies.

If a patient is unable to remain on brigatinib for 3 months or longer because of effectiveness or tolerability, Takeda will refund a yet unspecified amount of money to Point32Health. Brigatinib’s list price is $17,000 for a month’s treatment.

“Given the importance of facilitating cutting-edge oncology treatment and also the reality that not all patients show a positive response, reimbursement for oncology treatments is an area that is prime for innovative financing approaches,” said Michael Sherman, MD, chief medical officer and executive vice president, Point32Health, in a statement. “Collaborating with Takeda to share risk makes this agreement a crucial milestone in bringing cost-effectiveness to cancer care.”

The Pfizer program for crizotinib is somewhat different. For one thing, Pfizer’s refund is offered to any patient who qualifies and not just those who are covered by a specific plan. Second, Takeda is thus far only refunding money to the insurer, whereas Pfizer will also reimburse patients for out-of-pocket expenses.

There is a similar approach that has been offered by Novartis for tisagenlecleucel (Kymriah), the CAR T-cell therapy that launched with a daunting price tag of $475,000. After receiving backlash over the cost, Novartis announced that if the drug does not work after the first month, patients pay nothing.

In addition, Italy has been using this system for several years. Pharmaceutical companies must refund money if the drug fails to work. In 2015, the state-run health care system collected 200 million euros ($220 million) in refunds.

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

Takeda Pharmaceuticals is now the latest pharmaceutical company to offer a value-based agreement on one of its new targeted therapies.

The rebate offer is for brigatinib (Alunbrig) which is approved for the treatment of adults with anaplastic lymphoma kinase positive (ALK+) metastatic non–small cell lung cancer (NSCLC) as detected by an FDA-approved test.

The move follows a rebate offer from Pfizer for crizotinib (Xalkori), which is also approved for ALK+ (as well as ROS1+) NSCLC, and also for ALK+ anaplastic large cell lymphoma

For its offer, Takeda has teamed up with Point32Health, the second-largest health plan in New England with about 2.3 million members. The new agreement will make brigatinib widely available to patients who may benefit from its use, say the companies.

If a patient is unable to remain on brigatinib for 3 months or longer because of effectiveness or tolerability, Takeda will refund a yet unspecified amount of money to Point32Health. Brigatinib’s list price is $17,000 for a month’s treatment.

“Given the importance of facilitating cutting-edge oncology treatment and also the reality that not all patients show a positive response, reimbursement for oncology treatments is an area that is prime for innovative financing approaches,” said Michael Sherman, MD, chief medical officer and executive vice president, Point32Health, in a statement. “Collaborating with Takeda to share risk makes this agreement a crucial milestone in bringing cost-effectiveness to cancer care.”

The Pfizer program for crizotinib is somewhat different. For one thing, Pfizer’s refund is offered to any patient who qualifies and not just those who are covered by a specific plan. Second, Takeda is thus far only refunding money to the insurer, whereas Pfizer will also reimburse patients for out-of-pocket expenses.

There is a similar approach that has been offered by Novartis for tisagenlecleucel (Kymriah), the CAR T-cell therapy that launched with a daunting price tag of $475,000. After receiving backlash over the cost, Novartis announced that if the drug does not work after the first month, patients pay nothing.

In addition, Italy has been using this system for several years. Pharmaceutical companies must refund money if the drug fails to work. In 2015, the state-run health care system collected 200 million euros ($220 million) in refunds.

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

Takeda Pharmaceuticals is now the latest pharmaceutical company to offer a value-based agreement on one of its new targeted therapies.

The rebate offer is for brigatinib (Alunbrig) which is approved for the treatment of adults with anaplastic lymphoma kinase positive (ALK+) metastatic non–small cell lung cancer (NSCLC) as detected by an FDA-approved test.

The move follows a rebate offer from Pfizer for crizotinib (Xalkori), which is also approved for ALK+ (as well as ROS1+) NSCLC, and also for ALK+ anaplastic large cell lymphoma

For its offer, Takeda has teamed up with Point32Health, the second-largest health plan in New England with about 2.3 million members. The new agreement will make brigatinib widely available to patients who may benefit from its use, say the companies.

If a patient is unable to remain on brigatinib for 3 months or longer because of effectiveness or tolerability, Takeda will refund a yet unspecified amount of money to Point32Health. Brigatinib’s list price is $17,000 for a month’s treatment.

“Given the importance of facilitating cutting-edge oncology treatment and also the reality that not all patients show a positive response, reimbursement for oncology treatments is an area that is prime for innovative financing approaches,” said Michael Sherman, MD, chief medical officer and executive vice president, Point32Health, in a statement. “Collaborating with Takeda to share risk makes this agreement a crucial milestone in bringing cost-effectiveness to cancer care.”

The Pfizer program for crizotinib is somewhat different. For one thing, Pfizer’s refund is offered to any patient who qualifies and not just those who are covered by a specific plan. Second, Takeda is thus far only refunding money to the insurer, whereas Pfizer will also reimburse patients for out-of-pocket expenses.

There is a similar approach that has been offered by Novartis for tisagenlecleucel (Kymriah), the CAR T-cell therapy that launched with a daunting price tag of $475,000. After receiving backlash over the cost, Novartis announced that if the drug does not work after the first month, patients pay nothing.

In addition, Italy has been using this system for several years. Pharmaceutical companies must refund money if the drug fails to work. In 2015, the state-run health care system collected 200 million euros ($220 million) in refunds.

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

For patients with moderate to severe asthma, blockade with itepekimab, a new human IgG4P monoclonal antibody against the upstream alarmin interleukin-33, led to a reduction in events that indicate loss of asthma control. Treatment with itepekimab also led to an improvement in lung function compared with placebo, according to results of a phase 2 trial.

However, findings for a subgroup of patients treated with itepekimab in combination with dupilumab, an anti–interleukin-4–receptor alpha subunit and IL-13 monoclonal antibody, were not favorable in comparison with placebo, noted M. E. Wechsler, MD, and colleagues in an article published online in the New England Journal of Medicine.
 

New target

Despite the demonstrated efficacy of available biologic therapies targeting IgE, interleukin-4, interleukin-13, and interleukin-5 for treating moderate to severe type 2 asthma, many patients with type 2 or non–type 2 asthma continue to have symptoms, exacerbations, and reduced lung function. New therapies targeting alternative pathophysiologic pathways are needed.

Genomewide studies show that type 2 and non–type 2 inflammation that contributes to asthma and chronic obstructive pulmonary disease (COPD) are genetically associated with interleukin-33. This inflammation occurs when interleukin-33 binds to its cognate receptor (ST2) and engages the coreceptor interleukin-1 receptor accessory protein to initiate downstream signaling, activating cells of both the innate and adaptive immune systems.
 

Study details

The investigators conducted a multicenter, randomized, double-blind, placebo-controlled, parallel-group (four groups), proof-of-concept trial to evaluate the efficacy and safety of the interleukin-33 targeting itepekimab in comparison with placebo for adults with moderate to severe asthma. Dupilumab, which was the active comparator, was administered in combination with itepekimab to evaluate potential additive effects. Dupilumab’s efficacy in this population had been demonstrated previously.

All 296 patients (mean age, 49.1 years; 64% women) were receiving inhaled glucocorticoids plus long-acting beta-agonists (LABAs). They were randomly assigned in a 1:1:1:1 ratio to receive subcutaneous itepekimab (300 mg), itepekimab plus dupilumab (both at 300 mg; combination therapy), dupilumab (300 mg), or placebo every 2 weeks for 12 weeks. LABAs were discontinued at week 4, and inhaled glucocorticoids were tapered over weeks 6 through 9. The primary endpoint was the occurrence of an event indicating the loss of asthma control.
 

Promising results

Primary endpoint analysis at 12 weeks revealed a lower rate of asthma control–loss events in the itepekimab and dupilumab monotherapy groups but not in the combination group, compared with patients who received placebo. Events occurred in 22% of patients in the itepekimab group, in 27% of those in the combination group, in 19% of the dupilumab group, and in 41% of the placebo group. The odds ratios for comparisons with placebo were 0.42 for the itepekimab group (95% confidence interval, 0.20-0.88; P = .02); 0.33 in the dupilumab group (95% CI, 0.15-.70); and 0.52 in the combination group (95% CI, 0.26-1.06; P = .07) .

Following a similar pattern, forced expiratory volume in 1 second before use of a bronchodilator increased with both monotherapies but not with the combination or placebo. Although the trial was not powered to determine differences between itepekimab and dupilumab, the effects of dupilumab therapy were generally greater than those observed with itepekimab, especially for patients with type 2 asthma.

Also, asthma control and quality of life were improved with itepekimab and dupilumab monotherapy in comparison with placebo. There were also greater reductions in the mean blood eosinophil count.

The authors urge further research into the complexities of asthma physiology and encourage researchers to look for predictive biomarkers of anti–interleukin-33 blockade response. They conclude, “In this trial, we found that itepekimab monotherapy led to a lower incidence of events indicating loss of asthma control and to improved lung function, findings that are consistent with a role for interleukin-33 in the pathogenesis of exacerbations and airflow limitation in asthma.”
 

Examining results

In an accompanying editorial, Philip G. Bardin, PhD, and Paul S. Foster, DSc, ask why itepekimab and dupilumab, a combination based on a sound scientific rationale, failed. As monotherapies, both itepekimab and dupilumab are roughly similar in reducing asthma events and improving lung function; thus, is unlikely that inadequate dosing led to the failure of itepekimab.

Interleukin-33 is an attractive target because the cells it promotes secrete cytokines that induce asthma’s pathognomonic features, and biologic agents that target those cytokines (interleukin-5/-5R/-4/-13 axes) have been highly effective. They do not, however, prevent exacerbations after treatment.

Alternative pathways within or outside that paradigm are operant, and other epithelial alarmins, such as interleukin-25 and thymic stromal lymphopoietin, promote type 2 inflammation, Dr. Bardin and Dr. Foster state.

“Combination therapy with itepekimab and dupilumab may have failed because these pathways bypass interleukin-33,” they write. Also, preexisting ILC2 and TH2 cells may have residual capacity to release mediators. The short-term trial design, the editorialists write, may have contributed to the failure of the itepekimab/dupilumab combination; interleukin-33 may be appropriate as a target in a longer-term exacerbation-type trial “in which epithelial infection and other relevant stimuli instigate exacerbated disease. Combination therapy may be capable of lowering exacerbations rather than preventing loss of control in chronic disease.

“Clinical translation of basic science in asthma remains a challenge to be pursued. ... It is imperative to harness scientific insights from translational studies that frustrate our hopeful expectations – so that something can also be gained,” they conclude.
 

The role of interleukin-33

“Our study of itepekimab provides valuable insight into pathophysiology of severe asthma,” said Dr. Wechsler, professor of medicine at the NJH Cohen Family Asthma Institute, Denver, in an interview. “As blocking IL-33 reduced asthma worsening and improved lung function compared to placebo, it suggests that IL-33 plays an important role in asthma pathophysiology and may be a valuable target for a subset of patients with severe asthma,” he stated.

“Since the effect of itepekimab is comparable to that of dupilumab, it is suggested that patients may benefit from blockade of this pathway, but what remains to be seen is identifying which patients are more likely to respond better to one therapy vs. another. The future of blocking IL-33 remains exciting, and studies are being planned to evaluate its efficacy in airways diseases, including COPD,” he concluded.

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

For patients with moderate to severe asthma, blockade with itepekimab, a new human IgG4P monoclonal antibody against the upstream alarmin interleukin-33, led to a reduction in events that indicate loss of asthma control. Treatment with itepekimab also led to an improvement in lung function compared with placebo, according to results of a phase 2 trial.

However, findings for a subgroup of patients treated with itepekimab in combination with dupilumab, an anti–interleukin-4–receptor alpha subunit and IL-13 monoclonal antibody, were not favorable in comparison with placebo, noted M. E. Wechsler, MD, and colleagues in an article published online in the New England Journal of Medicine.
 

New target

Despite the demonstrated efficacy of available biologic therapies targeting IgE, interleukin-4, interleukin-13, and interleukin-5 for treating moderate to severe type 2 asthma, many patients with type 2 or non–type 2 asthma continue to have symptoms, exacerbations, and reduced lung function. New therapies targeting alternative pathophysiologic pathways are needed.

Genomewide studies show that type 2 and non–type 2 inflammation that contributes to asthma and chronic obstructive pulmonary disease (COPD) are genetically associated with interleukin-33. This inflammation occurs when interleukin-33 binds to its cognate receptor (ST2) and engages the coreceptor interleukin-1 receptor accessory protein to initiate downstream signaling, activating cells of both the innate and adaptive immune systems.
 

Study details

The investigators conducted a multicenter, randomized, double-blind, placebo-controlled, parallel-group (four groups), proof-of-concept trial to evaluate the efficacy and safety of the interleukin-33 targeting itepekimab in comparison with placebo for adults with moderate to severe asthma. Dupilumab, which was the active comparator, was administered in combination with itepekimab to evaluate potential additive effects. Dupilumab’s efficacy in this population had been demonstrated previously.

All 296 patients (mean age, 49.1 years; 64% women) were receiving inhaled glucocorticoids plus long-acting beta-agonists (LABAs). They were randomly assigned in a 1:1:1:1 ratio to receive subcutaneous itepekimab (300 mg), itepekimab plus dupilumab (both at 300 mg; combination therapy), dupilumab (300 mg), or placebo every 2 weeks for 12 weeks. LABAs were discontinued at week 4, and inhaled glucocorticoids were tapered over weeks 6 through 9. The primary endpoint was the occurrence of an event indicating the loss of asthma control.
 

Promising results

Primary endpoint analysis at 12 weeks revealed a lower rate of asthma control–loss events in the itepekimab and dupilumab monotherapy groups but not in the combination group, compared with patients who received placebo. Events occurred in 22% of patients in the itepekimab group, in 27% of those in the combination group, in 19% of the dupilumab group, and in 41% of the placebo group. The odds ratios for comparisons with placebo were 0.42 for the itepekimab group (95% confidence interval, 0.20-0.88; P = .02); 0.33 in the dupilumab group (95% CI, 0.15-.70); and 0.52 in the combination group (95% CI, 0.26-1.06; P = .07) .

Following a similar pattern, forced expiratory volume in 1 second before use of a bronchodilator increased with both monotherapies but not with the combination or placebo. Although the trial was not powered to determine differences between itepekimab and dupilumab, the effects of dupilumab therapy were generally greater than those observed with itepekimab, especially for patients with type 2 asthma.

Also, asthma control and quality of life were improved with itepekimab and dupilumab monotherapy in comparison with placebo. There were also greater reductions in the mean blood eosinophil count.

The authors urge further research into the complexities of asthma physiology and encourage researchers to look for predictive biomarkers of anti–interleukin-33 blockade response. They conclude, “In this trial, we found that itepekimab monotherapy led to a lower incidence of events indicating loss of asthma control and to improved lung function, findings that are consistent with a role for interleukin-33 in the pathogenesis of exacerbations and airflow limitation in asthma.”
 

Examining results

In an accompanying editorial, Philip G. Bardin, PhD, and Paul S. Foster, DSc, ask why itepekimab and dupilumab, a combination based on a sound scientific rationale, failed. As monotherapies, both itepekimab and dupilumab are roughly similar in reducing asthma events and improving lung function; thus, is unlikely that inadequate dosing led to the failure of itepekimab.

Interleukin-33 is an attractive target because the cells it promotes secrete cytokines that induce asthma’s pathognomonic features, and biologic agents that target those cytokines (interleukin-5/-5R/-4/-13 axes) have been highly effective. They do not, however, prevent exacerbations after treatment.

Alternative pathways within or outside that paradigm are operant, and other epithelial alarmins, such as interleukin-25 and thymic stromal lymphopoietin, promote type 2 inflammation, Dr. Bardin and Dr. Foster state.

“Combination therapy with itepekimab and dupilumab may have failed because these pathways bypass interleukin-33,” they write. Also, preexisting ILC2 and TH2 cells may have residual capacity to release mediators. The short-term trial design, the editorialists write, may have contributed to the failure of the itepekimab/dupilumab combination; interleukin-33 may be appropriate as a target in a longer-term exacerbation-type trial “in which epithelial infection and other relevant stimuli instigate exacerbated disease. Combination therapy may be capable of lowering exacerbations rather than preventing loss of control in chronic disease.

“Clinical translation of basic science in asthma remains a challenge to be pursued. ... It is imperative to harness scientific insights from translational studies that frustrate our hopeful expectations – so that something can also be gained,” they conclude.
 

The role of interleukin-33

“Our study of itepekimab provides valuable insight into pathophysiology of severe asthma,” said Dr. Wechsler, professor of medicine at the NJH Cohen Family Asthma Institute, Denver, in an interview. “As blocking IL-33 reduced asthma worsening and improved lung function compared to placebo, it suggests that IL-33 plays an important role in asthma pathophysiology and may be a valuable target for a subset of patients with severe asthma,” he stated.

“Since the effect of itepekimab is comparable to that of dupilumab, it is suggested that patients may benefit from blockade of this pathway, but what remains to be seen is identifying which patients are more likely to respond better to one therapy vs. another. The future of blocking IL-33 remains exciting, and studies are being planned to evaluate its efficacy in airways diseases, including COPD,” he concluded.

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

For patients with moderate to severe asthma, blockade with itepekimab, a new human IgG4P monoclonal antibody against the upstream alarmin interleukin-33, led to a reduction in events that indicate loss of asthma control. Treatment with itepekimab also led to an improvement in lung function compared with placebo, according to results of a phase 2 trial.

However, findings for a subgroup of patients treated with itepekimab in combination with dupilumab, an anti–interleukin-4–receptor alpha subunit and IL-13 monoclonal antibody, were not favorable in comparison with placebo, noted M. E. Wechsler, MD, and colleagues in an article published online in the New England Journal of Medicine.
 

New target

Despite the demonstrated efficacy of available biologic therapies targeting IgE, interleukin-4, interleukin-13, and interleukin-5 for treating moderate to severe type 2 asthma, many patients with type 2 or non–type 2 asthma continue to have symptoms, exacerbations, and reduced lung function. New therapies targeting alternative pathophysiologic pathways are needed.

Genomewide studies show that type 2 and non–type 2 inflammation that contributes to asthma and chronic obstructive pulmonary disease (COPD) are genetically associated with interleukin-33. This inflammation occurs when interleukin-33 binds to its cognate receptor (ST2) and engages the coreceptor interleukin-1 receptor accessory protein to initiate downstream signaling, activating cells of both the innate and adaptive immune systems.
 

Study details

The investigators conducted a multicenter, randomized, double-blind, placebo-controlled, parallel-group (four groups), proof-of-concept trial to evaluate the efficacy and safety of the interleukin-33 targeting itepekimab in comparison with placebo for adults with moderate to severe asthma. Dupilumab, which was the active comparator, was administered in combination with itepekimab to evaluate potential additive effects. Dupilumab’s efficacy in this population had been demonstrated previously.

All 296 patients (mean age, 49.1 years; 64% women) were receiving inhaled glucocorticoids plus long-acting beta-agonists (LABAs). They were randomly assigned in a 1:1:1:1 ratio to receive subcutaneous itepekimab (300 mg), itepekimab plus dupilumab (both at 300 mg; combination therapy), dupilumab (300 mg), or placebo every 2 weeks for 12 weeks. LABAs were discontinued at week 4, and inhaled glucocorticoids were tapered over weeks 6 through 9. The primary endpoint was the occurrence of an event indicating the loss of asthma control.
 

Promising results

Primary endpoint analysis at 12 weeks revealed a lower rate of asthma control–loss events in the itepekimab and dupilumab monotherapy groups but not in the combination group, compared with patients who received placebo. Events occurred in 22% of patients in the itepekimab group, in 27% of those in the combination group, in 19% of the dupilumab group, and in 41% of the placebo group. The odds ratios for comparisons with placebo were 0.42 for the itepekimab group (95% confidence interval, 0.20-0.88; P = .02); 0.33 in the dupilumab group (95% CI, 0.15-.70); and 0.52 in the combination group (95% CI, 0.26-1.06; P = .07) .

Following a similar pattern, forced expiratory volume in 1 second before use of a bronchodilator increased with both monotherapies but not with the combination or placebo. Although the trial was not powered to determine differences between itepekimab and dupilumab, the effects of dupilumab therapy were generally greater than those observed with itepekimab, especially for patients with type 2 asthma.

Also, asthma control and quality of life were improved with itepekimab and dupilumab monotherapy in comparison with placebo. There were also greater reductions in the mean blood eosinophil count.

The authors urge further research into the complexities of asthma physiology and encourage researchers to look for predictive biomarkers of anti–interleukin-33 blockade response. They conclude, “In this trial, we found that itepekimab monotherapy led to a lower incidence of events indicating loss of asthma control and to improved lung function, findings that are consistent with a role for interleukin-33 in the pathogenesis of exacerbations and airflow limitation in asthma.”
 

Examining results

In an accompanying editorial, Philip G. Bardin, PhD, and Paul S. Foster, DSc, ask why itepekimab and dupilumab, a combination based on a sound scientific rationale, failed. As monotherapies, both itepekimab and dupilumab are roughly similar in reducing asthma events and improving lung function; thus, is unlikely that inadequate dosing led to the failure of itepekimab.

Interleukin-33 is an attractive target because the cells it promotes secrete cytokines that induce asthma’s pathognomonic features, and biologic agents that target those cytokines (interleukin-5/-5R/-4/-13 axes) have been highly effective. They do not, however, prevent exacerbations after treatment.

Alternative pathways within or outside that paradigm are operant, and other epithelial alarmins, such as interleukin-25 and thymic stromal lymphopoietin, promote type 2 inflammation, Dr. Bardin and Dr. Foster state.

“Combination therapy with itepekimab and dupilumab may have failed because these pathways bypass interleukin-33,” they write. Also, preexisting ILC2 and TH2 cells may have residual capacity to release mediators. The short-term trial design, the editorialists write, may have contributed to the failure of the itepekimab/dupilumab combination; interleukin-33 may be appropriate as a target in a longer-term exacerbation-type trial “in which epithelial infection and other relevant stimuli instigate exacerbated disease. Combination therapy may be capable of lowering exacerbations rather than preventing loss of control in chronic disease.

“Clinical translation of basic science in asthma remains a challenge to be pursued. ... It is imperative to harness scientific insights from translational studies that frustrate our hopeful expectations – so that something can also be gained,” they conclude.
 

The role of interleukin-33

“Our study of itepekimab provides valuable insight into pathophysiology of severe asthma,” said Dr. Wechsler, professor of medicine at the NJH Cohen Family Asthma Institute, Denver, in an interview. “As blocking IL-33 reduced asthma worsening and improved lung function compared to placebo, it suggests that IL-33 plays an important role in asthma pathophysiology and may be a valuable target for a subset of patients with severe asthma,” he stated.

“Since the effect of itepekimab is comparable to that of dupilumab, it is suggested that patients may benefit from blockade of this pathway, but what remains to be seen is identifying which patients are more likely to respond better to one therapy vs. another. The future of blocking IL-33 remains exciting, and studies are being planned to evaluate its efficacy in airways diseases, including COPD,” he concluded.

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

Placebo treatment was found to be superior to treatment with risankizumab with respect to time to first asthma worsening and annualized rate of asthma worsening for adults with severe persistent asthma in a phase 2a clinical trial.

The randomized, double-blind, 24-week, parallel group, multicenter trial assessed risankizumab efficacy and safety in 214 adults with severe persistent asthma. The results were reported in The New England Journal of Medicine.

Risankizumab is a humanized, monoclonal antibody directed against subunit p19 of interleukin-23. It is approved for the treatment of moderate to severe psoriasis.

Interleukin-23 has been implicated in airway inflammation mediated by type 2 and type 17 cytokines. Noting that inhibition of interleukin-23 is effective in the treatment of psoriasis and Crohn’s disease, Christopher E. Brightling, MD, and colleagues investigated whether targeting interleukin-23 in asthma patients would improve disease control and reduce airway inflammation.
 

Study details

Patients received either 90 mg of risankizumab (subcutaneous) (n = 105) or placebo (n = 109) once every 4 weeks. Time to first asthma worsening was the primary endpoint. Worsening was defined as decline from baseline on 2 or more consecutive days. Deterioration was defined as a decrease of at least 30% in the morning peak expiratory flow or an increase from baseline of at least 50% in rescue medication puffs over 24 hours. In addition, a severe asthma exacerbation or an increase of 0.75 or more points on the five-item Asthma Control Questionnaire (scores range from 0 to 6, with higher scores indicating less control) were considered to be evidence of worsening. Annualized rate of asthma worsening was a secondary endpoint.

The mean age of the patients was 53 years; 66.5% of the patients were women.
 

Disappointing results

In the risankizumab group, median time to first asthma worsening was 40 days, significantly worse than the 86 days reported for the placebo group (hazard ratio, 1.46; 95% confidence interval, 1.05-2.04; P = .03). For annualized asthma worsening, the rate ratio for the comparison of risankizumab with placebo was 1.49 (95% CI, 1.12-1.99).

Among key secondary endpoints, the adjusted mean change in trough forced expiratory volume in 1 second (FEV₁₎ from baseline to week 24 was –0.05 L in the risankizumab group and –0.01 L in the placebo group. The adjusted mean change in FEV₁ after bronchodilator use from baseline to week 24 was –0.10 L in the risankizumab group and –0.03 L in the placebo group. Sputum transcriptomic pathway analysis showed that genes involved in the activation of natural killer cells and cytotoxic T cells and the activation of type 1 helper T and type 17 helper T transcription factors were downregulated by risankizumab. Rates of adverse events were similar among patients receiving risankizumab and those taking placebo.
 

Further trials unwarranted

“The findings not only failed to show benefit for any outcome but also showed asthma worsening occurred earlier and more frequently in those treated with risankizumab versus placebo,” Dr. Brightling, professor in the department of respiratory sciences at University of Leicester, England, said in an interview. “This study does not support any further trials for anti-IL23 in asthma.” Dr. Brightling speculated on the cause of accelerated asthma worsening with risankizumab.

“We found that the gene expression of key molecules involved in our response to infection was decreased in airway samples in those treated with risankizumab versus placebo. It is possible that the increased asthma worsening following risankizumab was related to this suppression of antimicrobial immunity,” he said.

He noted that risankizumab did not affect type-2/eosinophilic inflammation, which is the target for current asthma biologics, or gene expression of T2 molecules. “That suggests that this type of inflammation would have continued in the asthma patients during the trial irrespective of receiving risankizumab or placebo,” he said.
 

Caution with investigating biologicals

Downstream biologic responses to risankizumab were detectable, Philip G. Bardin, PhD, and Paul S. Foster, DSc, observed in an accompanying editorial, but there was no discernible clinical benefit, implying attenuation of apposite pathways. Current understanding of the basic science relevant to asthma, they stated, offers clues to the failure of risankizumab to benefit these patients with severe asthma. Although targeting the interleukin-23 and Th17 axis with risankizumab can reduce development of pathogenic Th17 cells, interleukin-23 is not critical for the development of Th17 cells.

“In contrast to pathways operated by interleukin-5 and interleukin-4R alpha, interleukin-23 has only a limited auxiliary role in amplifying type 2 responses. It is possible that the trial conducted by Brightling and colleagues failed because signaling through alternative disease pathways nullified inhibition of inter-leukin-23,” the editorialists wrote.

Dr. Bardin and Dr. Foster further speculate that because interleukin-23 is vital for effective mucosal immunity, risankizumab may have conferred to patients a predisposition to more severe or more frequent virus-induced exacerbations. They stated that generally, however, the reasons for risankizumab’s poorer outcomes compared to placebo are unclear. “Overall, these findings support a cautious approach in future research investigating biologic therapies in asthma,” they concluded.

The clinical trial was sponsored and funded by BI/AbbVie.

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

Placebo treatment was found to be superior to treatment with risankizumab with respect to time to first asthma worsening and annualized rate of asthma worsening for adults with severe persistent asthma in a phase 2a clinical trial.

The randomized, double-blind, 24-week, parallel group, multicenter trial assessed risankizumab efficacy and safety in 214 adults with severe persistent asthma. The results were reported in The New England Journal of Medicine.

Risankizumab is a humanized, monoclonal antibody directed against subunit p19 of interleukin-23. It is approved for the treatment of moderate to severe psoriasis.

Interleukin-23 has been implicated in airway inflammation mediated by type 2 and type 17 cytokines. Noting that inhibition of interleukin-23 is effective in the treatment of psoriasis and Crohn’s disease, Christopher E. Brightling, MD, and colleagues investigated whether targeting interleukin-23 in asthma patients would improve disease control and reduce airway inflammation.
 

Study details

Patients received either 90 mg of risankizumab (subcutaneous) (n = 105) or placebo (n = 109) once every 4 weeks. Time to first asthma worsening was the primary endpoint. Worsening was defined as decline from baseline on 2 or more consecutive days. Deterioration was defined as a decrease of at least 30% in the morning peak expiratory flow or an increase from baseline of at least 50% in rescue medication puffs over 24 hours. In addition, a severe asthma exacerbation or an increase of 0.75 or more points on the five-item Asthma Control Questionnaire (scores range from 0 to 6, with higher scores indicating less control) were considered to be evidence of worsening. Annualized rate of asthma worsening was a secondary endpoint.

The mean age of the patients was 53 years; 66.5% of the patients were women.
 

Disappointing results

In the risankizumab group, median time to first asthma worsening was 40 days, significantly worse than the 86 days reported for the placebo group (hazard ratio, 1.46; 95% confidence interval, 1.05-2.04; P = .03). For annualized asthma worsening, the rate ratio for the comparison of risankizumab with placebo was 1.49 (95% CI, 1.12-1.99).

Among key secondary endpoints, the adjusted mean change in trough forced expiratory volume in 1 second (FEV₁₎ from baseline to week 24 was –0.05 L in the risankizumab group and –0.01 L in the placebo group. The adjusted mean change in FEV₁ after bronchodilator use from baseline to week 24 was –0.10 L in the risankizumab group and –0.03 L in the placebo group. Sputum transcriptomic pathway analysis showed that genes involved in the activation of natural killer cells and cytotoxic T cells and the activation of type 1 helper T and type 17 helper T transcription factors were downregulated by risankizumab. Rates of adverse events were similar among patients receiving risankizumab and those taking placebo.
 

Further trials unwarranted

“The findings not only failed to show benefit for any outcome but also showed asthma worsening occurred earlier and more frequently in those treated with risankizumab versus placebo,” Dr. Brightling, professor in the department of respiratory sciences at University of Leicester, England, said in an interview. “This study does not support any further trials for anti-IL23 in asthma.” Dr. Brightling speculated on the cause of accelerated asthma worsening with risankizumab.

“We found that the gene expression of key molecules involved in our response to infection was decreased in airway samples in those treated with risankizumab versus placebo. It is possible that the increased asthma worsening following risankizumab was related to this suppression of antimicrobial immunity,” he said.

He noted that risankizumab did not affect type-2/eosinophilic inflammation, which is the target for current asthma biologics, or gene expression of T2 molecules. “That suggests that this type of inflammation would have continued in the asthma patients during the trial irrespective of receiving risankizumab or placebo,” he said.
 

Caution with investigating biologicals

Downstream biologic responses to risankizumab were detectable, Philip G. Bardin, PhD, and Paul S. Foster, DSc, observed in an accompanying editorial, but there was no discernible clinical benefit, implying attenuation of apposite pathways. Current understanding of the basic science relevant to asthma, they stated, offers clues to the failure of risankizumab to benefit these patients with severe asthma. Although targeting the interleukin-23 and Th17 axis with risankizumab can reduce development of pathogenic Th17 cells, interleukin-23 is not critical for the development of Th17 cells.

“In contrast to pathways operated by interleukin-5 and interleukin-4R alpha, interleukin-23 has only a limited auxiliary role in amplifying type 2 responses. It is possible that the trial conducted by Brightling and colleagues failed because signaling through alternative disease pathways nullified inhibition of inter-leukin-23,” the editorialists wrote.

Dr. Bardin and Dr. Foster further speculate that because interleukin-23 is vital for effective mucosal immunity, risankizumab may have conferred to patients a predisposition to more severe or more frequent virus-induced exacerbations. They stated that generally, however, the reasons for risankizumab’s poorer outcomes compared to placebo are unclear. “Overall, these findings support a cautious approach in future research investigating biologic therapies in asthma,” they concluded.

The clinical trial was sponsored and funded by BI/AbbVie.

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

Placebo treatment was found to be superior to treatment with risankizumab with respect to time to first asthma worsening and annualized rate of asthma worsening for adults with severe persistent asthma in a phase 2a clinical trial.

The randomized, double-blind, 24-week, parallel group, multicenter trial assessed risankizumab efficacy and safety in 214 adults with severe persistent asthma. The results were reported in The New England Journal of Medicine.

Risankizumab is a humanized, monoclonal antibody directed against subunit p19 of interleukin-23. It is approved for the treatment of moderate to severe psoriasis.

Interleukin-23 has been implicated in airway inflammation mediated by type 2 and type 17 cytokines. Noting that inhibition of interleukin-23 is effective in the treatment of psoriasis and Crohn’s disease, Christopher E. Brightling, MD, and colleagues investigated whether targeting interleukin-23 in asthma patients would improve disease control and reduce airway inflammation.
 

Study details

Patients received either 90 mg of risankizumab (subcutaneous) (n = 105) or placebo (n = 109) once every 4 weeks. Time to first asthma worsening was the primary endpoint. Worsening was defined as decline from baseline on 2 or more consecutive days. Deterioration was defined as a decrease of at least 30% in the morning peak expiratory flow or an increase from baseline of at least 50% in rescue medication puffs over 24 hours. In addition, a severe asthma exacerbation or an increase of 0.75 or more points on the five-item Asthma Control Questionnaire (scores range from 0 to 6, with higher scores indicating less control) were considered to be evidence of worsening. Annualized rate of asthma worsening was a secondary endpoint.

The mean age of the patients was 53 years; 66.5% of the patients were women.
 

Disappointing results

In the risankizumab group, median time to first asthma worsening was 40 days, significantly worse than the 86 days reported for the placebo group (hazard ratio, 1.46; 95% confidence interval, 1.05-2.04; P = .03). For annualized asthma worsening, the rate ratio for the comparison of risankizumab with placebo was 1.49 (95% CI, 1.12-1.99).

Among key secondary endpoints, the adjusted mean change in trough forced expiratory volume in 1 second (FEV₁₎ from baseline to week 24 was –0.05 L in the risankizumab group and –0.01 L in the placebo group. The adjusted mean change in FEV₁ after bronchodilator use from baseline to week 24 was –0.10 L in the risankizumab group and –0.03 L in the placebo group. Sputum transcriptomic pathway analysis showed that genes involved in the activation of natural killer cells and cytotoxic T cells and the activation of type 1 helper T and type 17 helper T transcription factors were downregulated by risankizumab. Rates of adverse events were similar among patients receiving risankizumab and those taking placebo.
 

Further trials unwarranted

“The findings not only failed to show benefit for any outcome but also showed asthma worsening occurred earlier and more frequently in those treated with risankizumab versus placebo,” Dr. Brightling, professor in the department of respiratory sciences at University of Leicester, England, said in an interview. “This study does not support any further trials for anti-IL23 in asthma.” Dr. Brightling speculated on the cause of accelerated asthma worsening with risankizumab.

“We found that the gene expression of key molecules involved in our response to infection was decreased in airway samples in those treated with risankizumab versus placebo. It is possible that the increased asthma worsening following risankizumab was related to this suppression of antimicrobial immunity,” he said.

He noted that risankizumab did not affect type-2/eosinophilic inflammation, which is the target for current asthma biologics, or gene expression of T2 molecules. “That suggests that this type of inflammation would have continued in the asthma patients during the trial irrespective of receiving risankizumab or placebo,” he said.
 

Caution with investigating biologicals

Downstream biologic responses to risankizumab were detectable, Philip G. Bardin, PhD, and Paul S. Foster, DSc, observed in an accompanying editorial, but there was no discernible clinical benefit, implying attenuation of apposite pathways. Current understanding of the basic science relevant to asthma, they stated, offers clues to the failure of risankizumab to benefit these patients with severe asthma. Although targeting the interleukin-23 and Th17 axis with risankizumab can reduce development of pathogenic Th17 cells, interleukin-23 is not critical for the development of Th17 cells.

“In contrast to pathways operated by interleukin-5 and interleukin-4R alpha, interleukin-23 has only a limited auxiliary role in amplifying type 2 responses. It is possible that the trial conducted by Brightling and colleagues failed because signaling through alternative disease pathways nullified inhibition of inter-leukin-23,” the editorialists wrote.

Dr. Bardin and Dr. Foster further speculate that because interleukin-23 is vital for effective mucosal immunity, risankizumab may have conferred to patients a predisposition to more severe or more frequent virus-induced exacerbations. They stated that generally, however, the reasons for risankizumab’s poorer outcomes compared to placebo are unclear. “Overall, these findings support a cautious approach in future research investigating biologic therapies in asthma,” they concluded.

The clinical trial was sponsored and funded by BI/AbbVie.

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

Lung cancer screening reduces mortality, but patient adherence to screening intervals is suboptimal in the United States, according to a review and meta-analysis published in the Journal of Thoracic Oncology.

“Lung cancer screening is effective in reducing mortality, particularly when patients adhere to follow-up recommendations standardized by the Lung CT Screening Reporting & Data System (Lung-RADS),” Yannan Lin, MD, MPH, of the University of California, Los Angeles, and colleagues wrote. ”Patient adherence to Lung-RADS–recommended screening intervals is suboptimal across clinical lung cancer screening programs in the U.S., especially among patients with Lung-RADS category 1-2 results.”

Lung cancer screening can identify tumors at earlier, more treatable stages, but patients with lung cancer diagnoses based on new nodules at incidence screening have shown shortened survivals. The National Lung Screening Trial (NLST) has shown a 20% relative reduction in lung cancer mortality with low-dose chest CT screening relative to chest radiography. The Lung-RADS guidelines to standardize the reporting of lung cancer screening were developed based on findings from the NLST and other screening studies, partly to reduce false-positive rates. Lung-RADS scores are based upon nodule size, characteristics and location, with management guidelines specific to Lung-RADS categories, ranging from low-dose chest CT in 12 months for Lung-RADS 1-2 to chest CT, PET/CT, or tissue sampling for Lung-RADS 4B/X.

The rate of adherence to lung cancer screening based on Lung-RADS guidelines is unclear. This systematic review and meta-analysis looked at patient adherence to Lung-RADS recommended screening intervals in clinical practice.

The meta-analysis included 21 studies. The pooled adherence rate was 57% for defined adherence, which included an annual incidence screen performed within 15 months, among 6,689 patients and 65% for anytime adherence among 5,085 patients. The authors noted that overall rates of adherence to Lung-RADS recommended screening intervals in clinical practices is low as compared with the over 90% adherence seen in the NLST, adversely affecting the mortality benefits of lung cancer screening.

Higher adherence rates were found in patients with Lung-RADS 3 (risk for lung cancer, 1%-2%) and 4 (risk, >5%) than Lung-RADS 1 and 2 (risk, <1%; P < .05), which the authors said suggests that tailored interventions based on Lung-RADS categories may be beneficial.

“It is likely that patients and referrers are more concerned about nodules at a higher risk for lung cancer, prompting greater adherence to recommended screening intervals in Lung-RADS 3-4,” the authors wrote. “It is crucial that patients and referrers alike understand that screening is most effective when performed regularly, including for those with negative baseline screens, as de novo nodules, those detected after a negative screen, are more aggressive than those detected at baseline screen.”

These low adherence rates seen in the clinical practices could be explained by patient characteristics, insurance coverage and interventions to ensure adherence, among other factors.

Further, inconsistent reporting of adherence rates was observed. Standardized reporting of adherence rates to lung cancer screening is needed to identify interventions to improve adherence, the authors wrote.

The authors of this study noted no conflicts of interest.

Lung cancer screening reduces mortality, but patient adherence to screening intervals is suboptimal in the United States, according to a review and meta-analysis published in the Journal of Thoracic Oncology.

“Lung cancer screening is effective in reducing mortality, particularly when patients adhere to follow-up recommendations standardized by the Lung CT Screening Reporting & Data System (Lung-RADS),” Yannan Lin, MD, MPH, of the University of California, Los Angeles, and colleagues wrote. ”Patient adherence to Lung-RADS–recommended screening intervals is suboptimal across clinical lung cancer screening programs in the U.S., especially among patients with Lung-RADS category 1-2 results.”

Lung cancer screening can identify tumors at earlier, more treatable stages, but patients with lung cancer diagnoses based on new nodules at incidence screening have shown shortened survivals. The National Lung Screening Trial (NLST) has shown a 20% relative reduction in lung cancer mortality with low-dose chest CT screening relative to chest radiography. The Lung-RADS guidelines to standardize the reporting of lung cancer screening were developed based on findings from the NLST and other screening studies, partly to reduce false-positive rates. Lung-RADS scores are based upon nodule size, characteristics and location, with management guidelines specific to Lung-RADS categories, ranging from low-dose chest CT in 12 months for Lung-RADS 1-2 to chest CT, PET/CT, or tissue sampling for Lung-RADS 4B/X.

The rate of adherence to lung cancer screening based on Lung-RADS guidelines is unclear. This systematic review and meta-analysis looked at patient adherence to Lung-RADS recommended screening intervals in clinical practice.

The meta-analysis included 21 studies. The pooled adherence rate was 57% for defined adherence, which included an annual incidence screen performed within 15 months, among 6,689 patients and 65% for anytime adherence among 5,085 patients. The authors noted that overall rates of adherence to Lung-RADS recommended screening intervals in clinical practices is low as compared with the over 90% adherence seen in the NLST, adversely affecting the mortality benefits of lung cancer screening.

Higher adherence rates were found in patients with Lung-RADS 3 (risk for lung cancer, 1%-2%) and 4 (risk, >5%) than Lung-RADS 1 and 2 (risk, <1%; P < .05), which the authors said suggests that tailored interventions based on Lung-RADS categories may be beneficial.

“It is likely that patients and referrers are more concerned about nodules at a higher risk for lung cancer, prompting greater adherence to recommended screening intervals in Lung-RADS 3-4,” the authors wrote. “It is crucial that patients and referrers alike understand that screening is most effective when performed regularly, including for those with negative baseline screens, as de novo nodules, those detected after a negative screen, are more aggressive than those detected at baseline screen.”

These low adherence rates seen in the clinical practices could be explained by patient characteristics, insurance coverage and interventions to ensure adherence, among other factors.

Further, inconsistent reporting of adherence rates was observed. Standardized reporting of adherence rates to lung cancer screening is needed to identify interventions to improve adherence, the authors wrote.

The authors of this study noted no conflicts of interest.

Lung cancer screening reduces mortality, but patient adherence to screening intervals is suboptimal in the United States, according to a review and meta-analysis published in the Journal of Thoracic Oncology.

“Lung cancer screening is effective in reducing mortality, particularly when patients adhere to follow-up recommendations standardized by the Lung CT Screening Reporting & Data System (Lung-RADS),” Yannan Lin, MD, MPH, of the University of California, Los Angeles, and colleagues wrote. ”Patient adherence to Lung-RADS–recommended screening intervals is suboptimal across clinical lung cancer screening programs in the U.S., especially among patients with Lung-RADS category 1-2 results.”

Lung cancer screening can identify tumors at earlier, more treatable stages, but patients with lung cancer diagnoses based on new nodules at incidence screening have shown shortened survivals. The National Lung Screening Trial (NLST) has shown a 20% relative reduction in lung cancer mortality with low-dose chest CT screening relative to chest radiography. The Lung-RADS guidelines to standardize the reporting of lung cancer screening were developed based on findings from the NLST and other screening studies, partly to reduce false-positive rates. Lung-RADS scores are based upon nodule size, characteristics and location, with management guidelines specific to Lung-RADS categories, ranging from low-dose chest CT in 12 months for Lung-RADS 1-2 to chest CT, PET/CT, or tissue sampling for Lung-RADS 4B/X.

The rate of adherence to lung cancer screening based on Lung-RADS guidelines is unclear. This systematic review and meta-analysis looked at patient adherence to Lung-RADS recommended screening intervals in clinical practice.

The meta-analysis included 21 studies. The pooled adherence rate was 57% for defined adherence, which included an annual incidence screen performed within 15 months, among 6,689 patients and 65% for anytime adherence among 5,085 patients. The authors noted that overall rates of adherence to Lung-RADS recommended screening intervals in clinical practices is low as compared with the over 90% adherence seen in the NLST, adversely affecting the mortality benefits of lung cancer screening.

Higher adherence rates were found in patients with Lung-RADS 3 (risk for lung cancer, 1%-2%) and 4 (risk, >5%) than Lung-RADS 1 and 2 (risk, <1%; P < .05), which the authors said suggests that tailored interventions based on Lung-RADS categories may be beneficial.

“It is likely that patients and referrers are more concerned about nodules at a higher risk for lung cancer, prompting greater adherence to recommended screening intervals in Lung-RADS 3-4,” the authors wrote. “It is crucial that patients and referrers alike understand that screening is most effective when performed regularly, including for those with negative baseline screens, as de novo nodules, those detected after a negative screen, are more aggressive than those detected at baseline screen.”

These low adherence rates seen in the clinical practices could be explained by patient characteristics, insurance coverage and interventions to ensure adherence, among other factors.

Further, inconsistent reporting of adherence rates was observed. Standardized reporting of adherence rates to lung cancer screening is needed to identify interventions to improve adherence, the authors wrote.

The authors of this study noted no conflicts of interest.

The Devil’s own face covering?

It’s been over a year and a half since the COVID-19 emergency was declared in the United States, and we’ve been starting to wonder what our good friend SARS-CoV-2 has left to give. The collective cynic/optimist in us figures that the insanity can’t last forever, right?

Tatyana Kolchugina/Getty

Maybe not forever, but …

A group of parents is suing the Central Bucks (Pa.) School District over school mask mandates, suggesting that the district has no legal authority to enforce such measures. Most of their arguments, Philadelphia Magazine says, are pretty standard stuff: Masks are causing depression, anxiety, and discomfort in their children; masks are a violation of their constitutional rights; and “masks are being used as a control mechanism over the population.”

There are some unusual claims, though. One of the parents, Shannon Harris, said that “wearing masks interferes with their religious duty to spread the word of God and forces them to participate in a satanic ritual,” according to the Philadelphia Inquirer.

Philadelphia Magazine decided to check on that “satanic ritual” claim by asking an expert, in this case a spokesperson for the Church of Satan. The Reverend Raul Antony said that “simply ‘wearing a mask’ is not a Satanic ritual, and anyone that genuinely thinks otherwise is a blithering idiot,” adding that the group’s rituals were available on its website.

COVID, you never let us down.
 

You’re the (hurricane) wind beneath my wings

Marriage isn’t easy. From finances to everyday stressors like work and children, maintaining a solid relationship is tough. Then a natural disaster shows up on top of everything else, and marriages actually improve, researchers found.

pxfuel

In a study published by Psychological Science, researchers surveyed 231 newlywed couples about the satisfaction of their marriage before and after Hurricane Harvey in 2017. They found after the hurricane couples had a “significant boost” in the satisfaction of their relationship.

One would think something like this would create what researchers call a “stress spillover,” creating a decrease in relationship satisfaction. Destruction to your home or even displacement after a natural disaster seems pretty stressful. But, “a natural disaster can really put things in perspective. People realize how important their partner is to them when they are jolted out of the day-to-day stress of life,” said Hannah Williamson, PhD, the lead author of the study.

And although everyone saw an increase, the biggest jumps in relationship satisfaction belonged to the people who were most unhappy before the hurricane. Unfortunately, the researchers also found that the effects were only temporary and the dissatisfaction came back within a year.

Dr. Williamson thinks there may be something to these findings that can be beneficial from a therapy standpoint where “couples can shift their perspective in a similar way without having to go through a natural disaster.”

Let’s hope she’s right, because the alternative is to seek out a rampaging hurricane every time your relationship is on the rocks, and that just seems impractical after the second or third year.
 

Not-so-essential oils

Many people use essential oils as a way to unwind and relax. Stressed? Can’t sleep? There’s probably an essential oil for that. However, it seems like these days a lot of things we love and/or think are good for us have a side that’s not so.

pxfuel

According to the Centers for Disease Control and Prevention, a woman from Georgia died from a rare bacteria called Burkholderia pseudomallei. There have been three previous infections in Kansas, Minnesota, and Texas throughout 2021; two of the four infections were in children. Melioidosis, the disease caused by B. pseudomallei, is usually found in southeast Asia and isn’t obvious or easy to diagnose, especially in places like decidedly untropical Minnesota.

The Georgia case was the real break in this medical mystery, as the infection was traced back to a Walmart product called “Better Homes and Gardens Essential Oil Infused Aromatherapy Room Spray with Gemstones” (a very pithy name). The bacteria were in the lavender and chamomile scent. The CDC is investigating all other product scents, and Walmart has recalled all lots of the product.

If you’ve got that particular essential oil, it’s probably for the best that you stop using it. Don’t worry, we’re sure there’s plenty of other essential oil–infused aromatherapy room sprays with gemstones out there for your scent-based needs.
 

Welcome to the Ministry of Sleep-Deprived Walks

Walking is simple, right? You put one foot in front of the other, and soon you’re walking out the door. Little kids can do it. Even zombies can walk, and they don’t even have brains.

riskms/Getty

Research from MIT and the University of São Paulo has shown that walking is a little trickier than we might think. One researcher in particular noticed that student volunteers tended to perform worse toward the end of semesters, as project deadlines and multiple exams crashed over their heads and they were deprived of solid sleep schedules.

In a study published in Scientific Reports, our intrepid walking researchers had a collection of students monitor their sleep patterns for 2 weeks; on average, the students got 6 hours per night, though some were able to compensate on weekends. On the final day of a 14-day period, some students pulled all-nighters while the rest were allowed to sleep as usual. Then all students performed a walking test involving keeping time with a metronome.

To absolutely no one’s surprise, the students who performed all-nighters before being tested walked the worst, but between the other students, the ones who compensated for sleep deprivation on weekends did better than those who got 6 hours every night, despite getting a similar amount of sleep overall. This effect persisted even when the compensating students performed their walking tests late in the week, just before they got their weekend beauty sleep.

The moral of the story? Sleep is good, and you should get more of it. But if you can’t, sleep in on weekends. Science has given you permission. All those suburban dads looking to get their teenagers up at 8 in the morning must be sweating right now.

The Devil’s own face covering?

It’s been over a year and a half since the COVID-19 emergency was declared in the United States, and we’ve been starting to wonder what our good friend SARS-CoV-2 has left to give. The collective cynic/optimist in us figures that the insanity can’t last forever, right?

Tatyana Kolchugina/Getty

Maybe not forever, but …

A group of parents is suing the Central Bucks (Pa.) School District over school mask mandates, suggesting that the district has no legal authority to enforce such measures. Most of their arguments, Philadelphia Magazine says, are pretty standard stuff: Masks are causing depression, anxiety, and discomfort in their children; masks are a violation of their constitutional rights; and “masks are being used as a control mechanism over the population.”

There are some unusual claims, though. One of the parents, Shannon Harris, said that “wearing masks interferes with their religious duty to spread the word of God and forces them to participate in a satanic ritual,” according to the Philadelphia Inquirer.

Philadelphia Magazine decided to check on that “satanic ritual” claim by asking an expert, in this case a spokesperson for the Church of Satan. The Reverend Raul Antony said that “simply ‘wearing a mask’ is not a Satanic ritual, and anyone that genuinely thinks otherwise is a blithering idiot,” adding that the group’s rituals were available on its website.

COVID, you never let us down.
 

You’re the (hurricane) wind beneath my wings

Marriage isn’t easy. From finances to everyday stressors like work and children, maintaining a solid relationship is tough. Then a natural disaster shows up on top of everything else, and marriages actually improve, researchers found.

pxfuel

In a study published by Psychological Science, researchers surveyed 231 newlywed couples about the satisfaction of their marriage before and after Hurricane Harvey in 2017. They found after the hurricane couples had a “significant boost” in the satisfaction of their relationship.

One would think something like this would create what researchers call a “stress spillover,” creating a decrease in relationship satisfaction. Destruction to your home or even displacement after a natural disaster seems pretty stressful. But, “a natural disaster can really put things in perspective. People realize how important their partner is to them when they are jolted out of the day-to-day stress of life,” said Hannah Williamson, PhD, the lead author of the study.

And although everyone saw an increase, the biggest jumps in relationship satisfaction belonged to the people who were most unhappy before the hurricane. Unfortunately, the researchers also found that the effects were only temporary and the dissatisfaction came back within a year.

Dr. Williamson thinks there may be something to these findings that can be beneficial from a therapy standpoint where “couples can shift their perspective in a similar way without having to go through a natural disaster.”

Let’s hope she’s right, because the alternative is to seek out a rampaging hurricane every time your relationship is on the rocks, and that just seems impractical after the second or third year.
 

Not-so-essential oils

Many people use essential oils as a way to unwind and relax. Stressed? Can’t sleep? There’s probably an essential oil for that. However, it seems like these days a lot of things we love and/or think are good for us have a side that’s not so.

pxfuel

According to the Centers for Disease Control and Prevention, a woman from Georgia died from a rare bacteria called Burkholderia pseudomallei. There have been three previous infections in Kansas, Minnesota, and Texas throughout 2021; two of the four infections were in children. Melioidosis, the disease caused by B. pseudomallei, is usually found in southeast Asia and isn’t obvious or easy to diagnose, especially in places like decidedly untropical Minnesota.

The Georgia case was the real break in this medical mystery, as the infection was traced back to a Walmart product called “Better Homes and Gardens Essential Oil Infused Aromatherapy Room Spray with Gemstones” (a very pithy name). The bacteria were in the lavender and chamomile scent. The CDC is investigating all other product scents, and Walmart has recalled all lots of the product.

If you’ve got that particular essential oil, it’s probably for the best that you stop using it. Don’t worry, we’re sure there’s plenty of other essential oil–infused aromatherapy room sprays with gemstones out there for your scent-based needs.
 

Welcome to the Ministry of Sleep-Deprived Walks

Walking is simple, right? You put one foot in front of the other, and soon you’re walking out the door. Little kids can do it. Even zombies can walk, and they don’t even have brains.

riskms/Getty

Research from MIT and the University of São Paulo has shown that walking is a little trickier than we might think. One researcher in particular noticed that student volunteers tended to perform worse toward the end of semesters, as project deadlines and multiple exams crashed over their heads and they were deprived of solid sleep schedules.

In a study published in Scientific Reports, our intrepid walking researchers had a collection of students monitor their sleep patterns for 2 weeks; on average, the students got 6 hours per night, though some were able to compensate on weekends. On the final day of a 14-day period, some students pulled all-nighters while the rest were allowed to sleep as usual. Then all students performed a walking test involving keeping time with a metronome.

To absolutely no one’s surprise, the students who performed all-nighters before being tested walked the worst, but between the other students, the ones who compensated for sleep deprivation on weekends did better than those who got 6 hours every night, despite getting a similar amount of sleep overall. This effect persisted even when the compensating students performed their walking tests late in the week, just before they got their weekend beauty sleep.

The moral of the story? Sleep is good, and you should get more of it. But if you can’t, sleep in on weekends. Science has given you permission. All those suburban dads looking to get their teenagers up at 8 in the morning must be sweating right now.

The Devil’s own face covering?

It’s been over a year and a half since the COVID-19 emergency was declared in the United States, and we’ve been starting to wonder what our good friend SARS-CoV-2 has left to give. The collective cynic/optimist in us figures that the insanity can’t last forever, right?

Tatyana Kolchugina/Getty

Maybe not forever, but …

A group of parents is suing the Central Bucks (Pa.) School District over school mask mandates, suggesting that the district has no legal authority to enforce such measures. Most of their arguments, Philadelphia Magazine says, are pretty standard stuff: Masks are causing depression, anxiety, and discomfort in their children; masks are a violation of their constitutional rights; and “masks are being used as a control mechanism over the population.”

There are some unusual claims, though. One of the parents, Shannon Harris, said that “wearing masks interferes with their religious duty to spread the word of God and forces them to participate in a satanic ritual,” according to the Philadelphia Inquirer.

Philadelphia Magazine decided to check on that “satanic ritual” claim by asking an expert, in this case a spokesperson for the Church of Satan. The Reverend Raul Antony said that “simply ‘wearing a mask’ is not a Satanic ritual, and anyone that genuinely thinks otherwise is a blithering idiot,” adding that the group’s rituals were available on its website.

COVID, you never let us down.
 

You’re the (hurricane) wind beneath my wings

Marriage isn’t easy. From finances to everyday stressors like work and children, maintaining a solid relationship is tough. Then a natural disaster shows up on top of everything else, and marriages actually improve, researchers found.

pxfuel

In a study published by Psychological Science, researchers surveyed 231 newlywed couples about the satisfaction of their marriage before and after Hurricane Harvey in 2017. They found after the hurricane couples had a “significant boost” in the satisfaction of their relationship.

One would think something like this would create what researchers call a “stress spillover,” creating a decrease in relationship satisfaction. Destruction to your home or even displacement after a natural disaster seems pretty stressful. But, “a natural disaster can really put things in perspective. People realize how important their partner is to them when they are jolted out of the day-to-day stress of life,” said Hannah Williamson, PhD, the lead author of the study.

And although everyone saw an increase, the biggest jumps in relationship satisfaction belonged to the people who were most unhappy before the hurricane. Unfortunately, the researchers also found that the effects were only temporary and the dissatisfaction came back within a year.

Dr. Williamson thinks there may be something to these findings that can be beneficial from a therapy standpoint where “couples can shift their perspective in a similar way without having to go through a natural disaster.”

Let’s hope she’s right, because the alternative is to seek out a rampaging hurricane every time your relationship is on the rocks, and that just seems impractical after the second or third year.
 

Not-so-essential oils

Many people use essential oils as a way to unwind and relax. Stressed? Can’t sleep? There’s probably an essential oil for that. However, it seems like these days a lot of things we love and/or think are good for us have a side that’s not so.

pxfuel

According to the Centers for Disease Control and Prevention, a woman from Georgia died from a rare bacteria called Burkholderia pseudomallei. There have been three previous infections in Kansas, Minnesota, and Texas throughout 2021; two of the four infections were in children. Melioidosis, the disease caused by B. pseudomallei, is usually found in southeast Asia and isn’t obvious or easy to diagnose, especially in places like decidedly untropical Minnesota.

The Georgia case was the real break in this medical mystery, as the infection was traced back to a Walmart product called “Better Homes and Gardens Essential Oil Infused Aromatherapy Room Spray with Gemstones” (a very pithy name). The bacteria were in the lavender and chamomile scent. The CDC is investigating all other product scents, and Walmart has recalled all lots of the product.

If you’ve got that particular essential oil, it’s probably for the best that you stop using it. Don’t worry, we’re sure there’s plenty of other essential oil–infused aromatherapy room sprays with gemstones out there for your scent-based needs.
 

Welcome to the Ministry of Sleep-Deprived Walks

Walking is simple, right? You put one foot in front of the other, and soon you’re walking out the door. Little kids can do it. Even zombies can walk, and they don’t even have brains.

riskms/Getty

Research from MIT and the University of São Paulo has shown that walking is a little trickier than we might think. One researcher in particular noticed that student volunteers tended to perform worse toward the end of semesters, as project deadlines and multiple exams crashed over their heads and they were deprived of solid sleep schedules.

In a study published in Scientific Reports, our intrepid walking researchers had a collection of students monitor their sleep patterns for 2 weeks; on average, the students got 6 hours per night, though some were able to compensate on weekends. On the final day of a 14-day period, some students pulled all-nighters while the rest were allowed to sleep as usual. Then all students performed a walking test involving keeping time with a metronome.

To absolutely no one’s surprise, the students who performed all-nighters before being tested walked the worst, but between the other students, the ones who compensated for sleep deprivation on weekends did better than those who got 6 hours every night, despite getting a similar amount of sleep overall. This effect persisted even when the compensating students performed their walking tests late in the week, just before they got their weekend beauty sleep.

The moral of the story? Sleep is good, and you should get more of it. But if you can’t, sleep in on weekends. Science has given you permission. All those suburban dads looking to get their teenagers up at 8 in the morning must be sweating right now.

Patient samples in outdoor courier lockboxes exposed to hot temperatures for as little as 4 hours are at risk of preanalytical error, according to results from a recent study published in the American Journal of Clinical Pathology.

“Our findings indicate that samples (centrifuged or not centrifuged) were impacted by extreme summer temperatures when stored for short periods of time inside commonly used steel lockboxes,” Joseph R. Wiencek, PhD, medical director of clinical chemistry, Vanderbilt University School of Medicine Core Laboratory in Nashville, said in an interview.

Dr. Wiencek and colleagues picked two dates during the summer of 2019 in a mid-Atlantic state to place two courier lockboxes (LabLocker-KF300) outside in hot temperatures (32º C) starting at 11 a.m., with one lockbox containing two 24-oz cold packs (Nordic NI24) and the other containing no cold packs. The researchers monitored the temperatures of each lockbox over the course of 4 hours.

Overall, eight participants had seven samples in lithium heparin drawn for two studies evaluating centrifuged or not centrifuged samples. In the first study, four participants had seven samples drawn, with one centrifuged sample serving as a control for each patient. The other six samples were wrapped in paper towels, placed in resealable plastic bags, and distributed evenly in the warm and cold lockboxes. The samples did not directly touch the cold packs in the cold lockbox. At 1 hour, 2 hours, and 4 hours, a participant’s sample was removed from each lockbox and centrifuged.

In the second study, another four participants had seven samples drawn. As in the first study, all samples were centrifuged and placed in the lockboxes. For both studies, when samples were centrifuged, plasma from samples was left on the gel barrier when analyzed for concentrations of C-reactive protein, a comprehensive metabolic panel, lactate dehydrogenase (LDH), a lipid panel, magnesium, and phosphorus (Abbott Architect c16000).

In the study of uncentrifuged samples, Dr. Wiencek and colleagues found that when the temperature outside ranged from 28.2º to 44.0º C (mean 40.4º C), the temperature of the cold lockbox was between 16.5º to 22.3º C (mean 22.3º C). The temperature ranged between 34.4º to 46.9º C (mean 42.6º C) in the warm lockbox. For centrifuged samples, the cold lockbox temperature was between 12.2º to 23.0º C (mean 18.0º C) and the warm lockbox was between 25. to 40.8º C (mean 35.2º C) when the outdoor temperature ranged from 27.2º to 46.3º C (mean 37.9º C).

The researchers also calculated the significant change limit (SCL) for each analyte in each sample, finding that aspartate aminotransferase, glucose, LDH, and potassium significantly exceeded the SCL in both the centrifuged and uncentrifuged samples, with the greatest changes seen at the 4-hour timepoint for samples in the warm lockbox (P < .05 for all).
 

Lockbox instructions are “consistently inconsistent”

In viewing instructions for lockboxes across institutions, Dr. Wiencek said the “outdoor courier lockbox instructions among private, academic and reference laboratories were consistently inconsistent.” For example, no laboratories cited time restrictions for samples in lockboxes, and their descriptions on the number of cold packs a laboratory should use and where the lockbox should be placed varied. The inconsistencies “highlighted the emergent need for standardization and guidance documents for institutions to implement,” Dr. Wiencek said.

One unanswered question is how widespread the problem is. It is unclear how many outdoor courier lockboxes are currently in use in the United States or globally; however, experts agreed it was a common occurrence, with some of the largest laboratory service providers offering outdoor courier lockboxes to their clients.

“Courier lockboxes are everywhere. All you need to do is walk around your clinics that are at your hospitals or clinics located around your grocery store to find them,” Dr. Wiencek said. “Some hang on doors, while others can be found on the ground in direct sunlight on a hot summer day.”

What’s more, institutions may not realize how leaving samples outdoors for extended periods can affect results. “Care teams are commonly unaware that samples placed in these poorly designed lockboxes can experience extreme summer or winter temperatures that may lead to incorrect results,” Dr. Wiencek said. “Healthcare providers need to understand the hidden dangers courier lockboxes have on the quality of their patient’s test results.”

Amy L. Pyle-Eilola, PhD, clinical chemistry director at Nationwide Children’s Hospital in Columbus, Ohio, said a major strength of the study by Dr. Wiencek and colleagues “is just that it was done at all.”

“I appreciate the real-world nature of this study and that it provides a snapshot of what conditions are really like in a lockbox in the summer,” she said in an interview.

In the clinical lab, receiving samples that had been sitting in a courier lockbox “is not uncommon,” Dr. Pyle-Eilola said.

“When I have encountered these situations, I have struggled to decide if it is still appropriate to run the tests. I always look to the medical literature for assistance with these situations, but there has been a paucity of information available on the impact of lockbox storage,” she explained.

The study by Dr. Wiencek and colleagues “provides some much-needed evidence for what is acceptable for lockbox storage conditions,” she said.
 

Areas of future research

Rodney E. Rohde, PhD, university distinguished chair and professor of the Clinical Laboratory Science (CLS) Program at Texas State University in San Marcos, said in an interview that the study “does a nice job of looking at multiple analytes and controlling for several variables,” but the sample size is small and the results may be difficult to generalize.

Dr. Pyle-Eilola highlighted another limitation — “a common shortcoming of these kinds of studies” — in the use of healthy donors for patient samples, which narrows the range of assay results.

“It is possible that more significant variation in results may be observed in additional analytes if the samples had higher concentrations of those analytes,” she said. “Moreover, this is clinically relevant as the samples stored in such lockboxes are not always from healthy individuals and have abnormal concentrations of analytes.”

Mario Plebani, MD, professor of clinical biochemistry and clinical molecular biology and chief of the department of laboratory medicine at University Hospital of Padova in Padova, Italy, agreed with that assessment.

“[T]he risks for errors and patient safety are higher for values near to the upper or lower reference value, and in general for samples collected in patients with particular diseases and clinical conditions,” he said in an interview.

“This paper deserves a commenting editorial to better highlight the urgent need for further studies on the same issue and in general on the risk in the pre-pre-analytical phase, including sample storage and transportation,” he noted.

Another area of future research is studying patient samples exposed to hotter or colder temperatures in outdoor courier lockboxes outside the mid-Atlantic area. “Here in Texas, temperatures can reach extreme heat levels,” Dr. Rohde said, who added that use of outdoor lockboxes is “very common in my region.”

Dr. Wiencek disclosed he has been a consultant on this research topic for Roche Diagnostics and received an honorarium for speaking on the subject from the American Association for Clinical Chemistry and American Society of Clinical Pathology. The other authors have no relevant conflict of interest. Dr. Pyle-Eilola, Dr. Rohde, and Dr. Plebani have disclosed no relevant financial relationships.

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

Patient samples in outdoor courier lockboxes exposed to hot temperatures for as little as 4 hours are at risk of preanalytical error, according to results from a recent study published in the American Journal of Clinical Pathology.

“Our findings indicate that samples (centrifuged or not centrifuged) were impacted by extreme summer temperatures when stored for short periods of time inside commonly used steel lockboxes,” Joseph R. Wiencek, PhD, medical director of clinical chemistry, Vanderbilt University School of Medicine Core Laboratory in Nashville, said in an interview.

Dr. Wiencek and colleagues picked two dates during the summer of 2019 in a mid-Atlantic state to place two courier lockboxes (LabLocker-KF300) outside in hot temperatures (32º C) starting at 11 a.m., with one lockbox containing two 24-oz cold packs (Nordic NI24) and the other containing no cold packs. The researchers monitored the temperatures of each lockbox over the course of 4 hours.

Overall, eight participants had seven samples in lithium heparin drawn for two studies evaluating centrifuged or not centrifuged samples. In the first study, four participants had seven samples drawn, with one centrifuged sample serving as a control for each patient. The other six samples were wrapped in paper towels, placed in resealable plastic bags, and distributed evenly in the warm and cold lockboxes. The samples did not directly touch the cold packs in the cold lockbox. At 1 hour, 2 hours, and 4 hours, a participant’s sample was removed from each lockbox and centrifuged.

In the second study, another four participants had seven samples drawn. As in the first study, all samples were centrifuged and placed in the lockboxes. For both studies, when samples were centrifuged, plasma from samples was left on the gel barrier when analyzed for concentrations of C-reactive protein, a comprehensive metabolic panel, lactate dehydrogenase (LDH), a lipid panel, magnesium, and phosphorus (Abbott Architect c16000).

In the study of uncentrifuged samples, Dr. Wiencek and colleagues found that when the temperature outside ranged from 28.2º to 44.0º C (mean 40.4º C), the temperature of the cold lockbox was between 16.5º to 22.3º C (mean 22.3º C). The temperature ranged between 34.4º to 46.9º C (mean 42.6º C) in the warm lockbox. For centrifuged samples, the cold lockbox temperature was between 12.2º to 23.0º C (mean 18.0º C) and the warm lockbox was between 25. to 40.8º C (mean 35.2º C) when the outdoor temperature ranged from 27.2º to 46.3º C (mean 37.9º C).

The researchers also calculated the significant change limit (SCL) for each analyte in each sample, finding that aspartate aminotransferase, glucose, LDH, and potassium significantly exceeded the SCL in both the centrifuged and uncentrifuged samples, with the greatest changes seen at the 4-hour timepoint for samples in the warm lockbox (P < .05 for all).
 

Lockbox instructions are “consistently inconsistent”

In viewing instructions for lockboxes across institutions, Dr. Wiencek said the “outdoor courier lockbox instructions among private, academic and reference laboratories were consistently inconsistent.” For example, no laboratories cited time restrictions for samples in lockboxes, and their descriptions on the number of cold packs a laboratory should use and where the lockbox should be placed varied. The inconsistencies “highlighted the emergent need for standardization and guidance documents for institutions to implement,” Dr. Wiencek said.

One unanswered question is how widespread the problem is. It is unclear how many outdoor courier lockboxes are currently in use in the United States or globally; however, experts agreed it was a common occurrence, with some of the largest laboratory service providers offering outdoor courier lockboxes to their clients.

“Courier lockboxes are everywhere. All you need to do is walk around your clinics that are at your hospitals or clinics located around your grocery store to find them,” Dr. Wiencek said. “Some hang on doors, while others can be found on the ground in direct sunlight on a hot summer day.”

What’s more, institutions may not realize how leaving samples outdoors for extended periods can affect results. “Care teams are commonly unaware that samples placed in these poorly designed lockboxes can experience extreme summer or winter temperatures that may lead to incorrect results,” Dr. Wiencek said. “Healthcare providers need to understand the hidden dangers courier lockboxes have on the quality of their patient’s test results.”

Amy L. Pyle-Eilola, PhD, clinical chemistry director at Nationwide Children’s Hospital in Columbus, Ohio, said a major strength of the study by Dr. Wiencek and colleagues “is just that it was done at all.”

“I appreciate the real-world nature of this study and that it provides a snapshot of what conditions are really like in a lockbox in the summer,” she said in an interview.

In the clinical lab, receiving samples that had been sitting in a courier lockbox “is not uncommon,” Dr. Pyle-Eilola said.

“When I have encountered these situations, I have struggled to decide if it is still appropriate to run the tests. I always look to the medical literature for assistance with these situations, but there has been a paucity of information available on the impact of lockbox storage,” she explained.

The study by Dr. Wiencek and colleagues “provides some much-needed evidence for what is acceptable for lockbox storage conditions,” she said.
 

Areas of future research

Rodney E. Rohde, PhD, university distinguished chair and professor of the Clinical Laboratory Science (CLS) Program at Texas State University in San Marcos, said in an interview that the study “does a nice job of looking at multiple analytes and controlling for several variables,” but the sample size is small and the results may be difficult to generalize.

Dr. Pyle-Eilola highlighted another limitation — “a common shortcoming of these kinds of studies” — in the use of healthy donors for patient samples, which narrows the range of assay results.

“It is possible that more significant variation in results may be observed in additional analytes if the samples had higher concentrations of those analytes,” she said. “Moreover, this is clinically relevant as the samples stored in such lockboxes are not always from healthy individuals and have abnormal concentrations of analytes.”

Mario Plebani, MD, professor of clinical biochemistry and clinical molecular biology and chief of the department of laboratory medicine at University Hospital of Padova in Padova, Italy, agreed with that assessment.

“[T]he risks for errors and patient safety are higher for values near to the upper or lower reference value, and in general for samples collected in patients with particular diseases and clinical conditions,” he said in an interview.

“This paper deserves a commenting editorial to better highlight the urgent need for further studies on the same issue and in general on the risk in the pre-pre-analytical phase, including sample storage and transportation,” he noted.

Another area of future research is studying patient samples exposed to hotter or colder temperatures in outdoor courier lockboxes outside the mid-Atlantic area. “Here in Texas, temperatures can reach extreme heat levels,” Dr. Rohde said, who added that use of outdoor lockboxes is “very common in my region.”

Dr. Wiencek disclosed he has been a consultant on this research topic for Roche Diagnostics and received an honorarium for speaking on the subject from the American Association for Clinical Chemistry and American Society of Clinical Pathology. The other authors have no relevant conflict of interest. Dr. Pyle-Eilola, Dr. Rohde, and Dr. Plebani have disclosed no relevant financial relationships.

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

Patient samples in outdoor courier lockboxes exposed to hot temperatures for as little as 4 hours are at risk of preanalytical error, according to results from a recent study published in the American Journal of Clinical Pathology.

“Our findings indicate that samples (centrifuged or not centrifuged) were impacted by extreme summer temperatures when stored for short periods of time inside commonly used steel lockboxes,” Joseph R. Wiencek, PhD, medical director of clinical chemistry, Vanderbilt University School of Medicine Core Laboratory in Nashville, said in an interview.

Dr. Wiencek and colleagues picked two dates during the summer of 2019 in a mid-Atlantic state to place two courier lockboxes (LabLocker-KF300) outside in hot temperatures (32º C) starting at 11 a.m., with one lockbox containing two 24-oz cold packs (Nordic NI24) and the other containing no cold packs. The researchers monitored the temperatures of each lockbox over the course of 4 hours.

Overall, eight participants had seven samples in lithium heparin drawn for two studies evaluating centrifuged or not centrifuged samples. In the first study, four participants had seven samples drawn, with one centrifuged sample serving as a control for each patient. The other six samples were wrapped in paper towels, placed in resealable plastic bags, and distributed evenly in the warm and cold lockboxes. The samples did not directly touch the cold packs in the cold lockbox. At 1 hour, 2 hours, and 4 hours, a participant’s sample was removed from each lockbox and centrifuged.

In the second study, another four participants had seven samples drawn. As in the first study, all samples were centrifuged and placed in the lockboxes. For both studies, when samples were centrifuged, plasma from samples was left on the gel barrier when analyzed for concentrations of C-reactive protein, a comprehensive metabolic panel, lactate dehydrogenase (LDH), a lipid panel, magnesium, and phosphorus (Abbott Architect c16000).

In the study of uncentrifuged samples, Dr. Wiencek and colleagues found that when the temperature outside ranged from 28.2º to 44.0º C (mean 40.4º C), the temperature of the cold lockbox was between 16.5º to 22.3º C (mean 22.3º C). The temperature ranged between 34.4º to 46.9º C (mean 42.6º C) in the warm lockbox. For centrifuged samples, the cold lockbox temperature was between 12.2º to 23.0º C (mean 18.0º C) and the warm lockbox was between 25. to 40.8º C (mean 35.2º C) when the outdoor temperature ranged from 27.2º to 46.3º C (mean 37.9º C).

The researchers also calculated the significant change limit (SCL) for each analyte in each sample, finding that aspartate aminotransferase, glucose, LDH, and potassium significantly exceeded the SCL in both the centrifuged and uncentrifuged samples, with the greatest changes seen at the 4-hour timepoint for samples in the warm lockbox (P < .05 for all).
 

Lockbox instructions are “consistently inconsistent”

In viewing instructions for lockboxes across institutions, Dr. Wiencek said the “outdoor courier lockbox instructions among private, academic and reference laboratories were consistently inconsistent.” For example, no laboratories cited time restrictions for samples in lockboxes, and their descriptions on the number of cold packs a laboratory should use and where the lockbox should be placed varied. The inconsistencies “highlighted the emergent need for standardization and guidance documents for institutions to implement,” Dr. Wiencek said.

One unanswered question is how widespread the problem is. It is unclear how many outdoor courier lockboxes are currently in use in the United States or globally; however, experts agreed it was a common occurrence, with some of the largest laboratory service providers offering outdoor courier lockboxes to their clients.

“Courier lockboxes are everywhere. All you need to do is walk around your clinics that are at your hospitals or clinics located around your grocery store to find them,” Dr. Wiencek said. “Some hang on doors, while others can be found on the ground in direct sunlight on a hot summer day.”

What’s more, institutions may not realize how leaving samples outdoors for extended periods can affect results. “Care teams are commonly unaware that samples placed in these poorly designed lockboxes can experience extreme summer or winter temperatures that may lead to incorrect results,” Dr. Wiencek said. “Healthcare providers need to understand the hidden dangers courier lockboxes have on the quality of their patient’s test results.”

Amy L. Pyle-Eilola, PhD, clinical chemistry director at Nationwide Children’s Hospital in Columbus, Ohio, said a major strength of the study by Dr. Wiencek and colleagues “is just that it was done at all.”

“I appreciate the real-world nature of this study and that it provides a snapshot of what conditions are really like in a lockbox in the summer,” she said in an interview.

In the clinical lab, receiving samples that had been sitting in a courier lockbox “is not uncommon,” Dr. Pyle-Eilola said.

“When I have encountered these situations, I have struggled to decide if it is still appropriate to run the tests. I always look to the medical literature for assistance with these situations, but there has been a paucity of information available on the impact of lockbox storage,” she explained.

The study by Dr. Wiencek and colleagues “provides some much-needed evidence for what is acceptable for lockbox storage conditions,” she said.
 

Areas of future research

Rodney E. Rohde, PhD, university distinguished chair and professor of the Clinical Laboratory Science (CLS) Program at Texas State University in San Marcos, said in an interview that the study “does a nice job of looking at multiple analytes and controlling for several variables,” but the sample size is small and the results may be difficult to generalize.

Dr. Pyle-Eilola highlighted another limitation — “a common shortcoming of these kinds of studies” — in the use of healthy donors for patient samples, which narrows the range of assay results.

“It is possible that more significant variation in results may be observed in additional analytes if the samples had higher concentrations of those analytes,” she said. “Moreover, this is clinically relevant as the samples stored in such lockboxes are not always from healthy individuals and have abnormal concentrations of analytes.”

Mario Plebani, MD, professor of clinical biochemistry and clinical molecular biology and chief of the department of laboratory medicine at University Hospital of Padova in Padova, Italy, agreed with that assessment.

“[T]he risks for errors and patient safety are higher for values near to the upper or lower reference value, and in general for samples collected in patients with particular diseases and clinical conditions,” he said in an interview.

“This paper deserves a commenting editorial to better highlight the urgent need for further studies on the same issue and in general on the risk in the pre-pre-analytical phase, including sample storage and transportation,” he noted.

Another area of future research is studying patient samples exposed to hotter or colder temperatures in outdoor courier lockboxes outside the mid-Atlantic area. “Here in Texas, temperatures can reach extreme heat levels,” Dr. Rohde said, who added that use of outdoor lockboxes is “very common in my region.”

Dr. Wiencek disclosed he has been a consultant on this research topic for Roche Diagnostics and received an honorarium for speaking on the subject from the American Association for Clinical Chemistry and American Society of Clinical Pathology. The other authors have no relevant conflict of interest. Dr. Pyle-Eilola, Dr. Rohde, and Dr. Plebani have disclosed no relevant financial relationships.

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

The benefits of Pfizer’s COVID-19 vaccine for children ages 5 to 11 outweigh its risks, according to an independent panel of vaccine experts that advises the Food and Drug Administration (FDA).
 

Seventeen of the 18 members of the Vaccines and Related Biological Products Advisory Committee (VRBPAC) on Oct. 26 voted to recommend the 10-microgram shot for kids, which is one-third the dose given to adults.

One member, Michael Kurilla, MD, director of the division of clinical innovation at the National Institutes of Health, Bethesda, Md., abstained from voting.

If the FDA follows the recommendation, as it typically does, and issues an Emergency Use Authorization for the vaccine, the shots could be available within days.

After the FDA’s final decision, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices will meet to make specific recommendations for its use. The CDC committee must stick closely to the conditions for use spelled out in the EUA, so their recommendations are likely to be similar to those made by the FDA. Their next meeting is scheduled for Nov. 2 and 3.

In the end, some on the panel felt uneasy with their decision.

“I voted yes primarily because I wanted to make sure that children who really need this vaccine, the Black and brown children of our country, get the vaccine,” said James Hildreth, MD, PhD, president and CEO of Meharry Medical College in Nashville.

“But to be honest, the best way to protect the health of some children will be to do nothing because they will be just fine,” he said.

Others said they were surprised by how difficult the decision had been.

“This is a much tougher one than we had expected going into it,” said committee member Eric Rubin, MD, editor and chief of the New England Journal of Medicine, during the FDA advisory committee’s meeting.

Ahead of the vote, the committee heard presentations outlining the expected benefits of vaccinating children along with potential risks.

“Children have been greatly impacted by the pandemic,” said Fiona Havers, MD, a medical officer with the CDC in Atlanta who reviewed the epidemiology of COVID-19 in kids.

In the second year of the pandemic, as more seniors have been vaccinated against the virus, COVID cases have largely shifted from older to younger age groups.

So far, there have been more than 1.9 million COVID-19 cases in children ages 5 through 11 in the United States.. Cases in kids saw a big jump in July and August with summer travel, schools reopening, and the dominance of the Delta variant.

And those are just the cases reported to the CDC. Regular testing of anonymous blood samples collected at sites across the United States indicates that 6 times as many kids have had COVID than what is reflected in official counts.

Last winter, blood sample testing showed about 13% of children had antibodies against the virus, suggesting they’d been infected. By this summer, that number had risen to 42%.

That figure clearly made an impression on many members of the committee who asked the FDA’s vaccine reviewers if they had tried to account for immunity from past infections in their modeling. They had not.

Some felt that even with a highly effective vaccine — new data presented by Pfizer showed the children’s dose was 90% effective at preventing symptomatic infections in kids — caution was warranted as much is still unknown about myocarditis, a rare side effect of the mRNA vaccines.

Myocarditis has been more common in younger age groups. It usually goes away over time but requires hospital care. It’s not known if myocarditis could have lingering effects for those who experience it.

There were no cases of myocarditis seen in Pfizer’s studies of the vaccine in children, and no other serious events were seen. Vaccine side effects reported in the Pfizer studies were mostly mild and included fatigue, headache, and pain at the injection site.

“We think we have optimized the immune response and minimized our reactions,” said William Gruber, MD, senior vice president vaccine research and clinical development at Pfizer.

But the studies didn’t include enough participants to pick up rare, but serious adverse events like myocarditis.

“We’re worried about a side effect that we can’t measure yet, but it’s probably real, and we see a benefit that isn’t the same as it is in older age groups,” said Dr. Rubin.

Benefits vs. risks

FDA modeled the benefits and risks for children under a variety of scenarios. The benefits of the vaccines to children very much depend on the amount of transmission in the community.

When transmission is high, the benefits to children — in terms of infections, hospitalizations, ICU admissions — clearly outweigh its risks.

But when COVID-19 rates are low in the community, as they were in June, FDA analysts predicted the vaccines might send more children to the hospital for myocarditis than the virus would.

The FDA noted that kids who are hospitalized for myocarditis tend not to be as ill as children with COVID-19, however.

“If the trends continue the way they are going, the emergency for children is not what we might think it would be. That was my concern,” Dr. Hildreth said.

But others warned against complacency.

“Thinking that this is going to be the end of the wave permanently may be a little overly optimistic,” said committee chairman Arnold Monto, MD, a professor of public health and epidemiology at the University of Michigan, Ann Arbor.

The majority of COVID-19 cases in children are mild. Only about 1% of kids are hospitalized for their infections, according to CDC data. But the rates of hospitalizations in kids are about 3 times higher for people of color — including Blacks, Hispanics, and Native Americans, as compared to Whites and Asian Americans.

Since the start of the pandemic, 94 children ages 5 to 11 have died, making it the eighth leading cause of death for kids this age last year.

More than 5,200 children have developed a delayed complication from their infections called Multi-System Inflammatory Syndrome (MIS-C).

MIS-C can be severe and require hospital care and can lead to myocarditis. Children ages 5 to 11 are the age group at greatest risk for this complication.

Kids can also get long COVID. There’s not a lot of data on how often this happens, though it appears to be less frequent in children than in adults.

But a survey in the United Kingdom found that 7%-8% of kids have symptoms from their infections that last longer than 12 weeks, Dr. Havers said. Symptoms that can linger for kids include fatigue, cough, muscle and joint pain, headaches, and insomnia.

More than 1 million children have been impacted by school closures so far this year, and quarantines have had lasting impacts on learning, social development, and mental health.

Even though kids aren’t usually COVID superspreaders, they can still pass the infection on to others.

“What is clear is that secondary transmission from children, both to other children and to adults, does occur,” Dr. Havers said.

For that reason, they can continue the spread of the virus and give it opportunities to mutate and become more dangerous.

Safety monitoring to continue

Some committee members referenced thousands of letters they had received within the past few days urging them to vote against the vaccine.

Jay Portnoy, MD, a professor of pediatrics at Children’s Mercy Hospital in Kansas City, Mo., said he had personally received about 4,000 emails.

“But I feel like I need to also represent the consumers, the parents that I see every day in the clinic who are terrified of sending their children to school because they’re not protected against COVID,” he said, explaining his vote to recommend authorization.

“Our kids are going to be dealing with this virus for many years to come. It’s going to come repeatedly. Getting this vaccine is just the first step that they can take to protect themselves from having bad outcomes,” Dr. Portnoy said.

Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, reminded members of the committee that there were several government surveillance systems in place to catch any potential safety issues in near real time.

“I really appreciate very much the concern here. The safety monitoring of this vaccine will continue,” Dr. Marks said. “I do view this as one of our greatest responsibilities.”

“I really am so grateful that we had this discussion and voted to approve,” said Capt. Amanda Cohn, MD, chief medical officer at the National Center for Immunization and Respiratory Diseases.

“I think the benefits in this age group really are super important even if they are lower than for other age groups.”

This article was updated 10/27/21.

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

The benefits of Pfizer’s COVID-19 vaccine for children ages 5 to 11 outweigh its risks, according to an independent panel of vaccine experts that advises the Food and Drug Administration (FDA).
 

Seventeen of the 18 members of the Vaccines and Related Biological Products Advisory Committee (VRBPAC) on Oct. 26 voted to recommend the 10-microgram shot for kids, which is one-third the dose given to adults.

One member, Michael Kurilla, MD, director of the division of clinical innovation at the National Institutes of Health, Bethesda, Md., abstained from voting.

If the FDA follows the recommendation, as it typically does, and issues an Emergency Use Authorization for the vaccine, the shots could be available within days.

After the FDA’s final decision, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices will meet to make specific recommendations for its use. The CDC committee must stick closely to the conditions for use spelled out in the EUA, so their recommendations are likely to be similar to those made by the FDA. Their next meeting is scheduled for Nov. 2 and 3.

In the end, some on the panel felt uneasy with their decision.

“I voted yes primarily because I wanted to make sure that children who really need this vaccine, the Black and brown children of our country, get the vaccine,” said James Hildreth, MD, PhD, president and CEO of Meharry Medical College in Nashville.

“But to be honest, the best way to protect the health of some children will be to do nothing because they will be just fine,” he said.

Others said they were surprised by how difficult the decision had been.

“This is a much tougher one than we had expected going into it,” said committee member Eric Rubin, MD, editor and chief of the New England Journal of Medicine, during the FDA advisory committee’s meeting.

Ahead of the vote, the committee heard presentations outlining the expected benefits of vaccinating children along with potential risks.

“Children have been greatly impacted by the pandemic,” said Fiona Havers, MD, a medical officer with the CDC in Atlanta who reviewed the epidemiology of COVID-19 in kids.

In the second year of the pandemic, as more seniors have been vaccinated against the virus, COVID cases have largely shifted from older to younger age groups.

So far, there have been more than 1.9 million COVID-19 cases in children ages 5 through 11 in the United States.. Cases in kids saw a big jump in July and August with summer travel, schools reopening, and the dominance of the Delta variant.

And those are just the cases reported to the CDC. Regular testing of anonymous blood samples collected at sites across the United States indicates that 6 times as many kids have had COVID than what is reflected in official counts.

Last winter, blood sample testing showed about 13% of children had antibodies against the virus, suggesting they’d been infected. By this summer, that number had risen to 42%.

That figure clearly made an impression on many members of the committee who asked the FDA’s vaccine reviewers if they had tried to account for immunity from past infections in their modeling. They had not.

Some felt that even with a highly effective vaccine — new data presented by Pfizer showed the children’s dose was 90% effective at preventing symptomatic infections in kids — caution was warranted as much is still unknown about myocarditis, a rare side effect of the mRNA vaccines.

Myocarditis has been more common in younger age groups. It usually goes away over time but requires hospital care. It’s not known if myocarditis could have lingering effects for those who experience it.

There were no cases of myocarditis seen in Pfizer’s studies of the vaccine in children, and no other serious events were seen. Vaccine side effects reported in the Pfizer studies were mostly mild and included fatigue, headache, and pain at the injection site.

“We think we have optimized the immune response and minimized our reactions,” said William Gruber, MD, senior vice president vaccine research and clinical development at Pfizer.

But the studies didn’t include enough participants to pick up rare, but serious adverse events like myocarditis.

“We’re worried about a side effect that we can’t measure yet, but it’s probably real, and we see a benefit that isn’t the same as it is in older age groups,” said Dr. Rubin.

Benefits vs. risks

FDA modeled the benefits and risks for children under a variety of scenarios. The benefits of the vaccines to children very much depend on the amount of transmission in the community.

When transmission is high, the benefits to children — in terms of infections, hospitalizations, ICU admissions — clearly outweigh its risks.

But when COVID-19 rates are low in the community, as they were in June, FDA analysts predicted the vaccines might send more children to the hospital for myocarditis than the virus would.

The FDA noted that kids who are hospitalized for myocarditis tend not to be as ill as children with COVID-19, however.

“If the trends continue the way they are going, the emergency for children is not what we might think it would be. That was my concern,” Dr. Hildreth said.

But others warned against complacency.

“Thinking that this is going to be the end of the wave permanently may be a little overly optimistic,” said committee chairman Arnold Monto, MD, a professor of public health and epidemiology at the University of Michigan, Ann Arbor.

The majority of COVID-19 cases in children are mild. Only about 1% of kids are hospitalized for their infections, according to CDC data. But the rates of hospitalizations in kids are about 3 times higher for people of color — including Blacks, Hispanics, and Native Americans, as compared to Whites and Asian Americans.

Since the start of the pandemic, 94 children ages 5 to 11 have died, making it the eighth leading cause of death for kids this age last year.

More than 5,200 children have developed a delayed complication from their infections called Multi-System Inflammatory Syndrome (MIS-C).

MIS-C can be severe and require hospital care and can lead to myocarditis. Children ages 5 to 11 are the age group at greatest risk for this complication.

Kids can also get long COVID. There’s not a lot of data on how often this happens, though it appears to be less frequent in children than in adults.

But a survey in the United Kingdom found that 7%-8% of kids have symptoms from their infections that last longer than 12 weeks, Dr. Havers said. Symptoms that can linger for kids include fatigue, cough, muscle and joint pain, headaches, and insomnia.

More than 1 million children have been impacted by school closures so far this year, and quarantines have had lasting impacts on learning, social development, and mental health.

Even though kids aren’t usually COVID superspreaders, they can still pass the infection on to others.

“What is clear is that secondary transmission from children, both to other children and to adults, does occur,” Dr. Havers said.

For that reason, they can continue the spread of the virus and give it opportunities to mutate and become more dangerous.

Safety monitoring to continue

Some committee members referenced thousands of letters they had received within the past few days urging them to vote against the vaccine.

Jay Portnoy, MD, a professor of pediatrics at Children’s Mercy Hospital in Kansas City, Mo., said he had personally received about 4,000 emails.

“But I feel like I need to also represent the consumers, the parents that I see every day in the clinic who are terrified of sending their children to school because they’re not protected against COVID,” he said, explaining his vote to recommend authorization.

“Our kids are going to be dealing with this virus for many years to come. It’s going to come repeatedly. Getting this vaccine is just the first step that they can take to protect themselves from having bad outcomes,” Dr. Portnoy said.

Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, reminded members of the committee that there were several government surveillance systems in place to catch any potential safety issues in near real time.

“I really appreciate very much the concern here. The safety monitoring of this vaccine will continue,” Dr. Marks said. “I do view this as one of our greatest responsibilities.”

“I really am so grateful that we had this discussion and voted to approve,” said Capt. Amanda Cohn, MD, chief medical officer at the National Center for Immunization and Respiratory Diseases.

“I think the benefits in this age group really are super important even if they are lower than for other age groups.”

This article was updated 10/27/21.

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

The benefits of Pfizer’s COVID-19 vaccine for children ages 5 to 11 outweigh its risks, according to an independent panel of vaccine experts that advises the Food and Drug Administration (FDA).
 

Seventeen of the 18 members of the Vaccines and Related Biological Products Advisory Committee (VRBPAC) on Oct. 26 voted to recommend the 10-microgram shot for kids, which is one-third the dose given to adults.

One member, Michael Kurilla, MD, director of the division of clinical innovation at the National Institutes of Health, Bethesda, Md., abstained from voting.

If the FDA follows the recommendation, as it typically does, and issues an Emergency Use Authorization for the vaccine, the shots could be available within days.

After the FDA’s final decision, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices will meet to make specific recommendations for its use. The CDC committee must stick closely to the conditions for use spelled out in the EUA, so their recommendations are likely to be similar to those made by the FDA. Their next meeting is scheduled for Nov. 2 and 3.

In the end, some on the panel felt uneasy with their decision.

“I voted yes primarily because I wanted to make sure that children who really need this vaccine, the Black and brown children of our country, get the vaccine,” said James Hildreth, MD, PhD, president and CEO of Meharry Medical College in Nashville.

“But to be honest, the best way to protect the health of some children will be to do nothing because they will be just fine,” he said.

Others said they were surprised by how difficult the decision had been.

“This is a much tougher one than we had expected going into it,” said committee member Eric Rubin, MD, editor and chief of the New England Journal of Medicine, during the FDA advisory committee’s meeting.

Ahead of the vote, the committee heard presentations outlining the expected benefits of vaccinating children along with potential risks.

“Children have been greatly impacted by the pandemic,” said Fiona Havers, MD, a medical officer with the CDC in Atlanta who reviewed the epidemiology of COVID-19 in kids.

In the second year of the pandemic, as more seniors have been vaccinated against the virus, COVID cases have largely shifted from older to younger age groups.

So far, there have been more than 1.9 million COVID-19 cases in children ages 5 through 11 in the United States.. Cases in kids saw a big jump in July and August with summer travel, schools reopening, and the dominance of the Delta variant.

And those are just the cases reported to the CDC. Regular testing of anonymous blood samples collected at sites across the United States indicates that 6 times as many kids have had COVID than what is reflected in official counts.

Last winter, blood sample testing showed about 13% of children had antibodies against the virus, suggesting they’d been infected. By this summer, that number had risen to 42%.

That figure clearly made an impression on many members of the committee who asked the FDA’s vaccine reviewers if they had tried to account for immunity from past infections in their modeling. They had not.

Some felt that even with a highly effective vaccine — new data presented by Pfizer showed the children’s dose was 90% effective at preventing symptomatic infections in kids — caution was warranted as much is still unknown about myocarditis, a rare side effect of the mRNA vaccines.

Myocarditis has been more common in younger age groups. It usually goes away over time but requires hospital care. It’s not known if myocarditis could have lingering effects for those who experience it.

There were no cases of myocarditis seen in Pfizer’s studies of the vaccine in children, and no other serious events were seen. Vaccine side effects reported in the Pfizer studies were mostly mild and included fatigue, headache, and pain at the injection site.

“We think we have optimized the immune response and minimized our reactions,” said William Gruber, MD, senior vice president vaccine research and clinical development at Pfizer.

But the studies didn’t include enough participants to pick up rare, but serious adverse events like myocarditis.

“We’re worried about a side effect that we can’t measure yet, but it’s probably real, and we see a benefit that isn’t the same as it is in older age groups,” said Dr. Rubin.

Benefits vs. risks

FDA modeled the benefits and risks for children under a variety of scenarios. The benefits of the vaccines to children very much depend on the amount of transmission in the community.

When transmission is high, the benefits to children — in terms of infections, hospitalizations, ICU admissions — clearly outweigh its risks.

But when COVID-19 rates are low in the community, as they were in June, FDA analysts predicted the vaccines might send more children to the hospital for myocarditis than the virus would.

The FDA noted that kids who are hospitalized for myocarditis tend not to be as ill as children with COVID-19, however.

“If the trends continue the way they are going, the emergency for children is not what we might think it would be. That was my concern,” Dr. Hildreth said.

But others warned against complacency.

“Thinking that this is going to be the end of the wave permanently may be a little overly optimistic,” said committee chairman Arnold Monto, MD, a professor of public health and epidemiology at the University of Michigan, Ann Arbor.

The majority of COVID-19 cases in children are mild. Only about 1% of kids are hospitalized for their infections, according to CDC data. But the rates of hospitalizations in kids are about 3 times higher for people of color — including Blacks, Hispanics, and Native Americans, as compared to Whites and Asian Americans.

Since the start of the pandemic, 94 children ages 5 to 11 have died, making it the eighth leading cause of death for kids this age last year.

More than 5,200 children have developed a delayed complication from their infections called Multi-System Inflammatory Syndrome (MIS-C).

MIS-C can be severe and require hospital care and can lead to myocarditis. Children ages 5 to 11 are the age group at greatest risk for this complication.

Kids can also get long COVID. There’s not a lot of data on how often this happens, though it appears to be less frequent in children than in adults.

But a survey in the United Kingdom found that 7%-8% of kids have symptoms from their infections that last longer than 12 weeks, Dr. Havers said. Symptoms that can linger for kids include fatigue, cough, muscle and joint pain, headaches, and insomnia.

More than 1 million children have been impacted by school closures so far this year, and quarantines have had lasting impacts on learning, social development, and mental health.

Even though kids aren’t usually COVID superspreaders, they can still pass the infection on to others.

“What is clear is that secondary transmission from children, both to other children and to adults, does occur,” Dr. Havers said.

For that reason, they can continue the spread of the virus and give it opportunities to mutate and become more dangerous.

Safety monitoring to continue

Some committee members referenced thousands of letters they had received within the past few days urging them to vote against the vaccine.

Jay Portnoy, MD, a professor of pediatrics at Children’s Mercy Hospital in Kansas City, Mo., said he had personally received about 4,000 emails.

“But I feel like I need to also represent the consumers, the parents that I see every day in the clinic who are terrified of sending their children to school because they’re not protected against COVID,” he said, explaining his vote to recommend authorization.

“Our kids are going to be dealing with this virus for many years to come. It’s going to come repeatedly. Getting this vaccine is just the first step that they can take to protect themselves from having bad outcomes,” Dr. Portnoy said.

Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, reminded members of the committee that there were several government surveillance systems in place to catch any potential safety issues in near real time.

“I really appreciate very much the concern here. The safety monitoring of this vaccine will continue,” Dr. Marks said. “I do view this as one of our greatest responsibilities.”

“I really am so grateful that we had this discussion and voted to approve,” said Capt. Amanda Cohn, MD, chief medical officer at the National Center for Immunization and Respiratory Diseases.

“I think the benefits in this age group really are super important even if they are lower than for other age groups.”

This article was updated 10/27/21.

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